NCBI Conserved Domain Search

Pleckstrin homology domain;

Pssm-ID: 465218 Cd Length: 143 Bit Score: 294.68 E-value: 2.96e-92

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  1457 VQCEGLSEQLVFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQITKPLGSSGTDKVFSPKSNLQYKMYKTP 1536
Cdd:pfam16652    1 VQCEGLSEQLVFNSLTNCLGPRKLLHSGKLYKVKSNKELVGFLFNDFLLLTQPVKPLSSAGTDKLFSSKSNIQYKMYKTP 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997330  1537 IFLNEVLVKLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKKKRE 1599
Cdd:pfam16652   81 IFLNEVMVKLPTDPSSSEPTFQLSHIDRVYTLKAESPNERTAWVKKIKEASELYIETEKKKRE 143

Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. There are two human ITSN genes: ITSN1 and ITSN2. They share significant sequence identity and a similar domain structure having both short and long isoforms produced by alternative splicing. The short isoform (ITSN-S) consists of two Eps15 homology domains (EH1 and EH2), a coiled-coil region (CCR) and five Src homology 3 domains (SH3A-E). The EH domains bind to Asn-Pro-Phe motifs and are implicated in endocytosis and vesicle transport. The SH3 domains bind to proline-rich sequences and are commonly found in proteins implicated in cell signalling pathways, cytoskeletal organization and membrane traffic. The long isoform (ITSN-L) contains three additional C-terminal domains, a Dbl homology domain (DH), a Pleckstrin homology domain (PH) and a C2 domain. The tandem DH-PH domains are present in all Dbl family of GEFs. ITSN acts specifically on Cdc42 through its DH domain with no portion of the PH domain making contact with Cdc42. This is in contrast to Dbs which requires the PH domain for full catalytic activity. The ITSN PH domain binds phosphoinositides. C2 domains are usually involved in Ca2+-dependent and Ca2+-independent phospholipid binding. There are more than 30 proteins that interact with ITSNs. ITSN-S is present in mammals, frogs, flies and nematodes, while ITSN-L is present only in vertebrates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270084 Cd Length: 132 Bit Score: 273.18 E-value: 7.97e-85

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1465 QLVFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQITKPLGSSGTDKVFSPKSNLQYKMYKTPIFLNEVLV 1544
Cdd:cd13264     1 QLIFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQPIKPLGSSGNDFVFDNKANIQYKMYKTPIFLNEVLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1545 KLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKK 1596
Cdd:cd13264    81 KLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKK 132

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 268.10 E-value: 5.39e-83

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1599 EKAYLVRSQRATGIGRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCI 1678
Cdd:cd08375     1 EKAYLARSQRASGIGRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1679 TVFERDQFSPDDFLGRTEIRVADIKKD-QGSKGPVTKCLLLHEVPTGEIVVRLDLQ 1733
Cdd:cd08375    81 TVFDRDFFSPDDFLGRTEIRVADILKEtKESKGPITKRLLLHEVPTGEVVVKLDLQ 136

Intersectin and clathrin adaptor AP2 binding region; INTAP is a natively unstructured region of intersectin 1 proteins, lying between the first pair of SH3 domains, that binds to the clathrin adaptor AP2. This binding forms an intersectin-AP2 complex that functions as an important regulator of clathrin-mediated SV recycling in synapses.

Pssm-ID: 435467 Cd Length: 115 Bit Score: 225.91 E-value: 1.25e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   820 KIPENEVPTPAKPVTDltSAPAPKLALRETPA-PL-PVTSSEPSTTPNNWADFSSTWPSSSNEKPETDNWDTWAAQPSLT 897
Cdd:pfam16617    1 KIPESEVPASVKPAAD--STAAPKVALRETPTtPLaPPTSSESSTASNNWADFSSTWPTNSSEKAETDNWDAWAAQPSLT 78

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 568997330   898 VPSAGQLRQRSAFTPATATGSSPSPVLGQGEKVEGLQ 934
Cdd:pfam16617   79 VPSAGQLRQRSAFTPATVTGSSPSPVLGQGEKVEGLQ 115

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

Pssm-ID: 238091 [Multi-domain] Cd Length: 181 Bit Score: 180.57 E-value: 8.27e-52

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1255 RQGYIHELIVTEENYVNDLQLVTEIFQKPLTESEL-LTEKEVAMIFVNWKELIMCNIKLLKALRVRKKMSGekMPVKMIG 1333
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1334 DILSAQLPHMQPYIRFCSCQLNGAALIQQKTDEAPDFKEFVKRLamDPRCKGMPLSSFILKPMQRVTRYPLIIKNILENT 1413
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKA--ESECGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156

                         170       180
                  ....*....|....*....|....*
gi 568997330 1414 PENHPDHSHLKHALEKAEELCSQVN 1438
Cdd:cd00160   157 PDGHEDREDLKKALEAIKEVASQVN 181

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

Pssm-ID: 214619 [Multi-domain] Cd Length: 180 Bit Score: 175.18 E-value: 5.70e-50

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   1259 IHELIVTEENYVNDLQLVTEIFQKPLTESE-LLTEKEVAMIFVNWKELIMCNIKLLKALRVRKKMSGekMPVKMIGDILS 1337
Cdd:smart00325    2 LKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWD--DSVERIGDVFL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   1338 AQLPHMQPYIRFCSCQLNGAALIQQKtDEAPDFKEFVKRLAMDPRCKGMPLSSFILKPMQRVTRYPLIIKNILENTPENH 1417
Cdd:smart00325   80 KLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158

                           170       180
                    ....*....|....*....|..
gi 568997330   1418 PDHSHLKHALEKAEELCSQVNE 1439
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

Pssm-ID: 459876 [Multi-domain] Cd Length: 176 Bit Score: 174.41 E-value: 1.07e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  1259 IHELIVTEENYVNDLQLVTEIFQKPLTESELLTEKEVAMIFVNWKELIMCNIKLLkaLRVRKKmsgEKMPVKMIGDILSA 1338
Cdd:pfam00621    2 IKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLK---EWISIQRIGDIFLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  1339 QLPHMQPYIRFCSCQLNGAALIQQKTDEAPDFKEFVKRLAMDPRCKGMPLSSFILKPMQRVTRYPLIIKNILENTPENHP 1418
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156

                          170       180
                   ....*....|....*....|
gi 568997330  1419 DHSHLKHALEKAEELCSQVN 1438
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 158.21 E-value: 3.37e-45

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330    238 EWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMSGQ 317
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80

                            90
                    ....*....|....*.
gi 568997330    318 PLPPVLPPEYIPPSFR 333
Cdd:smart00027   81 PIPASLPPSLIPPSKR 96

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 138.33 E-value: 1.47e-38

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1091 KKPEIAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSP 1155
Cdd:cd11993     1 KKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSP 65

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 133.97 E-value: 2.98e-37

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11987     1 YYRALYPFEARSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 55

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 132.40 E-value: 3.78e-36

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330     39 WAITVEERAKHDQQFLSLKP-IAGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQVEFSIAMKLIKLKLQGYQ 117
Cdd:smart00027    2 WAISPEDKAKYEQIFRSLDKnQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGYP 81

                            90
                    ....*....|....*
gi 568997330    118 LPSTLPPVMKQQPVA 132
Cdd:smart00027   82 IPASLPPSLIPPSKR 96

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 128.22 E-value: 3.45e-35

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKL 1152
Cdd:cd11839     1 IAQVIAPFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQARGKKRQIGWFPANYVKL 58

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 125.07 E-value: 4.24e-34

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1175 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11995     1 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVKL 54

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 121.24 E-value: 9.76e-33

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11991     1 EYVAMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 118.61 E-value: 8.08e-32

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11836     1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAEPGWLAGELKGKTGWFPANYVEK 55

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 115.59 E-value: 9.70e-31

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11840     1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVEP 53

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 114.04 E-value: 2.73e-30

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11989     1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 52

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 112.51 E-value: 1.02e-29

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11838     1 EYIALYPYESNEPGDLTFNAGDVILVTKKDGEWWTGTIGDRTGIFPSNYVRP 52

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 109.38 E-value: 1.26e-28

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQ-GQKGWFPKSYVKL 985
Cdd:cd11837     1 TATALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELEgGEEGWFPKSYVKE 53

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 108.91 E-value: 1.82e-28

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1175 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11996     1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 106.94 E-value: 1.14e-27

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLL 1153
Cdd:cd11994     1 IAQVTTAYVASGVEQLSLSPGQLILILKKNSSGWWLGELQARGKKRQKGWFPASHVKLL 59

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 104.74 E-value: 5.54e-27

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11990     1 KAQALCSWTAKKDNHLNFSKNDIITVLEQQENWWFGEVHGGRGWFPKSYVKL 52

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 100.76 E-value: 2.05e-25

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  249 YRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMS 315
Cdd:cd00052     1 YDQIFRSLDPDGDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 99.22 E-value: 7.55e-25

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   50 DQQFLSLKPI-AGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQVEFSIAMKLIKLKLQ 114
Cdd:cd00052     2 DQIFRSLDPDgDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 100.09 E-value: 1.01e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHI--TKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDD 1690
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKkkTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                           90
                   ....*....|....*..
gi 568997330  1691 FLGRTEIRVADIKKDQG 1707
Cdd:pfam00168   81 FIGEVRIPLSELDSGEG 97

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 96.23 E-value: 5.77e-24

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd11992     1 EYIALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVR 51

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 97.56 E-value: 7.04e-24

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   1614 RLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHI---TKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDD 1690
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEkkkTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90       100
                    ....*....|....*....|
gi 568997330   1691 FLGRTEIRVADIKKDQGSKG 1710
Cdd:smart00239   81 FIGQVTIPLSDLLLGGRHEK 100

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 96.75 E-value: 1.43e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1615 LMVNVVEGIELKPCRSHGKSNPYCEVTMGS-QCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDFLG 1693
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFLG 80

                          90
                  ....*....|....*
gi 568997330 1694 RTEIRVADIKKDQGS 1708
Cdd:cd00030    81 EVEIPLSELLDSGKE 95

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 92.63 E-value: 1.14e-22

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  765 VYYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11988     2 VNYRALYPFEARNHDEMSFNAGDIIQVDEKTVGEPGWLYGSFQGNFGWFPCNYVEK 57

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 88.36 E-value: 3.19e-21

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330   1174 VCQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV-SGQVGLFPSNYVK 1227
Cdd:smart00326    2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLgRGKEGLFPSNYVE 56

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 84.05 E-value: 9.21e-20

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV-SGQVGLFPSNY 1225
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELnGGREGLFPANY 51

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

Pssm-ID: 227709 [Multi-domain] Cd Length: 1175 Bit Score: 95.34 E-value: 2.38e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1244 LLDMLTPTERKRQGYIHELIVTEENYVNDLQLVTEIFQKPLTESELLTE----KEVAMIFVNWKELIMCNIKLLKALRVR 1319
Cdd:COG5422   474 VWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPEnarrNFIKHVFANINEIYAVNSKLLKALTNR 553

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1320 KKMSGekmPVKMIGDILSAQLPHMQPYIRFCSCQLNGAALIQQKTDEAPDFKEFVKRLAMDPRCKGMPLSSFILKPMQRV 1399
Cdd:COG5422   554 QCLSP---IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRL 630

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1400 TRYPLIIKNILENTPENHPDHSHLKHALEKAEELCSQVNEGVREKENsdRLEWIQahvqcegLSEQLVFNSVTNCLG--- 1476
Cdd:COG5422   631 ARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEN--RGDLFH-------LNQQLLFKPEYVNLGlnd 701

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1477 -PRKFLHSGKLY---KAKSNKELYG----FLFNDFLLLTQItKPLGSSGTDKVFSPKSNLQYkMYKTPIFLNEVLVKLPT 1548
Cdd:COG5422   702 eYRKIIFKGVLKrkaKSKTDGSLRGdiqfFLLDNMLLFCKA-KAVNKWRQHKVFQRPIPLEL-LFISPDEDSPDRAEYLK 779

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1549 D-PSGD--EPIFHISHIDRVY-------------TLRAESINERTAWVQKIK 1584
Cdd:COG5422   780 PaPSADvlDPAYNTKPPKNAYgfelygngqryqiTLYAETHAGRDTWLEHIK 831

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 81.52 E-value: 7.74e-19

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 92.31 E-value: 1.80e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEkQLEKQRELERQREEERRKEIERREAAKRELER 466
Cdd:COG1196   224 ELEAELLLLKLRELEAELEELEAELEELEAELEELEAELAELEAELE-ELRLELEELELELEEAQAEEYELLAELARLEQ 302

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  467 QRQLewERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAE 546
Cdd:COG1196   303 DIAR--LEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEE 380

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  547 IthlQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVF 626
Cdd:COG1196   381 L---EELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEE 457

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  627 NNQLKELREihskQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQPR 694
Cdd:COG1196   458 EEALLELLA----ELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGFLEGVKAALLLAGLRG 521

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 81.95 E-value: 4.33e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELK------PCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQf 1686
Cdd:cd08391     1 GVLRIHVIEAQDLVakdkfvGGLVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDP- 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 568997330 1687 SPDDFLGRTEIRVADIKKdqgsKGPVTKCLLLHEVPTGEIVVRL 1730
Cdd:cd08391    80 DKDDFLGRLSIDLGSVEK----KGFIDEWLPLEDVKSGRLHLKL 119

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 78.16 E-value: 1.28e-17

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1174 VCQVigMYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11875     1 KARV--LFDYEAENEDELTLREGDIVTILSKDceDKGWWKGELNGKRGVFPDNFVEP 55

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 89.04 E-value: 2.27e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  355 EEPSSEDEQQPEKKLPVTfeDKKRENFERGSVELEKRRQAL---LEQQRKEQERLAQLERAEQERKERERQEQERKRQLE 431
Cdd:PTZ00121 1345 AEAAKAEAEAAADEAEAA--EEKAEAAEKKKEEAKKKADAAkkkAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADE 1422

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  432 LEKQLEKQRELERQREEERRKEIERReaAKRELERQRQLEWERNRRQEllnqRNKEQEGTVVLKARRKTLEFELEALNDK 511
Cdd:PTZ00121 1423 AKKKAEEKKKADEAKKKAEEAKKADE--AKKKAEEAKKAEEAKKKAEE----AKKADEAKKKAEEAKKADEAKKKAEEAK 1496

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  512 KHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLG----RLIPEKQILSDQLKQVQQNSLHRDS 587
Cdd:PTZ00121 1497 KKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKadelKKAEELKKAEEKKKAEEAKKAEEDK 1576

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  588 LLTLKRALEAKELARQQLREQLDEVERETRSKLQEI------DVFNNQLKELREIhsKQQLQKQRSLEAARLKQKEQERK 661
Cdd:PTZ00121 1577 NMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAkkaeeaKIKAEELKKAEEE--KKKVEQLKKKEAEEKKKAEELKK 1654

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  662 SLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRK----PHEEDRLKREDSVRKKEAEERAKPEMQDKQSRLFHPHQEP 737
Cdd:PTZ00121 1655 AEEENKIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAaealKKEAEEAKKAEELKKKEAEEKKKAEELKKAEEENKIKAEE 1734


                  ..
gi 568997330  738 AK 739
Cdd:PTZ00121 1735 AK 1736

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 76.98 E-value: 2.79e-17

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11826     2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYV 51

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 86.91 E-value: 8.86e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  366 EKKLPVTfedkkRENFERgsV-----ELEKRRQALlEQQRKEQERLAQLERAEQERKER----ERQEQERKRQLELEKQL 436
Cdd:COG1196   178 ERKLEAT-----EENLER--LedilgELERQLEPL-ERQAEKAERYRELKEELKELEAEllllKLRELEAELEELEAELE 249

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  437 EKQRELErqreeerrkeieRREAAKRELERQRQLewERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLE 516
Cdd:COG1196   250 ELEAELE------------ELEAELAELEAELEE--LRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELE 315

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  517 GKLQDIRCRLATQRQEIESTNKSRELRIAEIThlqqqlqesqqmlgRLIPEKQILSDQLKQVQQnslhrdslltlkrALE 596
Cdd:COG1196   316 ERLEELEEELAELEEELEELEEELEELEEELE--------------EAEEELEEAEAELAEAEE-------------ALL 368

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  597 AKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREiHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRV 676
Cdd:COG1196   369 EAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEE-AEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEA 447

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  677 QERDKQWLEHVQQEEQPRPRKPHEEDRLKRE-DSVRKKEAEERAKPEMQDKQSRLFHPHQEPAKLATQAPWSttEKGPLT 755
Cdd:COG1196   448 AEEEAELEEEEEALLELLAELLEEAALLEAAlAELLEELAEAAARLLLLLEAEADYEGFLEGVKAALLLAGL--RGLAGA 525

                         410
                  ....*....|....*
gi 568997330  756 ISAQESVKVVYYRAL 770
Cdd:COG1196   526 VAVLIGVEAAYEAAL 540

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 75.07 E-value: 1.58e-16

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11823     6 YSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYV 51

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 74.38 E-value: 2.45e-16

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDG---DWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11842     3 VALYDFAGEQPGDLAFQKGDIITILKKSDsqnDWWTGRIGGREGIFPANYVEL 55

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 74.22 E-value: 3.37e-16

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11766     5 KFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYV 51

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 73.89 E-value: 3.67e-16

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVKE 53

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 73.16 E-value: 6.87e-16

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKE-DPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11804     3 VAKHDFKATAEDELSFKKGSILKVLNMEdDPNWYKAELDGKEGLIPKNYI 52

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 73.06 E-value: 7.05e-16

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVklTTD 1231
Cdd:cd11964     2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV--TAD 55

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 72.94 E-value: 7.29e-16

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11950     1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 73.14 E-value: 7.67e-16

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1175 CQVIgmYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11874     2 CKVL--FSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 72.56 E-value: 1.13e-15

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11949     2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 52

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 83.18 E-value: 1.23e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   389 EKRRQALLeQQRKEQERLAQLERAeqeRKERERQEQERKRQLEL-EKQLEKQrelerqreeerrkeierreAAKRELERQ 467
Cdd:TIGR02168  172 ERRKETER-KLERTRENLDRLEDI---LNELERQLKSLERQAEKaERYKELK-------------------AELRELELA 228

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   468 ---RQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIEstnksrelri 544
Cdd:TIGR02168  229 llvLRLEELREELEELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKELYALANEIS---------- 298

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   545 aeithlqqqlqesqqmlgRLIPEKQILSDQLKQVQQNslhrdslltlkraLEAKELARQQLREQLDEVERETRSKLQEID 624
Cdd:TIGR02168  299 ------------------RLEQQKQILRERLANLERQ-------------LEELEAQLEELESKLDELAEELAELEEKLE 347

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   625 VFNNQLKELREihskqqlqkqrSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRL 704
Cdd:TIGR02168  348 ELKEELESLEA-----------ELEELEAELEELESRLEELEEQLETLRSKVAQLELQIASLNNEIERLEARLERLEDRR 416

                          330       340       350
                   ....*....|....*....|....*....|....*....
gi 568997330   705 KREDSVRKKEAEERAKPEMQDKQSRLFHPHQEPAKLATQ 743
Cdd:TIGR02168  417 ERLQQEIEELLKKLEEAELKELQAELEELEEELEELQEE 455

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 74.77 E-value: 1.36e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIEL--KPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDD 1690
Cdd:cd04024     1 GVLRVHVVEAKDLaaKDRSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1691 FLGRTEIRVADIKKDqGSKGPVTKCLLLHEVPT-------GEIVVRLDL 1732
Cdd:cd04024    81 YLGEFDIALEEVFAD-GKTGQSDKWITLKSTRPgktsvvsGEIHLQFSW 128

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 73.95 E-value: 1.54e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   248 KYRQLFNSHdKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMHLIDVAMSG--QPLPPVLPP 325
Cdd:pfam12763   11 KYWEIFSGL-KPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIFDLVNGniADVPDELPD 89


                   ....*.
gi 568997330   326 EYIPPS 331
Cdd:pfam12763   90 WLVPGS 95

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 71.85 E-value: 1.95e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 568997330  1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV-SGQVGLFPS 1223
Cdd:pfam00018    3 LYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNkGGKEGLIPS 47

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 71.56 E-value: 2.53e-15

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11772     5 LYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYV 51

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 71.73 E-value: 2.67e-15

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1174 VCQVigMYDYTAQNDDELAFSKGQIINVLNK--EDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd12142     1 YCRV--LFDYNPVAPDELALKKGDVIEVISKetEDEGWWEGELNGRRGFFPDNFV 53

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 71.42 E-value: 3.40e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   1020 PGEEFIAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGD-KSGVFPSNYVR 1073
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKsDDGWWKGRLGRgKEGLFPSNYVE 56

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 70.98 E-value: 4.17e-15

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11951     6 YDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 70.72 E-value: 4.18e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568997330  1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:pfam14604    2 LYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 70.96 E-value: 4.91e-15

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11820     2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFVT 53

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 80.55 E-value: 5.40e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   390 KRRQALLEQQRKEQ-ERLAQlERAEQERKERERqEQERKRQLElEKQLEKQRELERQREEERRKEierreaaKRELERQR 468
Cdd:pfam17380  279 QHQKAVSERQQQEKfEKMEQ-ERLRQEKEEKAR-EVERRRKLE-EAEKARQAEMDRQAAIYAEQE-------RMAMERER 348

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   469 QLEWERNRRQELLNQRNKEQEGTVVLKARRktlefELEALndkkhQLEGKLQDIRCrlatqRQEIEStnkSRELRIAEit 548
Cdd:pfam17380  349 ELERIRQEERKRELERIRQEEIAMEISRMR-----ELERL-----QMERQQKNERV-----RQELEA---ARKVKILE-- 408

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   549 hlqqqlqesqQMLGRLIPEKQILSDQLKQVQQNSLHRD-SLLTLKRALE-----AKELARQQLREQLDEVERETRSKLQE 622
Cdd:pfam17380  409 ----------EERQRKIQQQKVEMEQIRAEQEEARQREvRRLEEERAREmervrLEEQERQQQVERLRQQEEERKRKKLE 478

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   623 IDvfnNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDkqwlEHVQQEEQPRPRKPHEED 702
Cdd:pfam17380  479 LE---KEKRDRKRAEEQRRKILEKELEERKQAMIEEERKRKLLEKEMEERQKAIYEEE----RRREAEEERRKQQEMEER 551

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 568997330   703 RLKREDSvrKKEAEERAKPEMQDKQSRLFHPHQEPAKLATQAPWST 748
Cdd:pfam17380  552 RRIQEQM--RKATEERSRLEAMEREREMMRQIVESEKARAEYEATT 595

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 70.26 E-value: 6.67e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330    763 KVVYYRALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGELK-GKTGWFPANYAE 819
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLE--KSDDGWWKGRLGrGKEGLFPSNYVE 56

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 71.64 E-value: 8.86e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330    45 ERAKHDQQFLSLKPIAGFITGDQARNFFFQSGLPQPVLAQIWALADMNNDGRMDQVEFSIAMKLIKLKLQGYQ--LPSTL 122
Cdd:pfam12763    8 EIKKYWEIFSGLKPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIFDLVNGNIadVPDEL 87


                   .
gi 568997330   123 P 123
Cdd:pfam12763   88 P 88

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 70.12 E-value: 1.04e-14

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPD----WWKGEVSGQVGLFPS 1223
Cdd:cd11762     5 LYDYEAQSDEELSFPEGAIIRILRKDDNGvddgWWEGEFNGRVGVFPS 52

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 69.68 E-value: 1.32e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11823     3 KALYSYTANREDELSLQPGDIIEVHEKQ--DDGWWLGELNGKKGIFPATYVE 52

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 72.74 E-value: 1.32e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1612 IGRLMVNVVEGIELKPCRSHGkSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQeVLCITVFERDQFSPDDF 1691
Cdd:cd04038     1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMA-PLKLEVFDKDTFSKDDS 78


                  ....*.
gi 568997330 1692 LGRTEI 1697
Cdd:cd04038    79 MGEAEI 84

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 69.28 E-value: 1.47e-14

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQ-VGLFPSNYVK 1227
Cdd:cd11825     5 LYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKkQKWFPANYVE 53

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 69.54 E-value: 1.65e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1175 CQVIgmYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12057     2 CKVL--FPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVKL 55

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 79.33 E-value: 1.67e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   382 ERGSVELEKRRQ-ALLEQQRKEQERLA------------QLERAEQERKERERQEQERKRQL-ELEKQLEK-QRELERQR 446
Cdd:TIGR02168  667 KTNSSILERRREiEELEEKIEELEEKIaelekalaelrkELEELEEELEQLRKELEELSRQIsALRKDLARlEAEVEQLE 746

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   447 EEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRL 526
Cdd:TIGR02168  747 ERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREALDELRAELTLLNEEAANLRERL 826

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   527 ATQRQEIESTNKS---RELRIAEITHLQQQLQESQQMLGRLIPEkqiLSDQLKQVQQnslhrdslltlkrALEAKELARQ 603
Cdd:TIGR02168  827 ESLERRIAATERRledLEEQIEELSEDIESLAAEIEELEELIEE---LESELEALLN-------------ERASLEEALA 890

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   604 QLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQR-SLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQ 682
Cdd:TIGR02168  891 LLRSELEELSEELRELESKRSELRRELEELREKLAQLELRLEGlEVRIDNLQERLSEEYSLTLEEAEALENKIEDDEEEA 970

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 69.28 E-value: 1.72e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVklTTDM 1232
Cdd:cd11963     3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV--TTDL 57

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 68.69 E-value: 2.35e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE-VSGQVGLFPSNYV 1226
Cdd:cd11812     2 VVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSlVNGQQGYFPANYV 52

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 68.64 E-value: 2.40e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGD-KSGVFPSNY 1071
Cdd:cd00174     2 ARALYDYEAQDDDELSFKKGDIITVLEKdDDGWWEGELNGgREGLFPANY 51

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 79.03 E-value: 2.89e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  359 SEDEQQPEKKLPVTFEDKKRENFERGSVElEKRRQALLEQQRKEQERLAQLERAEQERKERE---RQEQERKRQLELEKQ 435
Cdd:PTZ00121 1400 AEEDKKKADELKKAAAAKKKADEAKKKAE-EKKKADEAKKKAEEAKKADEAKKKAEEAKKAEeakKKAEEAKKADEAKKK 1478

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  436 LEKQRELERQREEERRKEIERREAAKRELERQRQLEW---ERNRRQELLNQRNKEQEGTVVLKA--RRKTLEF----ELE 506
Cdd:PTZ00121 1479 AEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAkkaEEAKKADEAKKAEEAKKADEAKKAeeKKKADELkkaeELK 1558

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  507 ALNDKKHQLEGKLQDIRCRLATQRQEIesTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRD 586
Cdd:PTZ00121 1559 KAEEKKKAEEAKKAEEDKNMALRKAEE--AKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVE 1636

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  587 SLLT-----------LKRALEAKELARQQLREQLDEVER---ETRSKLQEIDVFNNQLKelREIHSKQQLQKQRSLEAAR 652
Cdd:PTZ00121 1637 QLKKkeaeekkkaeeLKKAEEENKIKAAEEAKKAEEDKKkaeEAKKAEEDEKKAAEALK--KEAEEAKKAEELKKKEAEE 1714

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  653 LKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSR 729
Cdd:PTZ00121 1715 KKKAEELKKAEEENKIKAEEAKKEAEEDKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEELDEEDEK 1791

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 78.56 E-value: 3.49e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   371 VTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQER-----KRQLELEKQLEKQRELERQ 445
Cdd:TIGR02168  234 LEELREELEELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKElyalaNEISRLEQQKQILRERLAN 313

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   446 REEERrkeierreaaKRELERQRQLEWERNRRQELLNQRNKEQEgtvVLKARRKTLEFELEALNDKKHQLEGKLQDIRCR 525
Cdd:TIGR02168  314 LERQL----------EELEAQLEELESKLDELAEELAELEEKLE---ELKEELESLEAELEELEAELEELESRLEELEEQ 380

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   526 LATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDsLLTLKRALEAKELARQQL 605
Cdd:TIGR02168  381 LETLRSKVAQLELQIASLNNEIERLEARLERLEDRRERLQQEIEELLKKLEEAELKELQAE-LEELEEELEELQEELERL 459

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330   606 REQLDEVERETRSKLQEIDVFNNQLKELR-EIHSKQQLQKQRSLEAARLKQKEQERKSL 663
Cdd:TIGR02168  460 EEALEELREELEEAEQALDAAERELAQLQaRLDSLERLQENLEGFSEGVKALLKNQSGL 518

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 68.17 E-value: 4.24e-14

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11824     5 LYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLEK 53

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 69.90 E-value: 5.10e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1615 LMVNVVEGIELKPCRSHGKSNPYCEVTM-GSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDFLG 1693
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDLLG 80


                  ....*....
gi 568997330 1694 RTEIRVADI 1702
Cdd:cd04040    81 SAYIDLSDL 89

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 77.87 E-value: 5.90e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  352 RLPEEPSSEDEQQPEKKLPVTFEDKKRENFER--GSVELEKRRQALLEQQRKEQERLAQLERAEQERK--ERERQEQERK 427
Cdd:PTZ00121 1236 KKDAEEAKKAEEERNNEEIRKFEEARMAHFARrqAAIKAEEARKADELKKAEEKKKADEAKKAEEKKKadEAKKKAEEAK 1315

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  428 RQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQlEWERNRRQELLNQRNKEQEGTVVLKARRKTLEF-ELE 506
Cdd:PTZ00121 1316 KADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAAD-EAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKkKAD 1394

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  507 ALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNslhrd 586
Cdd:PTZ00121 1395 EAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKAEEAKKKAEEA----- 1469

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  587 slltlKRALEAKELARQQLR-EQLDEVERETRSKLQEIDVFNNQLK---ELREIHSKQQLQKQRSLEAAR----LKQKEQ 658
Cdd:PTZ00121 1470 -----KKADEAKKKAEEAKKaDEAKKKAEEAKKKADEAKKAAEAKKkadEAKKAEEAKKADEAKKAEEAKkadeAKKAEE 1544

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  659 ERKSLEL----------EKQKEDAQRRVQERDKQWL---EHVQQEEQPRP------------------RKPHEE----DR 703
Cdd:PTZ00121 1545 KKKADELkkaeelkkaeEKKKAEEAKKAEEDKNMALrkaEEAKKAEEARIeevmklyeeekkmkaeeaKKAEEAkikaEE 1624

                         410       420       430
                  ....*....|....*....|....*....|....*..
gi 568997330  704 LKREDSVRKKEAEERAKPEMQDKQSRLFHPHQEPAKL 740
Cdd:PTZ00121 1625 LKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKI 1661

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 67.73 E-value: 5.91e-14

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQ---VGLFPSNY 1225
Cdd:cd11821     5 LYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGDpsrRGVFPVSF 53

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 67.55 E-value: 6.28e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVEL 53

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 67.56 E-value: 6.55e-14

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330    931 EGLQAQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQ-GQKGWFPKSYVK 984
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDdGWWKGRLGrGKEGLFPSNYVE 56

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 67.45 E-value: 8.12e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDP--DWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSqnDWWTGRIGGREGIFPANYVEL 55

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 67.22 E-value: 8.80e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE--VSGQVGLFPSNY 1225
Cdd:cd11845     1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARhlSTGKEGYIPSNY 52

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 66.67 E-value: 1.19e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1175 CQVIgmYDYTAQNDDELAFSKGQIINVLnKEDPD-WWKGEVSGQVGLFPSNYV 1226
Cdd:cd11827     2 CKAL--YAYDAQDTDELSFNEGDIIEIL-KEDPSgWWTGRLRGKEGLFPGNYV 51

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 66.67 E-value: 1.45e-13

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11840     3 IALFPYTAQNEDELSFQKGDIInVLSKDDPDWWRGELNGQTGLFPSNYV 51

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 66.57 E-value: 1.54e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVS-GQVGLFPSNYVKL 1228
Cdd:cd11819     3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAkGQKGLFPANYVEL 54

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 66.57 E-value: 1.63e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11877     4 AKFNFEGTNEDELSFDKGDIITVTQVvEGGWWEGTLNGKTGWFPSNYVKE 53

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 66.29 E-value: 2.00e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11959     3 VALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGLFPANYVEL 53

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 66.07 E-value: 2.22e-13

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12052     6 FDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGLFPDNFVR 52

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 66.02 E-value: 2.47e-13

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   1092 KPEIAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqargKKRQIGWFPANYVK 1151
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRL----GRGKEGLFPSNYVE 56

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 75.10 E-value: 3.16e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   373 FEDKKRENFErgsvELEKRRQALLEQQRKEQERLAQLERAEQER--KERERQEQERKRQLEL-EKQLEKQrelerqreee 449
Cdd:TIGR02169  168 FDRKKEKALE----ELEEVEENIERLDLIIDEKRQQLERLRRERekAERYQALLKEKREYEGyELLKEKE---------- 233

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   450 rrkeieRREAAKRELERQRQ-LEWERNRRQELLNQRNKEQEgtvvlkARRKTLEFELEALNDKKhqlEGKLQDIRCRLAT 528
Cdd:TIGR02169  234 ------ALERQKEAIERQLAsLEEELEKLTEEISELEKRLE------EIEQLLEELNKKIKDLG---EEEQLRVKEKIGE 298

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   529 QRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQqnsLHRDSLLTLKRALEAKELARQQLREQ 608
Cdd:TIGR02169  299 LEAEIASLERSIAEKERELEDAEERLAKLEAEIDKLLAEIEELEREIEEER---KRRDKLTEEYAELKEELEDLRAELEE 375

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   609 LDEVERETRSKL----QEIDVFNNQLKEL-REIHSKQQLQKQRSLEAARLKQK--EQERKSLELEKQKEDAQRRVqerdk 681
Cdd:TIGR02169  376 VDKEFAETRDELkdyrEKLEKLKREINELkRELDRLQEELQRLSEELADLNAAiaGIEAKINELEEEKEDKALEI----- 450

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330   682 qwlehvqqEEQPRPRKPHEEDRLKREDSVRKKEAE-ERAKPEMQDKQSRLfhphqePAKLATQAPWSTTEKG 752
Cdd:TIGR02169  451 --------KKQEWKLEQLAADLSKYEQELYDLKEEyDRVEKELSKLQREL------AEAEAQARASEERVRG 508

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 74.97 E-value: 3.47e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  374 EDKKRENFERGSVELEKRRQALLEQQRkEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKE 453
Cdd:COG1196   397 ELAAQLEELEEAEEALLERLERLEEEL-EELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALL 475

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  454 IERREAAKRELERQRQLEWERNRRQE---------LLNQRNKEQEGTVVLKARRKTLEFELEALNDkkHQLEGKLQDIRC 524
Cdd:COG1196   476 EAALAELLEELAEAAARLLLLLEAEAdyegflegvKAALLLAGLRGLAGAVAVLIGVEAAYEAALE--AALAAALQNIVV 553

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  525 RLATQRQEIESTNKSRELRIAE---ITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALE-AKEL 600
Cdd:COG1196   554 EDDEVAAAAIEYLKAAKAGRATflpLDKIRARAALAAALARGAIGAAVDLVASDLREADARYYVLGDTLLGRTLVaARLE 633

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  601 ARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERD 680
Cdd:COG1196   634 AALRRAVTLAGRLREVTLEGEGGSAGGSLTGGSRRELLAALLEAEAELEELAERLAEEELELEEALLAEEEEERELAEAE 713

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  681 KQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSR 729
Cdd:COG1196   714 EERLEEELEEEALEEQLEAEREELLEELLEEEELLEEEALEELPEPPDL 762

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 65.61 E-value: 3.98e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKE-----DPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11876     5 LFDYDARGEDELTLRRGQPVEVLSKDaavsgDEGWWTGKIGDKVGIFPSNYV 56

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 75.09 E-value: 4.02e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   360 EDEQQPEKKLpvtfeDKKRENFERgsVElekrrqALLEQQRKEQERL-AQLERAEqerKERERQEQERKRQLELEKQ--L 436
Cdd:TIGR02168  172 ERRKETERKL-----ERTRENLDR--LE------DILNELERQLKSLeRQAEKAE---RYKELKAELRELELALLVLrlE 235

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   437 EKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLE 516
Cdd:TIGR02168  236 ELREELEELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKELYALANEISRLEQQKQILRERLANLE 315

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   517 GKLQdircRLATQRQEIESTNKSRELRIAEIthlqqqlqesqqmlgrlipEKQILSDqlkQVQQNSLhRDSLLTLKRALE 596
Cdd:TIGR02168  316 RQLE----ELEAQLEELESKLDELAEELAEL-------------------EEKLEEL---KEELESL-EAELEELEAELE 368

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   597 AKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREihSKQQLQKQRsleaARLKQKEQERKSLELEKQKEDAQRRV 676
Cdd:TIGR02168  369 ELESRLEELEEQLETLRSKVAQLELQIASLNNEIERLEA--RLERLEDRR----ERLQQEIEELLKKLEEAELKELQAEL 442

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330   677 QERDKQWLEHVQQEEQPRPRKPHEEDRLKredsvRKKEAEERAKPEMQDKQSRLF 731
Cdd:TIGR02168  443 EELEEELEELQEELERLEEALEELREELE-----EAEQALDAAERELAQLQARLD 492

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 75.18 E-value: 4.42e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  356 EPSSEDEQQPEKKlpVTFEDKKREnfERGSVElEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQ 435
Cdd:PTZ00121 1085 EDNRADEATEEAF--GKAEEAKKT--ETGKAE-EARKAEEAKKKAEDARKAEEARKAEDARKAEEARKAEDAKRVEIARK 1159

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  436 LEKqreLERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALndkKHQL 515
Cdd:PTZ00121 1160 AED---ARKAEEARKAEDAKKAEAARKAEEVRKAEELRKAEDARKAEAARKAEEERKAEEARKAEDAKKAEAV---KKAE 1233

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  516 EGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLI--PEKQILSDQLKQVQQnslhrdslltLKR 593
Cdd:PTZ00121 1234 EAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIKAEEARKADELkkAEEKKKADEAKKAEE----------KKK 1303

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  594 ALEAKELARQQLR-EQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDA 672
Cdd:PTZ00121 1304 ADEAKKKAEEAKKaDEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKKKADAA 1383

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  673 QRRVQERDKqwlehvqQEEQprpRKPHEEDRlKREDSVRKKEAEERAKPEMQDK 726
Cdd:PTZ00121 1384 KKKAEEKKK-------ADEA---KKKAEEDK-KKADELKKAAAAKKKADEAKKK 1426

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 74.79 E-value: 4.64e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  355 EEPSSEDE--QQPEKKLPVTFEDKKRENFERGSVELEKRRQAL--LEQQRKEQE--RLAQLERAEQERKERE-RQEQERK 427
Cdd:PTZ00121 1467 EEAKKADEakKKAEEAKKADEAKKKAEEAKKKADEAKKAAEAKkkADEAKKAEEakKADEAKKAEEAKKADEaKKAEEKK 1546

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  428 RQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGtvvlKARRKTLEFELEA 507
Cdd:PTZ00121 1547 KADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKA----EEAKKAEEAKIKA 1622

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  508 LNDKKHQLEGKLQDircrlATQRQEIESTNKSRELRIAEithlqqqlqesqqmlgrliPEKQILSDQLKQVQQNSLHRDS 587
Cdd:PTZ00121 1623 EELKKAEEEKKKVE-----QLKKKEAEEKKKAEELKKAE-------------------EENKIKAAEEAKKAEEDKKKAE 1678

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  588 llTLKRALEAKELARQQLREqldevERETRSKLQEIdvfnnQLKELREIHSKQQLQKQrslEAARLKQKEQERKSLELEK 667
Cdd:PTZ00121 1679 --EAKKAEEDEKKAAEALKK-----EAEEAKKAEEL-----KKKEAEEKKKAEELKKA---EEENKIKAEEAKKEAEEDK 1743

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330  668 QKEDaQRRVQERDKQWLEHVQQEEQPRP---RKPHE---EDRLKREDSVRKKEAEERAK 720
Cdd:PTZ00121 1744 KKAE-EAKKDEEEKKKIAHLKKEEEKKAeeiRKEKEaviEEELDEEDEKRRMEVDKKIK 1801

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 64.97 E-value: 4.74e-13

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11803     6 LYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYV 52

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 64.96 E-value: 4.83e-13

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11805     4 ALYDFNPQEPGELEFRRGDIITVLDSsDPDWWKGELRGRVGIFPANYV 51

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 74.62 E-value: 5.13e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   375 DKKRENFERGSVELEkrrqalleQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQrelerqreeerRKEI 454
Cdd:pfam02463  152 PERRLEIEEEAAGSR--------LKRKKKEALKKLIEETENLAELIIDLEELKLQELKLKEQAKK-----------ALEY 212

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   455 ERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKA---RRKTLEFELEALNDKKHQLEGKLQDIRCRLATQrQ 531
Cdd:pfam02463  213 YQLKEKLELEEEYLLYLDYLKLNEERIDLLQELLRDEQEEIEsskQEIEKEEEKLAQVLKENKEEEKEKKLQEEELKL-L 291

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   532 EIESTNKSRELRIAEITHLQQQLQESQQMLgrlipEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELAR--QQLREQL 609
Cdd:pfam02463  292 AKEEEELKSELLKLERRKVDDEEKLKESEK-----EKKKAEKELKKEKEEIEELEKELKELEIKREAEEEEeeELEKLQE 366

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   610 DEVERETR---SKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERksLELEKQKEDAQRRVQERDKQWLEH 686
Cdd:pfam02463  367 KLEQLEEEllaKKKLESERLSSAAKLKEEELELKSEEEKEAQLLLELARQLEDL--LKEEKKEELEILEEEEESIELKQG 444

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 568997330   687 VQQEEQprprkphEEDRLKREDSVRKKEAEERAKPEMQDKQSRLFHPHQE 736
Cdd:pfam02463  445 KLTEEK-------EELEKQELKLLKDELELKKSEDLLKETQLVKLQEQLE 487

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 64.63 E-value: 6.47e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVT-KKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11772     2 FRALYDYEAQHPDELSFEEGDLLYISdKSDPNWWKATCGGKTGLIPSNYV 51

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 64.60 E-value: 6.88e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11873     2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 64.68 E-value: 7.11e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11875     1 KARVLFDYEAENEDELTLREGDIVTILSKDCEDKGWWKGELNGKRGVFPDNFVE 54

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 64.48 E-value: 7.70e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1174 VCQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11956     1 EVEAVACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRGLIPHKYISV 55

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 64.34 E-value: 8.11e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDG--DWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11841     4 ALYSFEGQQPCDLSFQAGDRItVLTRTDSqfDWWEGRLRGRVGIFPANYV 53

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 64.41 E-value: 8.89e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGEL-KGKTGWFPANY 817
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLE--KDDDGWWEGELnGGREGLFPANY 51

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 73.62 E-value: 8.96e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   398 QQRKEQERLAQLERAEQERKE-RERQEQERKRQLELEK-QLEKQRELerqreeerrkeierreaakRELERQRQLEWERN 475
Cdd:pfam17380  263 QTMTENEFLNQLLHIVQHQKAvSERQQQEKFEKMEQERlRQEKEEKA-------------------REVERRRKLEEAEK 323

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   476 RRQELLnqrnkEQEGTVVLKARRKTLEFELEAlnDKKHQLEGKLQDIRCRLATQRQEIEstnKSRELRiaeithlqqqlq 555
Cdd:pfam17380  324 ARQAEM-----DRQAAIYAEQERMAMEREREL--ERIRQEERKRELERIRQEEIAMEIS---RMRELE------------ 381

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   556 esqqmlgRLIPEKQILSDQLKQvQQNSLHRDSLLTLKRALEAKELARQ--QLREQLDEVERETRSKLQEidvfnnqlKEL 633
Cdd:pfam17380  382 -------RLQMERQQKNERVRQ-ELEAARKVKILEEERQRKIQQQKVEmeQIRAEQEEARQREVRRLEE--------ERA 445

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   634 REIHSKQQLQKQRSLEAARLKQKEQE--RKSLELEKQKEDAQRRVQERDK---QWLEHVQQE--EQPRPRKPHEEDRLKR 706
Cdd:pfam17380  446 REMERVRLEEQERQQQVERLRQQEEErkRKKLELEKEKRDRKRAEEQRRKileKELEERKQAmiEEERKRKLLEKEMEER 525

                          330       340
                   ....*....|....*....|....*..
gi 568997330   707 EDSV------RKKEAEERAKPEMQDKQ 727
Cdd:pfam17380  526 QKAIyeeerrREAEEERRKQQEMEERR 552

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 64.32 E-value: 1.07e-12

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12061     6 FNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVR 52

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 64.15 E-value: 1.15e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  1174 VCQVIGmyDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:pfam07653    1 YGRVIF--DYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVEE 53

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 63.95 E-value: 1.20e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDP--DWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11841     1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRLRGRVGIFPANYVS 54

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 63.79 E-value: 1.31e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 568997330   769 ALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEES--EDGWWEGINTGRTGLVPANYVE 49

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 63.92 E-value: 1.34e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDpDWWKGEVS-GQVGLFPSNYVKL 1228
Cdd:cd11837     1 TATALYPWRAKKENHLSFAKGDIITVLEQQE-MWWFGELEgGEEGWFPKSYVKE 53

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 63.70 E-value: 1.45e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1174 VCQViGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKLT 1229
Cdd:cd12073     1 ICAV-ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVELL 55

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 63.52 E-value: 1.54e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11823     1 RCKALYSYTANREDELSLQPGDIIEVHEKQdDGWWLGELNGKKGIFPATYV 51

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 63.25 E-value: 1.69e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQargkKRQIGWFPANY 1149
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELN----GGREGLFPANY 51

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 72.78 E-value: 1.72e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   371 VTFEDKKREN--FERgSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQ-EQERKRQLELEKQLEKQRELerqre 447
Cdd:TIGR02168  661 ITGGSAKTNSsiLER-RREIEELEEKIEELEEKIAELEKALAELRKELEELEEElEQLRKELEELSRQISALRKD----- 734

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   448 eerrkeierreaAKRELERQRQLEWERNRRQELLNQRNKEQEGtvvLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLA 527
Cdd:TIGR02168  735 ------------LARLEAEVEQLEERIAQLSKELTELEAEIEE---LEERLEEAEEELAEAEAEIEELEAQIEQLKEELK 799

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   528 TQRQEIESTNKsrELRiaeithlqqqlqesqqmlgrlipEKQILSDQLKQVQQNSLHRDSLLtlKRALEAKELARQQLRE 607
Cdd:TIGR02168  800 ALREALDELRA--ELT-----------------------LLNEEAANLRERLESLERRIAAT--ERRLEDLEEQIEELSE 852

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   608 QLDEVERETRSKLQEIDVFNNQLKELreihSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQwLEHV 687
Cdd:TIGR02168  853 DIESLAAEIEELEELIEELESELEAL----LNERASLEEALALLRSELEELSEELRELESKRSELRRELEELREK-LAQL 927


                   ....*
gi 568997330   688 QQEEQ 692
Cdd:TIGR02168  928 ELRLE 932

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 65.78 E-value: 1.87e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQeVLCITVFERDQFSPDDFL 1692
Cdd:cd08377     1 GFLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIHD-VLEVTVYDEDKDKKPEFL 79

                          90
                  ....*....|.
gi 568997330 1693 GRTEIRVADIK 1703
Cdd:cd08377    80 GKVAIPLLSIK 90

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 63.15 E-value: 2.43e-12

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11786     4 ALYNYEGKEPGDLSFKKGDIILLRKRiDENWYHGECNGKQGFFPASYV 51

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 70.33 E-value: 2.48e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   390 KRRQALLEQQRKEQERLAQLER----AEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELE 465
Cdd:pfam13868   32 KRIKAEEKEEERRLDEMMEEEReralEEEEEKEEERKEERKRYRQELEEQIEEREQKRQEEYEEKLQEREQMDEIVERIQ 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   466 RQRQLEWERN--RRQELLNQRNKEQEgtvvLKARRKTLEFELEALNDKKhqLEGKLQDIRCRLATQRQEIESTNKSRELR 543
Cdd:pfam13868  112 EEDQAEAEEKleKQRQLREEIDEFNE----EQAEWKELEKEEEREEDER--ILEYLKEKAEREEEREAEREEIEEEKERE 185

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   544 IAEithlqqqlqesqqmlgrlipekqiLSDQLKQVQQNSLHRDSLLtLKRALEAKElaRQQLREQLDEVERETRSKLQEI 623
Cdd:pfam13868  186 IAR------------------------LRAQQEKAQDEKAERDELR-AKLYQEEQE--RKERQKEREEAEKKARQRQELQ 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   624 DVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERK-SLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEED 702
Cdd:pfam13868  239 QAREEQIELKERRLAEEAEREEEEFERMLRKQAEDEEIeQEEAEKRRMKRLEHRRELEKQIEEREEQRAAEREEELEEGE 318

                          330
                   ....*....|....*....
gi 568997330   703 RLKREDSVRKKE-AEERAK 720
Cdd:pfam13868  319 RLREEEAERRERiEEERQK 337

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 62.82 E-value: 2.87e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPD-WWKGEVSGQVGLFPSNYV 1226
Cdd:cd11843     2 VRALYDYEGQESDELSFKAGDILTKLEEEDEQgWCKGRLDGRVGLYPANYV 52

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 62.48 E-value: 3.17e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQ-GQKGWFPKSY 982
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDgWWEGELNgGREGLFPANY 51

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 62.74 E-value: 3.45e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKE-DPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11946     2 EAIAKYDFKATADDELSFKRGDILKVLNEEcDQNWYKAELNGKDGFIPKNYIEM 55

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 62.65 E-value: 3.52e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPD---WWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11894     2 VKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFNGRIGVFPSVLVE 55

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 62.72 E-value: 3.75e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11877     2 VRAKFNFEGTNEDELSFDKGDIITV--TQVVEGGWWEGTLNGKTGWFPSNYVK 52

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 62.34 E-value: 4.09e-12

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11826     3 VALYDYTADKDDELSFQEGDIIYVTKKNDDgWYEGVLNGVTGLFPGNYV 51

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 62.53 E-value: 5.04e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKD----GD--WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11876     4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsGDegWWTGKIGDKVGIFPSNYV 56

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 62.31 E-value: 5.17e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1175 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGL-FPSNYVK 1227
Cdd:cd11970     4 CAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 57

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 61.96 E-value: 6.86e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11971     1 KVVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVE 52

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 61.95 E-value: 7.22e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11972     4 KVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVE 55

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 70.18 E-value: 7.88e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELER 466
Cdd:COG4717    82 EAEEKEEEYAELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQELEALEAELAELPERLEELEERLEELREL 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  467 QRQLEWERNRRQELLNQRNKEQEGT-VVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRE---- 541
Cdd:COG4717   162 EEELEELEAELAELQEELEELLEQLsLATEEELQDLAEELEELQQRLAELEEELEEAQEELEELEEELEQLENELEaaal 241

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  542 ----------LRIAEITHLQQQLQESQQMLGRLIPEKQILSDQL------KQVQQNSLHRDSLLTLKRALEAKELARQQL 605
Cdd:COG4717   242 eerlkearllLLIAAALLALLGLGGSLLSLILTIAGVLFLVLGLlallflLLAREKASLGKEAEELQALPALEELEEEEL 321

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  606 REQLDEVERETRSKLQEIDVFNNQLKELREIHSK-QQLQKQRSLEAARLKQKE-QERKSLELEKQKEDAQRRVQERdKQW 683
Cdd:COG4717   322 EELLAALGLPPDLSPEELLELLDRIEELQELLREaEELEEELQLEELEQEIAAlLAEAGVEDEEELRAALEQAEEY-QEL 400

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  684 LEHVQQ-EEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSRL 730
Cdd:COG4717   401 KEELEElEEQLEELLGELEELLEALDEEELEEELEELEEELEELEEEL 448

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 61.71 E-value: 8.75e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd12142     1 YCRVLFDYNPVAPDELALKKGDVIEVISKETEDEGWWEGELNGRRGFFPDNFVM 54

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 61.71 E-value: 8.79e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKD----GD--WWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12059     4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsGDegWWTGKINDRVGIFPSNYVT 57

Caldesmon;

Pssm-ID: 460421 [Multi-domain] Cd Length: 495 Bit Score: 69.51 E-value: 9.02e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   410 ERAEQERKERERQEQERKRQLE--------LEKQLEKQRELERQREEERRKEIERREAA------KRELERQRQLEWERN 475
Cdd:pfam02029    5 EEAARERRRRAREERRRQKEEEepsgqvteSVEPNEHNSYEEDSELKPSGQGGLDEEEAfldrtaKREERRQKRLQEALE 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   476 RRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKL----------QDIRCRLATQRQEIESTNKSRELRIA 545
Cdd:pfam02029   85 RQKEFDPTIADEKESVAERKENNEEEENSSWEKEEKRDSRLGRYkeeeteirekEYQENKWSTEVRQAEEEGEEEEDKSE 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   546 EITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSklQEIDV 625
Cdd:pfam02029  165 EAEEVPTENFAKEEVKDEKIKKEKKVKYESKVFLDQKRGHPEVKSQNGEEEVTKLKVTTKRRQGGLSQSQERE--EEAEV 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   626 FNNQLKELREIhsKQQLQKQRSLEAARLKQKEQERkSLELE--KQKEDAQRRVQERDKQWLEhvQQEEQPRPRKPHEEDR 703
Cdd:pfam02029  243 FLEAEQKLEEL--RRRRQEKESEEFEKLRQKQQEA-ELELEelKKKREERRKLLEEEEQRRK--QEEAERKLREEEEKRR 317

                          330
                   ....*....|....*
gi 568997330   704 LKREDSVRKKEAEER 718
Cdd:pfam02029  318 MKEEIERRRAEAAEK 332

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 61.35 E-value: 9.07e-12

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVS-GQVGLFPSNYVKL 1228
Cdd:cd11962     6 YDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTNSkGESGLFPSNYVEL 54

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 61.76 E-value: 9.15e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12056     7 LFHYEGTNEDELDFKEGEIILIISKDtgEPGWWKGELNGKEGVFPDNFVSQ 57

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 61.52 E-value: 9.76e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1175 CQVigMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12054     3 CKV--LFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVK 53

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 61.38 E-value: 1.00e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYA 818
Cdd:cd12056     3 YCKALFHYEGTNEDELDFKEGEIILIISKDTGEPGWWKGELNGKEGVFPDNFV 55

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 61.28 E-value: 1.06e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVlNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11838     3 IALYPYESNEPGDLTFNAGDVILV-TKKDGEWWTGTIGDRTGIFPSNYVRP 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 70.56 E-value: 1.07e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  350 DQRLpeEPSSEDEQQPEKKLPVtfEDKKRENFERGSVELEKRRQALLEQQRKEQErlaQLERAEQERKERERQEQERKRQ 429
Cdd:PTZ00121 1069 DEGL--KPSYKDFDFDAKEDNR--ADEATEEAFGKAEEAKKTETGKAEEARKAEE---AKKKAEDARKAEEARKAEDARK 1141

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  430 LELEKQLEKQRELERQREEERRKEIERREAAK--RELERQRQLEwERNRRQELlnqrNKEQEGTVVLKARRKTLEFELEA 507
Cdd:PTZ00121 1142 AEEARKAEDAKRVEIARKAEDARKAEEARKAEdaKKAEAARKAE-EVRKAEEL----RKAEDARKAEAARKAEEERKAEE 1216

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  508 LndKKHQLEGKLQDIRcRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIP--EKQILSDQLKQVQQnslhr 585
Cdd:PTZ00121 1217 A--RKAEDAKKAEAVK-KAEEAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIkaEEARKADELKKAEE----- 1288

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  586 dslltLKRALEAKELARQQLREQLDEVERETRsKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLEL 665
Cdd:PTZ00121 1289 -----KKKADEAKKAEEKKKADEAKKKAEEAK-KADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAA 1362

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  666 EKQKEDAQRRVQERDKQWLEHVQQEEQPRprkphEEDRLKREDSVRKKEAEERAKPEMQDKQSRLFHPHQEPAKLATQAP 745
Cdd:PTZ00121 1363 EEKAEAAEKKKEEAKKKADAAKKKAEEKK-----KADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAK 1437


                  ....*.
gi 568997330  746 WSTTEK 751
Cdd:PTZ00121 1438 KKAEEA 1443

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 61.15 E-value: 1.15e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIInVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11991     1 EYVAMYTYESNEQGDLTFQQGDVI-LVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 61.17 E-value: 1.30e-11

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12060     8 FNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVR 54

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 61.11 E-value: 1.35e-11

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPD-WWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11976     6 YDFCARDRSELSLKEGDIIKILNKKGQQgWWRGEIYGRVGWFPANYVE 53

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 60.82 E-value: 1.54e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11781     3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYVEI 53

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 69.78 E-value: 1.66e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  351 QRLPEEPSSEDEQQPEKKLPVtfEDKKRENFERgsvELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL 430
Cdd:PTZ00121 1128 RKAEEARKAEDARKAEEARKA--EDAKRVEIAR---KAEDARKAEEARKAEDAKKAEAARKAEEVRKAEELRKAEDARKA 1202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  431 ELEKQLE---KQRELERQREEERRKEIERREAAKRELERQRQLEWERNR---RQELLNQRNKEQEGTVVLKARRKTLEFE 504
Cdd:PTZ00121 1203 EAARKAEeerKAEEARKAEDAKKAEAVKKAEEAKKDAEEAKKAEEERNNeeiRKFEEARMAHFARRQAAIKAEEARKADE 1282

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  505 LEALNDKKHQLEGKlqdircRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSlH 584
Cdd:PTZ00121 1283 LKKAEEKKKADEAK------KAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEA-A 1355

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  585 RDSLLTLKRALEAKELARQQLREQLDEVER--ETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAArlKQKEQERKS 662
Cdd:PTZ00121 1356 ADEAEAAEEKAEAAEKKKEEAKKKADAAKKkaEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAK--KKAEEKKKA 1433

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  663 LELEKQKEDAqRRVQERDKQWLEHVQQEEQprpRKPHEEDRLKREdsvRKKEAEERAKPEMQDKQSRLFHPHQEPAKLAT 742
Cdd:PTZ00121 1434 DEAKKKAEEA-KKADEAKKKAEEAKKAEEA---KKKAEEAKKADE---AKKKAEEAKKADEAKKKAEEAKKKADEAKKAA 1506


                  ..
gi 568997330  743 QA 744
Cdd:PTZ00121 1507 EA 1508

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 60.90 E-value: 1.74e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWK-------GEVSGQVGLFPSNY 1225
Cdd:cd11773     5 LYDYEPQTEDELTIQEDDILYLLEKSDDDWWKvklkvnsSDDDEPVGLVPATY 57

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 60.62 E-value: 1.76e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVG-LFPSNYVK 1227
Cdd:cd11969     2 VKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGKVQhYFPSNYVE 53

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 60.78 E-value: 1.85e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11772     2 FRALYDYEAQHPDELSFEEGDLLYISDKS--DPNWWKATCGGKTGLIPSNYVE 52

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 60.55 E-value: 2.00e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKE-----DPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd12059     5 VFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGIFPSNYV 56

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 69.33 E-value: 2.01e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   374 EDKKRENFERGSVELEK--RRQALLEQQRKEQ--ERLAQLERAEQERKERERQEQERKRQLE-LEKQLEK--QRELERQR 446
Cdd:TIGR02169  193 IDEKRQQLERLRREREKaeRYQALLKEKREYEgyELLKEKEALERQKEAIERQLASLEEELEkLTEEISEleKRLEEIEQ 272

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   447 EEERRKEIERREAAKRELERQRQL-----EWERNRRQELLNQRNKEQegtvvLKARRKTLEFELEALNDKKHQLEGKLQD 521
Cdd:TIGR02169  273 LLEELNKKIKDLGEEEQLRVKEKIgeleaEIASLERSIAEKERELED-----AEERLAKLEAEIDKLLAEIEELEREIEE 347

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   522 IRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNslhRDSLLTLKRALEAK--- 598
Cdd:TIGR02169  348 ERKRRDKLTEEYAELKEELEDLRAELEEVDKEFAETRDELKDYREKLEKLKREINELKRE---LDRLQEELQRLSEElad 424

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   599 ---ELARqqLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLEL---EKQKEDA 672
Cdd:TIGR02169  425 lnaAIAG--IEAKINELEEEKEDKALEIKKQEWKLEQLAADLSKYEQELYDLKEEYDRVEKELSKLQRELaeaEAQARAS 502


                   ....*..
gi 568997330   673 QRRVQER 679
Cdd:TIGR02169  503 EERVRGG 509

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 60.20 E-value: 2.46e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12046     1 QVVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGIFPSAFVE 52

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 60.40 E-value: 2.60e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNK--EDPDWWKGE-VSGQVGLFPSNYVKL 1228
Cdd:cd11767     2 VVALYPFTGENDEELSFEKGERLEIIEKpeDDPDWWKARnALGTTGLVPRNYVEV 56

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 60.11 E-value: 2.83e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV-SGQVGLFPSNYVKL 1228
Cdd:cd11960     5 LYDYQAADDTEISFDPGDIITDIEQIDEGWWRGTGpDGTYGLFPANYVEL 54

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 60.34 E-value: 2.86e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKE-----DPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd12058     5 LYDYEASGEDELSLRRGDVVEVLSQDaavsgDDGWWAGKIRHRLGIFPANYV 56

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 60.12 E-value: 3.09e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11840     1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDpDWWRGELNGQTGLFPSNYVEP 53

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 68.54 E-value: 3.55e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   475 NRRQEL--LNQRNKEQEGTV-VLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQ 551
Cdd:TIGR02168  674 ERRREIeeLEEKIEELEEKIaELEKALAELRKELEELEEELEQLRKELEELSRQISALRKDLARLEAEVEQLEERIAQLS 753

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   552 QQLqesqqmlGRLIPEKQILSDQLKQVQQnslhrdslltlkrALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLK 631
Cdd:TIGR02168  754 KEL-------TELEAEIEELEERLEEAEE-------------ELAEAEAEIEELEAQIEQLKEELKALREALDELRAELT 813

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   632 ELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQW---------LEHVQQEeqprpRKPHEED 702
Cdd:TIGR02168  814 LLNEEAANLRERLESLERRIAATERRLEDLEEQIEELSEDIESLAAEIEELEelieeleseLEALLNE-----RASLEEA 888

                          250       260       270
                   ....*....|....*....|....*....|....
gi 568997330   703 RLKREDSVRKKEAEERakpEMQDKQSRLFHPHQE 736
Cdd:TIGR02168  889 LALLRSELEELSEELR---ELESKRSELRRELEE 919

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 59.64 E-value: 4.03e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKL 1152
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGK-----TGWFPSNYVKE 53

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 59.66 E-value: 4.10e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNK--EDPDWWK-GEVSGQVGLFPSNYVKL 1228
Cdd:cd11904     3 VQALYPFSSSNDEELNFEKGEVMDVIEKpeNDPEWWKcRKANGQVGLVPKNYVTV 57

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 59.65 E-value: 4.83e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPD-WWKGEVS-GQVGLFPSNYV 1226
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDgWLEGRNSrGEVGLFPSSYV 53

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 59.25 E-value: 5.57e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11877     1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEgGWWEGTLNGKTGWFPSNYVKE 53

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 59.24 E-value: 5.87e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1175 CQVigMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12055     2 CQV--AFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIK 52

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 59.35 E-value: 5.96e-11

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKD-GDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11827     4 ALYAYDAQDTDELSFNEGDIIEILKEDpSGWWTGRLRGKEGLFPGNYV 51

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 67.65 E-value: 6.20e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  374 EDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQErkERERQEQERKRQLELEKQLEKQRELERQREEERRKE 453
Cdd:COG1196   398 LAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEE--EEEALEEAAEEEAELEEEEEALLELLAELLEEAALL 475

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  454 IERREAAKRELERQRQLEWERN--------------RRQELLNQRNKEQEGTVVLK-------------------ARRKT 500
Cdd:COG1196   476 EAALAELLEELAEAAARLLLLLeaeadyegflegvkAALLLAGLRGLAGAVAVLIGveaayeaaleaalaaalqnIVVED 555

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  501 LEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQML-------GRLIPEKQILSD 573
Cdd:COG1196   556 DEVAAAAIEYLKAAKAGRATFLPLDKIRARAALAAALARGAIGAAVDLVASDLREADARYYvlgdtllGRTLVAARLEAA 635

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  574 QLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREihSKQQLQKQRSLEAARL 653
Cdd:COG1196   636 LRRAVTLAGRLREVTLEGEGGSAGGSLTGGSRRELLAALLEAEAELEELAERLAEEELELEE--ALLAEEEEERELAEAE 713

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997330  654 KQKEQERKSLELEKQKEDAQRRvQERDKQWLEHVQQEEQPRPRKPHEED---------RLKRE 707
Cdd:COG1196   714 EERLEEELEEEALEEQLEAERE-ELLEELLEEEELLEEEALEELPEPPDleelereleRLERE 775

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 59.18 E-value: 6.40e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKE-DPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11830     3 KARYDFCARDMRELSLKEGDVVKIYNKKgQQGWWRGEINGRIGWFPSTYVE 53

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 58.95 E-value: 7.24e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11809     3 TAQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGLVPHKYITL 53

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 58.93 E-value: 7.75e-11

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTK-KDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12061     4 AKFNFQQTNEDELSFSKGDVIHVTRvEEGGWWEGTHNGRTGWFPSNYVR 52

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 58.66 E-value: 7.98e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLnKEDP--DWWKGEVSGQVGLFPSNY 1225
Cdd:cd11778     2 VEALYDYEAQGDDEISIRVGDRIAVI-RGDDgsGWTYGEINGVKGLFPTSY 51

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 58.55 E-value: 8.76e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11828     2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 53

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 58.44 E-value: 9.68e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKG-EVSGQVGLFPSNYVK 1227
Cdd:cd11768     1 IVVALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRArDKNGNEGYIPSNYVT 53

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 61.21 E-value: 9.80e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTM-----GSQCHITKTIQDTLNPKWNSNCQFFIR--DLEQEVLCITVFERDQ 1685
Cdd:cd08384    13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLkpdagKKSKHKTQVKKKTLNPEFNEEFFYDIKhsDLAKKTLEITVWDKDI 92


                  ....*...
gi 568997330 1686 FSPDDFLG 1693
Cdd:cd08384    93 GKSNDYIG 100

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 58.45 E-value: 1.16e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV---SGQV--GLFPSNY 1225
Cdd:cd11883     2 VVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIissSGKVkrGWFPSNY 55

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 58.45 E-value: 1.26e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11996     2 QVIAMYDYTANNEDELSFSKGQLInVLNKDDPDWWQGEINGVTGLFPSNYVKM 54

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 58.12 E-value: 1.30e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11823     4 ALYSYTANREDELSLQPGDIIEVHEKQDDgWWLGELNGKKGIFPATYV 51

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 58.07 E-value: 1.32e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVmVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11882     3 RALYACKAEDESELSFEPGQII-TNVQPSDEPGWLEGTLNGRTGLIPENYVE 53

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 58.26 E-value: 1.32e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNY 1225
Cdd:cd11818     5 LYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGIFPKNF 50

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 58.17 E-value: 1.36e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11806     2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 51

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 58.03 E-value: 1.54e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11976     3 KARYDFCARDRSELSLKEGDIIKI-LNKKGQQGWWRGEIYGRVGWFPANYVEE 54

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 58.03 E-value: 1.56e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11856     5 IADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLE 52

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 65.36 E-value: 1.84e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   354 PEEPSSEDEqqPEKKLPVTFEDKK-------RENFERGSVELEKRRQALLEQQRKEQErlaQLERAEQERKERERQEQER 426
Cdd:pfam15709  311 SEEERSEED--PSKALLEKREQEKasrdrlrAERAEMRRLEVERKRREQEEQRRLQQE---QLERAEKMREELELEQQRR 385

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   427 KRQLELEKQlekQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELE 506
Cdd:pfam15709  386 FEEIRLRKQ---RLEEERQRQEEEERKQRLQLQAAQERARQQQEEFRRKLQELQRKKQQEEAERAEAEKQRQKELEMQLA 462

                          170       180       190
                   ....*....|....*....|....*....|....
gi 568997330   507 AlnDKKHQLEGKLQDircRLATQRQEIESTNKSR 540
Cdd:pfam15709  463 E--EQKRLMEMAEEE---RLEYQRQKQEAEEKAR 491

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 57.66 E-value: 1.95e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd11873     1 EVIVEFDYDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 57.69 E-value: 1.97e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQII-NVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11882     1 RARALYACKAEDESELSFEPGQIItNVQPSDEPGWLEGTLNGRTGLIPENYVEF 54

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 57.50 E-value: 2.26e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVV-TKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12046     3 VALFSYEASQPEDLEFQKGDVILVlSKVNEDWLEGQCKGKIGIFPSAFVE 52

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 57.52 E-value: 2.44e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKE-DPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11948     1 EAVALYSFQATESDELPFQKGDILKILNMEdDQNWYKAELQGREGYIPKNYIKV 54

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 57.33 E-value: 2.46e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVS--GQVGLFPSNYVKL 1228
Cdd:cd11789     1 RYRAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMEGTVQrtGQSGMLPANYVEL 55

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 57.28 E-value: 2.50e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11766     1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSsDGWWRGECNGQVGWFPSNYV 51

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 57.35 E-value: 3.02e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11901     8 FNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 53

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 57.10 E-value: 3.23e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNY 1225
Cdd:cd11817     2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 57.03 E-value: 3.31e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11816     6 FDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 65.38 E-value: 3.53e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   360 EDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKER-ERQEQERKRQLELEKQLEK 438
Cdd:pfam02463  193 EELKLQELKLKEQAKKALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLLQELLRDEQEEiESSKQEIEKEEEKLAQVLK 272

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   439 QrelerqreeerrkeiERREAAKRELERQRQLEWERNRRQELLNQRNKEQegtvvlkaRRKTLEFELEALNDKKHQLEGK 518
Cdd:pfam02463  273 E---------------NKEEEKEKKLQEEELKLLAKEEEELKSELLKLER--------RKVDDEEKLKESEKEKKKAEKE 329

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   519 LQDIRCRLATQRQEIESTNKSRELRIAEIthlqqqlqesqqmlgrlipeKQILSDQLKQVQQNSLHRDSLLTLKRALEAK 598
Cdd:pfam02463  330 LKKEKEEIEELEKELKELEIKREAEEEEE--------------------EELEKLQEKLEQLEEELLAKKKLESERLSSA 389

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   599 ELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQErKSLELEKQKEDAQRRVQE 678
Cdd:pfam02463  390 AKLKEEELELKSEEEKEAQLLLELARQLEDLLKEEKKEELEILEEEEESIELKQGKLTEEK-EELEKQELKLLKDELELK 468

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330   679 RDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPE----MQDKQSRLFHPHQEPAKLATQAP 745
Cdd:pfam02463  469 KSEDLLKETQLVKLQEQLELLLSRQKLEERSQKESKARSGLKVLlaliKDGVGGRIISAHGRLGDLGVAVE 539

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 56.94 E-value: 3.60e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11920     6 VYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVE 53

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 56.75 E-value: 3.80e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGE-VQGQKGWFPKSYV 983
Cdd:cd11812     4 ALYDYTANRSDELTIHRGDIIRVLYKdNDNWWFGSlVNGQQGYFPANYV 52

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 56.91 E-value: 3.96e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANY 1149
Cdd:cd11883     1 VVVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKVKRGWFPSNY 55

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 56.94 E-value: 4.10e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTV---GdKSGVFPSNYVRL 1074
Cdd:cd11789     2 YRAMYDYAAADDDEVSFQEGDVIInVEIIDDGWMEGTVqrtG-QSGMLPANYVEL 55

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212942 [Multi-domain] Cd Length: 54 Bit Score: 56.75 E-value: 4.13e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLnKEDPDWW--KGEVSGQVGLFPSNYV 1226
Cdd:cd12009     2 VIAQYDFVPSNERDLQLKKGEKLQVL-KSDGEWWlaKSLTTGKEGYIPSNYV 52

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 56.89 E-value: 4.22e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11995     2 QVIGMYDYTAQNDDELAFSKGQIInVLNKEDPDWWKGELNGQVGLFPSNYVKL 54

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 64.99 E-value: 4.54e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   359 SEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERA---EQERKERERQEQERKRQLELEKQ 435
Cdd:pfam02463  662 SEVKASLSELTKELLEIQELQEKAESELAKEEILRRQLEIKKKEQREKEELKKLkleAEELLADRVQEAQDKINEELKLL 741

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   436 LEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKE---QEGTVVLKARRKTL---EFELEALN 509
Cdd:pfam02463  742 KQKIDEEEEEEEKSRLKKEEKEEEKSELSLKEKELAEEREKTEKLKVEEEKEeklKAQEEELRALEEELkeeAELLEEEQ 821

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   510 DKKHQLEGKLQDIRCRLAtqrQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLipEKQILSDQLKQVQQNSLHRDSLL 589
Cdd:pfam02463  822 LLIEQEEKIKEEELEELA---LELKEEQKLEKLAEEELERLEEEITKEELLQELL--LKEEELEEQKLKDELESKEEKEK 896

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   590 TLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELR----------------EIHSKQQLQKQRSLEAAR- 652
Cdd:pfam02463  897 EEKKELEEESQKLNLLEEKENEIEERIKEEAEILLKYEEEPEELLleeadekekeennkeeEEERNKRLLLAKEELGKVn 976

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 568997330   653 --------------------LKQKEQERKSLELEKQKEDAQRRVQERDKQW 683
Cdd:pfam02463  977 lmaieefeekeerynkdeleKERLEEEKKKLIRAIIEETCQRLKEFLELFV 1027

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 56.55 E-value: 4.80e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1172 PAVCQvigmYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11902     2 PAFVK----FAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYV 52

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 56.63 E-value: 5.45e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVL---EQQDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11841     1 EVTALYSFEGQQPCDLSFQAGDRITVLtrtDSQFDWWEGRLRGRVGIFPANYVS 54

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 64.40 E-value: 5.47e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL-ELEKQLE--KQRELERQREEERRKEIERREAAKRE 463
Cdd:COG4717   129 PLYQELEALEAELAELPERLEELEERLEELRELEEELEELEAELaELQEELEelLEQLSLATEEELQDLAEELEELQQRL 208

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  464 LERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLE-----------FELEALND---------------------- 510
Cdd:COG4717   209 AELEEELEEAQEELEELEEELEQLENELEAAALEERLKEarlllliaaalLALLGLGGsllsliltiagvlflvlgllal 288

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  511 ----------KKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLkQVQQ 580
Cdd:COG4717   289 lflllarekaSLGKEAEELQALPALEELEEEELEELLAALGLPPDLSPEELLELLDRIEELQELLREAEELEEEL-QLEE 367

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  581 NSLHRDSLL---------TLKRALEAKElARQQLREQLDEVERETRSKL----------------QEIDVFNNQLKELRE 635
Cdd:COG4717   368 LEQEIAALLaeagvedeeELRAALEQAE-EYQELKEELEELEEQLEELLgeleellealdeeeleEELEELEEELEELEE 446

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330  636 ihSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQW-------------LEHVQQEEQPR 694
Cdd:COG4717   447 --ELEELREELAELEAELEQLEEDGELAELLQELEELKAELRELAEEWaalklalelleeaREEYREERLPP 516

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 56.58 E-value: 6.10e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV---SG--QVGLFPSNYV 1226
Cdd:cd11887     4 VKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYvdsNGntKEGIFPKNFV 58

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 58.89 E-value: 6.13e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1614 RLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRD---LEQEVLCITVF-ERDQFSPD 1689
Cdd:cd04022     1 KLVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDpsrLSNLVLEVYVYnDRRSGRRR 80


                  ....*...
gi 568997330 1690 DFLGRTEI 1697
Cdd:cd04022    81 SFLGRVRI 88

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212742 [Multi-domain] Cd Length: 53 Bit Score: 56.34 E-value: 6.23e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11808     2 VVALYDYQEKSPREVSMKKGDILTLLNSSNKDWWKVEVNDRQGFVPAAYVK 52

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 64.31 E-value: 6.32e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  360 EDEQQPEKKLPVTFEDKKRENFER-GSV--------ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL 430
Cdd:PRK03918  227 EKEVKELEELKEEIEELEKELESLeGSKrkleekirELEERIEELKKEIEELEEKVKELKELKEKAEEYIKLSEFYEEYL 306

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  431 ELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKAR------RKT---- 500
Cdd:PRK03918  307 DELREIEKRLSRLEEEINGIEERIKELEEKEERLEELKKKLKELEKRLEELEERHELYEEAKAKKEElerlkkRLTgltp 386

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  501 --LEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKS-RELRIAEITHLQQQLQESQQMLGRLIPE-KQILSDQLK 576
Cdd:PRK03918  387 ekLEKELEELEKAKEEIEEEISKITARIGELKKEIKELKKAiEELKKAKGKCPVCGRELTEEHRKELLEEyTAELKRIEK 466

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  577 QVQQNSLHRDSLLTLKRALEaKELARQQ----LREQLDEVeRETRSKLQEIDV---------FNNQLKELREIHSKQQLQ 643
Cdd:PRK03918  467 ELKEIEEKERKLRKELRELE-KVLKKESelikLKELAEQL-KELEEKLKKYNLeelekkaeeYEKLKEKLIKLKGEIKSL 544

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  644 KQRSLEAARLKQK--EQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQpRPRKPHEE--------DRLKREDSVRKK 713
Cdd:PRK03918  545 KKELEKLEELKKKlaELEKKLDELEEELAELLKELEELGFESVEELEERLK-ELEPFYNEylelkdaeKELEREEKELKK 623

                         410
                  ....*....|....*....
gi 568997330  714 EAEE--RAKPEMQDKQSRL 730
Cdd:PRK03918  624 LEEEldKAFEELAETEKRL 642

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212708 [Multi-domain] Cd Length: 52 Bit Score: 55.93 E-value: 7.13e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDW-WKGEVSGQVGLFPSNYV 1226
Cdd:cd11774     1 QAKALYDYDKQTEEELSFNEGDTLDVYDDSDSDWiLVGFNGTQFGFVPANYI 52

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 58.41 E-value: 7.17e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTM---GSQCHI--TKTIQDTLNPKWNsncQFFI------RDLEQEVLCITVF 1681
Cdd:cd04031    16 SQLIVTVLQARDLPPRDDGSLRNPYVKVYLlpdRSEKSKrrTKTVKKTLNPEWN---QTFEysnvrrETLKERTLEVTVW 92

                          90       100
                  ....*....|....*....|
gi 568997330 1682 ERDQFSPDDFLGRTEIRVAD 1701
Cdd:cd04031    93 DYDRDGENDFLGEVVIDLAD 112

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 64.22 E-value: 7.18e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   362 EQQPEKKLPVTFEDKKRENFERGSVEL--EKRRQALLEQQRKE-----QERLAQLERAEQERKERERQEQERKRQLELEK 434
Cdd:TIGR00618  269 IEELRAQEAVLEETQERINRARKAAPLaaHIKAVTQIEQQAQRihtelQSKMRSRAKLLMKRAAHVKQQSSIEEQRRLLQ 348

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   435 QLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEgtvVLKARRKTLEFELEALNDKKHQ 514
Cdd:TIGR00618  349 TLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHTLQQQKTTLTQKLQSLCKELD---ILQREQATIDTRTSAFRDLQGQ 425

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   515 L---EGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGrlipEKQILSDQLKQVQQNSLHRDSLL-T 590
Cdd:TIGR00618  426 LahaKKQQELQQRYAELCAAAITCTAQCEKLEKIHLQESAQSLKEREQQLQ----TKEQIHLQETRKKAVVLARLLELqE 501

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   591 LKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREI-HSKQQLQKQRsleaARLKQKEQErkslelEKQK 669
Cdd:TIGR00618  502 EPCPLCGSCIHPNPARQDIDNPGPLTRRMQRGEQTYAQLETSEEDVyHQLTSERKQR----ASLKEQMQE------IQQS 571

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330   670 EDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSRL 730
Cdd:TIGR00618  572 FSILTQCDNRSKEDIPNLQNITVRLQDLTEKLSEAEDMLACEQHALLRKLQPEQDLQDVRL 632

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 56.21 E-value: 7.20e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE--VSGQVGLFPSNYV 1226
Cdd:cd12006     4 VALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARslTTGETGYIPSNYV 54

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 58.52 E-value: 7.22e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1615 LMVNVVEGIELKPCRSHGKSNPYCEVTM-------GSQCHITKTIQDTLNPKWnsNCQFFIR-DLEQEVLCITVFERDQF 1686
Cdd:cd04033     2 LRVKVLAGIDLAKKDIFGASDPYVKISLydpdgngEIDSVQTKTIKKTLNPKW--NEEFFFRvNPREHRLLFEVFDENRL 79

                          90       100
                  ....*....|....*....|....*....
gi 568997330 1687 SPDDFLGRTEIRVADIK-KDQGSKGPVTK 1714
Cdd:cd04033    80 TRDDFLGQVEVPLNNLPtETPGNERRYTF 108

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 275424 Cd Length: 124 Bit Score: 58.44 E-value: 7.66e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1478 RKFLHSGKLYKAkSNKEL---YGFLFNDFLLltqITKPLGSSGTDKVFS--PKSNLQYKMYKTPIFLNEvlvklptdpsg 1552
Cdd:cd13389    12 RKLIKEGELMKV-SRKEMqprYFFLFNDCLL---YTTPVQSSGMLKLNNelPLSGMKVKLPEDEEYSNE----------- 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1553 depiFHISHIDRVYTLRAESINERTAWVQKIKAAselyIETEKKKR 1598
Cdd:cd13389    77 ----FQIISTKRSFTLIASSEEERDEWVKALSRA----IEEHTKKQ 114

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 63.93 E-value: 8.26e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   399 QRKEQERLAQL-ERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERrkeierreaaKRELER-QRQLEWERNR 476
Cdd:TIGR02169  669 SRSEPAELQRLrERLEGLKRELSSLQSELRRIENRLDELSQELSDASRKIGEI----------EKEIEQlEQEEEKLKER 738

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   477 RQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQR--------QEIESTNKSRELRIAEIt 548
Cdd:TIGR02169  739 LEELEEDLSSLEQEIENVKSELKELEARIEELEEDLHKLEEALNDLEARLSHSRipeiqaelSKLEEEVSRIEARLREI- 817

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   549 hlqqqlqesQQMLGRLIPEKQILSDQLKQVQQnslhrdslltLKRALEAKELARQQlreQLDEVERETRSKLQEIDVFNN 628
Cdd:TIGR02169  818 ---------EQKLNRLTLEKEYLEKEIQELQE----------QRIDLKEQIKSIEK---EIENLNGKKEELEEELEELEA 875

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   629 QLKELREIHSKqqLQKQRslEAARLKQKEQERKSLELEKQKEDAQRRV----------QERDKQWLEHVQQEEQPRPRKP 698
Cdd:TIGR02169  876 ALRDLESRLGD--LKKER--DELEAQLRELERKIEELEAQIEKKRKRLselkaklealEEELSEIEDPKGEDEEIPEEEL 951

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 568997330   699 HEED----RLKREDSVRK------------KEAEERAKpEMQDKQSRLF 731
Cdd:TIGR02169  952 SLEDvqaeLQRVEEEIRAlepvnmlaiqeyEEVLKRLD-ELKEKRAKLE 999

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 56.16 E-value: 8.31e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTK-KDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12060     6 ARFNFKQTNEDELSVCKGDIIYVTRvEEGGWWEGTLNGKTGWFPSNYVR 54

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 56.06 E-value: 9.07e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd12057     1 YCKVLFPYEAQNEDELTIKEGDIVTLISKDCIDAGWWEGELNGRRGVFPDNFVK 54

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 55.73 E-value: 9.23e-10

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11964     5 AIYDFEAAEDNELTFKAGDIItILDDSDPNWWKGETPQGTGLFPSNFV 52

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 56.13 E-value: 9.26e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1181 YDYTAQNDD-ELAFSKGQIINVLNKEDP-----DWWKGEV-SGQVGLFPSNYV 1226
Cdd:cd11771     6 YDFTPENPEmELSLKKGDIVAVLSKTDPlgrdsEWWKGRTrDGRIGWFPSNYV 58

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 55.74 E-value: 9.78e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPD-WWKGEV-SGQVGLFPSNYVK 1227
Cdd:cd11997     3 RVRALYDYTGQEADELSFKAGEELLKIGEEDEQgWCKGRLlSGRIGLYPANYVE 56

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 57.17 E-value: 1.05e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   1480 FLHSGKLYKAKSN-----KELYGFLFNDFLLLtqitkplgssgtdkvFSPKSNLQYKMYKTPIFLNEVLVKLPTDPSGDE 1554
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLFNSTLLY---------------YKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSK 65

                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 568997330   1555 P--IFHISHIDR-VYTLRAESINERTAWVQKIKAAS 1587
Cdd:smart00233   66 KphCFEIKTSDRkTLLLQAESEEEREKWVEALRKAI 101

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 55.46 E-value: 1.11e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANYAEKI 821
Cdd:cd12061     3 RAKFNFQQTNEDELSFSKGDVIHVTRVEEG--GWWEGTHNGRTGWFPSNYVREI 54

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 55.77 E-value: 1.13e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKG--EVSGQVGLFPSNYVK 1227
Cdd:cd11780     5 LYSYTPQNEDELELREGDIVYVMEKCDDGWFVGtsERTGLFGTFPGNYVA 54

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 57.88 E-value: 1.16e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1614 RLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDFLG 1693
Cdd:cd04025     1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDFLG 80

                          90
                  ....*....|....*..
gi 568997330 1694 RTEIRVADIKKDQGSKG 1710
Cdd:cd04025    81 KVVFSIQTLQQAKQEEG 97

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 55.59 E-value: 1.23e-09

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11833     3 VALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 51

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 55.57 E-value: 1.24e-09

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDpDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11947     4 GKFDFTASGEDELSFKKGDVLKILSSDD-IWFKAELNGEEGYVPKNFV 50

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212703 [Multi-domain] Cd Length: 57 Bit Score: 55.39 E-value: 1.36e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLN-KEDPDWWKGE-VSGQVGLFPSNYVK 1227
Cdd:cd11769     3 ECIAKYNFNGASEEDLPFKKGDILTIVAvTKDPNWYKAKnKDGREGMIPANYVQ 56

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 55.33 E-value: 1.42e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPdWWKGELRGRVGIFPANYVQ 52

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 55.46 E-value: 1.48e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPD---WWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11807     2 VVYALFDYEAENGDELSFREGDELTVLRKGDDDeteWWWARLNDKEGYVPRNLLGL 57

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 55.02 E-value: 1.52e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  763 KVVyyrALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11826     1 KVV---ALYDYTADKDDELSFQEGDIIYV--TKKNDDGWYEGVLNGVTGLFPGNYVE 52

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 55.11 E-value: 1.55e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11838     3 IALYPYESNEPGDLTFNAGDVILVTKKDGEWWTGTIGDRTGIFPSNYVRP 52

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 55.05 E-value: 1.64e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDGD---WWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11875     4 VLFDYEAENEDELTLREGDIVTILSKDCEdkgWWKGELNGKRGVFPDNFVEP 55

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 57.32 E-value: 1.69e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1636 PYCEVTM-GSQCHITKTIQDTLNPKWNSNCQFFIRDleQEVLCITVFERDQFSPDD--FLGRTEIRVADIkkdQGSKGPV 1712
Cdd:cd08382    23 PFAVITVdGGQTHSTDVAKKTLDPKWNEHFDLTVGP--SSIITIQVFDQKKFKKKDqgFLGCVRIRANAV---LPLKDTG 97

                          90       100
                  ....*....|....*....|....*
gi 568997330 1713 TKCLLLH-------EVPTGEIVVRL 1730
Cdd:cd08382    98 YQRLDLRklkksdnLSVRGKIVVSL 122

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 55.05 E-value: 1.70e-09

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1183 YTAQNDDELAFSKGQIINVLNKEDpDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11990     8 WTAKKDNHLNFSKNDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKL 52

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 55.06 E-value: 1.74e-09

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11786     5 LYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQ 52

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212709 [Multi-domain] Cd Length: 57 Bit Score: 55.02 E-value: 1.78e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDP-DWWKGE--VSGQVGLFPSNYVKL 1228
Cdd:cd11775     6 LYDFDAQSDDELTVKEGDVVYILDDKKSkDWWMVEnvSTGKEGVVPASYIEI 57

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 55.00 E-value: 1.83e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYVKL 1228
Cdd:cd11916     6 ALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSrrTKQFGTFPGNYVKL 57

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 55.06 E-value: 1.91e-09

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                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVL--NKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11836     5 LYAFEARNPDEISFQPGDIIQVDesQVAEPGWLAGELKGKTGWFPANYV 53

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 55.04 E-value: 2.03e-09

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGD-----KSGVFPSNYV 1072
Cdd:cd11887     5 KALYPYESDHEDDLNFDVGQLITVTEEeDADWYFGEYVDsngntKEGIFPKNFV 58

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 55.01 E-value: 2.03e-09

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGD-KSGVFPSNYVRL 1074
Cdd:cd11819     3 KALYDYQAAEDNEISFVEGDIITqIEQIDEGWWLGVNAKgQKGLFPANYVEL 54

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 54.73 E-value: 2.04e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMV---DESqtgepGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11827     3 KALYAYDAQDTDELSFNEGDIIEIlkeDPS-----GWWTGRLRGKEGLFPGNYVEK 53

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 54.78 E-value: 2.09e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPG--GWWEGELQARgkkrqIGWFPANYV 1150
Cdd:cd12142     3 RVLFDYNPVAPDELALKKGDVIEVISKETEdeGWWEGELNGR-----RGFFPDNFV 53

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 56.88 E-value: 2.21e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1617 VNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDFLGRTE 1696
Cdd:cd08376     4 IVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDEFIGRCE 83

                          90
                  ....*....|
gi 568997330 1697 IRVADIKKDQ 1706
Cdd:cd08376    84 IDLSALPREQ 93

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 54.43 E-value: 2.31e-09

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGELKGKTGWFPANY 817
Cdd:cd11778     1 YVEALYDYEAQGDDEISIRVGDRIAVIRGDDGS-GWTYGEINGVKGLFPTSY 51

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 54.66 E-value: 2.34e-09

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                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1101 SYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYV 1150
Cdd:cd11823     7 SYTANREDELSLQPGDIIEVHEKQDDGWWLGEL--NGKK---GIFPATYV 51

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 54.52 E-value: 2.35e-09

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                   ....*....|....*....|....*....|....*....|....*..
gi 568997330  1025 IAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTV-GDKSGVFPS 1069
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIiVLEKSEDGWWKGRNkGGKEGLIPS 47

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 54.58 E-value: 2.38e-09

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11995     2 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPdWWKGELNGQVGLFPSNYVKL 54

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212796 Cd Length: 61 Bit Score: 54.89 E-value: 2.43e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1180 MYDYTAQNDDE-------LAFSKGQIINVLNKEDPDWWK----GEVSGQVGLFPS 1223
Cdd:cd11862     5 LFDYDPEEDPLipckeagLSFKKGDILQIVNQDDPNWWQarkvGDPNGRAGLIPS 59

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 54.45 E-value: 2.43e-09

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                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11961     4 ALYDYDAAEDNELSFFENDKIInIEFVDDDWWLGECHGSRGLFPSNYVEL 53

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 54.43 E-value: 2.57e-09

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gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11833     2 YVALYKFKPQENEDLEMRPGDKItLLDDSNEDWWKGKIEDRVGFFPANFV 51

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 54.57 E-value: 2.71e-09

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGD-VIVVTKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd11985     2 YVALYKFLPQENNDLPLQPGDrVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 52

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 54.34 E-value: 3.07e-09

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11840     3 IALFPYTAQNEDELSFQKGDIINVLSKD--DPDWWRGELNGQTGLFPSNYVE 52

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 54.11 E-value: 3.09e-09

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gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11815     5 LHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYRGKCKNTTGIFPANHVK 52

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 56.52 E-value: 3.15e-09

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gi 568997330 1614 RLMVNVVEGIELKPCRSHGKSNPYCEVTM-GSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLcITVFERDQFSPDDFL 1692
Cdd:cd04042     1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYgGKTVYKSKTIYKNLNPVWDEKFTLPIEDVTQPLY-IKVFDYDRGLTDDFM 79

                          90
                  ....*....|....
gi 568997330 1693 GRTEIRVADIKKDQ 1706
Cdd:cd04042    80 GSAFVDLSTLELNK 93

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212725 [Multi-domain] Cd Length: 59 Bit Score: 54.61 E-value: 3.16e-09

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQTGEP--GWLGG--ELKGKTGWFPANYAEK 820
Cdd:cd11791     2 LRVLYPYTPQEEDELELVPGDYIYVSPEELDSSsdGWVEGtsWLTGCSGLLPENYTEK 59

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 54.13 E-value: 3.21e-09

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gi 568997330   936 QALYPWRAKKDNHLNFNKSDVITVLEQQ-DMWWFGEVQ-GQKGWFP 979
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSeDGWWKGRNKgGKEGLIP 46

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 54.24 E-value: 3.22e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEV-QGQKGWFPKSYVKL 985
Cdd:cd11819     1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDEgWWLGVNaKGQKGLFPANYVEL 54

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 54.29 E-value: 3.31e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd11786     2 AKALYNYEGKEPGDLSFKKGDIILLRKRIDEnWYHGECNGKQGFFPASYVQ 52

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270065 Cd Length: 128 Bit Score: 56.52 E-value: 3.36e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1481 LHSGKLYKAKSNK--ELYGFLFNDFLLLTQITKPLG-SSGTDKVFS---------PKSNLQYKMYKTPIFLNEVLVK--L 1546
Cdd:cd13245     3 LHEGPLTLIESGKtlDVYLFLFDDMLLITKMKKNLKkKKSSDSENSmpsleltplIKEGGSYTVYKQPIPLDRLCLHdvD 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1547 PTDPS--GDEPIFHISHIDR------VYTLRAESINERTAWVQKIK 1584
Cdd:cd13245    83 PNEATanGLKHAFVLVHLNRyqqvigVYTLQASSENTKQTWMSKLR 128

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 54.04 E-value: 3.42e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11813     1 RAKALLDFERHDDDELGFRKNDIITIISQKDeHCWVGELNGLRGWFPAKFVEL 53

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 54.19 E-value: 3.54e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYV 1150
Cdd:cd11766     1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNG-----QVGWFPSNYV 51

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 54.27 E-value: 3.60e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKL 985
Cdd:cd11781     2 ARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYeGEHNGRVGIFPASYVEI 53

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 54.26 E-value: 3.68e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPD-WWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11978     4 IARYDFCARDMRELSLLKGDVVKIYTKMSTNgWWRGEVNGRVGWFPSTYVE 54

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 54.24 E-value: 3.82e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQ---VGLFPSNYVKL 1228
Cdd:cd11965     1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 56

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 61.62 E-value: 3.88e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  395 LLEQQRKE--QERLAQLERAEQERKERERQEQE-RKRQLELEKQLEKQrelerqreeerrkeierreaakRELERQRQL- 470
Cdd:PRK03918  445 LTEEHRKEllEEYTAELKRIEKELKEIEEKERKlRKELRELEKVLKKE----------------------SELIKLKELa 502

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  471 EWERNRRQEL-------LNQRNKEQEGT----VVLKARRKTLEFELE---ALNDKKHQLEGKLQDIRCRLATQRQEIE-- 534
Cdd:PRK03918  503 EQLKELEEKLkkynleeLEKKAEEYEKLkeklIKLKGEIKSLKKELEkleELKKKLAELEKKLDELEEELAELLKELEel 582

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  535 --STNKSRELRIAEIthlqqqlqesqqmlgrlipekqilsdqlkqvqqNSLHRD--SLLTLKRALEAKELARQQLREQLD 610
Cdd:PRK03918  583 gfESVEELEERLKEL---------------------------------EPFYNEylELKDAEKELEREEKELKKLEEELD 629

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  611 EVERETRSKLQEIDVFNNQLKELREIHSKQQ--------LQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQ 682
Cdd:PRK03918  630 KAFEELAETEKRLEELRKELEELEKKYSEEEyeelreeyLELSRELAGLRAELEELEKRREEIKKTLEKLKEELEEREKA 709

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  683 WLEhVQQEEQPRPRKPHEEDRLKRedsvRKKEAEERAKPEMQDKQSRLF 731
Cdd:PRK03918  710 KKE-LEKLEKALERVEELREKVKK----YKALLKERALSKVGEIASEIF 753

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 54.02 E-value: 4.03e-09

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNY 1071
Cdd:cd11817     3 VALYDFTGETEEDLSFQRGDRILVTEHlDAEWSRGRLNGREGIFPRAF 50

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 54.27 E-value: 4.21e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE--VSGQVGLFPSNYV 1226
Cdd:cd12007     4 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNYV 54

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 54.07 E-value: 4.36e-09

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd11949     4 ALFDFDPQEDGELGFRRGDFIeVMDNSDPNWWKGACHGQTGMFPRNYVT 52

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 53.80 E-value: 5.55e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11927     5 ALYNYEGKEPGDLKFSKGDIIILRRQvDENWYHGEVNGIHGFFPTNFVQI 54

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 53.69 E-value: 5.84e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd11949     2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPnWWKGACHGQTGMFPRNYVT 52

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 53.85 E-value: 6.00e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANYAEKI 821
Cdd:cd12060     5 KARFNFKQTNEDELSVCKGDIIYVTRVEEG--GWWEGTLNGKTGWFPSNYVREI 56

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 61.24 E-value: 6.02e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   351 QRLPEEPSSEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKrql 430
Cdd:TIGR02169  726 EQLEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELEARIEELEEDLHKLEEALNDLEARLSHSRIPEIQAELSK--- 802

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   431 eLEKQLEKQrelerqreeerrkeierrEAAKRELE-----RQRQLEWERNRRQELLNQRNKeqegtvvLKARRKTLEFEL 505
Cdd:TIGR02169  803 -LEEEVSRI------------------EARLREIEqklnrLTLEKEYLEKEIQELQEQRID-------LKEQIKSIEKEI 856

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   506 EALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLipeKQILSDQLKQVQQNSLHR 585
Cdd:TIGR02169  857 ENLNGKKEELEEELEELEAALRDLESRLGDLKKERDELEAQLRELERKIEELEAQIEKK---RKRLSELKAKLEALEEEL 933

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   586 DSLLTLKRALE---AKELARQQLREQLDEVERETRS----KLQEIDVFNNQLKELREIHSKQQ-LQKQRSLEAARLKQKE 657
Cdd:TIGR02169  934 SEIEDPKGEDEeipEEELSLEDVQAELQRVEEEIRAlepvNMLAIQEYEEVLKRLDELKEKRAkLEEERKAILERIEEYE 1013


                   ....*
gi 568997330   658 QERKS 662
Cdd:TIGR02169 1014 KKKRE 1018

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 53.45 E-value: 6.17e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11996     2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDPdWWQGEINGVTGLFPSNYVKM 54

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 53.58 E-value: 6.19e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11843     3 RALYDYEGQESDELSFKAGDILTKLEEED-EQGWCKGRLDGRVGLYPANYVE 53

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 53.48 E-value: 6.24e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGE-LKGKTGWFPANYAE 819
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGD-GWLEGRnSRGEVGLFPSSYVE 54

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 53.30 E-value: 6.58e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11870     1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGRVGIFPKCFVV 52

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

Pssm-ID: 464768 [Multi-domain] Cd Length: 374 Bit Score: 60.05 E-value: 6.63e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   397 EQQRKEQERLAQLERAEQERKERERQEQ-ERKRQLELEKQLE------KQRELERQREEERRKEIERREAAKRELERQRQ 469
Cdd:pfam15558   20 EQRMRELQQQAALAWEELRRRDQKRQETlERERRLLLQQSQEqwqaekEQRKARLGREERRRADRREKQVIEKESRWREQ 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   470 LEWERNRRQELLNQRNKEQEGTVVLKARR-KTLEFELEALNDKKHQLEGKLQDIRCRLATQR-----QEIESTNKSRELR 543
Cdd:pfam15558  100 AEDQENQRQEKLERARQEAEQRKQCQEQRlKEKEEELQALREQNSLQLQERLEEACHKRQLKereeqKKVQENNLSELLN 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   544 IAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQvQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSK-LQE 622
Cdd:pfam15558  180 HQARKVLVDCQAKAEELLRRLSLEQSLQRSQENY-EQLVEERHRELREKAQKEEEQFQRAKWRAEEKEEERQEHKEaLAE 258

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330   623 IDvfNNQLKELREIHSKQQLQK-QRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQ 689
Cdd:pfam15558  259 LA--DRKIQQARQVAHKTVQDKaQRARELNLEREKNHHILKLKVEKEEKCHREGIKEAIKKKEQRSEQ 324

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 53.37 E-value: 6.77e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11986     2 FVALYRFKALEKDDLDFHPGERItVIDDSNEEWWRGKIGEKTGYFPMNFI 51

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 53.49 E-value: 6.98e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE--VSGQVGLFPSNYV 1226
Cdd:cd11793     1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErlRDGERGWFPSSYT 53

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 59.55 E-value: 7.36e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   393 QALLEQQRKEQERLAQLERAEQERKERERqEQERKRQLELEKQLEKQRELERQreeerrkeierreAAKRELERQRqlew 472
Cdd:pfam13868   21 NKERDAQIAEKKRIKAEEKEEERRLDEMM-EEERERALEEEEEKEEERKEERK-------------RYRQELEEQI---- 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   473 ERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRcrlatqrQEIESTNKSRELRIAEIthlqq 552
Cdd:pfam13868   83 EEREQKRQEEYEEKLQEREQMDEIVERIQEEDQAEAEEKLEKQRQLREEID-------EFNEEQAEWKELEKEEE----- 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   553 qlqesqqmlgrLIPEKQILsDQLKQVQQNSLHRdslltlKRALEAKELARQQLREQLDEVERETRSKLQEIDvfnnqlkE 632
Cdd:pfam13868  151 -----------REEDERIL-EYLKEKAEREEER------EAEREEIEEEKEREIARLRAQQEKAQDEKAERD-------E 205

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   633 LReihskqqlqkqrsleaARLKQKEQERKslELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKRE-DSVR 711
Cdd:pfam13868  206 LR----------------AKLYQEEQERK--ERQKEREEAEKKARQRQELQQAREEQIELKERRLAEEAEREEEEfERML 267

                          330
                   ....*....|....*....
gi 568997330   712 KKEAEERAKPEMQDKQSRL 730
Cdd:pfam13868  268 RKQAEDEEIEQEEAEKRRM 286

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 59.78 E-value: 7.68e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  459 AAKRELER-QRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIestn 537
Cdd:COG4942    31 QLQQEIAElEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAELEKEIAELRAELEAQKEEL---- 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  538 kSRELRIAEithlqqqlqesqqMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQlrEQLDEVERETR 617
Cdd:COG4942   107 -AELLRALY-------------RLGRQPPLALLLSPEDFLDAVRRLQYLKYLAPARREQAEELRADL--AELAALRAELE 170

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  618 SKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQ 682
Cdd:COG4942   171 AERAELEALLAELEEERAALEALKAERQKLLARLEKELAELAAELAELQQEAEELEALIARLEAE 235

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 53.39 E-value: 7.82e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11928     5 ALYSYEGKEPGDLKFNKGDIIILRRKvDENWYHGELNGCHGFLPASYIQC 54

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 53.36 E-value: 7.92e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12052     1 EAIVEFDYKAQHEDELTITVGDIITkIKKDDGGWWEGEIKGRRGLFPDNFVR 52

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212836 [Multi-domain] Cd Length: 59 Bit Score: 53.52 E-value: 8.11e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNK--EDPDWWKGEVS-GQVGLFPSNYV 1226
Cdd:cd11903     6 LYPFSSVTEEELNFEKGETMEVIEKpeNDPEWWKCKNSrGQVGLVPKNYV 55

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 53.13 E-value: 8.11e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQDM---WWFGEVQGQKGWFPKSYV 983
Cdd:cd11836     3 RALYAFEARNPDEISFQPGDIIQVDESQVAepgWLAGELKGKTGWFPANYV 53

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 53.14 E-value: 8.58e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVS-GQVGLFPSNYV 1226
Cdd:cd11758     3 VRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARNSeGKTGMIPVPYV 53

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 53.02 E-value: 8.82e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMV---DESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd12058     2 WTALYDYEASGEDELSLRRGDVVEVlsqDAAVSGDDGWWAGKIRHRLGIFPANY 55

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 53.15 E-value: 8.96e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11828     2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKdWWWGSIRDEEGWFPASFVRL 53

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 53.00 E-value: 9.07e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568997330   937 ALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 984
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEEsEDGWWEGINTGRTGLVPANYVE 49

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 56.20 E-value: 9.27e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   389 EKRRQALLEQQRKEQERLAQLERAEQERKE-RERQEQERKRQLELEKQLEKQRELERQREEERrkeierreaAKRELERQ 467
Cdd:pfam05672   18 EKRRQAREQREREEQERLEKEEEERLRKEElRRRAEEERARREEEARRLEEERRREEEERQRK---------AEEEAEER 88

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 568997330   468 RQLEWERNRRQEllnQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGK 518
Cdd:pfam05672   89 EQREQEEQERLQ---KQKEEAEAKAREEAERQRQEREKIMQQEEQERLERK 136

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 53.19 E-value: 9.36e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1179 GMYDYTAQNDD--ELAFSKGQIINVLNKEDpDWWKGEVS-GQVGLFPSNYVKL 1228
Cdd:cd11855     4 ALYPYDASPDDpnELSFEKGEILEVSDTSG-KWWQARKSnGETGICPSNYLQL 55

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 53.03 E-value: 9.54e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPD-WWKGEV-SGQVGLFPSNYVK 1227
Cdd:cd11998     2 RVRALYDYDGQEQDELSFKAGDELTKLEDEDEQgWCKGRLdSGQVGLYPANYVE 55

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 52.62 E-value: 9.62e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568997330  1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEEsEDGWWEGINTGRTGLVPANYVE 49

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 60.57 E-value: 9.88e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   374 EDKKRENFERGSVEleKRRQAL---LEQQRKEQERLAQLERAEQE-RKERERQEQERKRQLELEK-----QLEKQRELER 444
Cdd:pfam01576  278 EDLESERAARNKAE--KQRRDLgeeLEALKTELEDTLDTTAAQQElRSKREQEVTELKKALEEETrsheaQLQEMRQKHT 355

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   445 QREEERRKEIERREAAKRELERQRQ-LEWERNRRQE---LLNQRNKEQEgtvvlkARRKTLEFELEALNDKKHQLEGKLQ 520
Cdd:pfam01576  356 QALEELTEQLEQAKRNKANLEKAKQaLESENAELQAelrTLQQAKQDSE------HKRKKLEGQLQELQARLSESERQRA 429

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   521 DIRCRLATQRQEIESTNKSreLRIAEithlqqqlqesqQMLGRLIPEKQILSDQLK----QVQQNSLHRDSLLTLKRALE 596
Cdd:pfam01576  430 ELAEKLSKLQSELESVSSL--LNEAE------------GKNIKLSKDVSSLESQLQdtqeLLQEETRQKLNLSTRLRQLE 495

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   597 AKelaRQQLREQLDEVERETRSKLQEIDVFNNQLKELRE--------IHSKQQLQK--QRSLEAARLKQKEQERKSLELE 666
Cdd:pfam01576  496 DE---RNSLQEQLEEEEEAKRNVERQLSTLQAQLSDMKKkleedagtLEALEEGKKrlQRELEALTQQLEEKAAAYDKLE 572

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330   667 KQKEDAQrrvQERDKQW--LEHVQQEEQPRPRKPHEEDR-LKREDSVRKKEAEER--AKPEMQDKQSR 729
Cdd:pfam01576  573 KTKNRLQ---QELDDLLvdLDHQRQLVSNLEKKQKKFDQmLAEEKAISARYAEERdrAEAEAREKETR 637

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 53.03 E-value: 1.03e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11803     5 ALYDFEPENEGELGFKEGDIITLTNQiDENWYEGMVNGQSGFFPVNYV 52

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 52.91 E-value: 1.03e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd11950     4 ALYDFEALEDDELGFNSGDVIeVLDSSNPSWWKGRLHGKLGLFPANYVA 52

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 53.09 E-value: 1.04e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVL--EQQDMWWFGE--VQGQKGWFPKSYVK 984
Cdd:cd11779     2 RVKALYPHAAGGETQLSFEEGDVITLLgpEPRDGWHYGEneRSGRRGWFPIAYTE 56

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 52.90 E-value: 1.04e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKD-GD--WWTGTVGDKSGVFPSNYV 1072
Cdd:cd12056     6 ALFHYEGTNEDELDFKEGEIILIISKDtGEpgWWKGELNGKEGVFPDNFV 55

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 52.98 E-value: 1.04e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 568997330   935 AQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKLI 986
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKdNDGWWEGETGGRVGLVPSTAVEEI 54

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 52.90 E-value: 1.05e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd12047     1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFA 51

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 52.71 E-value: 1.11e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKeDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11992     1 EYIALYPYSSSEPGDLTFNEGEEILVTQK-DGEWWTGSIEDRTGIFPSNYVR 51

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 52.65 E-value: 1.17e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYVK 1151
Cdd:cd11873     4 VEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTL--NGKR---GMFPDNFVK 52

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 52.85 E-value: 1.17e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTK-KDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11820     5 ALYDFEAAEDNELTFKAGEIITVLDdSDPNWWKGSNHRGEGLFPANFV 52

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 52.65 E-value: 1.18e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVmVDESQTgEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11873     2 VIVEFDYDAEEPDELTLKVGDII-TNVKKM-EEGWWEGTLNGKRGMFPDNFVKV 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 60.37 E-value: 1.22e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   362 EQQPEKKLpvTFEDKKREnfergsvELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQ------ERKRQLELEKQ 435
Cdd:TIGR00618  238 TQQSHAYL--TQKREAQE-------EQLKKQQLLKQLRARIEELRAQEAVLEETQERINRARKaaplaaHIKAVTQIEQQ 308

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   436 LEKQRELERQREEERRKEIERREAAKR---ELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKK 512
Cdd:TIGR00618  309 AQRIHTELQSKMRSRAKLLMKRAAHVKqqsSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHTLQQQK 388

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   513 HQLEGKLQ------------------------DIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEK 568
Cdd:TIGR00618  389 TTLTQKLQslckeldilqreqatidtrtsafrDLQGQLAHAKKQQELQQRYAELCAAAITCTAQCEKLEKIHLQESAQSL 468

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   569 QILSDQLKQVQQNSLH--RDSLLTLKRALEAKELAR---------------------------------QQLREQLDEVE 613
Cdd:TIGR00618  469 KEREQQLQTKEQIHLQetRKKAVVLARLLELQEEPCplcgscihpnparqdidnpgpltrrmqrgeqtyAQLETSEEDVY 548

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   614 RETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQER------KSLELEKQKEDAQRR------------ 675
Cdd:TIGR00618  549 HQLTSERKQRASLKEQMQEIQQSFSILTQCDNRSKEDIPNLQNITVRlqdlteKLSEAEDMLACEQHAllrklqpeqdlq 628

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997330   676 --------VQERDKQWLEHVQQEEQPRPRKPHEED-RLKREDSVRKKEAEERAKPEMQDKQSRL 730
Cdd:TIGR00618  629 dvrlhlqqCSQELALKLTALHALQLTLTQERVREHaLSIRVLPKELLASRQLALQKMQSEKEQL 692

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 52.54 E-value: 1.31e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQII-NVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12053     1 EYIVEYDYDAVHEDELTIRVGEIIrNVKKLEEEGWLEGELNGRRGMFPDNFVK 53

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 52.63 E-value: 1.32e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKE----DPDWWKGEVSGQ-VGLFPSNYVKL 1228
Cdd:cd11864     3 RAEYDFVAESEDELSFRAGDKLRLAPKElqprVRGWLLATVDGQkIGLVPANYVKI 58

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 52.67 E-value: 1.38e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKS-----GVFPSNY 1071
Cdd:cd11883     3 VALYDFTPKSKNQLSFKAGDIIyVLNKDPSGWWDGVIISSSgkvkrGWFPSNY 55

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 52.65 E-value: 1.40e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 986
Cdd:cd11803     2 CCRALYDFEPENEGELGFKEGDIITLTNQIDENWYeGMVNGQSGFFPVNYVEVL 55

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 52.71 E-value: 1.41e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVV-TKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11963     6 ALYDFEAVEDNELTFKHGEIIIVlDDSDANWWKGENHRGVGLFPSNFV 53

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 52.63 E-value: 1.45e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11830     4 ARYDFCARDMRELSLKEGDVVKI-YNKKGQQGWWRGEINGRIGWFPSTYVEE 54

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 52.40 E-value: 1.47e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE--VSGQVGLFPSNYVKL 1228
Cdd:cd11783     2 YVALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTslRTGQSGVFPGNYVQP 55

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 52.40 E-value: 1.47e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDGD-----WWTGTVGDKSGVFPS 1069
Cdd:cd11762     4 ALYDYEAQSDEELSFPEGAIIRILRKDDNgvddgWWEGEFNGRVGVFPS 52

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 54.58 E-value: 1.53e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1633 KSNPYCEV---TMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFsPDDFLGRTEIRVADIKKDQgsk 1709
Cdd:cd04036    20 TPDCYVELwlpTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDDHLGTVLFDVSKLKLGE--- 95

                          90       100
                  ....*....|....*....|....*
gi 568997330 1710 gPVTKCLLLHEVPTGEIVVRLDLQL 1734
Cdd:cd04036    96 -KVRVTFSLNPQGKEELEVEFLLEL 119

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 52.64 E-value: 1.57e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKD----GD--WWTGTVGDKSGVFPSNYV 1072
Cdd:cd12058     4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsGDdgWWAGKIRHRLGIFPANYV 56

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 52.42 E-value: 1.57e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  769 ALYPFESRSHDEITIQPGDIV----MVDEsqtgepGWLGGELKGKTGWFPANYAE 819
Cdd:cd11959     4 ALYDYQAADDDEISFDPDDIItnieMIDE------GWWRGVCRGKYGLFPANYVE 52

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 52.59 E-value: 1.58e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1027 MYTYESSEQGDLTFQQGDVIVVTKK---DGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd12057     5 LFPYEAQNEDELTIKEGDIVTLISKdciDAGWWEGELNGRRGVFPDNFVKL 55

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 52.37 E-value: 1.66e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11974     6 LWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVRL 54

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 52.10 E-value: 1.78e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANY 817
Cdd:cd11818     3 RALYDFTGENEDELSFKAGDIITELESIDEE--WMSGELRGKSGIFPKNF 50

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 59.69 E-value: 1.86e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   351 QRLPEEPSSEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL 430
Cdd:TIGR02168  750 AQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREALDELRAELTLLNEEAANLRERLESL 829

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   431 ELEKQLEKQRELERQREEERRKEIERREAAKRElERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALND 510
Cdd:TIGR02168  830 ERRIAATERRLEDLEEQIEELSEDIESLAAEIE-ELEELIEELESELEALLNERASLEEALALLRSELEELSEELRELES 908

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   511 KKHQLEGKLQDIRCRLATQRQEIESTnksrELRIAEIThlqQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRdsllt 590
Cdd:TIGR02168  909 KRSELRRELEELREKLAQLELRLEGL----EVRIDNLQ---ERLSEEYSLTLEEAEALENKIEDDEEEARRRLKR----- 976

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330   591 LKRAL------------EAKEL----------------ARQQLREQLDEVERETRSKLQE-IDVFNNQLKEL 633
Cdd:TIGR02168  977 LENKIkelgpvnlaaieEYEELkerydfltaqkedlteAKETLEEAIEEIDREARERFKDtFDQVNENFQRV 1048

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 52.21 E-value: 1.88e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  1024 FIAMYTYESSEQGDLTFQQGDVIVVTKKD-GDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDnDGWWEGETGGRVGLVPSTAVEE 53

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 51.95 E-value: 1.92e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQK-GWFPKSYVK 984
Cdd:cd11825     2 VKALYDYRAQRPDELSFCKHAIITNVEKEDgGWWRGDYGGKKqKWFPANYVE 53

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 52.28 E-value: 2.05e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKE----DPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11895     4 ALYSYTGQSPEELSFPEGALIRLLPRAqdgvDDGFWRGEFGGRVGVFPSLLVE 56

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 52.14 E-value: 2.06e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLE-QQDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEfVDDDWWLGECHGSRGLFPSNYVEL 53

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 51.82 E-value: 2.06e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 568997330   768 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELK-GKTGWFPA 815
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKS--EDGWWKGRNKgGKEGLIPS 47

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 52.08 E-value: 2.07e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMV---DESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd12059     1 VWTAVFDYEASAEDELTLRRGDRVEVlskDSAVSGDEGWWTGKINDRVGIFPSNY 55

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 52.02 E-value: 2.30e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPdWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11989     1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 52

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176006 [Multi-domain] Cd Length: 111 Bit Score: 53.80 E-value: 2.45e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1632 GKSNPYCEVTM---GSQCHITKTIQDTLNPKWNSNCqfFI----RDLE-QEVLCITVFERDQFSPDDFLGRTEIRVADIK 1703
Cdd:cd04041    21 GSSDPYVTASFakfGKPLYSTRIIRKDLNPVWEETW--FVlvtpDEVKaGERLSCRLWDSDRFTADDRLGRVEIDLKELI 98


                  ..
gi 568997330 1704 KD 1705
Cdd:cd04041    99 ED 100

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 51.85 E-value: 2.48e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNK--EDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11952     3 VYALWDYSAEFPDELSFKEGDMVTVLRKdgEGTDWWWASLCGREGYVPRNYFGL 56

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 51.75 E-value: 2.56e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLnKEDPDWWKGE--VSGQVGLFPSNYV 1226
Cdd:cd12005     1 LVVALYSYEPSHDGDLGFEKGEKLRIL-EQSGEWWKAQslTTGQEGFIPFNFV 52

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 51.94 E-value: 2.64e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPD-----WWKG--EVSGQVGLFPSNYVK 1227
Cdd:cd11790     9 HDYTAEDTDELTFEKGDVILVIPFDDPEeqdegWLMGvkESTGCRGVFPENFTE 62

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 58.42 E-value: 2.66e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   388 LEKRRQALLEQQRKEQERlAQLERAEQERKERERQEQERKRQLELEKqlEKQRELERQREEERRKEIERREAAKRELERQ 467
Cdd:pfam15709  325 LEKREQEKASRDRLRAER-AEMRRLEVERKRREQEEQRRLQQEQLER--AEKMREELELEQQRRFEEIRLRKQRLEEERQ 401

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   468 RQLEWERNRRQellnQRNKEQEgtvvlKARRKTLEF--ELEALNDKKHQLEGKlqdiRCRLATQRQeiestnKSRELRIA 545
Cdd:pfam15709  402 RQEEEERKQRL----QLQAAQE-----RARQQQEEFrrKLQELQRKKQQEEAE----RAEAEKQRQ------KELEMQLA 462


                   .
gi 568997330   546 E 546
Cdd:pfam15709  463 E 463

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 51.43 E-value: 2.75e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGD-VIVVTKKDGDWW------TGtvgdKSGVFPSNY 1071
Cdd:cd11845     2 YVALYDYEARTDDDLSFKKGDrLQILDDSDGDWWlarhlsTG----KEGYIPSNY 52

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212932 [Multi-domain] Cd Length: 56 Bit Score: 51.48 E-value: 2.94e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYV 1226
Cdd:cd11999     3 RVRAVYDYTGQEPDELSFKAGEELLKVEDEDEQGWCKGVtdGGAVGLYPANYV 55

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 51.54 E-value: 3.18e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVS-GQVGLFPSNYVKL 1228
Cdd:cd11770     2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAENSkGNRGLVPKTYLKV 54

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.

Pssm-ID: 431111 [Multi-domain] Cd Length: 766 Bit Score: 58.68 E-value: 3.47e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   567 EKQI--LSDQLKQVQQNSLHRDS-LLTLKRALEAKELARQQLREQldeVERETRSKLQEIDVFNNQLKELREIHSKQQ-- 641
Cdd:pfam10174  414 DKQLagLKERVKSLQTDSSNTDTaLTTLEEALSEKERIIERLKEQ---REREDRERLEELESLKKENKDLKEKVSALQpe 490

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   642 ----------LQKQRSLEAARLKQKEQERKSLE--LEKQKEDAQRRVQERDKqwlehVQQEEQPRPRKPHEEDRLK--RE 707
Cdd:pfam10174  491 ltekesslidLKEHASSLASSGLKKDSKLKSLEiaVEQKKEECSKLENQLKK-----AHNAEEAVRTNPEINDRIRllEQ 565

                          170
                   ....*....|....*..
gi 568997330   708 DSVRKKEAEERAKPEMQ 724
Cdd:pfam10174  566 EVARYKEESGKAQAEVE 582

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 51.60 E-value: 3.50e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKED----PDWWKGEVSGQVGLFPSNY 1225
Cdd:cd11800     1 YYYALYTFEARSPGELSVTEGQVVTVLEKHDlkgnPEWWLVEDRGKQGYVPSNY 54

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 51.18 E-value: 3.87e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGE--LKGKTGWFPANYAE 819
Cdd:cd11793     4 CVHAYTAQQPDELTLEEGDVVNV--LRKMPDGWYEGErlRDGERGWFPSSYTE 54

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 51.18 E-value: 3.87e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKrqiGWFPANYV 1150
Cdd:cd11793     2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERLRDGER---GWFPSSYT 53

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 51.44 E-value: 4.01e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM---WWFGEVQGQKGWFPKSYVKLI 986
Cdd:cd12057     1 YCKVLFPYEAQNEDELTIKEGDIVTLISKDCIdagWWEGELNGRRGVFPDNFVKLL 56

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212942 [Multi-domain] Cd Length: 54 Bit Score: 51.35 E-value: 4.07e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGT--VGDKSGVFPSNYV 1072
Cdd:cd12009     3 IAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWLAKslTTGKEGYIPSNYV 52

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 50.97 E-value: 4.15e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQD--MWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11948     1 EAVALYSFQATESDELPFQKGDILKILNMEDdqNWYKAELQGREGYIPKNYIKV 54

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 50.97 E-value: 4.22e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGD-KSGVFPSNYV 1072
Cdd:cd11812     3 VALYDYTANRSDELTIHRGDIIRVLYKDNDnWWFGSLVNgQQGYFPANYV 52

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 58.44 E-value: 4.27e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   393 QALLEQQRKEQERLAQLERAEQ------ERKERERQEQERKRQLELEKQLEKQ--RELERQREEERRKEIERREAAKREL 464
Cdd:TIGR00618  156 QFLKAKSKEKKELLMNLFPLDQytqlalMEFAKKKSLHGKAELLTLRSQLLTLctPCMPDTYHERKQVLEKELKHLREAL 235

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   465 ERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEgkLQDIRCRLATQRQEIESTNKSRELRI 544
Cdd:TIGR00618  236 QQTQQSHAYLTQKREAQEEQLKKQQLLKQLRARIEELRAQEAVLEETQERIN--RARKAAPLAAHIKAVTQIEQQAQRIH 313

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   545 AEITHLQQQLQESQQMLGRLIpeKQILSDQLKQVQQNSLHRDSLLtLKRALEAKELARQQLREQLDEVEReTRSKLQEID 624
Cdd:TIGR00618  314 TELQSKMRSRAKLLMKRAAHV--KQQSSIEEQRRLLQTLHSQEIH-IRDAHEVATSIREISCQQHTLTQH-IHTLQQQKT 389

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   625 VFNNQLKELREIHSKQ---------QLQKQRSLE----AARLKQKEQER----------KSLELEKQKEDAQRRVQERDK 681
Cdd:TIGR00618  390 TLTQKLQSLCKELDILqreqatidtRTSAFRDLQgqlaHAKKQQELQQRyaelcaaaitCTAQCEKLEKIHLQESAQSLK 469

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330   682 QWLEHVQQEEQPRPRkpheEDRLKREDSVRKKEAEERAKPemqdKQSRLFHPHQE 736
Cdd:TIGR00618  470 EREQQLQTKEQIHLQ----ETRKKAVVLARLLELQEEPCP----LCGSCIHPNPA 516

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 50.88 E-value: 4.48e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11959     2 AVALYDYQAADDDEISFDPDDIITNIEMIDEgWWRGVCRGKYGLFPANYVEL 53

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 50.79 E-value: 4.75e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11874     4 VLFSYTPQNEDELELKVGDTIEVLGEVEEgWWEGKLNGKVGVFPSNFVKE 53

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 50.89 E-value: 4.89e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKsdsQNDWWTGRIGGREGIFPANYVEL 55

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 51.16 E-value: 5.25e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1022 EEFIAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11972     3 EKVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDgWYEGVMNGVTGLFPGNYV 54

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 50.71 E-value: 5.28e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11856     2 YVAIADYEAQGDDEISLQEGEVVEVLE--KNDSGWWYVRKGDKEGWVPASYLEP 53

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 51.16 E-value: 5.48e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYVKL 1228
Cdd:cd11935     6 MYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGTVqrTGRTGMLPANYIEF 56

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 50.59 E-value: 5.50e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11950     1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNpSWWKGRLHGKLGLFPANYVA 52

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 50.72 E-value: 5.64e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVdESQTGEpGWLGGELKGKTGWFPANYAE 819
Cdd:cd11803     3 CRALYDFEPENEGELGFKEGDIITL-TNQIDE-NWYEGMVNGQSGFFPVNYVE 53

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212769 [Multi-domain] Cd Length: 54 Bit Score: 50.91 E-value: 5.69e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1183 YTAQNDDELAFSKGQIINVLN---KEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11835     8 YTAQAPDELSLEVGDIVSVIDmppPEESTWWRGKKGFQVGFFPSECV 54

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 58.00 E-value: 6.27e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  495 KARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQqlqesqqmlgrlipEKQI--LS 572
Cdd:COG4913   609 RAKLAALEAELAELEEELAEAEERLEALEAELDALQERREALQRLAEYSWDEIDVASA--------------EREIaeLE 674

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  573 DQLKQVQQNSlhrDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIH---SKQQLQKQRSLE 649
Cdd:COG4913   675 AELERLDASS---DDLAALEEQLEELEAELEELEEELDELKGEIGRLEKELEQAEEELDELQDRLeaaEDLARLELRALL 751

                         170       180       190
                  ....*....|....*....|....*....|
gi 568997330  650 AARLKQKEQERKSLELEKQKEDAQRRVQER 679
Cdd:COG4913   752 EERFAAALGDAVERELRENLEERIDALRAR 781

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 50.67 E-value: 6.33e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGElqaRGKKRqiGWFPANYVKLL 1153
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGE---TGGRV--GLVPSTAVEEI 54

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 50.57 E-value: 6.42e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 983
Cdd:cd11951     2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDpNWWRGRISGRVGFFPRNYV 51

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 50.54 E-value: 6.71e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd11820     2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPnWWKGSNHRGEGLFPANFVT 53

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 50.79 E-value: 6.75e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11978     5 ARYDFCARDMRELSLLKGDVVKI-YTKMSTNGWWRGEVNGRVGWFPSTYVEE 55

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 56.47 E-value: 6.90e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   374 EDKKRENFERGSVEL-----EKRRQALLEQQRKEQERLAQLERAEQERKE--RERQEQERKR---QLELEKQLEKQrele 443
Cdd:pfam13868   64 EEERKEERKRYRQELeeqieEREQKRQEEYEEKLQEREQMDEIVERIQEEdqAEAEEKLEKQrqlREEIDEFNEEQ---- 139

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   444 rqreeerrkeierreAAKRELERQRQLEWER------NRRQELLNQRNKEQEGTVVLKARRKT-LEFELEALNDKKHQLE 516
Cdd:pfam13868  140 ---------------AEWKELEKEEEREEDErileylKEKAEREEEREAEREEIEEEKEREIArLRAQQEKAQDEKAERD 204

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   517 gklqdircRLATQRQEIESTNKSRELRIAEIthlqqqlqesqqmlgrlipEKQIlsDQLKQVQQnslHRDSLLTLKRALE 596
Cdd:pfam13868  205 --------ELRAKLYQEEQERKERQKEREEA-------------------EKKA--RQRQELQQ---AREEQIELKERRL 252

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   597 AKELAR-QQLREQLDEVERETRSKLQEidvfNNQLKELREIHSKQQLQKQRSL-EAARLKQKEQERKSLELEKQKEDAQR 674
Cdd:pfam13868  253 AEEAEReEEEFERMLRKQAEDEEIEQE----EAEKRRMKRLEHRRELEKQIEErEEQRAAEREEELEEGERLREEEAERR 328


                   ....*...
gi 568997330   675 RVQERDKQ 682
Cdd:pfam13868  329 ERIEEERQ 336

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 50.46 E-value: 6.94e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1029 TYESSEqgdLTFQQGDVIVVTK-KDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11828    10 TMDPEE---LGFKAGDVIEVLDmSDKDWWWGSIRDEEGWFPASFVRL 53

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 50.43 E-value: 6.98e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568997330 1182 DYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11796     7 DLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGIFPEGFV 51

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 52.67 E-value: 7.03e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1614 RLMVNVVEGIELKPCRSHGKSNPYCevtmgsQCHI-----------TKTIQDTLNPKWNSNCQFF-IR--DLEQEVLCIT 1679
Cdd:cd04035    16 ALHCTIIRAKGLKAMDANGLSDPYV------KLNLlpgaskatklrTKTVHKTRNPEFNETLTYYgITeeDIQRKTLRLL 89

                          90       100
                  ....*....|....*....|....*..
gi 568997330 1680 VFERDQFSpDDFLGRTEIRVADIKKDQ 1706
Cdd:cd04035    90 VLDEDRFG-NDFLGETRIPLKKLKPNQ 115

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 50.33 E-value: 7.35e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 983
Cdd:cd11964     2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDpNWWKGETPQGTGLFPSNFV 52

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 50.49 E-value: 7.36e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDEsQTGEpgWLGGELKGKTGWFPANYAEK 820
Cdd:cd11838     1 EYIALYPYESNEPGDLTFNAGDVILVTK-KDGE--WWTGTIGDRTGIFPSNYVRP 52

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 57.62 E-value: 7.42e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  375 DKKRENFERGSVELEKRRQALLEQQRKEQ-ERLAQLERaEQERKERERQEQERKRQlELEKQLEKQRELERQREEERRKE 453
Cdd:COG4913   308 EAELERLEARLDALREELDELEAQIRGNGgDRLEQLER-EIERLERELEERERRRA-RLEALLAALGLPLPASAEEFAAL 385

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  454 IERREAAKRELERQRqlEWERNRRQELLNQRNKeqegtvvLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQ---- 529
Cdd:COG4913   386 RAEAAALLEALEEEL--EALEEALAEAEAALRD-------LRRELRELEAEIASLERRKSNIPARLLALRDALAEAlgld 456

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  530 -------------RQE--------------------------------IESTNKSRELRIAEITHLQQQLQESQQMLGRL 564
Cdd:COG4913   457 eaelpfvgelievRPEeerwrgaiervlggfaltllvppehyaaalrwVNRLHLRGRLVYERVRTGLPDPERPRLDPDSL 536

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  565 IPE------------KQILS-----------DQLK----------QVQQNS----------LHRDSLL--TLKRALEAKE 599
Cdd:COG4913   537 AGKldfkphpfrawlEAELGrrfdyvcvdspEELRrhpraitragQVKGNGtrhekddrrrIRSRYVLgfDNRAKLAALE 616

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  600 LARQQLREQLDEVE-------------RETRSKLQEIDVFNNQLKELREIHSK-QQLQKQR-SLEAA---------RLKQ 655
Cdd:COG4913   617 AELAELEEELAEAEerlealeaeldalQERREALQRLAEYSWDEIDVASAEREiAELEAELeRLDASsddlaaleeQLEE 696

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997330  656 KEQERKslELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRkphEEDRLKREDSVRKKEAEERAKPEMQDKQSR 729
Cdd:COG4913   697 LEAELE--ELEEELDELKGEIGRLEKELEQAEEELDELQDR---LEAAEDLARLELRALLEERFAAALGDAVER 765

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 50.64 E-value: 7.70e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11988     5 RALYPFEARNHDEMSFNAGDIIQVDEKtvgEPGWLYGSFQGNFGWFPCNYVE 56

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 50.55 E-value: 8.04e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE--VSGQVGLFPSNYV 1226
Cdd:cd11784     3 VALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLslVTGRVGIFPSNYV 53

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 50.22 E-value: 8.21e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd12073     4 VALYDYQGEGDDEISFDPQETITdIEMVDEGWWKGTCHGHRGLFPANYVEL 54

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 50.12 E-value: 8.23e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11866     4 GLWDCSGNEPDELSFKRGDLIYIISKEydSFGWWVGELNGKVGLVPKDYL 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 50.34 E-value: 8.27e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQV---GLFPSNYV 1226
Cdd:cd11966     1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPtrrGAFPVSFV 54

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 50.43 E-value: 8.47e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPG--GWWEGELQARgkkrqIGWFPANYVKL 1152
Cdd:cd11875     2 ARVLFDYEAENEDELTLREGDIVTILSKDCEdkGWWKGELNGK-----RGVFPDNFVEP 55

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 50.36 E-value: 8.55e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEV-----QGQKGWFPKSY 982
Cdd:cd11883     3 VALYDFTPKSKNQLSFKAGDIIYVLNKDPSgWWDGVIisssgKVKRGWFPSNY 55

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 50.40 E-value: 8.72e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11977     5 ARYNFAARDMRELSLREGDVVRIYSRIGGDQGWWKGETNGRIGWFPSTYVEE 56

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 50.35 E-value: 9.02e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11919     7 FDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIEL 54

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 50.20 E-value: 9.04e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1102 YAATGpEQ----LTLAPGQLILIRKKNPGGWWEGElqargKKRQIGWFPANYV 1150
Cdd:cd11829     6 YAFTG-EQhqqgLSFEAGELIRVLQAPDGGWWEGE-----KDGLRGWFPASYV 52

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 50.02 E-value: 9.14e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDK-SGVFPSNYV 1072
Cdd:cd11825     4 ALYDYRAQRPDELSFCKHAIITnVEKEDGGWWRGDYGGKkQKWFPANYV 52

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 50.07 E-value: 9.36e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd12061     3 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGgWWEGTHNGRTGWFPSNYVR 52

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 49.96 E-value: 9.51e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11766     2 AVVKFNYEAQREDELSLRKGDRVLVLEKSSD--GWWRGECNGQVGWFPSNYVTE 53

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 50.04 E-value: 9.99e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11782     6 YNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQ 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 50.04 E-value: 1.03e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPD---WWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11844     5 LYDNVAESPDELAFRRGDILTVLEQNTAGlegWWLCSLRGRQGIAPGNRLKL 56

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 50.20 E-value: 1.07e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMV---DESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd11876     4 ALFDYDARGEDELTLRRGQPVEVlskDAAVSGDEGWWTGKIGDKVGIFPSNY 55

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 49.95 E-value: 1.08e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11985     3 VALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 52

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 50.11 E-value: 1.08e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1097 QVIA--SYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVKL 1152
Cdd:cd11840     1 QVIAlfPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNG-----QTGLFPSNYVEP 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 50.01 E-value: 1.14e-07

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                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTV---GDKSGVFPSNY 1071
Cdd:cd11821     4 ALYDCQADNDDELTFSEGEIIVVTGEeDDEWWEGHIegdPSRRGVFPVSF 53

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 50.01 E-value: 1.19e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVM----VDEsqtgepGWLGGELK--GKTGWFPANYAEK 820
Cdd:cd11789     2 YRAMYDYAAADDDEVSFQEGDVIInveiIDD------GWMEGTVQrtGQSGMLPANYVEL 55

Second Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212945 Cd Length: 62 Bit Score: 49.98 E-value: 1.19e-07

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1178 IGMYDYTAQ----NDD----ELAFSKGQIINVLNKEDPD-WWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12012     3 VALFDYDPLtmspNPDaaeeELPFKEGQLIKVYGDKDADgFYLGEINGRRGLVPCNMVS 61

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 50.00 E-value: 1.20e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVmVDESQTGEpGWLGG--ELKGKTGWFPANYAEKI 821
Cdd:cd11934     5 YRAVYDYNAADEDEVSFQDGDTI-VNVQQIDD-GWMYGtvERTGDTGMLPANYVEAI 59

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 50.02 E-value: 1.22e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKE---DPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11884     2 VVAVRAYITRDQTLLSFHKGDVIKLLPKEgplDPGWLFGTLDGRSGAFPKEYV 54

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 49.70 E-value: 1.23e-07

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGD-KSGVFPSNYVRL 1074
Cdd:cd11960     4 ALYDYQAADDTEISFDPGDIITdIEQIDEGWWRGTGPDgTYGLFPANYVEL 54

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176009 [Multi-domain] Cd Length: 124 Bit Score: 52.17 E-value: 1.25e-07

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1612 IGRLMVNVVEGIELKPCRSHGKS-NPYCEVTMGSQCHI--TKTIQDTLNPKWNSNcQFFIRDLEQEVLCITVFERDQFSP 1688
Cdd:cd04044     1 IGVLAVTIKSARGLKGSDIIGGTvDPYVTFSISNRRELarTKVKKDTSNPVWNET-KYILVNSLTEPLNLTVYDFNDKRK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1689 DDFLGRTEIRVADIkKDQGSKGPVTKCLLLHEVPTGEIvvRLDLQLF 1735
Cdd:cd04044    80 DKLIGTAEFDLSSL-LQNPEQENLTKNLLRNGKPVGEL--NYDLRFF 123

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 49.83 E-value: 1.35e-07

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  769 ALYPFESRSHDEITIQPGDIV----MVDEsqtgepGWLGGELKGKTGWFPANYAE 819
Cdd:cd12073     5 ALYDYQGEGDDEISFDPQETItdieMVDE------GWWKGTCHGHRGLFPANYVE 53

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 49.72 E-value: 1.39e-07

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGE--VSGQVGLFPSNYV 1226
Cdd:cd12008     3 VALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHslTTGQTGYIPSNYV 53

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 49.43 E-value: 1.39e-07

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  768 RALYPFESRSHDE-ITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd11829     3 RTLYAFTGEQHQQgLSFEAGELIRV--LQAPDGGWWEGEKDGLRGWFPASY 51

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 49.64 E-value: 1.44e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGK-----TGWFPANYAEK 820
Cdd:cd11839     3 QVIAPFTATAENQLSLAVGQLVLVRKKSPS--GWWEGELQARgkkrqIGWFPANYVKL 58

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 50.02 E-value: 1.48e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMV---DESQTGEPGWLGG--ELKGKTGWFPANYAEKI 821
Cdd:cd11790     6 RATHDYTAEDTDELTFEKGDVILVipfDDPEEQDEGWLMGvkESTGCRGVFPENFTERI 64

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 49.68 E-value: 1.50e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1101 SYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVK 1151
Cdd:cd12061     7 NFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGR-----TGWFPSNYVR 52

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 49.77 E-value: 1.51e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQ---DMWWFGEVQGQKGWFPKSYV 983
Cdd:cd12142     3 RVLFDYNPVAPDELALKKGDVIEVISKEtedEGWWEGELNGRRGFFPDNFV 53

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 49.42 E-value: 1.51e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1182 DYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11813     7 DFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFVEL 53

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 49.65 E-value: 1.53e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTG--TVGDKSGVFPSNYVRLKD 1076
Cdd:cd12007     3 FVALYDYEARTTEDLSFKKGERFqIINNTEGDWWEArsIATGKNGYIPSNYVAPAD 58

Mitotic checkpoint protein; This family consists of several eukaryotic mitotic checkpoint (Mitotic arrest deficient or MAD) proteins. The mitotic spindle checkpoint monitors proper attachment of the bipolar spindle to the kinetochores of aligned sister chromatids and causes a cell cycle arrest in prometaphase when failures occur. Multiple components of the mitotic spindle checkpoint have been identified in yeast and higher eukaryotes. In S.cerevisiae, the existence of a Mad1-dependent complex containing Mad2, Mad3, Bub3 and Cdc20 has been demonstrated.

Pssm-ID: 461677 [Multi-domain] Cd Length: 660 Bit Score: 56.29 E-value: 1.58e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   375 DKKRENFE--RGSVELEKRRQALLEQQRKE-------QERLAQLERAEQERKERERQEQERKRQL-----ELEKQLEKQR 440
Cdd:pfam05557   17 EKKQMELEhkRARIELEKKASALKRQLDREsdrnqelQKRIRLLEKREAEAEEALREQAELNRLKkkyleALNKKLNEKE 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   441 ELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQegtvvlKARRKTLEFELEALNDKKHQL---EG 517
Cdd:pfam05557   97 SQLADAREVISCLKNELSELRRQIQRAELELQSTNSELEELQERLDLL------KAKASEAEQLRQNLEKQQSSLaeaEQ 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   518 KLQDIRCRLATQRQ--EIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQL----KQVQQNSLHRDSLLTL 591
Cdd:pfam05557  171 RIKELEFEIQSQEQdsEIVKNSKSELARIPELEKELERLREHNKHLNENIENKLLLKEEVedlkRKLEREEKYREEAATL 250

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   592 KRALEAKELARQQ-----------------LREQLDEVERETRSKLQEIDVFNNQLKELReihsKQQLQKQRSLEAARLK 654
Cdd:pfam05557  251 ELEKEKLEQELQSwvklaqdtglnlrspedLSRRIEQLQQREIVLKEENSSLTSSARQLE----KARRELEQELAQYLKK 326

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330   655 QKEQERKSLELEKQKEDAQRRV----QERD--KQWLEHVQQEEQPRPRKPHEEDRLK 705
Cdd:pfam05557  327 IEDLNKKLKRHKALVRRLQRRVllltKERDgyRAILESYDKELTMSNYSPQLLERIE 383

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 49.55 E-value: 1.61e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTgePGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11805     3 QALYDFNPQEPGELEFRRGDIITVLDSSD--PDWWKGELRGRVGIFPANYVQP 53

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 49.23 E-value: 1.67e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  768 RALYPFESRSHDEITIQPGDIV----MVDEsqtgepGWLGGEL-KGKTGWFPANYAE 819
Cdd:cd11819     3 KALYDYQAAEDNEISFVEGDIItqieQIDE------GWWLGVNaKGQKGLFPANYVE 53

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 49.26 E-value: 1.70e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGE--VQGQKGWFPKSYV 983
Cdd:cd11793     1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKmPDGWYEGErlRDGERGWFPSSYT 53

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 49.48 E-value: 1.74e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGTVGDKS------GVFPSNYV 1072
Cdd:cd11847     2 YKALWDFKARGDEELSFQAGDQFRIAERSGDWWTALKLDRAggvvaqGFVPNNYL 56

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 49.24 E-value: 1.81e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11826     4 ALYDYTADKDDELSFQEGDIIYVTkKNDDGWYEGVLNGVTGLFPGNYV 51

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 49.17 E-value: 1.83e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd11856     1 SYVAIADYEAQGDDEISLQEGEVVeVLEKNDSGWWYVRKGDKEGWVPASYLE 52

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 49.23 E-value: 1.96e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1101 SYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYVK 1151
Cdd:cd12060     9 NFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKT-----GWFPSNYVR 54

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 49.34 E-value: 1.97e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11827     1 QCKALYAYDAQDTDELSFNEGDIIEILkEDPSGWWTGRLRGKEGLFPGNYV 51

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 49.03 E-value: 2.03e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQDM--WWFGEVQGQKGWFPKSY 982
Cdd:cd11778     3 EALYDYEAQGDDEISIRVGDRIAVIRGDDGsgWTYGEINGVKGLFPTSY 51

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176064 [Multi-domain] Cd Length: 126 Bit Score: 51.30 E-value: 2.14e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1617 VNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDL-----EQEVLCITVFERDQFSPDDF 1691
Cdd:cd08682     3 VTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSFELPGLlsgngNRATLQLTVMHRNLLGLDKF 82

                          90
                  ....*....|....*...
gi 568997330 1692 LGRTEIRVADIKKDQGSK 1709
Cdd:cd08682    83 LGQVSIPLNDLDEDKGRR 100

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 49.28 E-value: 2.17e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTG---TVGDkSGVFPSNYV 1072
Cdd:cd12006     3 FVALYDYEARTEDDLSFHKGEKFqILNSSEGDWWEArslTTGE-TGYIPSNYV 54

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 49.29 E-value: 2.23e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11974     3 AEALWDHVTMDDQELAFKAGDVIRVLEASNKdWWWGRNEDREAWFPASFVRL 54

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 48.89 E-value: 2.33e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVL--EQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11875     1 KARVLFDYEAENEDELTLREGDIVTILskDCEDKgWWKGELNGKRGVFPDNFVEP 55

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 56.13 E-value: 2.35e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   374 EDKKRENFERGSVELEKRRQALLEQQRKEQER------------LAQLERAEQErkERERQEQERKRQLELEKQLEKQRE 441
Cdd:TIGR00618  184 MEFAKKKSLHGKAELLTLRSQLLTLCTPCMPDtyherkqvlekeLKHLREALQQ--TQQSHAYLTQKREAQEEQLKKQQL 261

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   442 LERqreeerrkeierreaAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKAR---RKTLEFELEALNDKKHQLEGK 518
Cdd:TIGR00618  262 LKQ---------------LRARIEELRAQEAVLEETQERINRARKAAPLAAHIKAVtqiEQQAQRIHTELQSKMRSRAKL 326

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   519 LQDiRCRLATQRQEIESTNKSRELRIAEitHLQQQLQESQQMLGRLIPEKQI-LSDQLKQVQQNSLHRDSLLTLKRALEA 597
Cdd:TIGR00618  327 LMK-RAAHVKQQSSIEEQRRLLQTLHSQ--EIHIRDAHEVATSIREISCQQHtLTQHIHTLQQQKTTLTQKLQSLCKELD 403

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   598 KELARQQLREQLDEVERETRSKL---QEIDVFNNQLKELREIHSKQQLQ--KQRSLEAARLKQKEQERKslELEKQKEDA 672
Cdd:TIGR00618  404 ILQREQATIDTRTSAFRDLQGQLahaKKQQELQQRYAELCAAAITCTAQceKLEKIHLQESAQSLKERE--QQLQTKEQI 481

                          330       340
                   ....*....|....*....|....
gi 568997330   673 QRRVqERDKQWLEHVQQEEQPRPR 696
Cdd:TIGR00618  482 HLQE-TRKKAVVLARLLELQEEPC 504

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 48.95 E-value: 2.36e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTG---TVGdKSGVFPSNYV 1072
Cdd:cd12008     2 FVALYDYESRTETDLSFKKGERLqIVNNTEGDWWLAhslTTG-QTGYIPSNYV 53

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 50.68 E-value: 2.38e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1632 GKSNPYCEVTMGSQ-CHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFErDQFSPDDFLGRTEIRVADI 1702
Cdd:cd04052    11 GLLSPYAELYLNGKlVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKD-DRDRHDPVLGSVSISLNDL 81

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 55.82 E-value: 2.45e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  373 FEDKKRENFERGSVELEKRRQALleQQRKEQERLAQ---LERAEQERKE----RERQEQERKRQLELEKQLEKQRELERQ 445
Cdd:PRK02224  304 LDDADAEAVEARREELEDRDEEL--RDRLEECRVAAqahNEEAESLREDaddlEERAEELREEAAELESELEEAREAVED 381

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  446 REEERRKEIERREAAKRELE-RQRQLEWERNRRQELLNQRNKeqegtvvLKARRKTLEFELEALND---KKHQL--EGKL 519
Cdd:PRK02224  382 RREEIEELEEEIEELRERFGdAPVDLGNAEDFLEELREERDE-------LREREAELEATLRTARErveEAEALleAGKC 454

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  520 ----QDIR----------CR-----LATQRQEIESTNKSRELRIAEITHLQQQlqesqqmlgrlipEKQIlsDQLKQVQQ 580
Cdd:PRK02224  455 pecgQPVEgsphvetieeDRerveeLEAELEDLEEEVEEVEERLERAEDLVEA-------------EDRI--ERLEERRE 519

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  581 NSlhrDSLLTLKRA-LEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKqqLQKQRSLEAARLKQKEQE 659
Cdd:PRK02224  520 DL---EELIAERREtIEEKRERAEELRERAAELEAEAEEKREAAAEAEEEAEEAREEVAE--LNSKLAELKERIESLERI 594

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  660 RKSLELEKQKEDAQRRVQERDKQWLEHVQQE----EQPRPRK-----PHEEDRLK--REDSVRKKEAEERAKPEMQDK 726
Cdd:PRK02224  595 RTLLAAIADAEDEIERLREKREALAELNDERrerlAEKRERKreleaEFDEARIEeaREDKERAEEYLEQVEEKLDEL 672

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 48.86 E-value: 2.45e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGD----WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11884     3 VAVRAYITRDQTLLSFHKGDVIKLLPKEGPldpgWLFGTLDGRSGAFPKEYV 54

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 51.99 E-value: 2.52e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1647 HITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDqfspDDFLGRTEIRVADIKKD 1705
Cdd:cd08676    91 KVTEVKPQTLNPVWNETFRFEVEDVSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSC 145

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 48.89 E-value: 2.61e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11782     1 EARAKYNFNADTGVELSFRKGDVITLTRRvDENWYEGRIGGRQGIFPVSYV 51

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 48.74 E-value: 2.63e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDP--DWWKGEVSGQVGLFPSNYV 1226
Cdd:cd12045     4 GLWDCTGDQPDELSFKRGDTIYILSKEYNrfGWWVGEMKGTIGLVPKAYI 53

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 48.87 E-value: 2.67e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd12076     3 YTVIYPYTARDQDEINLEKGAVVEV--IQKNLEGWWKIRYQGKEGWAPASYLKK 54

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 49.00 E-value: 2.67e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMV-DESqtgEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11820     4 RALYDFEAAEDNELTFKAGEIITVlDDS---DPNWWKGSNHRGEGLFPANFVTA 54

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 48.91 E-value: 2.74e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQ--TGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11800     1 YYYALYTFEARSPGELSVTEGQVVTVLEKHdlKGNPEWWLVEDRGKQGYVPSNYLAK 57

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 48.81 E-value: 2.79e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  768 RALYPFESRSHD-EITIQPGDIVMVDE--SQTGEP-GWLGGELK-GKTGWFPANYAE 819
Cdd:cd11771     3 RALYDFTPENPEmELSLKKGDIVAVLSktDPLGRDsEWWKGRTRdGRIGWFPSNYVE 59

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 48.90 E-value: 2.87e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1172 PAVCQVIgmYDYTAQNDDELAFSKGQIINVLNKEDPD-WWKG-EVSGQVGLFPSNYVKL 1228
Cdd:cd11761     1 PVTCKVL--YSYEAQRPDELTITEGEELEVIEDGDGDgWVKArNKSGEVGYVPENYLQF 57

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 48.65 E-value: 2.89e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANYAEK 820
Cdd:cd11833     1 TYVALYKFKPQENEDLEMRPGDKITLLDDSNED--WWKGKIEDRVGFFPANFVQR 53

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 48.52 E-value: 2.92e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11824     2 YSVLYDYTAQEDDELSISKGDVVAVIEKgEDGWWTVERNGQKGLVPGTYLEK 53

Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1 is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. NoxO1 contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of NoxO1. The tandem SH3 domains of NoxO1 interact with the PRR of p22phox, which also complexes with Nox1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212957 Cd Length: 53 Bit Score: 48.49 E-value: 3.20e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1183 YTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12024     8 YEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRAGYVPSMYLQP 53

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 48.63 E-value: 3.23e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSY 982
Cdd:cd11818     1 KARALYDFTGENEDELSFKAGDIITELESIDEEWMsGELRGKSGIFPKNF 50

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176063 [Multi-domain] Cd Length: 118 Bit Score: 50.71 E-value: 3.29e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTI----QdtlNPKWNSNCQFFIRDLEQEVLCITVFErDQFSP 1688
Cdd:cd08681     1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKTDfrggQ---HPEWDEELRFEITEDKKPILKVAVFD-DDKRK 76

                          90
                  ....*....|....*.
gi 568997330 1689 DDFLGRTEIrvaDIKK 1704
Cdd:cd08681    77 PDLIGDTEV---DLSP 89

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 55.13 E-value: 3.31e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   351 QRLPEEPSSEDEQQPEKKLpvtFEDKKRENFERGSVELEKRRQAL-----LEQQRKEQERLAQLERAEQERKERErQEQE 425
Cdd:pfam17380  388 QQKNERVRQELEAARKVKI---LEEERQRKIQQQKVEMEQIRAEQeearqREVRRLEEERAREMERVRLEEQERQ-QQVE 463

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   426 RKRQLElEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKtlEFEL 505
Cdd:pfam17380  464 RLRQQE-EERKRKKLELEKEKRDRKRAEEQRRKILEKELEERKQAMIEEERKRKLLEKEMEERQKAIYEEERRR--EAEE 540

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 568997330   506 EALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSREL 542
Cdd:pfam17380  541 ERRKQQEMEERRRIQEQMRKATEERSRLEAMEREREM 577

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 48.79 E-value: 3.33e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11927     5 ALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNGIHGFFPTNFVQI 54

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 48.48 E-value: 3.40e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1101 SYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQiGWFPANYVK 1151
Cdd:cd11825     7 DYRAQRPDELSFCKHAIITNVEKEDGGWWRGDY---GGKKQ-KWFPANYVE 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 48.44 E-value: 3.41e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIvMVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd12065     3 KAVYPCEAEHSSELSFEVGAI-FEDVTLSREPGWLEGTLNGKRGLIPENYVE 53

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212977 Cd Length: 53 Bit Score: 48.70 E-value: 3.50e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDP--DWWKGEVSGQVGLFPSNYV 1226
Cdd:cd12044     4 GLWDCFGDNPDELSFQRGDLIYILSKEYNmyGWWVGELNGIVGIVPKDYL 53

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 48.73 E-value: 3.52e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPD---WWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12003     6 LYDNAAESPEELSFRRGDVLMVLKREHGSlpgWWLCSLHGQQGIAPANRLRL 57

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 48.38 E-value: 3.53e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11928     4 KALYSYEGKEPGDLKFNKGDIIILRRKVDeNWYHGELNGCHGFLPASYIQC 54

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 48.48 E-value: 3.56e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIV-MVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11884     1 YVVAVRAYITRDQTLLSFHKGDVIkLLPKEGPLDPGWLFGTLDGRSGAFPKEYVQ 55

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 48.84 E-value: 3.57e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYVK 1227
Cdd:cd11934     7 AVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGTVerTGDTGMLPANYVE 57

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 48.46 E-value: 3.58e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGElqarGKKRQIGWFPANYVKL 1152
Cdd:cd11819     2 AKALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGV----NAKGQKGLFPANYVEL 54

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 48.67 E-value: 3.61e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd12073     3 AVALYDYQGEGDDEISFDPQETITDIEMVDEgWWKGTCHGHRGLFPANYVEL 54

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 48.47 E-value: 3.68e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNK--EDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11977     4 VARYNFAARDMRELSLREGDVVRIYSRigGDQGWWKGETNGRIGWFPSTYVE 55

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 55.11 E-value: 3.97e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   406 LAQLERAEQERKERERQeqerkrQLEL-EKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQ- 483
Cdd:pfam05483  361 LEELLRTEQQRLEKNED------QLKIiTMELQKKSSELEEMTKFKNNKEVELEELKKILAEDEKLLDEKKQFEKIAEEl 434

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   484 RNKEQEGTVVLKARRKT---LEFELEALNDKKHQLEGKLQDIRCRLATQR-QEIESTNKSRELRIAEithlqqqlqesqq 559
Cdd:pfam05483  435 KGKEQELIFLLQAREKEihdLEIQLTAIKTSEEHYLKEVEDLKTELEKEKlKNIELTAHCDKLLLEN------------- 501

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   560 mlGRLIPEKQILSDQLKQVQQ----NSLHRDSLLTLKRALEAKELarqQLREQLDEVERETRSKLQEIDVFNNQLKElre 635
Cdd:pfam05483  502 --KELTQEASDMTLELKKHQEdiinCKKQEERMLKQIENLEEKEM---NLRDELESVREEFIQKGDEVKCKLDKSEE--- 573

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   636 ihskqqlqKQRSLEAARLKQKEQERKsleLEKQKEDAQRRVQERDKqWLEHVQQEEQPRPRKPHEEDRLKR--EDSVRKK 713
Cdd:pfam05483  574 --------NARSIEYEVLKKEKQMKI---LENKCNNLKKQIENKNK-NIEELHQENKALKKKGSAENKQLNayEIKVNKL 641

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 568997330   714 EAEERAKPEMQDKQSRLFHPHQEPAKLATQAPWSTTEKGPLTisAQESVKV 764
Cdd:pfam05483  642 ELELASAKQKFEEIIDNYQKEIEDKKISEEKLLEEVEKAKAI--ADEAVKL 690

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 48.40 E-value: 3.99e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11976     2 AKARYDFCARDRSELSLKEGDIIKILNKkgQQGWWRGEIYGRVGWFPANYVE 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 48.44 E-value: 4.00e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI--VVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11882     4 ALYACKAEDESELSFEPGQIItnVQPSDEPGWLEGTLNGRTGLIPENYVEF 54

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 48.45 E-value: 4.03e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQKG-WFPKSYVKLIS 987
Cdd:cd11970     7 KALFDYKAQREDELTFTKNAIIQNVEKQEgGWWRGDYGGKKQlWFPSNYVEEIS 60

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 48.33 E-value: 4.03e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11988     7 LYPFEARNHDEMSFNAGDIIQVDEKTvgEPGWLYGSFQGNFGWFPCNYVE 56

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 48.27 E-value: 4.04e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVT--KKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11948     1 EAVALYSFQATESDELPFQKGDILKILnmEDDQNWYKAELQGREGYIPKNYIKV 54

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];

Pssm-ID: 443091 [Multi-domain] Cd Length: 379 Bit Score: 54.45 E-value: 4.16e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  494 LKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKsrelriaEITHLQQQlqesqqmlgrlIPEKQ-ILS 572
Cdd:COG3883    28 LQAELEAAQAELDALQAELEELNEEYNELQAELEALQAEIDKLQA-------EIAEAEAE-----------IEERReELG 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  573 DQLKQVQQNSLHRDSLLTLkraLEAKELArqQLREQLDEVERETRSKLQEIDVFNNQLKELREIhsKQQLQKQrsLEAAR 652
Cdd:COG3883    90 ERARALYRSGGSVSYLDVL---LGSESFS--DFLDRLSALSKIADADADLLEELKADKAELEAK--KAELEAK--LAELE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  653 LKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSRLFH 732
Cdd:COG3883   161 ALKAELEAAKAELEAQQAEQEALLAQLSAEEAAAEAQLAELEAELAAAEAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA 240

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330  733 PHQEPAKLATQAPWSTTEKGPLTISAQESVKVVYYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGG 804
Cdd:COG3883   241 AAAASAAGAGAAGAAGAAAGSAGAAGAAAGAAGAGAAAASAAGGGAGGAGGGGGGGGAASGGSGGGSGGAGG 312

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 48.26 E-value: 4.17e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11951     4 AQYDFSAEDPSQLSFRRGDIIeVLDCPDPNWWRGRISGRVGFFPRNYV 51

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 47.97 E-value: 4.26e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqargKKRQIGWFPA 1147
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRN----KGGKEGLIPS 47

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 48.40 E-value: 4.42e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11929     2 RAKALCNYRGHNPGDLKFNKGDVILLRRQLDEnWYLGEINGVSGIFPASSVEV 54

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 48.03 E-value: 4.43e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11766     1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDgWWRGECNGQVGWFPSNYV 51

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 54.64 E-value: 4.91e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   398 QQRKEQERLAQLERAEQERKERERQEQERKRQL-ELEKQLEKQRELERQREEERRKEIERREAAKRELER-QRQLEwerN 475
Cdd:TIGR04523  195 KLLKLELLLSNLKKKIQKNKSLESQISELKKQNnQLKDNIEKKQQEINEKTTEISNTQTQLNQLKDEQNKiKKQLS---E 271

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   476 RRQELLNQRNKEQEgtvvLKARRKTLEFELEALNDKKHQleGKLQDIRCRLATQRQEIESTnksrELRIAEIthlqqqlq 555
Cdd:TIGR04523  272 KQKELEQNNKKIKE----LEKQLNQLKSEISDLNNQKEQ--DWNKELKSELKNQEKKLEEI----QNQISQN-------- 333

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   556 esqqmlgrlipEKQIlsDQLKQVQQNslhrdslltLKRALEAKELARQQLREQLDE-------VERETRSKLQEIDVFNN 628
Cdd:TIGR04523  334 -----------NKII--SQLNEQISQ---------LKKELTNSESENSEKQRELEEkqneiekLKKENQSYKQEIKNLES 391

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   629 QLKELreihsKQQLQKQRSLEaarlKQKEQERKSLELEKQKEDAQrrvQERDKQwlEHVQQEEqprprkphEEDRLKRED 708
Cdd:TIGR04523  392 QINDL-----ESKIQNQEKLN----QQKDEQIKKLQQEKELLEKE---IERLKE--TIIKNNS--------EIKDLTNQD 449


                   ....*....
gi 568997330   709 SVRKKEAEE 717
Cdd:TIGR04523  450 SVKELIIKN 458

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 54.98 E-value: 4.91e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   355 EEPSSEDEQQPEKKLpVTFEDKKRENFERgSVELEKRRQALLEQQRKEQER-LAQLERAEQERKERERQEQERKRQLELE 433
Cdd:pfam02463  252 EIESSKQEIEKEEEK-LAQVLKENKEEEK-EKKLQEEELKLLAKEEEELKSeLLKLERRKVDDEEKLKESEKEKKKAEKE 329

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   434 K--------QLEKQrelerqreeerrkeierreaaKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFEL 505
Cdd:pfam02463  330 LkkekeeieELEKE---------------------LKELEIKREAEEEEEEELEKLQEKLEQLEEELLAKKKLESERLSS 388

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   506 EA-LNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEIthlqqqlqesqqmlgRLIPEKQILSDQLKQVQQNSLH 584
Cdd:pfam02463  389 AAkLKEEELELKSEEEKEAQLLLELARQLEDLLKEEKKEELEI---------------LEEEEESIELKQGKLTEEKEEL 453

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   585 RDSLLTL---KRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQkQRSLEAARLKQKEQERK 661
Cdd:pfam02463  454 EKQELKLlkdELELKKSEDLLKETQLVKLQEQLELLLSRQKLEERSQKESKARSGLKVLLAL-IKDGVGGRIISAHGRLG 532

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   662 SLELEKQKEDAQR-----RVQERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPE 722
Cdd:pfam02463  533 DLGVAVENYKVAIstaviVEVSATADEVEERQKLVRALTELPLGARKLRLLIPKLKLPLKSIAVLE 598

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 47.98 E-value: 5.35e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11986     3 VALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKIGEKTGYFPMNFI 51

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212933 Cd Length: 57 Bit Score: 47.95 E-value: 5.44e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPD---WWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12000     6 LYDNKADCSDELAFRRGDILTVLEQNVPGsegWWKCLLHGRQGLAPANRLQL 57

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 48.09 E-value: 5.44e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKED---PDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11954     3 VYALWDYEAQNADELSFQEGDAITILRRKDdseTEWWWARLNDKEGYVPKNLLGL 57

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 48.01 E-value: 5.48e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11929     6 LCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEINGVSGIFPASSVEV 54

Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full length form of the previously-identified tumor supressor, p53-binding protein 2 (p53BP2). ASPP2 activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). It plays a central role in regulating apoptosis and cell growth; ASPP2-deficient mice show postnatal death. Downregulated expression of ASPP2 is frequently found in breast tumors, lung cancer, and diffuse large B-cell lymphoma where it is correlated with a poor clinical outcome. ASPP2 contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP2 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212886 [Multi-domain] Cd Length: 57 Bit Score: 48.02 E-value: 5.49e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPD---WWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11953     3 VYALWDYEGESDDELSFKEGDCMTILRREDEDeteWWWARLNDKEGYVPRNLLGL 57

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 47.99 E-value: 5.55e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11928     6 LYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCHGFLPASYIQC 54

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 47.88 E-value: 5.61e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKED----PDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12141     5 VYTFKARSPNELSVSANQRVRILEFSDltgnKEWWLAEANGQKGYVPSNYIR 56

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 48.08 E-value: 5.63e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11992     4 ALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVR 51

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 48.08 E-value: 5.98e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYVK 1227
Cdd:cd11933     7 MYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVqrTGKTGMLPANYVE 56

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 47.88 E-value: 6.16e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTK-KDGDWWTGTV--GDKSGVFPSNYV 1072
Cdd:cd11889     4 AVYSWAGETEGDLGFLEGDLIEVLSiGDGSWWSGKLrrNGAEGIFPSNFV 53

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 47.96 E-value: 6.17e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQ---GQKGWFPKSYVKL 985
Cdd:cd11872     4 AIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGFSLrnkSLKGIFPKSYVHI 55

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 48.08 E-value: 6.46e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMvdESQTGEPGWLGGELK--GKTGWFPANYAEKI 821
Cdd:cd11933     4 FRAMYDYRAADDDEVSFKDGDTIV--NVQTIDEGWMYGTVQrtGKTGMLPANYVEAI 58

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 47.69 E-value: 7.01e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMvdESQTGEPGWLGGELK--GKTGWFPANYAEKI 821
Cdd:cd11935     3 YRAMYDYSAQDEDEVSFRDGDYIV--NVQPIDEGWMYGTVQrtGRTGMLPANYIEFV 57

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 47.78 E-value: 7.17e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11975     9 AVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFVRL 58

Borrelia P83/100 protein; This family consists of several Borrelia P83/P100 antigen proteins.

Pssm-ID: 114011 [Multi-domain] Cd Length: 489 Bit Score: 53.85 E-value: 7.18e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   564 LIP-EKQILSDQLKQVQQNSLHRDSLLtlKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQL 642
Cdd:pfam05262  157 VIPlKKNILSGNVSDVDTDSISDKKVV--EALREDNEKGVNFRRDMTDLKERESQEDAKRAQQLKEELDKKQIDADKAQQ 234

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   643 QKQRSLEAARLKQKEQERKSLELEKQKEDA-------QRRVQERDKQWLEHVQQE-----EQPRPRKPHEEDRLKREDSV 710
Cdd:pfam05262  235 KADFAQDNADKQRDEVRQKQQEAKNLPKPAdtsspkeDKQVAENQKREIEKAQIEikkndEEALKAKDHKAFDLKQESKA 314


                   ....*...
gi 568997330   711 RKKEAEER 718
Cdd:pfam05262  315 SEKEAEDK 322

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 47.67 E-value: 7.26e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11991     4 AMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 47.63 E-value: 7.28e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11929     5 ALCNYRGHNPGDLKFNKGDVILLRRQlDENWYLGEINGVSGIFPASSVEV 54

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 47.64 E-value: 7.50e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMV-DESqtgEPGWLGGELKGKTGWFPANY 817
Cdd:cd11964     4 RAIYDFEAAEDNELTFKAGDIITIlDDS---DPNWWKGETPQGTGLFPSNF 51

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 47.88 E-value: 7.53e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDM-----WWFGEVQGQKGWFPKSYVK 984
Cdd:cd12141     4 AVYTFKARSPNELSVSANQRVRILEFSDLtgnkeWWLAEANGQKGYVPSNYIR 56

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 47.68 E-value: 7.82e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1021 GEEFIAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTV---GDkSGVFPSNYV 1072
Cdd:cd11934     2 GKRYRAVYDYNAADEDEVSFQDGDTIVnVQQIDDGWMYGTVertGD-TGMLPANYV 56

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 47.33 E-value: 8.23e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12076     6 IYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLK 53

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 49.10 E-value: 8.30e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1629 RSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQ 1685
Cdd:cd04050    16 KSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKT 72

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 47.33 E-value: 8.70e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANYAE 819
Cdd:cd11781     3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKN--WYEGEHNGRVGIFPASYVE 52

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 47.33 E-value: 8.72e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYVKL 985
Cdd:cd11839     2 AQVIAPFTATAENQLSLAVGQLVLVRKKSPSgWWEGELQArgkkrQIGWFPANYVKL 58

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 47.28 E-value: 8.87e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1097 QVIA--SYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVKL 1152
Cdd:cd11996     2 QVIAmyDYTANNEDELSFSKGQLINVLNKDDPDWWQGEING-----VTGLFPSNYVKM 54

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 47.32 E-value: 8.88e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKD--GDWWTG-TVGDKSGVFPSNYV 1072
Cdd:cd11763     4 ALYDFDSQPSGELSLRAGEVLTITRQDvgDGWLEGrNSRGEVGLFPSSYV 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 47.25 E-value: 9.36e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  765 VYYRALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGGEL-KGKTGWFPANYAE 819
Cdd:cd11998     1 VRVRALYDYDGQEQDELSFKAGDELTKLEDED-EQGWCKGRLdSGQVGLYPANYVE 55

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212699 [Multi-domain] Cd Length: 51 Bit Score: 47.03 E-value: 9.43e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPdWWKGEVS-GQVGLFPSNYV 1226
Cdd:cd11765     2 VVAKYDYTAQGDQELSIKKNEKLTLLDDSKH-WWKVQNSsNQTGYVPSNYV 51

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 47.33 E-value: 9.45e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  768 RALYPFESRSHDEITIQPGDIV-MVDESqtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11874     3 KVLFSYTPQNEDELELKVGDTIeVLGEV---EEGWWEGKLNGKVGVFPSNFVK 52

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 53.42 E-value: 9.51e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   590 TLKRALEAKELARQQLREQ-----LDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQErksle 664
Cdd:pfam15709  323 ALLEKREQEKASRDRLRAEraemrRLEVERKRREQEEQRRLQQEQLERAEKMREELELEQQRRFEEIRLRKQRLE----- 397

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330   665 lekqkEDAQRRVQERDKQWLEhvQQEEQPRPRKPHEEDRLKREDSVRKKEAEE--RAKPEMQ 724
Cdd:pfam15709  398 -----EERQRQEEEERKQRLQ--LQAAQERARQQQEEFRRKLQELQRKKQQEEaeRAEAEKQ 452

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 47.41 E-value: 9.75e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYV 1150
Cdd:cd11827     2 CKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRL--RGKE---GLFPGNYV 51

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 47.13 E-value: 1.01e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11950     3 RALYDFEALEDDELGFNSGDVIEVLDSS--NPSWWKGRLHGKLGLFPANYVA 52

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

Pssm-ID: 274303 [Multi-domain] Cd Length: 346 Bit Score: 52.93 E-value: 1.01e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   611 EVERETRSKLQEIDVFNNQLKELREihSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQE 690
Cdd:TIGR02794   51 QANRIQQQKKPAAKKEQERQKKLEQ--QAEEAEKQRAAEQARQKELEQRAAAEKAAKQAEQAAKQAEEKQKQAEEAKAKQ 128

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 568997330   691 EQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSR 729
Cdd:TIGR02794  129 AAEAKAKAEAEAERKAKEEAAKQAEEEAKAKAAAEAKKK 167

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 47.12 E-value: 1.03e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  936 QALYPWRAKKDNH-LNFNKSDVITVLEQQD-MWWFGEVQGQKGWFPKSYV 983
Cdd:cd11829     3 RTLYAFTGEQHQQgLSFEAGELIRVLQAPDgGWWEGEKDGLRGWFPASYV 52

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 47.01 E-value: 1.03e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQ-GQKGWFPKSYVKL 985
Cdd:cd11960     2 ARALYDYQAADDTEISFDPGDIITDIEQIDEgWWRGTGPdGTYGLFPANYVEL 54

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 46.94 E-value: 1.05e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1025 IAMYTYESS---EQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNY 1071
Cdd:cd11787     3 KALYDFEMKdedEKDCLTFKKGDVITVIRRvDENWAEGRLGDKIGIFPISF 53

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 47.31 E-value: 1.06e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1021 GEEFIAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTV--GDKSGVFPSNYV 1072
Cdd:cd11933     1 GKSFRAMYDYRAADDDEVSFKDGDTIVnVQTIDEGWMYGTVqrTGKTGMLPANYV 55

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 54.03 E-value: 1.07e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   389 EKRRQALLEQQRKEQERLAQlerAEQERKERERQEQerkrQLELEK-QLEKQRELERQREEERRKEIERREAAKRELER- 466
Cdd:pfam01576    4 EEEMQAKEEELQKVKERQQK---AESELKELEKKHQ----QLCEEKnALQEQLQAETELCAEAEEMRARLAARKQELEEi 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   467 ----QRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCR---LATQRQEIESTNKS 539
Cdd:pfam01576   77 lhelESRLEEEEERSQQLQNEKKKMQQHIQDLEEQLDEEEAARQKLQLEKVTTEAKIKKLEEDillLEDQNSKLSKERKL 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   540 RELRIAEITHLQQQLQESQQMLGRLIPEKQI----LSDQLKQVQQNslhRDSLLTLKRALEAK------ELARQQ----- 604
Cdd:pfam01576  157 LEERISEFTSNLAEEEEKAKSLSKLKNKHEAmisdLEERLKKEEKG---RQELEKAKRKLEGEstdlqeQIAELQaqiae 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   605 LREQLDEVERETRSKLQEID----VFNNQLKELREIHSK-QQLQKQRSLEAARLKQKEQERKSL--ELEKQKEDAQrrvq 677
Cdd:pfam01576  234 LRAQLAKKEEELQAALARLEeetaQKNNALKKIRELEAQiSELQEDLESERAARNKAEKQRRDLgeELEALKTELE---- 309

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330   678 erDKQWLEHVQQEeqPRPRKPHEEDRLKR--EDSVRKKEAEERakpEMQDKQSRLFHPHQE 736
Cdd:pfam01576  310 --DTLDTTAAQQE--LRSKREQEVTELKKalEEETRSHEAQLQ---EMRQKHTQALEELTE 363

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 47.24 E-value: 1.09e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11830     2 AKARYDFCARDMRELSLKEGDVVKIYNKkgQQGWWRGEINGRIGWFPSTYVE 53

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 46.92 E-value: 1.15e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDV--IVVTKKDGdWWTG--TVGDKsGVFPSNYVRL 1074
Cdd:cd11770     1 LYEALSDFQAEQEGDLSFKKGEVlrIISKRADG-WWLAenSKGNR-GLVPKTYLKV 54

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212840 [Multi-domain] Cd Length: 55 Bit Score: 47.26 E-value: 1.15e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKG-EVSGQVGLFPSNYV 1226
Cdd:cd11907     2 QVKALYDFLPREPSNLALKRAEEYLILEQYDPHWWKArDRYGNEGLIPSNYV 53

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 47.25 E-value: 1.17e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDGD--WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11976     4 ARYDFCARDRSELSLKEGDIIKILNKKGQqgWWRGEIYGRVGWFPANYV 52

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 47.07 E-value: 1.18e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12016     2 KYITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYLK 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 46.92 E-value: 1.19e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQGQ---KGWFPKSY 982
Cdd:cd11821     2 VRALYDCQADNDDELTFSEGEIIVVTGEEDdEWWEGHIEGDpsrRGVFPVSF 53

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 47.10 E-value: 1.19e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11947     1 EARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAELNGEEGYVPKNFV 50

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 49.09 E-value: 1.23e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1617 VNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITK--TIQDTLNPKWNsncQFFIRD--LEQE-VLCITVFERDQFSPDDF 1691
Cdd:cd04037     4 VYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRdnYIPNTLNPVFG---KMFELEatLPGNsILKISVMDYDLLGSDDL 80


                  ....*.
gi 568997330 1692 LGRTEI 1697
Cdd:cd04037    81 IGETVI 86

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 47.03 E-value: 1.23e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11959     3 VALYDYQAADDDEISFDPDDIITnIEMIDEGWWRGVCRGKYGLFPANYVEL 53

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 46.98 E-value: 1.24e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGTV-GDKSGVFPSNYVRL 1074
Cdd:cd11837     3 TALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELeGGEEGWFPKSYVKE 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 53.43 E-value: 1.29e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   360 EDEQQPEKKlpvtFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQ 439
Cdd:TIGR00618  430 KKQQELQQR----YAELCAAAITCTAQCEKLEKIHLQESAQSLKEREQQLQTKEQIHLQETRKKAVVLARLLELQEEPCP 505

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   440 RELERQREEERRKEIERREAAKRELER---------------QRQLEWERNRRQELLNQRNKEQEGTVVL---------- 494
Cdd:TIGR00618  506 LCGSCIHPNPARQDIDNPGPLTRRMQRgeqtyaqletseedvYHQLTSERKQRASLKEQMQEIQQSFSILtqcdnrsked 585

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   495 -------------------KARRKTLEF---ELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQ 552
Cdd:TIGR00618  586 ipnlqnitvrlqdlteklsEAEDMLACEqhaLLRKLQPEQDLQDVRLHLQQCSQELALKLTALHALQLTLTQERVREHAL 665

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   553 QLQESQQMLG----RLIPEKQILSDQLKQVQQNSLHRDSLLtlkRALEAKELARQQLREQLDEVERETRSKLQEIDVFNN 628
Cdd:TIGR00618  666 SIRVLPKELLasrqLALQKMQSEKEQLTYWKEMLAQCQTLL---RELETHIEEYDREFNEIENASSSLGSDLAAREDALN 742

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   629 Q-LKELREihskQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQ----EEQPRPRKPHEEDR 703
Cdd:TIGR00618  743 QsLKELMH----QARTVLKARTEAHFNNNEEVTAALQTGAELSHLAAEIQFFNRLREEDTHLlktlEAEIGQEIPSDEDI 818

                          410
                   ....*....|....
gi 568997330   704 LKREDSVRKKEAEE 717
Cdd:TIGR00618  819 LNLQCETLVQEEEQ 832

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 46.95 E-value: 1.29e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQD---MWW-FGEVQGQKGWFPKSYVKL 985
Cdd:cd11904     4 QALYPFSSSNDEELNFEKGEVMDVIEKPEndpEWWkCRKANGQVGLVPKNYVTV 57

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 46.94 E-value: 1.30e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 983
Cdd:cd11963     3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDAnWWKGENHRGVGLFPSNFV 53

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 53.38 E-value: 1.31e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  390 KRRQALLEQQRKE-QERLAQLERAEQERKERERQEQERKRQLE-LEKQLEKQrelerqreeerrkeiERREAAKRELERQ 467
Cdd:COG4913   609 RAKLAALEAELAElEEELAEAEERLEALEAELDALQERREALQrLAEYSWDE---------------IDVASAEREIAEL 673

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  468 RQlewernRRQELLNQRNKEQEgtvvLKARRKTLEFELEALNDKKHQLEGKLQdircRLATQRQEIEstnksRELRIAEI 547
Cdd:COG4913   674 EA------ELERLDASSDDLAA----LEEQLEELEAELEELEEELDELKGEIG----RLEKELEQAE-----EELDELQD 734

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  548 THLQQQLQESQQMLGRLIPE-KQILSDQLKQVQQNSLHRDslltLKRALEAKELARQQLREQLDEVERETRSKLQEIDV- 625
Cdd:COG4913   735 RLEAAEDLARLELRALLEERfAAALGDAVERELRENLEER----IDALRARLNRAEEELERAMRAFNREWPAETADLDAd 810

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330  626 ------FNNQLKELREIHSKQQLQKqrsLEAARLKQKEQERKSL--ELEKQKEDAQRRVQE 678
Cdd:COG4913   811 leslpeYLALLDRLEEDGLPEYEER---FKELLNENSIEFVADLlsKLRRAIREIKERIDP 868

RNase Y N-terminal region;

Pssm-ID: 463456 [Multi-domain] Cd Length: 201 Bit Score: 51.04 E-value: 1.33e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   568 KQILSDQLKQVQqnslhrdsllTLKR--ALEAKELArQQLREqldEVERETRSKLQEIDVFNNQLKELREIHSKQ--QL- 642
Cdd:pfam12072   37 KRIIEEAKKEAE----------TKKKeaLLEAKEEI-HKLRA---EAERELKERRNELQRQERRLLQKEETLDRKdeSLe 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   643 QKQRSLEAarlKQKEQERKSLELEKQKEDAQRRVQERdKQWLEHVQ--QEEQPRPRKPHE-EDRLKREDSVRKKEAEERA 719
Cdd:pfam12072  103 KKEESLEK---KEKELEAQQQQLEEKEEELEELIEEQ-RQELERISglTSEEAKEILLDEvEEELRHEAAVMIKEIEEEA 178

                          170
                   ....*....|
gi 568997330   720 KpEMQDKQSR 729
Cdd:pfam12072  179 K-EEADKKAK 187

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 46.84 E-value: 1.35e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11921     7 FDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYVEV 54

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 52.46 E-value: 1.35e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  494 LKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNksRELRIAEithlqQQLQESQQMLGRLIPE------ 567
Cdd:COG4942    25 AEAELEQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALA--RRIRALE-----QELAALEAELAELEKEiaelra 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  568 -----KQILSDQLKQVQQNS--------LHRDSLLTLKRALEAKELARQQLREQLDEVeretRSKLQEIDVFNNQLKELR 634
Cdd:COG4942    98 eleaqKEELAELLRALYRLGrqpplallLSPEDFLDAVRRLQYLKYLAPARREQAEEL----RADLAELAALRAELEAER 173

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330  635 EihSKQQLQKQRSLEAARLKQKEQERKSL--ELEKQKEDAQRRVQERDKQW------LEHVQQEEQPRPRKP 698
Cdd:COG4942   174 A--ELEALLAELEEERAALEALKAERQKLlaRLEKELAELAAELAELQQEAeelealIARLEAEAAAAAERT 243

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 46.86 E-value: 1.36e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWegelQARGKKRQiGWFPANYVK 1151
Cdd:cd11856     4 AIADYEAQGDDEISLQEGEVVEVLEKNDSGWW----YVRKGDKE-GWVPASYLE 52

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 46.74 E-value: 1.37e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVdESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd11812     4 ALYDYTANRSDELTIHRGDIIRV-LYKDNDNWWFGSLVNGQQGYFPANY 51

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 46.98 E-value: 1.41e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11974     5 ALWDHVTMDDQELAFKAGDVIrVLEASNKDWWWGRNEDREAWFPASFVRL 54

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 46.76 E-value: 1.42e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDK-SGVFPSNYV 1072
Cdd:cd11969     4 ALYDYRAKRSDELSFCKGALIHnVSKETGGWWKGDYGGKvQHYFPSNYV 52

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 46.76 E-value: 1.49e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVV-TKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11956     3 EAVACFDYTGRTAQELSFKRGDVLLLhSKASSDWWRGEHNGMRGLIPHKYISV 55

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 46.71 E-value: 1.49e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGD-KSGVFPSNYVRL 1074
Cdd:cd11962     3 VVLYDYEKDEDNEIELVEGEIVTnIEMVDEDWWMGTNSKgESGLFPSNYVEL 54

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 46.98 E-value: 1.51e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDM-----WWFGEVQGQKGWFPKSY 982
Cdd:cd11800     4 ALYTFEARSPGELSVTEGQVVTVLEKHDLkgnpeWWLVEDRGKQGYVPSNY 54

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212847 [Multi-domain] Cd Length: 59 Bit Score: 46.73 E-value: 1.54e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568997330  949 LNFNKSDVITVL--EQQDMWWFGEVQG--QKGWFPKSYVK 984
Cdd:cd11914    18 LRFNRGDIITVLvpEARNGWLYGKLEGssRQGWFPEAYVK 57

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212839 [Multi-domain] Cd Length: 55 Bit Score: 46.74 E-value: 1.55e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKG-EVSGQVGLFPSNYV 1226
Cdd:cd11906     3 VVALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRArDKNGREGYIPSNYV 53

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 46.60 E-value: 1.55e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDGD----WWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11807     5 ALFDYEAENGDELSFREGDELTVLRKGDDdeteWWWARLNDKEGYVPRNLLGL 57

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 46.87 E-value: 1.58e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11927     3 AKALYNYEGKEPGDLKFSKGDIIILRRQVDEnWYHGEVNGIHGFFPTNFVQI 54

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 49.12 E-value: 1.59e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHI-----TKTIQDTLNPKWNsncQFFIRDLEQE-----VLCITVFE 1682
Cdd:cd00276    14 ERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKlkkkkTSVKKGTLNPVFN---EAFSFDVPAEqleevSLVITVVD 90

                          90
                  ....*....|....*
gi 568997330 1683 RDQFSPDDFLGRTEI 1697
Cdd:cd00276    91 KDSVGRNEVIGQVVL 105

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 46.94 E-value: 1.66e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK----DGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11954     5 ALWDYEAQNADELSFQEGDAITILRRkddsETEWWWARLNDKEGYVPKNLLGL 57

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 53.20 E-value: 1.70e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  350 DQRLPEEPSSEDEQQPEKKLPVTFEDKKR-ENFERGSVE-LEKRRQALLEQQRKEQERLAQlERAEQERKERERQEQ-ER 426
Cdd:PTZ00266  431 DKDHAERARIEKENAHRKALEMKILEKKRiERLEREERErLERERMERIERERLERERLER-ERLERDRLERDRLDRlER 509

                          90
                  ....*....|...
gi 568997330  427 KRQLELEK-QLEK 438
Cdd:PTZ00266  510 ERVDRLERdRLEK 522

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 46.83 E-value: 1.71e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKED----PDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11941     1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDkkgsPEWSLVEVNGQRGYVPSSYL 55

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 46.53 E-value: 1.81e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGG--ELKGKTGWFPANYAEK 820
Cdd:cd11780     2 YRALYSYTPQNEDELELREGDIVYV--MEKCDDGWFVGtsERTGLFGTFPGNYVAR 55

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 46.54 E-value: 1.91e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYV 1150
Cdd:cd11902     3 AFVKFAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNG-----QIGWFPSNYV 52

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 46.48 E-value: 1.92e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1102 YAATGPEQLTLAPGQLI-LIRKKNPGGWWEGELQARgkkrqIGWFPANYVK 1151
Cdd:cd11976     8 FCARDRSELSLKEGDIIkILNKKGQQGWWRGEIYGR-----VGWFPANYVE 53

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 51.84 E-value: 1.95e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   360 EDEQQPEKKLpvTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLA--QLERAEQERK-ERERQEQERKRQLELEKQL 436
Cdd:pfam13868  113 EDQAEAEEKL--EKQRQLREEIDEFNEEQAEWKELEKEEEREEDERILeyLKEKAEREEErEAEREEIEEEKEREIARLR 190

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   437 EKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQEL--LNQRNKEQegtVVLKARRKTLEFELEAlndkkhq 514
Cdd:pfam13868  191 AQQEKAQDEKAERDELRAKLYQEEQERKERQKEREEAEKKARQRqeLQQAREEQ---IELKERRLAEEAEREE------- 260

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   515 lEGKLQDIRCRLATQRQEIESTNKSRELRiaeithlqqqlqesqqmlgrlipeKQILSDQLKQVQQNSLHRdsLLTLKRA 594
Cdd:pfam13868  261 -EEFERMLRKQAEDEEIEQEEAEKRRMKR------------------------LEHRRELEKQIEEREEQR--AAEREEE 313

                          250       260
                   ....*....|....*....|....*...
gi 568997330   595 LEAKELARQQLREQLDEVERETRSKLQE 622
Cdd:pfam13868  314 LEEGERLREEEAERRERIEEERQKKLKE 341

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 46.49 E-value: 1.97e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKG--EVSGQVGLFPSNYV 1226
Cdd:cd11918     7 VYQYRPQNEDELELREGDRVDVMQQCDDGWFVGvsRRTQKFGTFPGNYV 55

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 46.43 E-value: 2.01e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYVK 1151
Cdd:cd12052     8 YKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRR-----GLFPDNFVR 52

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 53.02 E-value: 2.09e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  374 EDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKE 453
Cdd:COG1196   426 LEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEG 505

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  454 IERREAAKRELERQRQL--------EWE-------RNRRQELLNQRNKEQEGTVV-----LKARRKTLEFELEALNDKKH 513
Cdd:COG1196   506 FLEGVKAALLLAGLRGLagavavliGVEaayeaalEAALAAALQNIVVEDDEVAAaaieyLKAAKAGRATFLPLDKIRAR 585

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  514 QLEGKLQDIRCR------LATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQN------ 581
Cdd:COG1196   586 AALAAALARGAIgaavdlVASDLREADARYYVLGDTLLGRTLVAARLEAALRRAVTLAGRLREVTLEGEGGSAGgsltgg 665

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  582 SLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERK 661
Cdd:COG1196   666 SRRELLAALLEAEAELEELAERLAEEELELEEALLAEEEEERELAEAEEERLEEELEEEALEEQLEAEREELLEELLEEE 745

                         330       340       350
                  ....*....|....*....|....*....|...
gi 568997330  662 SL----------------ELEKQKEDAQRRVQE 678
Cdd:COG1196   746 ELleeealeelpeppdleELERELERLEREIEA 778

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 46.24 E-value: 2.10e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVV-TKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11809     1 EATAQFDYTGRSERELSFKKGDSLTLyRQVSDDWWRGQLNGQDGLVPHKYITL 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 46.16 E-value: 2.12e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568997330 1183 YTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11982     9 YQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPSDCV 52

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 46.19 E-value: 2.19e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 984
Cdd:cd11782     1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYeGRIGGRQGIFPVSYVQ 52

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 46.07 E-value: 2.19e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYVK 1151
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGIN--TGRT---GLVPANYVE 49

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 46.18 E-value: 2.24e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd12076     5 VIYPYTARDQDEINLEKGAVVEVIQKNlEGWWKIRYQGKEGWAPASYLK 53

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 46.93 E-value: 2.26e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11973    22 ALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVRL 71

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212785 Cd Length: 62 Bit Score: 46.54 E-value: 2.33e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1177 VIGMYDY----TAQNDD---ELAFSKGQIINVLNKEDPD-WWKGEVSG-QVGLFPSNYVK 1227
Cdd:cd11851     2 MVALYDYnpetMSPNDDpeeELSFHAGDVVRVYGPMDEDgFYYGELEGgRKGLVPSNFVQ 61

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 46.20 E-value: 2.34e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDG---DWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11836     4 ALYAFEARNPDEISFQPGDIIQVDESQVaepGWLAGELKGKTGWFPANYV 53

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 45.98 E-value: 2.43e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11870     3 VALHRYEAQGPEDLGFREGDTIdVLSEVNEAWLEGHSDGRVGIFPKCFV 51

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 52.61 E-value: 2.45e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  389 EKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE---------KQLEKQrelerqreeerrkeierREA 459
Cdd:COG4913   287 QRRLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQirgnggdrlEQLERE-----------------IER 349

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  460 AKRELERQRQlewERNRRQELLNQ-------------RNKEQegtvvLKARRKTLEFELEALNDKKHQLEGKLQDIRCRL 526
Cdd:COG4913   350 LERELEERER---RRARLEALLAAlglplpasaeefaALRAE-----AAALLEALEEELEALEEALAEAEAALRDLRREL 421


                  ....*....
gi 568997330  527 ATQRQEIES 535
Cdd:COG4913   422 RELEAEIAS 430

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213013 Cd Length: 62 Bit Score: 46.49 E-value: 2.51e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1179 GMYDYTAQNDD-------ELAFSKGQIINVLNKEDPDWWKGEVSGQ----VGLFPS 1223
Cdd:cd12080     4 AQFDYDPKKDNlipckeaGLKFQTGDIIQIINKDDSNWWQGRVEGSgeesAGLIPS 59

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 52.75 E-value: 2.55e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   352 RLPEEPSSEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQ-EQERKRQL 430
Cdd:TIGR02168  324 QLEELESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQiASLNNEIE 403

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   431 ELEKQLEKQRELERQREeerrkeierreaAKRELERQRQLEWERNRRQELLNQRNKEQEGtvvLKARRKTLEFELEALND 510
Cdd:TIGR02168  404 RLEARLERLEDRRERLQ------------QEIEELLKKLEEAELKELQAELEELEEELEE---LQEELERLEEALEELRE 468

                          170       180       190
                   ....*....|....*....|....*....|.
gi 568997330   511 KKHQLEGKLQDIRCRLATQRQEIESTNKSRE 541
Cdd:TIGR02168  469 ELEEAEQALDAAERELAQLQARLDSLERLQE 499

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 51.83 E-value: 2.62e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  376 KKRENFERGSVELEKRRQALLEQQRKEQER--LAQLERAEQERKERERQEQERKRQLE-LEKQLEKQRELerqreeerrk 452
Cdd:COG4372     5 GEKVGKARLSLFGLRPKTGILIAALSEQLRkaLFELDKLQEELEQLREELEQAREELEqLEEELEQARSE---------- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  453 eIERREAAKRELERQ-RQLEWERNRRQELLNQRNKEQEgtvVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQ 531
Cdd:COG4372    75 -LEQLEEELEELNEQlQAAQAELAQAQEELESLQEEAE---ELQEELEELQKERQDLEQQRKQLEAQIAELQSEIAEREE 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  532 EIESTNKSRELRIAEITHLQQQLQESQQMLGRlipekQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDE 611
Cdd:COG4372   151 ELKELEEQLESLQEELAALEQELQALSEAEAE-----QALDELLKEANRNAEKEEELAEAEKLIESLPRELAEELLEAKD 225

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  612 VERE----TRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHV 687
Cdd:COG4372   226 SLEAklglALSALLDALELEEDKEELLEEVILKEIEELELAILVEKDTEEEELEIAALELEALEEAALELKLLALLLNLA 305

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  688 QQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSRLFHPHQE 736
Cdd:COG4372   306 ALSLIGALEDALLAALLELAKKLELALAILLAELADLLQLLLVGLLDND 354

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 52.53 E-value: 2.74e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   371 VTFEDKKRENFERGSVELEKRRQALlEQQRKEQERLAQLERAEQERKER--ERQEQERKRQLELEKQLEkQRELERQREE 448
Cdd:pfam12128  456 ATATPELLLQLENFDERIERAREEQ-EAANAEVERLQSELRQARKRRDQasEALRQASRRLEERQSALD-ELELQLFPQA 533

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   449 ERRKEIERREAAKRELERQRQLEWERNRRQEL---LNQRNKEQEGTVV-LKARRKTLE-----FELEALNDKKHQLEGKL 519
Cdd:pfam12128  534 GTLLHFLRKEAPDWEQSIGKVISPELLHRTDLdpeVWDGSVGGELNLYgVKLDLKRIDvpewaASEEELRERLDKAEEAL 613

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   520 QDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQilSDQLKQVQQNSLHRDSLLTLKRALEAK- 598
Cdd:pfam12128  614 QSAREKQAAAEEQLVQANGELEKASREETFARTALKNARLDLRRLFDEKQ--SEKDKKNKALAERKDSANERLNSLEAQl 691

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   599 ---ELARQQLREQLDEVERETRSKLQE-----IDVFNNQLKELreihsKQQLQKQRSLEAARLKQKEQERK-SL------ 663
Cdd:pfam12128  692 kqlDKKHQAWLEEQKEQKREARTEKQAywqvvEGALDAQLALL-----KAAIAARRSGAKAELKALETWYKrDLaslgvd 766

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   664 ------------ELEKQKEDAQRRVQE--RDKQWLEHVQQEEQPR--PRKPHEEDRLKR-EDSVRKKEAE---ERAKPEM 723
Cdd:pfam12128  767 pdviaklkreirTLERKIERIAVRRQEvlRYFDWYQETWLQRRPRlaTQLSNIERAISElQQQLARLIADtklRRAKLEM 846


                   ....*.
gi 568997330   724 QDKQSR 729
Cdd:pfam12128  847 ERKASE 852

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 45.78 E-value: 2.87e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYV 1150
Cdd:cd11826     4 ALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGV-----TGLFPGNYV 51

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 45.97 E-value: 2.88e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1180 MYDYTA-QNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11829     5 LYAFTGeQHQQGLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 45.96 E-value: 3.01e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGGELKGKTGWFPANY 817
Cdd:cd11948     4 ALYSFQATESDELPFQKGDILKILNMED-DQNWYKAELQGREGYIPKNY 51

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 45.82 E-value: 3.07e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVM----VDESqtgepgWLGGELKGKTGWFPANYAE 819
Cdd:cd11786     1 CAKALYNYEGKEPGDLSFKKGDIILlrkrIDEN------WYHGECNGKQGFFPASYVQ 52

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 45.72 E-value: 3.08e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1097 QVIA--SYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVKL 1152
Cdd:cd11995     2 QVIGmyDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNG-----QVGLFPSNYVKL 54

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 45.96 E-value: 3.27e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKG-EVSGQVGLFPSNYV 1226
Cdd:cd11905     3 VVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWWKArDKYGKEGYIPSNYV 53

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 46.09 E-value: 3.38e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQARgkkrqIGWFPANYV 1150
Cdd:cd12058     4 ALYDYEASGEDELSLRRGDVVEVLSQDAAvsgddGWWAGKIRHR-----LGIFPANYV 56

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 45.74 E-value: 3.39e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESqtgEPGWLGGELKGKTGWFPANY 817
Cdd:cd11991     2 YVAMYTYESNEQGDLTFQQGDVILVTKK---DGDWWTGTVGDKTGVFPSNY 49

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 51.30 E-value: 3.69e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  397 EQQRKEQERLAQLERA-EQERKERERQEQERKRQLELEKQLEKQrelerqreeerrkeierreaakrelerqrqlewern 475
Cdd:COG4942    20 DAAAEAEAELEQLQQEiAELEKELAALKKEEKALLKQLAALERR------------------------------------ 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  476 rrqelLNQRNKEQEgtvVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQ 555
Cdd:COG4942    64 -----IAALARRIR---ALEQELAALEAELAELEKEIAELRAELEAQKEELAELLRALYRLGRQPPLALLLSPEDFLDAV 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  556 ESQQMLGRLIPEKQILSDQLKQVQQNslhrdsLLTLKRALEAKelaRQQLREQLDEVERETRsklqeidvfnnQLKELRE 635
Cdd:COG4942   136 RRLQYLKYLAPARREQAEELRADLAE------LAALRAELEAE---RAELEALLAELEEERA-----------ALEALKA 195

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  636 IHSK--QQLQKQRSLEAARLKQKEQERKSLE-----LEKQKEDAQRRV 676
Cdd:COG4942   196 ERQKllARLEKELAELAAELAELQQEAEELEaliarLEAEAAAAAERT 243

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 46.16 E-value: 3.77e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11973    20 AEALWDHVTMDDQELGFKAGDVIEVMDATNKeWWWGRVLDSEGWFPASFVRL 71

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 45.53 E-value: 3.88e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1027 MYTYESSEQGDLTFQQGDVIVVTKK---DGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd12142     5 LFDYNPVAPDELALKKGDVIEVISKeteDEGWWEGELNGRRGFFPDNFV 53

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 45.37 E-value: 3.89e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 983
Cdd:cd11772     4 ALYDYEAQHPDELSFEEGDLLYISDKSDPnWWKATCGGKTGLIPSNYV 51

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 275388 [Multi-domain] Cd Length: 92 Bit Score: 46.77 E-value: 3.93e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1482 HSGKLYK-----AKSNKELYGFLFNDFLLLTQitkplgsSGTDKVFSPKsnlqykmykTPIFLNEVLVKLPTDPSGDEPI 1556
Cdd:cd00821     1 KEGYLLKrggggLKSWKKRWFVLFEGVLLYYK-------SKKDSSYKPK---------GSIPLSGILEVEEVSPKERPHC 64

                          90       100
                  ....*....|....*....|....*...
gi 568997330 1557 FHISH-IDRVYTLRAESINERTAWVQKI 1583
Cdd:cd00821    65 FELVTpDGRTYYLQADSEEERQEWLKAL 92

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 45.77 E-value: 3.94e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330  939 YPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11902     7 FAYVAEREDELSLVKGSRVTVMEKcSDGWWRGSYNGQIGWFPSNYV 52

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 48.47 E-value: 3.99e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTM-----GSQCHITKTIQDTLNPKWN---SNCQFFIRDLEQEVLCITVFERD 1684
Cdd:cd04020    27 GELHVWVKEAKNLPALKSGGTSDSFVKCYLlpdksKKSKQKTPVVKKSVNPVWNhtfVYDGVSPEDLSQACLELTVWDHD 106


                  ....*....
gi 568997330 1685 QFSPDDFLG 1693
Cdd:cd04020   107 KLSSNDFLG 115

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 45.41 E-value: 4.17e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYV 1150
Cdd:cd11901     4 AYVKFNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQ-----VGWFPSNYV 53

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 45.47 E-value: 4.24e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVmVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11960     3 RALYDYQAADDTEISFDPGDII-TDIEQIDEGWWRGTGPDGTYGLFPANYVE 53

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 51.56 E-value: 4.24e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   387 ELEKRRQALLEQQRKEQERL----AQLERAEQERKERERQEQERKRQLElEKQLEKQRELERQREEERRKEIERREAAkr 462
Cdd:TIGR04523  222 ELKKQNNQLKDNIEKKQQEInektTEISNTQTQLNQLKDEQNKIKKQLS-EKQKELEQNNKKIKELEKQLNQLKSEIS-- 298

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   463 ELERQRQLEWERNRRQELLNQRNKEQEgtvvlkarrktLEFELEALNDKKHQLEGKLQDIRcrlaTQRQEIESTNKSREL 542
Cdd:TIGR04523  299 DLNNQKEQDWNKELKSELKNQEKKLEE-----------IQNQISQNNKIISQLNEQISQLK----KELTNSESENSEKQR 363

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   543 RIAE----ITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLL-TLKRALEAKELARQQLREQLDEVERETR 617
Cdd:TIGR04523  364 ELEEkqneIEKLKKENQSYKQEIKNLESQINDLESKIQNQEKLNQQKDEQIkKLQQEKELLEKEIERLKETIIKNNSEIK 443

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   618 SKLQEIDVFNNQLKELREIHSKQQLQ----------KQRSLEAAR--LKQKEQERKSLELEKQK-EDAQRRVQERDKQWL 684
Cdd:TIGR04523  444 DLTNQDSVKELIIKNLDNTRESLETQlkvlsrsinkIKQNLEQKQkeLKSKEKELKKLNEEKKElEEKVKDLTKKISSLK 523

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|..
gi 568997330   685 EHVQQEEQPRPRKPHE----EDRLKREDSVRKKEAEERAKPEMQDKQSRLFH 732
Cdd:TIGR04523  524 EKIEKLESEKKEKESKisdlEDELNKDDFELKKENLEKEIDEKNKEIEELKQ 575

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212829 [Multi-domain] Cd Length: 55 Bit Score: 45.34 E-value: 4.27e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  768 RALYPFESRSHDEITIQPG-DIVMVDESQTGepGWLGGE-LKGKTGWFPANYAE 819
Cdd:cd11896     3 RALYSFQSENKEEINIQENeELVIFSENSLD--GWLQGQnSRGETGLFPASYVE 54

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 45.60 E-value: 4.27e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  771 YPFESRSHDEITIQPGDIVMvDESQTGEPGWLGGELKGKTGWFPANYAEKI 821
Cdd:cd12053     6 YDYDAVHEDELTIRVGEIIR-NVKKLEEEGWLEGELNGRRGMFPDNFVKEI 55

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 45.32 E-value: 4.30e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMV-DESQTgepGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11985     2 YVALYKFLPQENNDLPLQPGDRVMVvDDSNE---DWWKGKSGDRVGFFPANFVQR 53

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 45.31 E-value: 4.48e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1102 YAATGPEQLTLAPGQLILI-RKKNPGGWWEGELQARgkkrqIGWFPANYVK 1151
Cdd:cd11830     8 FCARDMRELSLKEGDVVKIyNKKGQQGWWRGEINGR-----IGWFPSTYVE 53

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 49.92 E-value: 4.51e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  468 RQLEWERNRRQELLNQRNKEQEGtvvLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEi 547
Cdd:COG1579    20 DRLEHRLKELPAELAELEDELAA---LEARLEAAKTELEDLEKEIKRLELEIEEVEARIKKYEEQLGNVRNNKEYEALQ- 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  548 thlqqqlqesqqmlgrlipeKQIlsDQLKQvqQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFN 627
Cdd:COG1579    96 --------------------KEI--ESLKR--RISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELDEEL 151

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 568997330  628 NQLKELREIHSKQQLQKQRSLEAARLKQKEQERKS 662
Cdd:COG1579   152 AELEAELEELEAEREELAAKIPPELLALYERIRKR 186

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 45.53 E-value: 4.62e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELK--GKTGWFPANYAEK 820
Cdd:cd11785     2 YRVIVPYPPQSEAELELKEGDIVFVHKKR--EDGWFKGTLQrtGKTGLFPGSFVES 55

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 45.34 E-value: 4.79e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  935 AQALYPWRAKKD-NHLNFNKSDVITVLEQQDM------WWFGEVQ-GQKGWFPKSYV 983
Cdd:cd11771     2 CRALYDFTPENPeMELSLKKGDIVAVLSKTDPlgrdseWWKGRTRdGRIGWFPSNYV 58

Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of central nervous system tissues. srGAP2 is expressed in zones of neuronal differentiation. It plays a role in the regeneration of neurons and axons. srGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42. It impacts cell migration by regulating actin and microtubule cytoskeletal dynamics. The association between srGAP3 haploinsufficiency and mental retardation is under debate. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212888 [Multi-domain] Cd Length: 53 Bit Score: 45.32 E-value: 4.94e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11955     1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYI 51

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212997 Cd Length: 56 Bit Score: 45.49 E-value: 4.98e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1179 GMYDYTAQNDDELAFSKGQII-NVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12064     5 ALYACKAEHDSELSFTAGTVFdNVHPSQEPGWLEGTLNGKTGLIPENYVEF 55

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 45.41 E-value: 5.15e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYV 983
Cdd:cd11887     6 ALYPYESDHEDDLNFDVGQLITVTEEEDAdWYFGEYVDsngntKEGIFPKNFV 58

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 45.39 E-value: 5.17e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  933 LQAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 986
Cdd:cd11920     1 LPARAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYeGEHHGRVGIFPISYVEKL 55

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 45.08 E-value: 5.26e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKK--DGdWWTGT--VGDKSGVFPSNYV 1072
Cdd:cd11783     2 YVALYPYKPQKPDELELRKGEMYTVTEKcqDG-WFKGTslRTGQSGVFPGNYV 53

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 51.31 E-value: 5.37e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  432 LEKQLEKQRElerqreEERRKEIERREAAKRELERQRQlewernRRQELLNQRNKEQEgtvvLKARRKTLEFELEALNDK 511
Cdd:COG4717    47 LLERLEKEAD------ELFKPQGRKPELNLKELKELEE------ELKEAEEKEEEYAE----LQEELEELEEELEELEAE 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  512 KHQLEGKLQDIRCRLATQRQEIESTNKSRELriaeithlqqqlqesqqmlgrlipekQILSDQLKQVQQnslHRDSLLTL 591
Cdd:COG4717   111 LEELREELEKLEKLLQLLPLYQELEALEAEL--------------------------AELPERLEELEE---RLEELREL 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  592 KRALEAKELARQQLREQLDEVERETR-SKLQEIDVFNNQLKELREihSKQQLQKQRSLEAARLKQKEQERKSLELEKQKE 670
Cdd:COG4717   162 EEELEELEAELAELQEELEELLEQLSlATEEELQDLAEELEELQQ--RLAELEEELEEAQEELEELEEELEQLENELEAA 239


                  ....*...
gi 568997330  671 DAQRRVQE 678
Cdd:COG4717   240 ALEERLKE 247

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 45.18 E-value: 5.57e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  765 VYYrALYPFESRSHDEITIQPGDIVMVDE--SQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd12141     1 VYY-AVYTFKARSPNELSVSANQRVRILEfsDLTGNKEWWLAEANGQKGYVPSNYIRK 57

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 45.38 E-value: 5.61e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  933 LQAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd12060     2 LVVKARFNFKQTNEDELSVCKGDIIYVTRVEEGgWWEGTLNGKTGWFPSNYVR 54

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 45.18 E-value: 5.72e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd12046     1 QVVALFSYEASQPEDLEFQKGDVILVLSKvNEDWLEGQCKGKIGIFPSAFVE 52

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 45.37 E-value: 5.74e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGT--VGDKSGVFPSNYV 1072
Cdd:cd12004     3 VALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARslTTKKEGFIPSNYV 52

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 45.27 E-value: 5.96e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKN--PGGWWEGELQARGkkrqiGWFPANYVKLL 1153
Cdd:cd12057     3 KVLFPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRR-----GVFPDNFVKLL 56

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 50.58 E-value: 6.01e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  602 RQQLREQldEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDK 681
Cdd:PRK09510   77 AEEQRKK--KEQQQAEELQQKQAAEQERLKQLEKERLAAQEQKKQAEEAAKQAALKQKQAEEAAAKAAAAAKAKAEAEAK 154

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330  682 QWLEHVQQEEQPRPRKPHEEDRLKREDSVRKK-EAEERAKPEMQDKQ 727
Cdd:PRK09510  155 RAAAAAKKAAAEAKKKAEAEAAKKAAAEAKKKaEAEAAAKAAAEAKK 201

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 44.96 E-value: 6.11e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1027 MYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12054     6 LFEYVPQNEDELELKVGDIIDINEEvEEGWWSGTLNGKSGLFPSNFVK 53

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 47.20 E-value: 6.12e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1632 GKSNPYCEVTM-GSQCHITKTIQDTLNPKWNsNCQFFIRDLEQEVLCITVFERDQFSPDDFLGRTEIRVAD-IKKDQ--- 1706
Cdd:cd04045    20 GKIDPYVRVLVnGIVKGRTVTISNTLNPVWD-EVLYVPVTSPNQKITLEVMDYEKVGKDRSLGSVEINVSDlIKKNEdgk 98

                          90
                  ....*....|....*.
gi 568997330 1707 ----GSKGPVTKCLLL 1718
Cdd:cd04045    99 yveyDDEEERLKRLLS 114

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 51.26 E-value: 6.21e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   352 RLPEEPSSEDEQQPEKKLPVTFEDKKREN-FERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERK--- 427
Cdd:pfam05483   78 RLYSKLYKEAEKIKKWKVSIEAELKQKENkLQENRKIIEAQRKAIQELQFENEKVSLKLEEEIQENKDLIKENNATRhlc 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   428 --------RQLELEKQLEKQRELERQREEERRKEIERREAAKREL---------------------------ERQRQLEW 472
Cdd:pfam05483  158 nllketcaRSAEKTKKYEYEREETRQVYMDLNNNIEKMILAFEELrvqaenarlemhfklkedhekiqhleeEYKKEIND 237

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   473 ERNRRQELLNQ----RNKEQEGTVVL-KARRKTLEFE---------LEALNDKKHQLEGKLQDIR--------------- 523
Cdd:pfam05483  238 KEKQVSLLLIQitekENKMKDLTFLLeESRDKANQLEektklqdenLKELIEKKDHLTKELEDIKmslqrsmstqkalee 317

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   524 ---------CRLATQRQ-EIESTNKSRELRIAEITHLQQQLQESQQMlgrLIPEKQIL---SDQLK------QVQQNSLH 584
Cdd:pfam05483  318 dlqiatktiCQLTEEKEaQMEELNKAKAAHSFVVTEFEATTCSLEEL---LRTEQQRLeknEDQLKiitmelQKKSSELE 394

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   585 RDSLLTLKRALEAKELAR-----QQL---REQLDEVERETRSKLQEIdVFNNQLKElREIHSKQ-QLQKQRSLEAARLKQ 655
Cdd:pfam05483  395 EMTKFKNNKEVELEELKKilaedEKLldeKKQFEKIAEELKGKEQEL-IFLLQARE-KEIHDLEiQLTAIKTSEEHYLKE 472

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330   656 KEQERKSLELEKQKE------------DAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPE 722
Cdd:pfam05483  473 VEDLKTELEKEKLKNieltahcdklllENKELTQEASDMTLELKKHQEDIINCKKQEERMLKQIENLEEKEMNLRDELE 551

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 45.37 E-value: 6.24e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYVK 1227
Cdd:cd11917    10 LYNYMPRNEDELELREGDVIDVMEKCDDGWFVGTSrrTKFFGTFPGNYVK 59

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 44.93 E-value: 6.51e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGD--WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11830     3 KARYDFCARDMRELSLKEGDVVKIYNKKGQqgWWRGEINGRIGWFPSTYV 52

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 47.26 E-value: 6.59e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1617 VNVVEGIELKPCRSHGKSNPYceVTM-----GSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDF 1691
Cdd:cd04043     5 IRIVRAENLKADSSNGLSDPY--VTLvdtngKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDL 82


                  ....*..
gi 568997330 1692 LGRTEIR 1698
Cdd:cd04043    83 CGRASLK 89

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 50.72 E-value: 6.60e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   567 EKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLR-EQLDEVERETRSKLQEIDVFNNQLKELREIHSK-QQLQK 644
Cdd:pfam15709  358 EEQRRLQQEQLERAEKMREELELEQQRRFEEIRLRKQRLEeERQRQEEEERKQRLQLQAAQERARQQQEEFRRKlQELQR 437

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   645 QRsleaarlKQKEQERKSLELEKQKEdaqrrvqerdkqwLEHVQQEEQPRPRKPHEEDRLkrEDSVRKKEAEERAKPEMQ 724
Cdd:pfam15709  438 KK-------QQEEAERAEAEKQRQKE-------------LEMQLAEEQKRLMEMAEEERL--EYQRQKQEAEEKARLEAE 495

                          170       180
                   ....*....|....*....|....*...
gi 568997330   725 DKQSRlfhpHQEPAKLA-TQAPWSTTEK 751
Cdd:pfam15709  496 ERRQK----EEEAARLAlEEAMKQAQEQ 519

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 45.02 E-value: 6.66e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKkrqIGWFPANYVKL 1152
Cdd:cd11874     2 CKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKL--NGK---VGVFPSNFVKE 53

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 50.92 E-value: 6.88e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  568 KQILSDQLKQVQQNslhRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRS 647
Cdd:COG4717    66 PELNLKELKELEEE---LKEAEEKEEEYAELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQELEALEAELA 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  648 LEAARLKQKEQERKSL-ELEKQKEDAQRRVQERDKQwleHVQQEEQPRPRKPHEEDRLKRE-DSVRKKEAEERAkpEMQD 725
Cdd:COG4717   143 ELPERLEELEERLEELrELEEELEELEAELAELQEE---LEELLEQLSLATEEELQDLAEElEELQQRLAELEE--ELEE 217

                         170       180
                  ....*....|....*....|....*.
gi 568997330  726 KQSRLFHPHQEPAKLATQAPWSTTEK 751
Cdd:COG4717   218 AQEELEELEEELEQLENELEAAALEE 243

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 44.81 E-value: 7.03e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd12047     3 VAQHDYSAQGPEDLEFSQGDTIdILSEVNQEWLEGHCDGRIGIFPKCFA 51

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 44.70 E-value: 7.35e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQ-----DMWWFGEVQGQKGWFP 979
Cdd:cd11762     2 VRALYDYEAQSDEELSFPEGAIIRILRKDdngvdDGWWEGEFNGRVGVFP 51

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 44.78 E-value: 7.42e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSY 982
Cdd:cd11817     2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAeWSRGRLNGREGIFPRAF 50

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 44.98 E-value: 7.56e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLnKEDPDWWKGE--VSGQVGLFPSNYV 1226
Cdd:cd12004     2 VVALYPYDGIHEDDLSFKKGEKLKVI-EEHGEWWKARslTTKKEGFIPSNYV 52

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270064 Cd Length: 100 Bit Score: 46.07 E-value: 7.63e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1478 RKFLHSG--KLYKAKSNK-ELYGFLFNDFLLltqITKPLGSSGtDKvfspksnlqYKMYKTPIFLNEVLVKLPTDPSGde 1554
Cdd:cd13244     1 RRLLLEGdlRLKEGKGSKvDVHCFLFTDMLL---ICKPVKRKK-DR---------LKVIRPPYLVDKLVVQELKDPGG-- 65

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 568997330 1555 piFHISHIDR------VYTLRAESINERTAWVQKIK 1584
Cdd:cd13244    66 --FLLVYLNEfhtavaAYTFQTSSQEDTRRWLDAIR 99

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 47.26 E-value: 7.64e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTM-----GSQCHITKTIQDTLNPKWNSncQFFIrDLEQE----VLCITVFER 1683
Cdd:cd04026    13 NKLTVEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNE--TFTF-DLKPAdkdrRLSIEVWDW 89

                          90       100
                  ....*....|....*....|...
gi 568997330 1684 DQFSPDDFLGRTEIRVADIKKDQ 1706
Cdd:cd04026    90 DRTTRNDFMGSLSFGVSELIKMP 112

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 44.76 E-value: 7.71e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330  939 YPWRAKKDNHLNFNKSDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd12016     7 QAYKAENEDEIGFETGVVVEVIQKNlDGWWKIRYQGKEGWAPATYLK 53

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 44.79 E-value: 8.05e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11869     4 ALFDFTGNSKLELNFKAGDVIfLLSRVNKDWLEGTVRGATGIFPLSFVKI 53

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 44.91 E-value: 8.05e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAEKI 821
Cdd:cd11921     4 RLKFDFQAQSPKELTLQKGDIVYIHKEV--DKNWLEGEHHGRVGIFPANYVEVL 55

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212971 Cd Length: 61 Bit Score: 45.05 E-value: 8.21e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1181 YDYTAQNDD-------ELAFSKGQIINVLNKEDPDWWKG---EVSGQVGLFPSNYV 1226
Cdd:cd12038     6 FDYNPYNDNlipckeaGLKFSKGEILQIVNREDPNWWQAshvKEGGSAGLIPSQFL 61

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 44.72 E-value: 8.50e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVE 54

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 44.81 E-value: 8.98e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQARgkkrqIGWFPANYV 1150
Cdd:cd11876     8 YDARGEDELTLRRGQPVEVLSKDAAvsgdeGWWTGKIGDK-----VGIFPSNYV 56

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 44.63 E-value: 9.48e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11971     3 VAIYDYSKDKDDELSFMEGAIIYVIKKNDDgWYEGVCNGVTGLFPGNYV 51

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 44.35 E-value: 9.76e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPS 1223
Cdd:cd11832     1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPS 48

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 44.32 E-value: 9.82e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11816     3 VARFDFEGEQEDELSFSEGDVITLKEYVGEeWAKGELNGKIGIFPLNFV 51

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 46.54 E-value: 1.01e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1614 RLMVNVVEGIELKPCrshgKSNPYCEVTMGSQCHITKTIQDTLNPKWNsncQFFI--RDLEQE-VLCITVFERDqFSPDD 1690
Cdd:cd08378     1 YLYVRVVKARGLPAN----SNDPVVEVKLGNYKGSTKAIERTSNPEWN---QVFAfsKDRLQGsTLEVSVWDKD-KAKDD 72

                          90
                  ....*....|..
gi 568997330 1691 FLGRTEIRVADI 1702
Cdd:cd08378    73 FLGGVCFDLSEV 84

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 44.56 E-value: 1.01e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd12021     2 YRAIADYEKSSKSEMALKTGDVVEVVEKS--ENGWWFCQLKAKRGWVPASYLE 52

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 44.57 E-value: 1.04e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYV 1226
Cdd:cd11926     3 VAIYPYTPRKEDELELRKGEMFLVFERCQDGWFKGTSmhTSKIGVFPGNYV 53

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 44.59 E-value: 1.05e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDKSGV-FPSNYV 1072
Cdd:cd11970     8 ALFDYKAQREDELTFTKNAIIQnVEKQEGGWWRGDYGGKKQLwFPSNYV 56

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 48.77 E-value: 1.06e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE-KQLEKQRELerqreeerrkeierreAAKRELE 465
Cdd:COG1579    14 ELDSELDRLEHRLKELPAELAELEDELAALEARLEAAKTELEDLEKEiKRLELEIEE----------------VEARIKK 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  466 RQRQLEWERNRRQelLNQRNKEQEGtvvLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIA 545
Cdd:COG1579    78 YEEQLGNVRNNKE--YEALQKEIES---LKRRISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELDEELA 152


                  ..
gi 568997330  546 EI 547
Cdd:COG1579   153 EL 154

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is also called Cbl-Interacting Protein 4 (CLIP4), T cell Ubiquitin LigAnd (TULA), or T cell receptor Signaling (STS)-2. It is only found in lymphoid cells and exhibits weak phosphatase activity. UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF. It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212870 [Multi-domain] Cd Length: 60 Bit Score: 44.62 E-value: 1.09e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGE--PGWLGG--ELKGKTGWFPANYAEK 820
Cdd:cd11937     4 RALFQYKPQNIDELMLSPGDYIFVDPTQQSEasEGWVIGisHRTGCRGFLPENYTER 60

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 44.25 E-value: 1.11e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  933 LQAQALYPWRAKKDNHLNFNKSDVITVL--EQQDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11946     1 MEAIAKYDFKATADDELSFKRGDILKVLneECDQNWYKAELNGKDGFIPKNYIEM 55

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212999 Cd Length: 55 Bit Score: 44.28 E-value: 1.11e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQII-NVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd12066     1 QAKAMYSCKAEHSHELSFPQGAIFsNVYPSVEPGWLKATYEGKTGLVPENYV 52

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 44.16 E-value: 1.12e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd11856     4 AIADYEAQGDDEISLQEGEVVEVLEKNDSgWWYVRKGDKEGWVPASYLE 52

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 44.12 E-value: 1.16e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   766 YYRALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGELKGKTGWFPANYAEKI 821
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLG--KDNDGWWEGETGGRVGLVPSTAVEEI 54

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 44.18 E-value: 1.16e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVIT-VLEQQDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11873     4 VEFDYDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 44.32 E-value: 1.20e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  933 LQAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11975     5 VSAEAVWDHVTMANRELAFKAGDVIKVLDASNKdWWWGQIDDEEGWFPASFVRL 58

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 46.77 E-value: 1.22e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1632 GKSNPYCEVTMGSQCHITKTIQDTLNPKWNsncQFFI----------RDLEQE--VLCITVFERDQFSPDDFLGRTEIR 1698
Cdd:cd04017    20 GLSDPFARVSFLNQSQETEVIKETLSPTWD---QTLIfdevelygspEEIAQNppLVVVELFDQDSVGKDEFLGRSVAK 95

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 44.02 E-value: 1.25e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11869     5 LFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVKI 53

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 44.18 E-value: 1.27e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSG--QVGLFPSNYVKL 1228
Cdd:cd11924     2 EAVAQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITGtgRQGIFPASYVQV 56

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, also called Insulin Receptor Tyrosine Kinase Substrate (IRTKS); BAIAP2L1 or IRTKS is widely expressed, serves as a substrate for the insulin receptor, and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRTKS has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212846 Cd Length: 58 Bit Score: 44.14 E-value: 1.30e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 568997330  949 LNFNKSDVITVL--EQQDMWWFGE--VQGQKGWFPKSYVKL 985
Cdd:cd11913    18 LSFAQGDVITLLipEEKDGWLYGEhdTTKARGWFPSSYTRP 58

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 43.88 E-value: 1.31e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVL-EQQDMWWF-GEVQGQKGWFPKSYV 983
Cdd:cd11804     1 EAVAKHDFKATAEDELSFKKGSILKVLnMEDDPNWYkAELDGKEGLIPKNYI 52

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212703 [Multi-domain] Cd Length: 57 Bit Score: 44.22 E-value: 1.34e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1021 GEEFIAMYTYESSEQGDLTFQQGDVIVVTK--KDGDWWTG-TVGDKSGVFPSNYV 1072
Cdd:cd11769     1 GTECIAKYNFNGASEEDLPFKKGDILTIVAvtKDPNWYKAkNKDGREGMIPANYV 55

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 43.80 E-value: 1.39e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1025 IAMYTYESSEQGDLTFQQGD-VIVVTKKDGDWWtgTVGDK---SGVFPSNYVR 1073
Cdd:cd11768     3 VALYDFQPIEPGDLPLEKGEeYVVLDDSNEHWW--RARDKngnEGYIPSNYVT 53

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 44.01 E-value: 1.40e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTVGDKSGVFPSNY 1071
Cdd:cd11818     4 ALYDFTGENEDELSFKAGDIITeLESIDEEWMSGELRGKSGIFPKNF 50

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 46.96 E-value: 1.40e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   592 KRALEAKelaRQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLElEKQKED 671
Cdd:pfam05672   13 ARILAEK---RRQAREQREREEQERLEKEEEERLRKEELRRRAEEERARREEEARRLEEERRREEEERQRKAE-EEAEER 88

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 568997330   672 AQRRVQERDKQWLEhvQQEEQPRPRKPHEEDRLKREDSVRKKEAE--ERAK 720
Cdd:pfam05672   89 EQREQEEQERLQKQ--KEEAEAKAREEAERQRQEREKIMQQEEQErlERKK 137

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 43.91 E-value: 1.44e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWW---KGEVSGQvGLFPSNYVKL 1228
Cdd:cd11858     5 LYDFAGSVANELSLKKDDIVYIVQKEDNGWWlakKLDESKE-GWVPAAYLEE 55

Src Homology 3 domain of SH3 domain-binding protein 4; SH3 domain-binding protein 4 (SH3BP4) is also called transferrin receptor trafficking protein (TTP). SH3BP4 is an endocytic accessory protein that interacts with endocytic proteins including clathrin and dynamin, and regulates the internalization of the transferrin receptor (TfR). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212691 Cd Length: 52 Bit Score: 43.86 E-value: 1.47e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11757     1 EVVAIKDYCPTNFTTLKFSKGDHLYVLDTSGGEWWYAHNTTEMGYIPSSYVQ 52

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 43.87 E-value: 1.48e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  933 LQAQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11901     2 LPAYVKFNYTAEREDELSLVKGTKVIVMEKcSDGWWRGSYNGQVGWFPSNYV 53

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 43.64 E-value: 1.62e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYV 1226
Cdd:cd11889     5 VYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLrrNGAEGIFPSNFV 53

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 43.89 E-value: 1.65e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKN--PGGWWEGELqaRGKkrqIGWFPANYV 1150
Cdd:cd11836     3 RALYAFEARNPDEISFQPGDIIQVDESQvaEPGWLAGEL--KGK---TGWFPANYV 53

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 43.67 E-value: 1.66e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQIgWFPANYVK 1151
Cdd:cd11969     8 YRAKRSDELSFCKGALIHNVSKETGGWWKGDY---GGKVQH-YFPSNYVE 53

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212858 Cd Length: 57 Bit Score: 43.83 E-value: 1.67e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYV 1226
Cdd:cd11925     4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSlrTGVSGVFPGNYV 54

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 43.86 E-value: 1.71e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQ--DMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11978     3 AIARYDFCARDMRELSLLKGDVVKIYTKMstNGWWRGEVNGRVGWFPSTYVE 54

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 43.92 E-value: 1.72e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd11841     4 ALYSFEGQQPCDLSFQAGDRITVLTRTDSQFDWWEGRLRGRVGIFPANY 52

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 43.83 E-value: 1.79e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd11987     4 ALYPFEARSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 54

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 43.48 E-value: 1.79e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDE---LAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNY 1225
Cdd:cd11787     1 QCKALYDFEMKDEDEkdcLTFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 53

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 43.56 E-value: 1.80e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1026 AMYTYESSEQ--GDLTFQQGDVIVVTKKDGDWWTGTVGD-KSGVFPSNYVRL 1074
Cdd:cd11855     4 ALYPYDASPDdpNELSFEKGEILEVSDTSGKWWQARKSNgETGICPSNYLQL 55

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 49.13 E-value: 1.83e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  375 DKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQ-EQERKRQLELEKQLEkqrelerqreeerrke 453
Cdd:COG4372    41 DKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQlQAAQAELAQAQEELE---------------- 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  454 ierreAAKRELER-QRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQdircRLATQRQE 532
Cdd:COG4372   105 -----SLQEEAEElQEELEELQKERQDLEQQRKQLEAQIAELQSEIAEREEELKELEEQLESLQEELA----ALEQELQA 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  533 IESTNKSREL-RIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDE 611
Cdd:COG4372   176 LSEAEAEQALdELLKEANRNAEKEEELAEAEKLIESLPRELAEELLEAKDSLEAKLGLALSALLDALELEEDKEELLEEV 255

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  612 VERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEE 691
Cdd:COG4372   256 ILKEIEELELAILVEKDTEEEELEIAALELEALEEAALELKLLALLLNLAALSLIGALEDALLAALLELAKKLELALAIL 335

                         330       340
                  ....*....|....*....|....*....
gi 568997330  692 QPRPRKPHEEDRLKREDSVRKKEAEERAK 720
Cdd:COG4372   336 LAELADLLQLLLVGLLDNDVLELLSKGAE 364

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 43.78 E-value: 1.94e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 983
Cdd:cd12058     4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsgdDGWWAGKIRHRLGIFPANYV 56

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 43.46 E-value: 1.95e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPAN 816
Cdd:cd11982     3 FMAVKPYQSQAEGEISLSKGEKIKV--LSVGEGGFWEGQVKGRVGWFPSD 50

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 43.80 E-value: 1.98e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAEKI 821
Cdd:cd12054     4 KVLFEYVPQNEDELELKVGDIIDINEEV--EEGWWSGTLNGKSGLFPSNFVKEL 55

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 43.36 E-value: 2.02e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  766 YYRALYPFESRSHDEITIQPGD-IVMVDESQTgepGWLGGELKGKTGWFPANY 817
Cdd:cd11986     1 YFVALYRFKALEKDDLDFHPGErITVIDDSNE---EWWRGKIGEKTGYFPMNF 50

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 43.88 E-value: 2.05e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKLISG 988
Cdd:cd12001     5 AKALYDNVAESPDELSFRKGDIMTVLERDtqglDGWWLCSLHGRQGIVPGNRLKILVG 62

Src Homology 3 domain of the p85 regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212710 Cd Length: 72 Bit Score: 44.04 E-value: 2.13e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVD-------------ESQTGEPGWLGG--ELKGKTGWFPANYAE 819
Cdd:cd11776     3 YRALYDYEKERDEDIILKTGDVLVVEnpellalgvpdgkETVPKPEGWLEGknERTGERGDFPGTYVE 70

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 43.53 E-value: 2.13e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILIRKKNPG--GWWEGELqaRGkkrQIGWFPANYVK 1151
Cdd:cd11841     1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRL--RG---RVGIFPANYVS 54

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 43.44 E-value: 2.19e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1180 MYDYTAQNDDELAFSKGQII-NVLNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12065     5 VYPCEAEHSSELSFEVGAIFeDVTLSREPGWLEGTLNGKRGLIPENYVEI 54

Centrosomal protein of 63 kDa; CEP63 is a family of eukaryotic proteins involved in centriole activity.

Pssm-ID: 465338 [Multi-domain] Cd Length: 264 Bit Score: 47.89 E-value: 2.27e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   393 QALLEQQRKEQERL-AQLERAEQERKE--RERQEQERKRQLEL-------EKQLEKQRELERQREEERRKEIERREAAKR 462
Cdd:pfam17045   48 RNTLERKHKEIGLLrQQLEELEKGKQElvAKYEQQLQKLQEELsklkrsyEKLQRKQLKEAREEAKSREEDRSELSRLNG 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   463 ELE--RQRQLEWERnrrqellnQRNKEQEGTVVLKARRKTLEFELE---------ALNDKKHQLEGKLQDIRcRLATQRQ 531
Cdd:pfam17045  128 KLEefRQKSLEWEQ--------QRLQYQQQVASLEAQRKALAEQSSliqsaayqvQLEGRKQCLEASQSEIQ-RLRSKLE 198

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330   532 EIESTNKSRELriaEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQ-QNSLHRDSLLTLKRALEAKE 599
Cdd:pfam17045  199 RAQDSLCAQEL---ELERLRMRVSELGDSNRKLLEEQQRLLEELRMSQrQLQVLQNELMELKATLQSQD 264

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 43.48 E-value: 2.34e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1025 IAMYTYESSEQgdLTFQQGDVIVVTKKDGD-WWTGTV---GDK--SGVFPSNYVRL 1074
Cdd:cd11839     5 IAPFTATAENQ--LSLAVGQLVLVRKKSPSgWWEGELqarGKKrqIGWFPANYVKL 58

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 49.35 E-value: 2.34e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  378 RENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKqLEKQRELerqreeerrkeierr 457
Cdd:PTZ00266  432 KDHAERARIEKENAHRKALEMKILEKKRIERLEREERERLERERMERIERERLERER-LERERLE--------------- 495

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 568997330  458 eaaKRELERQRQLEWERNRRQELlnQRNKEQegtvvlKARRKT 500
Cdd:PTZ00266  496 ---RDRLERDRLDRLERERVDRL--ERDRLE------KARRNS 527

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 48.61 E-value: 2.40e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQALLEQQRKEQERLAQLER----AEQERKERERQEQERKRQL-ELEKQLEKQRELERQREEERRKEIERREAAK 461
Cdd:COG4942    24 EAEAELEQLQQEIAELEKELAALKKeekaLLKQLAALERRIAALARRIrALEQELAALEAELAELEKEIAELRAELEAQK 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  462 RELERQRQLEWERNRRQE---LLNQRNKEQEGTVV---------LKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQ 529
Cdd:COG4942   104 EELAELLRALYRLGRQPPlalLLSPEDFLDAVRRLqylkylapaRREQAEELRADLAELAALRAELEAERAELEALLAEL 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  530 RQEIESTNKSRElriaeithlqqqlqesqqmlgrlipEKQILSDQLKQvqqnslhrdSLLTLKRALEAKELARQQLREQL 609
Cdd:COG4942   184 EEERAALEALKA-------------------------ERQKLLARLEK---------ELAELAAELAELQQEAEELEALI 229

                         250
                  ....*....|
gi 568997330  610 DEVERETRSK 619
Cdd:COG4942   230 ARLEAEAAAA 239

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 49.01 E-value: 2.44e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  592 KRALEAKELARQQLREQLDEVERETRSKLQEIdvfNNQLKELREIHSKQQLQKQRSLEAA--RLKQKEQ---------ER 660
Cdd:PRK12704   31 AKIKEAEEEAKRILEEAKKEAEAIKKEALLEA---KEEIHKLRNEFEKELRERRNELQKLekRLLQKEEnldrklellEK 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  661 KSLELEKQKEDAQRRVQERDKQW--LEHVQQEEQPRPRK-----PHE---------EDRLKREDSVRKKEAEERAKpEMQ 724
Cdd:PRK12704  108 REEELEKKEKELEQKQQELEKKEeeLEELIEEQLQELERisgltAEEakeillekvEEEARHEAAVLIKEIEEEAK-EEA 186


                  ....*
gi 568997330  725 DKQSR 729
Cdd:PRK12704  187 DKKAK 191

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 43.44 E-value: 2.45e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVG--DKSGVFPSNYV 1072
Cdd:cd11780     2 YRALYSYTPQNEDELELREGDIVYVMEKCDDgWFVGTSErtGLFGTFPGNYV 53

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 43.48 E-value: 2.46e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568997330 1183 YTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12077     9 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 53

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 43.11 E-value: 2.51e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYV 983
Cdd:cd11796     1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFrGELNGRRGIFPEGFV 51

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 43.39 E-value: 2.52e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMV--DESQTGEPGWLGGELKG-KTGWFPANY 817
Cdd:cd11864     3 RAEYDFVAESEDELSFRAGDKLRLapKELQPRVRGWLLATVDGqKIGLVPANY 55

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 43.15 E-value: 2.53e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQarGKKrqiGWFPANYV 1150
Cdd:cd11806     4 AIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHN--GCC---GYIPASHL 51

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 43.44 E-value: 2.71e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTG-WFPANYAEKI 821
Cdd:cd11970     7 KALFDYKAQREDELTFTKNAIIQNVEKQEG--GWWRGDYGGKKQlWFPSNYVEEI 59

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 43.41 E-value: 2.75e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 986
Cdd:cd11919     2 PARAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYeGEHHGRVGIFPRSYIELL 55

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 43.45 E-value: 2.78e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIV-VTKKDGDWWTGTV--GDKSGVFPSNYVRL 1074
Cdd:cd11935     5 AMYDYSAQDEDEVSFRDGDYIVnVQPIDEGWMYGTVqrTGRTGMLPANYIEF 56

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 48.95 E-value: 2.91e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   366 EKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLE------RAEQERKERERQEQER---KRQLELE--- 433
Cdd:pfam05483  332 EKEAQMEELNKAKAAHSFVVTEFEATTCSLEELLRTEQQRLEKNEdqlkiiTMELQKKSSELEEMTKfknNKEVELEelk 411

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   434 -------------KQLEKQRELERQREEERRKEIERREAAKRELERQ-------------------RQLEWERNRRQEL- 480
Cdd:pfam05483  412 kilaedeklldekKQFEKIAEELKGKEQELIFLLQAREKEIHDLEIQltaiktseehylkevedlkTELEKEKLKNIELt 491

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   481 -----LNQRNKE---------------QEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIE-STNKS 539
Cdd:pfam05483  492 ahcdkLLLENKEltqeasdmtlelkkhQEDIINCKKQEERMLKQIENLEEKEMNLRDELESVREEFIQKGDEVKcKLDKS 571

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   540 RELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQnsLHRDS-LLTLKRALEAKELARQQLREQLDEVERE-TR 617
Cdd:pfam05483  572 EENARSIEYEVLKKEKQMKILENKCNNLKKQIENKNKNIEE--LHQENkALKKKGSAENKQLNAYEIKVNKLELELAsAK 649

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   618 SKLQEI-DVFNNQL--KELREIHSKQQLQKQRSL--EAARLkQKEQERKSLE--------LEKQKEDAQRRVQERDKQW- 683
Cdd:pfam05483  650 QKFEEIiDNYQKEIedKKISEEKLLEEVEKAKAIadEAVKL-QKEIDKRCQHkiaemvalMEKHKHQYDKIIEERDSELg 728

                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|.
gi 568997330   684 LEHVQQEEQPRPRKPHEED--RLKRE-DSVRKK---EAEERAKPEMQDKQS 728
Cdd:pfam05483  729 LYKNKEQEQSSAKAALEIElsNIKAElLSLKKQleiEKEEKEKLKMEAKEN 779

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 45.44 E-value: 3.05e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1615 LMVNVVEGIELKPCRShGKSNPYCEVTMGSQCHI----TKTIQDTLNPKWNSNCQF---------------FIRDLEQEV 1675
Cdd:cd08675     1 LSVRVLECRDLALKSN-GTCDPFARVTLNYSSKTdtkrTKVKKKTNNPRFDEAFYFeltigfsyekksfkvEEEDLEKSE 79

                          90       100
                  ....*....|....*....|....
gi 568997330 1676 LCITVFERDQFSPDDFLGrtEIRV 1699
Cdd:cd08675    80 LRVELWHASMVSGDDFLG--EVRI 101

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 47.01 E-value: 3.05e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   572 SDQLKQVQQNSLHRDSL------LTLKRALEAKELARQQLREQLDEVERETRSKLqeidvfnNQLKELREIHSKQQLQKQ 645
Cdd:pfam13904   38 LTYARKLEGLKLERQPLeayenwLAAKQRQRQKELQAQKEEREKEEQEAELRKRL-------AKEKYQEWLQRKARQQTK 110

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997330   646 RSLEAARLKQKEQERKSL---ELEKQKEDAQRRVQErdkQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEE 717
Cdd:pfam13904  111 KREESHKQKAAESASKSLakpERKVSQEEAKEVLQE---WERKKLEQQQRKREEEQREQLKKEEEEQERKQLAEK 182

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 43.22 E-value: 3.06e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPG-----GWWEGELQARgkkrqIGWFPANYV 1150
Cdd:cd12059     8 YEASAEDELTLRRGDRVEVLSKDSAvsgdeGWWTGKINDR-----VGIFPSNYV 56

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 42.90 E-value: 3.07e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMvdESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11961     3 KALYDYDAAEDNELSFFENDKII--NIEFVDDDWWLGECHGSRGLFPSNYVE 52

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 48.26 E-value: 3.13e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  363 QQPEKKlpvtfeDKKRENFERGSVElEKRRQALLEQQRKEQERLAQLERA-EQERKERERQEQERKRQLELEKQLEKQRE 441
Cdd:PRK09510   67 QQQQQK------SAKRAEEQRKKKE-QQQAEELQQKQAAEQERLKQLEKErLAAQEQKKQAEEAAKQAALKQKQAEEAAA 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  442 LERQREEER---RKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTlefELEALNDKKHQLEGK 518
Cdd:PRK09510  140 KAAAAAKAKaeaEAKRAAAAAKKAAAEAKKKAEAEAAKKAAAEAKKKAEAEAAAKAAAEAKK---KAEAEAKKKAAAEAK 216

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 43.03 E-value: 3.16e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1096 AQVIASYAATGPE-QLTLAPGQLILIRKK-----NPGGWWEGelqaRGKKRQIGWFPANYV 1150
Cdd:cd11771     2 CRALYDFTPENPEmELSLKKGDIVAVLSKtdplgRDSEWWKG----RTRDGRIGWFPSNYV 58

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 45.81 E-value: 3.17e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   379 ENFERGSVELEKRRQALLEQQRK--EQERLAQLE--RAEQERKERERQEQERKRQLELEKQLE----KQRELERQREEER 450
Cdd:pfam15346   26 EELEKRKDEIEAEVERRVEEARKimEKQVLEELEreREAELEEERRKEEEERKKREELERILEennrKIEEAQRKEAEER 105

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   451 RkeierreaakRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKAR-RKTLEFEL 505
Cdd:pfam15346  106 L----------AMLEEQRRMKEERQRREKEEEEREKREQQKILNKKNsRPKLSFSL 151

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212946 Cd Length: 61 Bit Score: 43.14 E-value: 3.17e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1176 QVIGMYDYTAQ----NDD---ELAFSKGQIINVLNKEDPD-WWKGEVSGQVGLFPSNYVK 1227
Cdd:cd12013     1 RMVALFDYDPResspNVDaevELSFRAGDIITVFGEMDEDgFYYGELNGQRGLVPSNFLE 60

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 43.14 E-value: 3.25e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWegeLQARGKKRQIGWFPANYVKL 1152
Cdd:cd11858     8 FAGSVANELSLKKDDIVYIVQKEDNGWW---LAKKLDESKEGWVPAAYLEE 55

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 42.86 E-value: 3.36e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGE-VQGQKGWFPKSYVKL 985
Cdd:cd11962     2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEdWWMGTnSKGESGLFPSNYVEL 54

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176070 [Multi-domain] Cd Length: 110 Bit Score: 44.61 E-value: 3.37e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1629 RSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSncQFFI-----RDLEQEVLCITVFERDQFSPDDFLGRTEI 1697
Cdd:cd08688    16 RSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNS--EWFRfevddEELQDEPLQIRVMDHDTYSANDAIGKVYI 87

Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are similar to the coiled-coil transcriptional coactivator protein coexpressed by Mus musculus (CoCoA/CALCOCO1). This protein binds to a highly conserved N-terminal domain of p160 coactivators, such as GRIP1, and thus enhances transcriptional activation by a number of nuclear receptors. CALCOCO1 has a central coiled-coil region with three leucine zipper motifs, which is required for its interaction with GRIP1 and may regulate the autonomous transcriptional activation activity of the C-terminal region.

Pssm-ID: 462303 [Multi-domain] Cd Length: 488 Bit Score: 48.35 E-value: 3.44e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   351 QRLPEEPSSEDEQQPEKKlpvtfedKKRENFERGSVELEKRRQALLEQQRKEQERLAQLE-------------RAEQER- 416
Cdd:pfam07888   83 AELKEELRQSREKHEELE-------EKYKELSASSEELSEEKDALLAQRAAHEARIRELEediktltqrvlerETELERm 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   417 KERERQEQERKRQLELEK---QLEKQRELERQREEERRKEIERREAAKRELERQrQLEWERNRRQELLNQRNKEQEGTVV 493
Cdd:pfam07888  156 KERAKKAGAQRKEEEAERkqlQAKLQQTEEELRSLSKEFQELRNSLAQRDTQVL-QLQDTITTLTQKLTTAHRKEAENEA 234

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   494 LKARRKTLEfelEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSReLRIAEIT-HLQQQLQESQQMLGRLIPEKQILs 572
Cdd:pfam07888  235 LLEELRSLQ---ERLNASERKVEGLGEELSSMAAQRDRTQAELHQAR-LQAAQLTlQLADASLALREGRARWAQERETL- 309

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   573 dqlkqvQQNS-LHRDSLLTLKRALeakelarQQLREQLDEvERETRSKL-----QEIDVFNNQLKElreihSKQQLQKQR 646
Cdd:pfam07888  310 ------QQSAeADKDRIEKLSAEL-------QRLEERLQE-ERMEREKLevelgREKDCNRVQLSE-----SRRELQELK 370

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 568997330   647 SleAARLKQKEQERksLELEKQkedaqrrvqerdkQWLEHVQQEEQ 692
Cdd:pfam07888  371 A--SLRVAQKEKEQ--LQAEKQ-------------ELLEYIRQLEQ 399

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 42.73 E-value: 3.49e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGGELKGKTGWFPANY 817
Cdd:cd11804     3 VAKHDFKATAEDELSFKKGSILKVLNMED-DPNWYKAELDGKEGLIPKNY 51

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 43.01 E-value: 3.53e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEV--QGQKGWFPKSYVK 984
Cdd:cd11939     1 QVQCVHPYVSQEPDELSLELADVLNILDKtDDGWIFGERlhDQERGWFPSSVVE 54

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 43.02 E-value: 3.62e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  765 VYYRALYPFESRSHDEITIQPGDIVMvDESQTGEPGWLGGEL-KGKTGWFPANYAE 819
Cdd:cd11997     2 VRVRALYDYTGQEADELSFKAGEELL-KIGEEDEQGWCKGRLlSGRIGLYPANYVE 56

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 42.79 E-value: 3.75e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIV-VTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11843     4 ALYDYEGQESDELSFKAGDILTkLEEEDEQgWCKGRLDGRVGLYPANYV 52

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212890 Cd Length: 52 Bit Score: 42.59 E-value: 3.75e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11957     1 EVKALCHHIATEPGQLSFNKGDILqVLSRADGDWLRCSLGPDSGLVPIAYV 51

Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85alpha interacts with activated FGFR3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212843 Cd Length: 75 Bit Score: 43.35 E-value: 3.79e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVD-------------ESQTGEPGWLGG--ELKGKTGWFPANYAEKI 821
Cdd:cd11910     4 YRALYDYKKEREEDIDLHLGDILTVNkgsllalgfsegqEARPEEIGWLNGynETTGERGDFPGTYVEYI 73

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 43.00 E-value: 3.83e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1183 YTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSG-----QVGLFPSNYVKL 1228
Cdd:cd11994     8 YVASGVEQLSLSPGQLILILKKNSSGWWLGELQArgkkrQKGWFPASHVKL 58

Extracytoplasmic sensor domain CHASE3 (specificity unknown) [Signal transduction mechanisms];

Pssm-ID: 444089 [Multi-domain] Cd Length: 530 Bit Score: 48.36 E-value: 3.92e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  379 ENFERGSVELEKRRQAL---LEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEK-------------QREL 442
Cdd:COG5278    79 EPYEEARAEIDELLAELrslTADNPEQQARLDELEALIDQWLAELEQVIALRRAGGLEAALALvrsgegkalmdeiRARL 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  443 ERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDI 522
Cdd:COG5278   159 LLLALALAALLLAAAALLLLLLALAALLALAELLLLALARALAALLLLLLLEAELAAAAALLAAAAALAALAALELLAAL 238

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  523 RCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELAR 602
Cdd:COG5278   239 ALALALLLAALLLALLAALALAALLAAALLALAALLLALAAAAALAAAAALELAAAEALALAELELELLLAAAAAAAAAA 318

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  603 QQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQ 682
Cdd:COG5278   319 AAAAAALAALLALALATALAAAAAALALLAALLAEAAAAAAEEAEAAAEAAAAALAGLAEVEAEGAAEAVELEVLAIAAA 398

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330  683 WLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSRLFHPHQEPAKLATQA 744
Cdd:COG5278   399 AAAAAAEAAAAAAAAAAASAAEALELAEALAEALALAEEEALALAAASSELAEAGAALALAA 460

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212845 [Multi-domain] Cd Length: 55 Bit Score: 42.60 E-value: 3.94e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWW----KGevSGQVGLFPSNYVKL 1228
Cdd:cd11912     5 LYDYTASGDDEVSISEGEEVTVLEPDDGSGWtkvrNG--SGEEGLVPTSYIEI 55

Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are similar to the coiled-coil transcriptional coactivator protein coexpressed by Mus musculus (CoCoA/CALCOCO1). This protein binds to a highly conserved N-terminal domain of p160 coactivators, such as GRIP1, and thus enhances transcriptional activation by a number of nuclear receptors. CALCOCO1 has a central coiled-coil region with three leucine zipper motifs, which is required for its interaction with GRIP1 and may regulate the autonomous transcriptional activation activity of the C-terminal region.

Pssm-ID: 462303 [Multi-domain] Cd Length: 488 Bit Score: 48.35 E-value: 4.01e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   387 ELEKRRQALLEQQRKEQERLAQL-ERAEQERKERERQEQERKRQL-----ELEKQLEKQRELERQREEERR------KEI 454
Cdd:pfam07888   45 ELLQAQEAANRQREKEKERYKRDrEQWERQRRELESRVAELKEELrqsreKHEELEEKYKELSASSEELSEekdallAQR 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   455 ERREAAKRELE------------RQRQLEWERNRRQELLNQRNKEQegtvvlkARRKTLEFELEALNDKKHQLEGKLQDI 522
Cdd:pfam07888  125 AAHEARIRELEediktltqrvleRETELERMKERAKKAGAQRKEEE-------AERKQLQAKLQQTEEELRSLSKEFQEL 197

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   523 RCRLA---TQRQEIESTnksrelrIAEITHlqqqlqesqqmlgrlipekQILSDQLKQVQQNSLHRDsLLTLKRALEAKE 599
Cdd:pfam07888  198 RNSLAqrdTQVLQLQDT-------ITTLTQ-------------------KLTTAHRKEAENEALLEE-LRSLQERLNASE 250

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   600 LARQQLREQLDEV--ERET------RSKLQEIDVfNNQLKE----LREIHSKQQLQKQRSLEAARLKQKEQERKSLELEK 667
Cdd:pfam07888  251 RKVEGLGEELSSMaaQRDRtqaelhQARLQAAQL-TLQLADaslaLREGRARWAQERETLQQSAEADKDRIEKLSAELQR 329

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   668 QKEDAQRRVQERDKQWLE--------HVQQEEQPRprkphEEDRLKREDSVRKKEAEERakpeMQDKQSRLFHPHQEPAK 739
Cdd:pfam07888  330 LEERLQEERMEREKLEVElgrekdcnRVQLSESRR-----ELQELKASLRVAQKEKEQL----QAEKQELLEYIRQLEQR 400

                          410
                   ....*....|..
gi 568997330   740 L--ATQAPWSTT 749
Cdd:pfam07888  401 LetVADAKWSEA 412

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 42.57 E-value: 4.07e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTG-TVGDKS--GVFPSNYVRLK 1075
Cdd:cd11872     3 VAIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGfSLRNKSlkGIFPKSYVHIK 56

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 42.69 E-value: 4.10e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEKI 821
Cdd:cd11920     4 RAVYDFKAQTSKELSFKKGDTVYI--LRKIDQNWYEGEHHGRVGIFPISYVEKL 55

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 42.71 E-value: 4.12e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11781     3 RALYPFKAQSAKELSLKKGDIIYIRRQiDKNWYEGEHNGRVGIFPASYV 51

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 42.70 E-value: 4.13e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGD--WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11978     4 IARYDFCARDMRELSLLKGDVVKIYTKMSTngWWRGEVNGRVGWFPSTYV 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 48.43 E-value: 4.15e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   388 LEKRRQALLEQQRKEQERLAQLERaEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELERQ 467
Cdd:TIGR00618  592 ITVRLQDLTEKLSEAEDMLACEQH-ALLRKLQPEQDLQDVRLHLQQCSQELALKLTALHALQLTLTQERVREHALSIRVL 670

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   468 RQLEWERNRRQELLNQRNKEQegtvvLKARRKTLEFELEALndkkHQLEGKLQDIRcrlaTQRQEIESTNKSRELRIAei 547
Cdd:TIGR00618  671 PKELLASRQLALQKMQSEKEQ-----LTYWKEMLAQCQTLL----RELETHIEEYD----REFNEIENASSSLGSDLA-- 735

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   548 thlqqqlqesqqmlgrlipekqilsdqlkqvQQNSLHRDSLltlkraLEAKELARQQLREQLDEVERETRSKLQEIDVfN 627
Cdd:TIGR00618  736 -------------------------------AREDALNQSL------KELMHQARTVLKARTEAHFNNNEEVTAALQT-G 777

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   628 NQLKEL-REIHSKQQLQKQRSLEAARLK-QKEQERKSLELEK--QKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDR 703
Cdd:TIGR00618  778 AELSHLaAEIQFFNRLREEDTHLLKTLEaEIGQEIPSDEDILnlQCETLVQEEEQFLSRLEEKSATLGEITHQLLKYEEC 857

                          330
                   ....*....|...
gi 568997330   704 LKREDSVRKKEAE 716
Cdd:TIGR00618  858 SKQLAQLTQEQAK 870

Src Homology 3 domain of Saccharomyces cerevisiae Nap1-binding protein 2 and similar fungal proteins; This subfamily includes Saccharomyces cerevisiae Nbp2 (Nucleosome assembly protein 1 (Nap1)-binding protein 2), Schizosaccharomyces pombe Skb5, and similar proteins. Nbp2 interacts with Nap1, which is essential for maintaining proper nucleosome structures in transcription and replication. It is also the binding partner of the yeast type II protein phosphatase Ptc1p and serves as a scaffolding protein that brings seven kinases in close contact to Ptc1p. Nbp2 plays a role many cell processes including organelle inheritance, mating hormone response, cell wall stress, mitotic cell growth at elevated temperatures, and high osmolarity. Skb5 interacts with the p21-activated kinase (PAK) homolog Shk1, which is critical for fission yeast cell viability. Skb5 activates Shk1 and plays a role in regulating cell morphology and growth under hypertonic conditions. Nbp2 and Skb5 contain an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212799 Cd Length: 55 Bit Score: 42.50 E-value: 4.53e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWW--KGEVSGQVGLFPSNYVKL 1228
Cdd:cd11865     1 RAVALYDFEPEHDNELGFAEGQILFILYKHGQGWLiaEDESGGKTGLVPEEFVSY 55

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 42.69 E-value: 4.55e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1027 MYTYESSEQGDLTFQQGDVIVVT-KKDGDWWTGTV---GDKSGVFPSNYVRL 1074
Cdd:cd11965     5 IYDCQADNDDELTFVEGEVIIVTgEEDQEWWIGHIegqPERKGVFPVSFVHI 56

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 42.67 E-value: 4.61e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQIgWFPANYVK 1151
Cdd:cd11970    12 YKAQREDELTFTKNAIIQNVEKQEGGWWRGDY---GGKKQL-WFPSNYVE 57

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212836 [Multi-domain] Cd Length: 59 Bit Score: 42.74 E-value: 4.63e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQD---MWW-FGEVQGQKGWFPKSYVKLIS 987
Cdd:cd11903     4 QTLYPFSSVTEEELNFEKGETMEVIEKPEndpEWWkCKNSRGQVGLVPKNYVVVLS 59

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 44.70 E-value: 4.74e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQ---DTLNPKWNSNCQFFIR--DLEQEVLCITVFERDQFS 1687
Cdd:cd08387    16 GILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKQSKihkKTLNPEFDESFVFEVPpqELPKRTLEVLLYDFDQFS 95

                          90
                  ....*....|....*
gi 568997330 1688 PDDFLGRTEIRVADI 1702
Cdd:cd08387    96 RDECIGVVELPLAEV 110

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 43.08 E-value: 4.91e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVRLK 1075
Cdd:cd11973    22 ALWDHVTMDDQELGFKAGDVIeVMDATNKEWWWGRVLDSEGWFPASFVRLR 72

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 42.69 E-value: 4.92e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQ---KGWFPKSYVKLI 986
Cdd:cd11965     1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQeWWIGHIEGQperKGVFPVSFVHIL 57

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 42.31 E-value: 4.92e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQ--DMWWFGE-VQGQKGWFPKSYV 983
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTITRQDvgDGWLEGRnSRGEVGLFPSSYV 53

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 48.30 E-value: 5.04e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   359 SEDEQQPEKklpvtfEDKKRENFER--------GSVELEKRRQALLEQQRKEQE----RLAQLERA--EQERKERERQE- 423
Cdd:pfam12128  207 EDDGVVPPK------SRLNRQQVEHwirdiqaiAGIMKIRPEFTKLQQEFNTLEsaelRLSHLHFGykSDETLIASRQEe 280

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   424 -QERKRQLELE-KQLEKQRELERQREEERRKEIERREAAKR-ELERqrqLEwERNRR--QELLNQRNKEQEgtvvlkaRR 498
Cdd:pfam12128  281 rQETSAELNQLlRTLDDQWKEKRDELNGELSAADAAVAKDRsELEA---LE-DQHGAflDADIETAAADQE-------QL 349

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   499 KTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKsrelriAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQv 578
Cdd:pfam12128  350 PSWQSELENLEERLKALTGKHQDVTAKYNRRRSKIKEQNN------RDIAGIKDKLAKIREARDRQLAVAEDDLQALES- 422

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   579 QQNSLHRDSLLTLKRALEAKELARQQLREQLDEV--ERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQK 656
Cdd:pfam12128  423 ELREQLEAGKLEFNEEEYRLKSRLGELKLRLNQAtaTPELLLQLENFDERIERAREEQEAANAEVERLQSELRQARKRRD 502

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....
gi 568997330   657 EQERKslelekqKEDAQRRVQERdKQWLEHVQQEEQPRPRKPHE 700
Cdd:pfam12128  503 QASEA-------LRQASRRLEER-QSALDELELQLFPQAGTLLH 538

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 42.67 E-value: 5.05e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1021 GEEFIAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKS--GVFPSNYVR 1073
Cdd:cd11917     4 GEPFQALYNYMPRNEDELELREGDVIDVMEKcDDGWFVGTSRRTKffGTFPGNYVK 59

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 42.36 E-value: 5.15e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESqtGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd11824     2 YSVLYDYTAQEDDELSISKGDVVAVIEK--GEDGWWTVERNGQKGLVPGTYLEK 53

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 42.39 E-value: 5.22e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANY 817
Cdd:cd11816     3 VARFDFEGEQEDELSFSEGDVITLKEYVGEE--WAKGELNGKIGIFPLNF 50

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 42.49 E-value: 5.51e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYV 983
Cdd:cd11833     4 ALYKFKPQENEDLEMRPGDKITLLDDSNEdWWKGKIEDRVGFFPANFV 51

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 42.31 E-value: 5.55e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMV-DESQTgepGWLGGELKGKTGWFPANY 817
Cdd:cd11963     5 RALYDFEAVEDNELTFKHGEIIIVlDDSDA---NWWKGENHRGVGLFPSNF 52

Afadin- and alpha -actinin-Binding; This family is found in mammals where it is localized at cell-cell adherens junctions, and in Sch. pombe and other fungi where it anchors spindle-pole bodies to spindle microtubules. It is a coiled-coil structure, and in pombe, it is required for anchoring the minus end of spindle microtubules to the centrosome equivalent, the spindle-pole body. The name ADIP derives from the family being composed of Afadin- and alpha -Actinin-Binding Proteins localized at Cell-Cell Adherens Junctions.

Pssm-ID: 463295 [Multi-domain] Cd Length: 151 Bit Score: 45.00 E-value: 5.62e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   570 ILSDQLKQVQQNSLHRDSLLTLKRALEAkELARQQ-----LREQLDEVERETRSKLQEIDVFNNQLKELREIHS--KQQL 642
Cdd:pfam11559   39 VIYELLQQRDRDLEFRESLNETIRTLEA-EIERLQskierLKTQLEDLERELALLQAKERQLEKKLKTLEQKLKneKEEL 117

                           90       100       110
                   ....*....|....*....|....*....|
gi 568997330   643 QKQRSLEAARLKQKEQE--RKSLELEKQKE 670
Cdd:pfam11559  118 QRLKNALQQIKTQFAHEvkKRDREIEKLKE 147

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212698 [Multi-domain] Cd Length: 54 Bit Score: 42.25 E-value: 5.76e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDpDWWKGEVS-GQVGLFPSN 1224
Cdd:cd11764     5 LYDFTARNSKELSVLKGEYLEVLDDSR-QWWKVRNSrGQVGYVPHN 49

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 42.69 E-value: 5.78e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEKI 821
Cdd:cd11972     7 AIYDYTKDKEDELSFQEGAIIYV--IKKNDDGWYEGVMNGVTGLFPGNYVESI 57

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 42.29 E-value: 5.95e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPG--GWWEGELqargkKRQIGWFPANYVK 1151
Cdd:cd11987     8 FEARSHDEITIQPGDIVMVDESQTGepGWLGGEL-----KGKTGWFPANYAE 54

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 42.29 E-value: 6.13e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12055     4 VAFSYLPQNEDELELKVGDIIeVVGEVEEGWWEGVLNGKTGMFPSNFIK 52

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 42.29 E-value: 6.13e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQargKKRQIGWFPANYVKLL 1153
Cdd:cd11916     5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSR---RTKQFGTFPGNYVKLL 58

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 42.31 E-value: 6.15e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQtGEpgWLGGELKGKTGWFPANY 817
Cdd:cd11992     2 YIALYPYSSSEPGDLTFNEGEEILVTQKD-GE--WWTGSIEDRTGIFPSNY 49

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 42.33 E-value: 6.34e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1028 YTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11901     8 FNYTAEREDELSLVKGTKVIVMEKCSDgWWRGSYNGQVGWFPSNYV 53

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 47.81 E-value: 6.58e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   351 QRLPEEPSSEDEQQPEKKLpvtfEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERA--EQERKERERQ--EQER 426
Cdd:pfam17380  438 RRLEEERAREMERVRLEEQ----ERQQQVERLRQQEEERKRKKLELEKEKRDRKRAEEQRRKilEKELEERKQAmiEEER 513

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   427 KRQLeLEKQLEKQRELerqreeerrkeIErreaakrELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKtlefeLE 506
Cdd:pfam17380  514 KRKL-LEKEMEERQKA-----------IY-------EEERRREAEEERRKQQEMEERRRIQEQMRKATEERSR-----LE 569

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 568997330   507 ALNDKKHQLegklqdircrlatqRQEIESTNKSRELRIA 545
Cdd:pfam17380  570 AMEREREMM--------------RQIVESEKARAEYEAT 594

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 42.10 E-value: 6.71e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKD-GDWWT-GTVGDKSGVFPSNY 1071
Cdd:cd11778     4 ALYDYEAQGDDEISIRVGDRIAVIRGDdGSGWTyGEINGVKGLFPTSY 51

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 42.11 E-value: 6.74e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1022 EEFIAMYTYESSEQGDLTFQQG-DVIVVTKKDGDWWTGTvgDK---SGVFPSNYVRLK 1075
Cdd:cd11905     1 EIVVAMYDFQPTEPHDLRLETGeEYVILEKNDVHWWKAR--DKygkEGYIPSNYVTGK 56

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 41.96 E-value: 6.76e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVK 1151
Cdd:cd11786     2 AKALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNG-----KQGFFPASYVQ 52

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 41.99 E-value: 6.93e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQTGepGW-LGGELKG-KTGWFPANYAE 819
Cdd:cd11858     2 YKALYDFAGSVANELSLKKDDIVYIVQKEDN--GWwLAKKLDEsKEGWVPAAYLE 54

Coiled-coil domain-containing protein 158; CCDC158 is a family of proteins found in eukaryotes. The function is not known.

Pssm-ID: 464943 [Multi-domain] Cd Length: 1112 Bit Score: 47.81 E-value: 6.98e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   392 RQALLEQQRKEQErlAQLER---AEQERKERERQEQERKR------QLELEKQLEKQRELERQREEERRKEIERREAAKR 462
Cdd:pfam15921  109 RQSVIDLQTKLQE--MQMERdamADIRRRESQSQEDLRNQlqntvhELEAAKCLKEDMLEDSNTQIEQLRKMMLSHEGVL 186

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   463 ELERQRQLEWERNRRQELLNQRNK-----EQEGTVVLKARRKtLEFELEALNDKKHQLEGKLQDIRCR-------LATQR 530
Cdd:pfam15921  187 QEIRSILVDFEEASGKKIYEHDSMstmhfRSLGSAISKILRE-LDTEISYLKGRIFPVEDQLEALKSEsqnkielLLQQH 265

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   531 QE-IESTNKSRELRIAEITHLQQQLQEsqqmlgrlipEKQILSDQLKQVQQNSLHRDSLLTlkRALEAKELARQQLREQL 609
Cdd:pfam15921  266 QDrIEQLISEHEVEITGLTEKASSARS----------QANSIQSQLEIIQEQARNQNSMYM--RQLSDLESTVSQLRSEL 333

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   610 DEVERETRSKLQEID----VFNNQLKELREIHSK---------QQLQKQrsleAARLKQKEQErksLELEKQKedaQRRV 676
Cdd:pfam15921  334 REAKRMYEDKIEELEkqlvLANSELTEARTERDQfsqesgnldDQLQKL----LADLHKREKE---LSLEKEQ---NKRL 403

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   677 QERDKQ---WLEHVQQEEQPRPRkphEEDRLKREDSVRKKEAE---ERAKPEMQDKQSRL 730
Cdd:pfam15921  404 WDRDTGnsiTIDHLRRELDDRNM---EVQRLEALLKAMKSECQgqmERQMAAIQGKNESL 460

Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces cerevisiae proteins BOI1 and BOI2, and similar proteins. They contain an N-terminal SH3 domain, a Sterile alpha motif (SAM), and a Pleckstrin homology (PH) domain at the C-terminus. BOI1 and BOI2 interact with the SH3 domain of Bem1p, a protein involved in bud formation. They promote polarized cell growth and participates in the NoCut signaling pathway, which is involved in the control of cytokinesis. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212819 Cd Length: 55 Bit Score: 41.93 E-value: 7.06e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMV--DESQTGEpGW-LGGELK-GKTGWFPANY 817
Cdd:cd11886     1 LLIVIHDFNARSEDELTLKPGDKIELieDDEEFGD-GWyLGRNLRtGETGLFPVVF 55

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 41.93 E-value: 7.20e-05

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 568997330  949 LNFNKSDVITVL-EQQDM---WWFGEVQGQKGWFPKSYV 983
Cdd:cd11884    16 LSFHKGDVIKLLpKEGPLdpgWLFGTLDGRSGAFPKEYV 54

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 42.13 E-value: 7.25e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIV-MVDESqtgEPGWLGGELKGKTGWFPANY 817
Cdd:cd11949     1 YVQALFDFDPQEDGELGFRRGDFIeVMDNS---DPNWWKGACHGQTGMFPRNY 50

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212997 Cd Length: 56 Bit Score: 42.02 E-value: 7.35e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGdIVMVDESQTGEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd12064     4 KALYACKAEHDSELSFTAG-TVFDNVHPSQEPGWLEGTLNGKTGLIPENYVE 54

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 41.80 E-value: 7.39e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGELK-GKTGWFPANY 817
Cdd:cd11845     2 YVALYDYEARTDDDLSFKKGDRLQILDDSDGD-WWLARHLStGKEGYIPSNY 52

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 41.92 E-value: 7.63e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLI-LIRKKNPGGWWEGELQaRGKKRqiGWFPANYVK 1151
Cdd:cd11779     4 KALYPHAAGGETQLSFEEGDVItLLGPEPRDGWHYGENE-RSGRR--GWFPIAYTE 56

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 41.71 E-value: 7.66e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1097 QVIA--SYAATGPEQLTLAPGQLILIRKKNPGGWWEGelQARGKkrqIGWFPANYVK 1151
Cdd:cd12046     1 QVVAlfSYEASQPEDLEFQKGDVILVLSKVNEDWLEG--QCKGK---IGIFPSAFVE 52

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 41.80 E-value: 7.69e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330  771 YPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANY 817
Cdd:cd12052     6 FDYKAQHEDELTITVGDIITKIKKDDG--GWWEGEIKGRRGLFPDNF 50

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 41.73 E-value: 8.13e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTG---TVGdKSGVFPSNYV 1072
Cdd:cd12005     3 VALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAqslTTG-QEGFIPFNFV 52

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 42.00 E-value: 8.15e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLI-LIRKKNPG---GWWEGELQARgkkrqIGWFPA 1147
Cdd:cd11762     1 LVRALYDYEAQSDEELSFPEGAIIrILRKDDNGvddGWWEGEFNGR-----VGVFPS 52

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 47.81 E-value: 8.16e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  366 EKKLPVTFEDKKRENFERGSVE-LEKRR-------QALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELE 433
Cdd:PTZ00266  456 EKKRIERLEREERERLERERMErIERERlererleRERLERDRLERDRLDRLERERVDRLERDRLEKARRNSYFLK 531

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 41.88 E-value: 8.27e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1026 AMYTYESSEQG-DLTFQQGDVIVVTKK------DGDWWTGTVGD-KSGVFPSNYV 1072
Cdd:cd11771     4 ALYDFTPENPEmELSLKKGDIVAVLSKtdplgrDSEWWKGRTRDgRIGWFPSNYV 58

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 41.58 E-value: 8.45e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANY 817
Cdd:cd11837     2 ATALYPWRAKKENHLSFAKGDIITVLEQQ--EMWWFGELEGGEEGWFPKSY 50

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 42.34 E-value: 8.68e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1179 GMYDYTAQNDDELAFSKGQIINVLNKEDP---DWWKGEVSGQVGLFPSNYVKLTTDM 1232
Cdd:cd12001     7 ALYDNVAESPDELSFRKGDIMTVLERDTQgldGWWLCSLHGRQGIVPGNRLKILVGM 63

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 41.53 E-value: 8.76e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPDWWK-GEVSGQVGLFPSNYVK 1227
Cdd:cd11849     5 LYDFKSAEPNTLSFSEGETFLLLERSNAHWWLvTNHSGETGYVPANYVK 53

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212856 [Multi-domain] Cd Length: 57 Bit Score: 41.83 E-value: 8.91e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSG--QVGLFPSNYVKL 1228
Cdd:cd11923     2 EAVAKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGtnRQGIFPVSYVEV 56

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212725 [Multi-domain] Cd Length: 59 Bit Score: 41.90 E-value: 8.91e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1174 VCQVIgmYDYTAQNDDELAFSKGQIINVLNKE---DPDWWKGEVS---GQVGLFPSNYV 1226
Cdd:cd11791     1 VLRVL--YPYTPQEEDELELVPGDYIYVSPEEldsSSDGWVEGTSwltGCSGLLPENYT 57

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 41.58 E-value: 9.24e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1097 QVIASYA--ATGPEQLTLAPGQLILIRKKNPGgWWEGELQargkKRQIGWFPANYVKL 1152
Cdd:cd11837     1 TATALYPwrAKKENHLSFAKGDIITVLEQQEM-WWFGELE----GGEEGWFPKSYVKE 53

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 42.00 E-value: 9.61e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11975     9 AVWDHVTMANRELAFKAGDVIkVLDASNKDWWWGQIDDEEGWFPASFVRL 58

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 41.80 E-value: 9.65e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330  939 YPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd12052     6 FDYKAQHEDELTITVGDIITKIKKDDGgWWEGEIKGRRGLFPDNFVR 52

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 47.53 E-value: 9.66e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   355 EEPSSED-EQQPEKKLPVTFE--DKKRENFERGSVELEKRRQALLEQQRKE----------QERLAQL--------ERAE 413
Cdd:pfam12128  591 DVPEWAAsEEELRERLDKAEEalQSAREKQAAAEEQLVQANGELEKASREEtfartalknaRLDLRRLfdekqsekDKKN 670

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   414 QERKERERQEQERKRQLELE-KQLEKQRELERQREEERrkeierreaaKRELERQRQLEWernrrQELLNQRnKEQEGTV 492
Cdd:pfam12128  671 KALAERKDSANERLNSLEAQlKQLDKKHQAWLEEQKEQ----------KREARTEKQAYW-----QVVEGAL-DAQLALL 734

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   493 V--LKARRKTLEFELEALN-DKKHQLEGKLQD--IRCRLATQRQEIESTNKSRELRIAEITHLQQQLQEsqqmlgRLIPE 567
Cdd:pfam12128  735 KaaIAARRSGAKAELKALEtWYKRDLASLGVDpdVIAKLKREIRTLERKIERIAVRRQEVLRYFDWYQE------TWLQR 808

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   568 KQILSDQLKQVQQNSLHRDSllTLKRALEAKELARQQL---REQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQK 644
Cdd:pfam12128  809 RPRLATQLSNIERAISELQQ--QLARLIADTKLRRAKLemeRKASEKQQVRLSENLRGLRCEMSKLATLKEDANSEQAQG 886

                          330       340
                   ....*....|....*....|....*.
gi 568997330   645 QRSLEAARLKQKEQERKSLELEKQKE 670
Cdd:pfam12128  887 SIGERLAQLEDLKLKRDYLSESVKKY 912

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 41.56 E-value: 9.83e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330  940 PWRAKKDNHLNFNKSDVITVLEQQ-DMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd12077     8 PYTSQGKDEIGFEKGVTVEVIQKNlEGWWYIRYLGKEGWAPASYLK 53

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212736 [Multi-domain] Cd Length: 52 Bit Score: 41.50 E-value: 9.98e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINV--LNKEDPDWWKGEVSGQVGLFPSNY 1225
Cdd:cd11802     5 LYDYDAEDSTELSLLADEVITVyeLPGMDEDYMMGERGSQRGKVPVAY 52

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 41.84 E-value: 1.01e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYVKLI 986
Cdd:cd11994     2 AQVTTAYVASGVEQLSLSPGQLILILKKNSSgWWLGELQArgkkrQKGWFPASHVKLL 59

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 41.52 E-value: 1.11e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF---GEVQGQKGWFPKSYVK 984
Cdd:cd11780     3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWFvgtSERTGLFGTFPGNYVA 54

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 46.96 E-value: 1.12e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  386 VELEKRRQALLEQQRKEQERLAQlERAEQERKeRERQEQERKRQLELEKQLEKQRELerqreeerrkeierreAAKRELE 465
Cdd:PRK02224  505 VEAEDRIERLEERREDLEELIAE-RRETIEEK-RERAEELRERAAELEAEAEEKREA----------------AAEAEEE 566

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  466 RQRQLEW--ERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQR---QEIEStnKSR 540
Cdd:PRK02224  567 AEEAREEvaELNSKLAELKERIESLERIRTLLAAIADAEDEIERLREKREALAELNDERRERLAEKRerkRELEA--EFD 644

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  541 ELRIAEithlqqqlqesqqmlgrLIPEKQILSDQLKQV----QQNSLHRDSLLTLKRALEAKELARQQLREQLDEVErET 616
Cdd:PRK02224  645 EARIEE-----------------AREDKERAEEYLEQVeeklDELREERDDLQAEIGAVENELEELEELRERREALE-NR 706


                  ....*
gi 568997330  617 RSKLQ 621
Cdd:PRK02224  707 VEALE 711

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 41.55 E-value: 1.12e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKDGD--WWTGTVGDKSGVFPSNYVRLK 1075
Cdd:cd11946     2 EAIAKYDFKATADDELSFKRGDILKVLNEECDqnWYKAELNGKDGFIPKNYIEMK 56

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 41.56 E-value: 1.15e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWegELQARGKKrqiGWFPANYVK 1151
Cdd:cd12076     5 VIYPYTARDQDEINLEKGAVVEVIQKNLEGWW--KIRYQGKE---GWAPASYLK 53

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 41.41 E-value: 1.17e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNpGGWWEGELQarGKKRQIGWFPANYVKL 1152
Cdd:cd11872     4 AIYNFQGDGEHQLSLQVGDTVQILEEC-EGWYRGFSL--RNKSLKGIFPKSYVHI 55

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 41.33 E-value: 1.18e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDeSQTGEPGWLGgELKGKTGWFPANYAE 819
Cdd:cd11813     3 KALLDFERHDDDELGFRKNDIITII-SQKDEHCWVG-ELNGLRGWFPAKFVE 52

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212736 [Multi-domain] Cd Length: 52 Bit Score: 41.12 E-value: 1.19e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM---WWFGEVQGQKGWFPKSY 982
Cdd:cd11802     1 KARVLYDYDAEDSTELSLLADEVITVYELPGMdedYMMGERGSQRGKVPVAY 52

Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. It has been shown to interact with CSF1R, c-Cbl, LAT, CD247, and Zap70. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212944 Cd Length: 55 Bit Score: 41.27 E-value: 1.21e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWT--GTVGDKSGVFPSNYV 1072
Cdd:cd12011     2 AVALCNFPSGGPTELSIRMGEQLTILSEDGDWWKvsSAVTGRECYIPSNYV 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 41.80 E-value: 1.22e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQDM----WWFGEVQGQKGWFPKSYVKLI-SGP 989
Cdd:cd12003     3 AKALYDNAAESPEELSFRRGDVLMVLKREHGslpgWWLCSLHGQQGIAPANRLRLLpTAP 62

Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212855 [Multi-domain] Cd Length: 58 Bit Score: 41.52 E-value: 1.24e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSG--QVGLFPSNYVKL 1228
Cdd:cd11922     2 EAIAKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGtsRQGIFPITYVDV 56

Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4) and similar proteins such as Formin Binding Protein 17 (FBP17) and FormiN Binding Protein 1-Like (FNBP1L), as well as yeast Bzz1 (or Bzz1p). CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. Bzz1 is also a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Members of this subfamily contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain as well as at least one C-terminal SH3 domain. Bzz1 contains a second SH3 domain at the C-terminus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212711 [Multi-domain] Cd Length: 55 Bit Score: 41.44 E-value: 1.24e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGELK-GKTGWFPANYA 818
Cdd:cd11777     3 KALYAFVGSSEGTISMTEGEKLSLVEEDKGD-GWTRVRRDtGEEGYVPTSYI 53

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 46.68 E-value: 1.25e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  505 LEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQEsqqmlgrlipekqiLSDQLKQVQQN-SL 583
Cdd:COG4717    48 LERLEKEADELFKPQGRKPELNLKELKELEEELKEAEEKEEEYAELQEELEE--------------LEEELEELEAElEE 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  584 HRDSLLTLKRALEAKELA--RQQLREQLDEVERETRSKLQEIDVFNNQLKELREIhSKQQLQKQRSLEAARLKQKEQERK 661
Cdd:COG4717   114 LREELEKLEKLLQLLPLYqeLEALEAELAELPERLEELEERLEELRELEEELEEL-EAELAELQEELEELLEQLSLATEE 192

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  662 SLE-LEKQKEDAQRRVQERDKQwLEHVQQEeqprpRKPHEEDRLKREDSVRKKEAEER 718
Cdd:COG4717   193 ELQdLAEELEELQQRLAELEEE-LEEAQEE-----LEELEEELEQLENELEAAALEER 244

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212969 Cd Length: 63 Bit Score: 41.63 E-value: 1.25e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1181 YDYTAQnDDE--------LAFSKGQIINVLNKEDPDWWK----GEVSGQ--VGLFPS 1223
Cdd:cd12036     6 FDYDPE-DDPyipcrelgLSFQKGDILHVISQEDPNWWQayreGEEDNQslAGLIPS 61

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 46.69 E-value: 1.26e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQALLEQQRKEQE---RLAQLERAEQERKERERQEQE-RKRQLELEKQLekqrelerqreeerrkeierreaaKR 462
Cdd:PRK12704   35 EAEEEAKRILEEAKKEAEaikKEALLEAKEEIHKLRNEFEKElRERRNELQKLE------------------------KR 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997330  463 ELERQRQLEwernRRQELLNQRNKEqegtvvLKARRKTLEFELEALNDKKHQLEGKLQDircrlatQRQEIES 535
Cdd:PRK12704   91 LLQKEENLD----RKLELLEKREEE------LEKKEKELEQKQQELEKKEEELEELIEE-------QLQELER 146

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins; This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212968 Cd Length: 62 Bit Score: 41.65 E-value: 1.27e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1177 VIGMYDYTAQNDD-------ELAFSKGQIINVLNKEDPDWWKGEV----SGQVGLFPS 1223
Cdd:cd12035     2 VRAQFDYDPSKDDlipcqqaGIAFKTGDILQIISKDDHNWWQARKpgasKEPAGLIPS 59

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 41.40 E-value: 1.28e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd11815     3 VVLHDFPAEHSDDLSLNSGEIVYLLEKiDTEWYRGKCKNTTGIFPANHVK 52

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 41.20 E-value: 1.28e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11824     1 KYSVLYDYTAQEDDELSISKGDVVAVIEKGEDgWWTVERNGQKGLVPGTYL 51

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176004 [Multi-domain] Cd Length: 108 Bit Score: 43.01 E-value: 1.33e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1636 PYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEV-LCITVFERDQFSPDDFLGRTEIRVADIKKDQGSKGPVTK 1714
Cdd:cd04039    28 PFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVYPHEKNFdIQFKVLDKDKFSFNDYVATGSLSVQELLNAAPQPDPETG 107

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 41.10 E-value: 1.33e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYVK 1151
Cdd:cd12021     3 RAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAKR-----GWVPASYLE 52

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212811 [Multi-domain] Cd Length: 54 Bit Score: 41.12 E-value: 1.33e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1181 YDYTAQNDDELAFSKGQIINVLNKEDPD-WWKGE--VSGQVGLFPSNY 1225
Cdd:cd11878     6 YDYRAQTPGELSFSKGDFFHVIGEEDQGeWYEATnpVTGKRGLVPKSY 53

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 43.42 E-value: 1.38e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCR-----SHGKSN-----PYCEVTMgSQCHI--TKTIQDTLNPKWNsncQFFIRDLEQ-EVLCIT 1679
Cdd:cd04014     4 GTLKIKICEAVDLKPTDwstrhAVPKKGsqlldPYVSIDV-DDTHIgkTSTKPKTNSPVWN---EEFTTEVHNgRNLELT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1680 VFERDQFSPDDFLGRTEIRVADIKKDQGSKgpvtKCLLLHEVPTGEIVVRLDLQ 1733
Cdd:cd04014    80 VFHDAAIGPDDFVANCTISFEDLIQRGSGS----FDLWVDLEPQGKLHVKIELK 129

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 41.39 E-value: 1.38e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1178 IGMYDYTAQNDDELAFSKGQIINVLNKEDpDWW----KGEVSGQV--GLFPSNYV 1226
Cdd:cd11847     3 KALWDFKARGDEELSFQAGDQFRIAERSG-DWWtalkLDRAGGVVaqGFVPNNYL 56

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 45.08 E-value: 1.38e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   389 EKRRQALLEQQRKEQERLAQLERAEQ-ERKERERQEQ--ERKRQLELEKQLEKQRELERQREEERRKEIERREAAkrELE 465
Cdd:pfam13904   63 AKQRQRQKELQAQKEEREKEEQEAELrKRLAKEKYQEwlQRKARQQTKKREESHKQKAAESASKSLAKPERKVSQ--EEA 140

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 568997330   466 RQRQLEWERNRRQELLNQRNKEQEgtvvLKARRKTLEFELEALNDKKHQ 514
Cdd:pfam13904  141 KEVLQEWERKKLEQQQRKREEEQR----EQLKKEEEEQERKQLAEKAWQ 185

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 41.53 E-value: 1.41e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLISGP 989
Cdd:cd11972     7 AIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYeGVMNGVTGLFPGNYVESIMHY 60

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 46.34 E-value: 1.49e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  597 AKELARQQlREQLDEVERETRSKLQEidvfNNQLKELREihsKQQLQKQRsleaarLKQKEQERKsLELEKQKEDAQRRV 676
Cdd:PRK09510   61 VEQYNRQQ-QQQKSAKRAEEQRKKKE----QQQAEELQQ---KQAAEQER------LKQLEKERL-AAQEQKKQAEEAAK 125

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  677 QERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKK---EAEERAKPEMQDKQ 727
Cdd:PRK09510  126 QAALKQKQAEEAAAKAAAAAKAKAEAEAKRAAAAAKKaaaEAKKKAEAEAAKKA 179

RIB43A; This family consists of several RIB43A-like eukaryotic proteins. Ciliary and flagellar microtubules contain a specialized set of protofilaments, termed ribbons, that are composed of tubulin and several associated proteins. RIB43A was first characterized in the unicellular biflagellate, Chlamydomonas reinhardtii although highly related sequences are present in several higher eukaryotes including humans. The function of this protein is unknown although the structure of RIB43A and its association with the specialized protofilament ribbons and with basal bodies is relevant to the proposed role of ribbons in forming and stabilising doublet and triplet microtubules and in organizing their three-dimensional structure. Human RIB43A homologs could represent a structural requirement in centriole replication in dividing cells.

Pssm-ID: 461780 [Multi-domain] Cd Length: 372 Bit Score: 46.04 E-value: 1.55e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   398 QQRKEQERLAQLERAEQERKER----------------ERQEQERKRQLELEKQLEKQRELERQREEERRKEIErreaaK 461
Cdd:pfam05914    1 VDLKEAAAIERRRQREEERKSRifnarnrtigvdvealDKQVEEKKRQEAAEKAREEAFAEEMVQNDKIALMLE-----K 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   462 RELERQRQLEwernrrQELLNQRNKEQEgtvvLKARRktlEFELEALNDKKHQLEGKL--QDIRCRLAT-QRQEIESTNk 538
Cdd:pfam05914   76 REEEDRRRLN------KELNEFRQQHQR----PETRR---EFDLNDPDALKKDLPARVsdDDPRCGPSSmQKFEGEDLN- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   539 sRELRIAEithlqqqlqesQQMLGRLIPEKQIlsDQLKQVQQNSLHRDSLLTLKRaleakeLARQQLREQLDEVERETRS 618
Cdd:pfam05914  142 -REERKKL-----------QQEQMREWLEQQI--EEKKQAEEEEKHAELLYDQKR------LERDRRALELAKLEEECRR 201

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   619 KL-QEIDVFN-NQLKELREihsKQQLQKQRSLEA----------------------------------------ARLK-- 654
Cdd:pfam05914  202 AVnAATKNFNqALAAEQAE---RRRLEKRQEQEDnlaeiynhltsdlltenpevaqsslgphrvipdrwkgmspEQLKei 278

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 568997330   655 QKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEqprpRKPHEEDRLKRE 707
Cdd:pfam05914  279 RKEQEQQREEKERRREEEKQRDAEWDRQRLELARAAL----LLEREQQRLRRE 327

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 41.07 E-value: 1.57e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDG---DWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11952     5 ALWDYSAEFPDELSFKEGDMVTVLRKDGegtDWWWASLCGREGYVPRNYFGL 56

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 41.13 E-value: 1.57e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF---GEVQGQKGWFPKSYVKLI 986
Cdd:cd11916     5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFvgtSRRTKQFGTFPGNYVKLL 58

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 41.16 E-value: 1.59e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPG-GWWEGElQARGKkrqIGWFPANYV 1150
Cdd:cd11763     2 VRALYDFDSQPSGELSLRAGEVLTITRQDVGdGWLEGR-NSRGE---VGLFPSSYV 53

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 41.10 E-value: 1.59e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVG--DKSGVFPSNYVRL 1074
Cdd:cd11924     2 EAVAQYTFKGDLEVELSFRKGEHICLIRKvNENWYEGRITgtGRQGIFPASYVQV 56

Cancer susceptibility candidate 1 N-terminus; This presumed domain is functionally uncharacterized. This domain family is found in eukaryotes, and is approximately 200 amino acids in length. The family is found in association with pfam12366. There are two completely conserved residues (N and W) that may be functionally important.

Pssm-ID: 464947 [Multi-domain] Cd Length: 201 Bit Score: 44.66 E-value: 1.63e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   397 EQQRKEQERLaQLERAEQERKERERQEQERKRQLE-----LEKQLEKqrelerqreEERRKEIERREAAKRELERQRQLE 471
Cdd:pfam15927    2 RLREEEEERL-RAEEEEAERLEEERREEEEEERLAaeqdrRAEELEE---------LKHLLEERKEALEKLRAEAREEAE 71


                   ...
gi 568997330   472 WER 474
Cdd:pfam15927   72 WER 74

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176011 [Multi-domain] Cd Length: 126 Bit Score: 43.04 E-value: 1.65e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1617 VNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLcITVFERDQFSpDDFLGRTE 1696
Cdd:cd04046     7 VHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIK-IQVWNSNLLC-DEFLGQAT 84


                  .
gi 568997330 1697 I 1697
Cdd:cd04046    85 L 85

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 41.18 E-value: 1.67e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11844     2 ARALYDNVAESPDELAFRRGDILTVLEQNtaglEGWWLCSLRGRQGIAPGNRLKL 56

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 41.23 E-value: 1.67e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMV--DESQTGEPGWLGGELKGKTGWFPA 815
Cdd:cd11762     1 LVRALYDYEAQSDEELSFPEGAIIRIlrKDDNGVDDGWWEGEFNGRVGVFPS 52

RIB43A; This family consists of several RIB43A-like eukaryotic proteins. Ciliary and flagellar microtubules contain a specialized set of protofilaments, termed ribbons, that are composed of tubulin and several associated proteins. RIB43A was first characterized in the unicellular biflagellate, Chlamydomonas reinhardtii although highly related sequences are present in several higher eukaryotes including humans. The function of this protein is unknown although the structure of RIB43A and its association with the specialized protofilament ribbons and with basal bodies is relevant to the proposed role of ribbons in forming and stabilising doublet and triplet microtubules and in organizing their three-dimensional structure. Human RIB43A homologs could represent a structural requirement in centriole replication in dividing cells.

Pssm-ID: 461780 [Multi-domain] Cd Length: 372 Bit Score: 46.04 E-value: 1.67e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   388 LEKRRQAllEQQRKEQ-----ER-----LAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQreeerrkeierr 457
Cdd:pfam05914    9 IERRRQR--EEERKSRifnarNRtigvdVEALDKQVEEKKRQEAAEKAREEAFAEEMVQNDKIALMLE------------ 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   458 eaaKRELERQRQLEWE----RNRRQELLNQRNKEQEGTVVLKARRKTLE--------------FELEALNDKKHQLEGKL 519
Cdd:pfam05914   75 ---KREEEDRRRLNKElnefRQQHQRPETRREFDLNDPDALKKDLPARVsdddprcgpssmqkFEGEDLNREERKKLQQE 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   520 QdIRCRLATQRQEIESTNKSRelRIAEITHlqqqlqesqqmlgrlipEKQILSDQLKQVQQNSLHRDSlltlKRALEA-- 597
Cdd:pfam05914  152 Q-MREWLEQQIEEKKQAEEEE--KHAELLY-----------------DQKRLERDRRALELAKLEEEC----RRAVNAat 207

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   598 ----KELARQQLREQLDEVERETRSKLQEI------DVFN-------------------------NQLKELREIHSKQQL 642
Cdd:pfam05914  208 knfnQALAAEQAERRRLEKRQEQEDNLAEIynhltsDLLTenpevaqsslgphrvipdrwkgmspEQLKEIRKEQEQQRE 287

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   643 QKQRSLEAARLKQKEQERKSLE-----LEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRK 697
Cdd:pfam05914  288 EKERRREEEKQRDAEWDRQRLElaraaLLLEREQQRLRRELRRQLDEENLQLAQEQKARQ 347

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 40.84 E-value: 1.69e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11806     4 AIADFVATDDSQLSFESGDKLLVLRKpSVDWWWAEHNGCCGYIPASHL 51

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 46.64 E-value: 1.72e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   465 ERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEfELEALNDK-KHQLEGKLQDircrlatQRQEIESTNKSREL- 542
Cdd:pfam05483   86 EAEKIKKWKVSIEAELKQKENKLQENRKIIEAQRKAIQ-ELQFENEKvSLKLEEEIQE-------NKDLIKENNATRHLc 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   543 --------RIAEITHLQQQLQESQQMLGRLIP---EKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDE 611
Cdd:pfam05483  158 nllketcaRSAEKTKKYEYEREETRQVYMDLNnniEKMILAFEELRVQAENARLEMHFKLKEDHEKIQHLEEEYKKEIND 237

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   612 VERETRSKLQEIDVFNNQLKE----LREIHSK-QQLQKQRSLEAARLKQKEQERKSL--ELEKQKEDAQRRVQ-----ER 679
Cdd:pfam05483  238 KEKQVSLLLIQITEKENKMKDltflLEESRDKaNQLEEKTKLQDENLKELIEKKDHLtkELEDIKMSLQRSMStqkalEE 317

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   680 DKQWL----------EHVQQEEQPRPRKPHE------------EDRLKREDSVRKKEAEERAK---PEMQDKQSRL 730
Cdd:pfam05483  318 DLQIAtkticqlteeKEAQMEELNKAKAAHSfvvtefeattcsLEELLRTEQQRLEKNEDQLKiitMELQKKSSEL 393

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 43.09 E-value: 1.75e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1615 LMVNVVEGIELKPCRSHGKSNPYCEVTM---GSQCHITKTIQDTLNPKWNSNCQF--F-IRDLEQEVLCITVFERDQFSP 1688
Cdd:cd08386    18 LTLKILKAVELPAKDFSGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFegFpYEKLQQRVLYLQVLDYDRFSR 97

                          90
                  ....*....|....*
gi 568997330 1689 DDFLGRTEIRVADIK 1703
Cdd:cd08386    98 NDPIGEVSLPLNKVD 112

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 40.87 E-value: 1.79e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESqtGEPGWLGGELK-------GKTGWFPANY 817
Cdd:cd11773     2 YKALYDYEPQTEDELTIQEDDILYLLEK--SDDDWWKVKLKvnssdddEPVGLVPATY 57

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 46.58 E-value: 1.83e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   388 LEKRRQALLEQQRKEQE---RLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKREL 464
Cdd:TIGR00606  188 LETLRQVRQTQGQKVQEhqmELKYLKQYKEKACEIRDQITSKEAQLESSREIVKSYENELDPLKNRLKEIEHNLSKIMKL 267

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   465 E------RQRQLEWErNRRQELLNQRNKEQEGTVvlkarrktlefelEALNDKKHQLEGKLQDIRCRLATQRQEIESTNK 538
Cdd:TIGR00606  268 DneikalKSRKKQME-KDNSELELKMEKVFQGTD-------------EQLNDLYHNHQRTVREKERELVDCQRELEKLNK 333

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   539 SRELRIAEIThlqqqlqesqqmlgRLIPEKQILSDQLKQVQQNSLHRDSlltlkraleakELARQQLREQLDEVERETRS 618
Cdd:TIGR00606  334 ERRLLNQEKT--------------ELLVEQGRLQLQADRHQEHIRARDS-----------LIQSLATRLELDGFERGPFS 388

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   619 KLQeIDVFNNQLKELREIHSKQQLQKQRSL-EAARLKQKEQErkslELEKQKEDAQRRVQ------ERDKQWLEHVQQEE 691
Cdd:TIGR00606  389 ERQ-IKNFHTLVIERQEDEAKTAAQLCADLqSKERLKQEQAD----EIRDEKKGLGRTIElkkeilEKKQEELKFVIKEL 463

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   692 QprPRKPHEEDRLKREDSVRKKE-----AEERAKPEMQDKQSRLFHPHQ---------EPAKLATQAPWSTTEKGPLTIS 757
Cdd:TIGR00606  464 Q--QLEGSSDRILELDQELRKAErelskAEKNSLTETLKKEVKSLQNEKadldrklrkLDQEMEQLNHHTTTRTQMEMLT 541

                          410       420       430
                   ....*....|....*....|....*....|
gi 568997330   758 AQESVKvvyYRALYPFESRSHDEITIQPGD 787
Cdd:TIGR00606  542 KDKMDK---DEQIRKIKSRHSDELTSLLGY 568

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 40.81 E-value: 1.83e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGG-ELKGKTGWFPANYAEK 820
Cdd:cd11761     6 VLYSYEAQRPDELTITEGEELEVIEDGDGD-GWVKArNKSGEVGYVPENYLQF 57

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. ITK is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, ITK plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, ITK is crucial for the development of T-helper(Th)2 effector responses. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212841 [Multi-domain] Cd Length: 56 Bit Score: 40.77 E-value: 1.85e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWK-GEVSGQVGLFPSNYV 1226
Cdd:cd11908     3 VIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRvQDKNGHEGYVPSSYL 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 41.10 E-value: 1.85e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVT-KKDGDWWTGTV-GD--KSGVFPSNYV 1072
Cdd:cd11966     4 ALYNCVADNPDELTFSEGEIIIVDgEEDKEWWIGHIdGEptRRGAFPVSFV 54

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 40.79 E-value: 1.89e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKL 1152
Cdd:cd11781     2 ARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGR-----VGIFPASYVEI 53

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212935 Cd Length: 57 Bit Score: 41.12 E-value: 1.90e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKED---PDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12002     5 LYDNVPECAEELAFRKGDILTVIEQNTgglEGWWLCSLHGRQGIAPGNRLKL 56

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 40.85 E-value: 1.94e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11809     1 EATAQFDYTGRSERELSFKKGDSLTLYRQvSDDWWRGQLNGQDGLVPHKYITL 53

Src homology 3 domain of Endophilin-B2; Endophilin-B2, also called SH3GLB2 (SH3-domain GRB2-like endophilin B2), is a cytoplasmic protein that interacts with the apoptosis inducer Bax. It is overexpressed in prostate cancer metastasis and has been identified as a cancer antigen with potential utility in immunotherapy. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain. The related protein endophilin-B1 interacts with amphiphysin 1 and dynamin 1 through its SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212877 Cd Length: 55 Bit Score: 40.75 E-value: 1.94e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINV--LNKEDPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd11944     5 LYDYEAADSSELALLADELITVysLPGMDPDWLIGERGNQKGKVPVTYLEL 55

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 45.57 E-value: 2.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  639 KQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRprkphEEDRLKREdsvRKKEAEER 718
Cdd:PRK09510   66 RQQQQQKSAKRAEEQRKKKEQQQAEELQQKQAAEQERLKQLEKERLAAQEQKKQAE-----EAAKQAAL---KQKQAEEA 137

                          90       100
                  ....*....|....*....|....*.
gi 568997330  719 AKPEMQDKQSRLFHPHQEPAKLATQA 744
Cdd:PRK09510  138 AAKAAAAAKAKAEAEAKRAAAAAKKA 163

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212935 Cd Length: 57 Bit Score: 40.74 E-value: 2.06e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQ----DMWWFGEVQGQKGWFPKSYVKLI 986
Cdd:cd12002     2 ARALYDNVPECAEELAFRKGDILTVIEQNtgglEGWWLCSLHGRQGIAPGNRLKLL 57

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 40.95 E-value: 2.09e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1094 EIAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWegelQARGKKRQIGWFPANYV 1150
Cdd:cd11905     1 EIVVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWW----KARDKYGKEGYIPSNYV 53

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 40.78 E-value: 2.09e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11874     1 RCKVLFSYTPQNEDELELKVGDTIEVLGEvEEGWWEGKLNGKVGVFPSNFVKE 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 40.77 E-value: 2.12e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1099 IASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYV 1150
Cdd:cd11982     6 VKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGR-----VGWFPSDCV 52

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 46.19 E-value: 2.29e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  375 DKKRENFErgsvELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEerrkei 454
Cdd:PRK02224  471 EEDRERVE----ELEAELEDLEEEVEEVEERLERAEDLVEAEDRIERLEERREDLEELIAERRETIEEKRERAE------ 540

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  455 eRREAAKRELERQRQlEWeRNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNdkkhqlegKLQDIRCRLATQRQEIE 534
Cdd:PRK02224  541 -ELRERAAELEAEAE-EK-REAAAEAEEEAEEAREEVAELNSKLAELKERIESLE--------RIRTLLAAIADAEDEIE 609

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  535 STNKSRElRIAEITHLqqqlqesqqmlgrlipEKQILSDQLKQVQQ--NSLHRDSLLTLKRALEAKELARQQLREQLDEV 612
Cdd:PRK02224  610 RLREKRE-ALAELNDE----------------RRERLAEKRERKREleAEFDEARIEEAREDKERAEEYLEQVEEKLDEL 672

                         250       260
                  ....*....|....*....|....*
gi 568997330  613 eRETRSKLQ-EIDVFNNQLKELREI 636
Cdd:PRK02224  673 -REERDDLQaEIGAVENELEELEEL 696

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 40.42 E-value: 2.32e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1022 EEFIAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGD-KSGVFPSNYV 1072
Cdd:cd11758     1 EYVRALFDFPGNDDEDLPFKKGEILTVIRKPEEqWWNARNSEgKTGMIPVPYV 53

Second Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212865 Cd Length: 57 Bit Score: 40.59 E-value: 2.37e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1174 VCQVIGMYDY----TAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11932     1 LCRALYNFDLkeknREESKDCLKFQKDDIITVISRVDENWAEGKLGDQVGIFPILFV 57

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 40.58 E-value: 2.37e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1094 EIAQVIASYAATGPEQLTLAPGQLILIRKKNPG--GWWEGELQarGKKrqiGWFPANYVKL 1152
Cdd:cd12056     2 EYCKALFHYEGTNEDELDFKEGEIILIISKDTGepGWWKGELN--GKE---GVFPDNFVSQ 57

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 40.55 E-value: 2.47e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGelqARGKKRQIGWFPANYVKL 1152
Cdd:cd11940     3 QCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEG---VRLSDGERGWFPQSHVEE 55

Second Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212865 Cd Length: 57 Bit Score: 40.59 E-value: 2.51e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1026 AMYTYE-----SSEQGD-LTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11932     4 ALYNFDlkeknREESKDcLKFQKDDIItVISRVDENWAEGKLGDQVGIFPILFV 57

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 40.55 E-value: 2.52e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGElqarGKKRQIGWFPANYVKL 1152
Cdd:cd11962     2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGT----NSKGESGLFPSNYVEL 54

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 40.68 E-value: 2.52e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVM----VDESqtgepgWLGGELKGKTGWFPANYAE 819
Cdd:cd11928     2 CGKALYSYEGKEPGDLKFNKGDIIIlrrkVDEN------WYHGELNGCHGFLPASYIQ 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 40.50 E-value: 2.55e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTK-KDGDWWTGTVGDKSGVFPS 1069
Cdd:cd11832     2 FIAVKSYSPQEEGEISLHKGDRVKVLSiGEGGFWEGSVRGRTGWFPS 48

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 can also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRSp53 has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212848 Cd Length: 59 Bit Score: 40.77 E-value: 2.56e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330  934 QAQALYPwRAKKDNH--LNFNKSDVITVL--EQQDMWWFGEVQGQK--GWFPKSYVKLI 986
Cdd:cd11915     2 RVQAIFS-HAAGDNStlLSFKEGDYITLLvpEARDGWHYGECEKTKmrGWFPFSYTRVL 59

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 42.32 E-value: 2.60e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1632 GKSNPYCEVTMGSQCHITKTIQDT-LNPKWNSNCQFFIRDLEQEV---LCITVFERDQFSPDDFLGRTEIRVADI 1702
Cdd:cd04049    20 GKIDPYVIIQCRTQERKSKVAKGDgRNPEWNEKFKFTVEYPGWGGdtkLILRIMDKDNFSDDDFIGEATIHLKGL 94

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 40.34 E-value: 2.61e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd12054     2 QCKVLFEYVPQNEDELELKVGDIIDINEEvEEGWWSGTLNGKSGLFPSNFVK 53

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 46.29 E-value: 2.65e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  352 RLPEEPSSEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALL---EQQRKEQERLAQLE-----RAEQERKERE--- 420
Cdd:PTZ00121 1581 RKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELkkaEEEKKKVEQLKKKEaeekkKAEELKKAEEenk 1660

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  421 -RQEQERKRQlELEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLnQRNKEQEGTVVLKARRK 499
Cdd:PTZ00121 1661 iKAAEEAKKA-EEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKKAEEL-KKAEEENKIKAEEAKKE 1738

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330  500 TLEFELEALNDKKHqlEGKLQDIRCRLATQRQEIESTNKSRELRIAE 546
Cdd:PTZ00121 1739 AEEDKKKAEEAKKD--EEEKKKIAHLKKEEEKKAEEIRKEKEAVIEE 1783

ribonuclease Y;

Pssm-ID: 178867 [Multi-domain] Cd Length: 535 Bit Score: 45.63 E-value: 2.66e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  595 LEAKELARQqLREqldEVERETRSKLQEIDVFNNQLKEL--------REIHSKQQL--QKQRSLEAARLKQKEQERKSLE 664
Cdd:PRK00106   75 LEAKEEARK-YRE---EIEQEFKSERQELKQIESRLTERatsldrkdENLSSKEKTleSKEQSLTDKSKHIDEREEQVEK 150

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  665 LEKQKEDAQRRVQErdkqwlehVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKpEMQDKQSR 729
Cdd:PRK00106  151 LEEQKKAELERVAA--------LSQAEAREIILAETENKLTHEIATRIREAEREVK-DRSDKMAK 206

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 40.37 E-value: 2.84e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK---DGDWWTGTVGDKSGVFPSNY 1071
Cdd:cd11987     4 ALYPFEARSHDEITIQPGDIVMVDESqtgEPGWLGGELKGKTGWFPANY 52

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 40.58 E-value: 2.86e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd12056     5 KALFHYEGTNEDELDFKEGEIILIISKdtgEPGWWKGELNGKEGVFPDNFVSQ 57

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 40.29 E-value: 2.88e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKLL 1153
Cdd:cd11921     9 FQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGR-----VGIFPANYVEVL 55

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 41.78 E-value: 2.94e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  1482 HSGKLYK-----AKSNKELYGFLFNDFLLLtqitkplgssgtdkvFSPKSNLQYKMYKTPIFLNEV-LVKLPTDPSGDEP 1555
Cdd:pfam00169    3 KEGWLLKkgggkKKSWKKRYFVLFDGSLLY---------------YKDDKSGKSKEPKGSISLSGCeVVEVVASDSPKRK 67

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 568997330  1556 -IFHISHID----RVYTLRAESINERTAWVQKIKAASE 1588
Cdd:pfam00169   68 fCFELRTGErtgkRTYLLQAESEEERKDWIKAIQSAIR 105

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212845 [Multi-domain] Cd Length: 55 Bit Score: 40.28 E-value: 2.98e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGEpGW----LGGelkGKTGWFPANYAE 819
Cdd:cd11912     3 KVLYDYTASGDDEVSISEGEEVTVLEPDDGS-GWtkvrNGS---GEEGLVPTSYIE 54

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 45.98 E-value: 2.99e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   375 DKKRENFERGSVELEKRRQALlEQQRKEQERLAQLERAEQERKERERQEQERKRQ------LELEKQLEKQRELERQREE 448
Cdd:pfam12128  400 AKIREARDRQLAVAEDDLQAL-ESELREQLEAGKLEFNEEEYRLKSRLGELKLRLnqatatPELLLQLENFDERIERARE 478

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   449 ERRKEIERREAAKRELERQRQLEWERNRR-----QELLNQRNKEQEGTVVLKARRKTLefeLEALNDKK---HQLEGKLQ 520
Cdd:pfam12128  479 EQEAANAEVERLQSELRQARKRRDQASEAlrqasRRLEERQSALDELELQLFPQAGTL---LHFLRKEApdwEQSIGKVI 555

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   521 D----IRCRLATQRQEI----ESTNKSRELRIAEITHlqqqlqesqqmlgrliPEKQILSDQLKqvQQNSLHRDSLLTLK 592
Cdd:pfam12128  556 SpellHRTDLDPEVWDGsvggELNLYGVKLDLKRIDV----------------PEWAASEEELR--ERLDKAEEALQSAR 617

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   593 RALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARlKQKEQERKSLelekqkeDA 672
Cdd:pfam12128  618 EKQAAAEEQLVQANGELEKASREETFARTALKNARLDLRRLFDEKQSEKDKKNKALAERK-DSANERLNSL-------EA 689

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330   673 QRRVQERD-KQWLEHVQQE------EQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQ 727
Cdd:pfam12128  690 QLKQLDKKhQAWLEEQKEQkreartEKQAYWQVVEGALDAQLALLKAAIAARRSGAKAELKA 751

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 40.40 E-value: 3.02e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEK 820
Cdd:cd12077     3 YVTVQPYTSQGKDEIGFEKGVTVEV--IQKNLEGWWYIRYLGKEGWAPASYLKK 54

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 40.03 E-value: 3.04e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKDGD--WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11804     1 EAVAKHDFKATAEDELSFKKGSILKVLNMEDDpnWYKAELDGKEGLIPKNYI 52

Nop53 (60S ribosomal biogenesis); This nucleolar family of proteins are involved in 60S ribosomal biogenesis. They are specifically involved in the processing beyond the 27S stage of 25S rRNA maturation. This family contains sequences that bear similarity to the glioma tumour suppressor candidate region gene 2 protein (p60). This protein has been found to interact with herpes simplex type 1 regulatory proteins.

Pssm-ID: 462259 [Multi-domain] Cd Length: 353 Bit Score: 44.98 E-value: 3.05e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   386 VELEKRRQALLEQQRKEQERLAQLERAEQERK------------ERERQEQERKRQLELEKQLEKqrelerqreeerrke 453
Cdd:pfam07767  209 KKRLKEEEKLERVLEKIAESAATAEAREEKRKtkaqrnkekrrkEEEREAKEEKALKKKLAQLER--------------- 273

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 568997330   454 ierreaAKRELERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRK 499
Cdd:pfam07767  274 ------LKEIAKEIAEKEKEREEKAEARKREKRKKKKEEKKLRPRK 313

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 40.36 E-value: 3.07e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTV--GDKSGVFPSNYVRL 1074
Cdd:cd11916     6 ALYSYAPQNDDELELRDGDIVDVMEKcDDGWFVGTSrrTKQFGTFPGNYVKL 57

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 40.36 E-value: 3.09e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGG-ELKGKTGWFPANYAE 819
Cdd:cd11897     3 RALYDFRSENPGEISLREHEVLSLCSEQDIE-GWLEGvNSRGDRGLFPASYVE 54

Crescentin protein; This entry represents a bacterial equivalent to Intermediate Filament proteins, named crescentin, whose cytoskeletal function is required for the vibrioid and helical shapes of Caulobacter crescentus. Without crescentin, the cells adopt a straight-rod morphology. Crescentin has characteriztic features of IF proteins including the ability to assemble into filaments in vitro without energy or cofactor requirements. In vivo, crescentin forms a helical structure that colocalizes with the inner cell curvatures beneath the cytoplasmic membrane.

Pssm-ID: 437057 [Multi-domain] Cd Length: 401 Bit Score: 45.06 E-value: 3.14e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   375 DKKRENFERGSVELEKRRQALLEQQRKEQERLAQLE--RAEQERKERERQEQERkRQLELEKQLEKQRELERQREEERRK 452
Cdd:pfam19220   30 SQLIEPIEAILRELPQAKSRLLELEALLAQERAAYGklRRELAGLTRRLSAAEG-ELEELVARLAKLEAALREAEAAKEE 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   453 ---EIERREAAKRELERQRQLEWERNRrqellnqrnkeqegtvVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQ 529
Cdd:pfam19220  109 lriELRDKTAQAEALERQLAAETEQNR----------------ALEEENKALREEAQAAEKALQRAEGELATARERLALL 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   530 RQEIESTNKSRE---LRIAEIThlqqqlQESQQMLGRLIPEKQILSDQLKQ-VQQNSLHRDSLLTLKRALEAKELARQQL 605
Cdd:pfam19220  173 EQENRRLQALSEeqaAELAELT------RRLAELETQLDATRARLRALEGQlAAEQAERERAEAQLEEAVEAHRAERASL 246

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   606 REQLDEVERETRSKLQEIDVFNNQLKELREihskqqlqKQRSLEaARLKQKEQERKSLE-----LEKQKEDAQRRVQERD 680
Cdd:pfam19220  247 RMKLEALTARAAATEQLLAEARNQLRDRDE--------AIRAAE-RRLKEASIERDTLErrlagLEADLERRTQQFQEMQ 317


                   ....*
gi 568997330   681 KQWLE 685
Cdd:pfam19220  318 RARAE 322

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 40.19 E-value: 3.16e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1028 YTYESSEQGdLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11829     8 FTGEQHQQG-LSFEAGELIRVLQApDGGWWEGEKDGLRGWFPASYV 52

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 40.34 E-value: 3.22e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMV---DESqtgepGWLGGEL-----KGKTGWFPANY 817
Cdd:cd11883     3 VALYDFTPKSKNQLSFKAGDIIYVlnkDPS-----GWWDGVIisssgKVKRGWFPSNY 55

Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. It has been shown to interact with CSF1R, c-Cbl, LAT, CD247, and Zap70. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212944 Cd Length: 55 Bit Score: 40.11 E-value: 3.23e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNkEDPDWWK--GEVSGQVGLFPSNYV 1226
Cdd:cd12011     1 VAVALCNFPSGGPTELSIRMGEQLTILS-EDGDWWKvsSAVTGRECYIPSNYV 52

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 40.38 E-value: 3.26e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1101 SYAATGPEQLTLAPGQLILIRKKNPG--GWWEGELQARgkkrqIGWFPANYVK 1151
Cdd:cd11977     8 NFAARDMRELSLREGDVVRIYSRIGGdqGWWKGETNGR-----IGWFPSTYVE 55

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212869 Cd Length: 62 Bit Score: 40.41 E-value: 3.28e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVM---VDESQTGEpGWLGGE--LKGKTGWFPANYAEK 820
Cdd:cd11936     5 QVIYPYTPQNDDELELVPGDYIFmspMEQTSTSE-GWIYGTslTTGCSGLLPENYITK 61

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 40.20 E-value: 3.30e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 984
Cdd:cd11870     1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLeGHSDGRVGIFPKCFVV 52

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 39.98 E-value: 3.54e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1101 SYAATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYV 1150
Cdd:cd11772     7 DYEAQHPDELSFEEGDLLYISDKSDPNWWKATC--GGKT---GLIPSNYV 51

biotin carboxyl carrier protein of acetyl-CoA carboxylase

Pssm-ID: 215533 [Multi-domain] Cd Length: 274 Bit Score: 44.44 E-value: 3.58e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  155 PVPMGSIPVVGMSPPLVSSVPPAAvPPLANGAPPVIQPLPAFAHP---AATLPKSS----------SFSRS-GPGS---- 216
Cdd:PLN02983  142 PQPPPPAPVVMMQPPPPHAMPPAS-PPAAQPAPSAPASSPPPTPAsppPAKAPKSShpplkspmagTFYRSpAPGEppfv 220

                          90
                  ....*....|
gi 568997330  217 QLNTKLQKAQ 226
Cdd:PLN02983  221 KVGDKVQKGQ 230

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 39.93 E-value: 3.58e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYV 1150
Cdd:cd11984     5 AVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRT-----GWFPADCV 52

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 45.44 E-value: 3.62e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  376 KKRENFERGSVELEKRRQALLEQQRKEQE-RLAQLER-----AEQERKERERQEQERKRQLELEKQLEKqrelerqrEEE 449
Cdd:PRK03918  171 IKEIKRRIERLEKFIKRTENIEELIKEKEkELEEVLReineiSSELPELREELEKLEKEVKELEELKEE--------IEE 242

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  450 RRKEIERREAAKRELE-RQRQLEwernRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLAT 528
Cdd:PRK03918  243 LEKELESLEGSKRKLEeKIRELE----ERIEELKKEIEELEEKVKELKELKEKAEEYIKLSEFYEEYLDELREIEKRLSR 318

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  529 QRQEIESTNK------SRELRIAEITHLQQQLQESQQMlgrlIPEKQILSDQLKQVQQNSLHRDSLLT------LKRALE 596
Cdd:PRK03918  319 LEEEINGIEErikeleEKEERLEELKKKLKELEKRLEE----LEERHELYEEAKAKKEELERLKKRLTgltpekLEKELE 394

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  597 AKELARQQLREQLDEVERETRSKLQEIDVFNNQLKEL-----------REI--HSKQQLQKQRSLEaarLKQKEQERKsl 663
Cdd:PRK03918  395 ELEKAKEEIEEEISKITARIGELKKEIKELKKAIEELkkakgkcpvcgRELteEHRKELLEEYTAE---LKRIEKELK-- 469

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  664 ELEKQKEDAQRRVQERDKqwlehvQQEEQPRPRKPHE--------EDRLKredSVRKKEAEERAK 720
Cdd:PRK03918  470 EIEEKERKLRKELRELEK------VLKKESELIKLKElaeqlkelEEKLK---KYNLEELEKKAE 525

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 40.20 E-value: 3.63e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWEGelQARGKkrqIGWFPANYVKLL 1153
Cdd:cd12073     9 YQGEGDDEISFDPQETITDIEMVDEGWWKG--TCHGH---RGLFPANYVELL 55

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 39.99 E-value: 3.68e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11920     5 AVYDFKAQTSKELSFKKGDTVYILRKiDQNWYEGEHHGRVGIFPISYV 52

DNA polymerase III subunits gamma and tau; Provisional

Pssm-ID: 184923 [Multi-domain] Cd Length: 624 Bit Score: 45.44 E-value: 3.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   66 DQARNFFFQSglPQPVLAQIWALADMNNDGR---MDQVEFSIAMKLIKLKLqgyqlpSTLPPVMKQQ----------PVA 132
Cdd:PRK14959  311 DEARQWLGWA--KRFEPAHIHACWQMTLEGQrrvLTSLEPAMALELLLLNL------AMLPRLMPVEslrpsgggasAPS 382

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  133 ISSAPAFGIGGIASMPPLTAVApvPMGSIPVVGMSPplvSSVPPAAVPPLANGAPPV----IQPLPAF----AHPAATLP 204
Cdd:PRK14959  383 GSAAEGPASGGAATIPTPGTQG--PQGTAPAAGMTP---SSAAPATPAPSAAPSPRVpwddAPPAPPRsgipPRPAPRMP 457


                  ....
gi 568997330  205 KSSS 208
Cdd:PRK14959  458 EASP 461

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212955 [Multi-domain] Cd Length: 53 Bit Score: 39.82 E-value: 3.75e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1182 DYTAQNDDELAFSKGQIINVLNKEDPDWW---KGEVSgqvGLFPSNYVK 1227
Cdd:cd12022     7 AYTAVEEDELTLLEGEAIEVIHKLLDGWWvvrKGEVT---GYFPSMYLQ 52

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 42.17 E-value: 3.75e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1632 GKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLcITVFERD---------QFS--PDDFLGRTEIRV 1699
Cdd:cd04027    20 GTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIK-VRVWDEDddiksrlkqKFTreSDDFLGQTIIEV 97

putative mechanosensitive channel protein; Provisional

Pssm-ID: 236798 [Multi-domain] Cd Length: 1109 Bit Score: 45.43 E-value: 3.77e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  351 QRLPEEPSSEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQ--ERLAQLERaeqerkererQEQERKR 428
Cdd:PRK10929   82 AELRQQLNNERDEPRSVPPNMSTDALEQEILQVSSQLLEKSRQAQQEQDRAREisDSLSQLPQ----------QQTEARR 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  429 QL-ELEKQLEKQRELERQREEERRKEIERREAAKR----ELERQrQLEweRNRRQELLNQRnkeqegtvvlkarrktlef 503
Cdd:PRK10929  152 QLnEIERRLQTLGTPNTPLAQAQLTALQAESAALKalvdELELA-QLS--ANNRQELARLR------------------- 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  504 eLEALNDKKHQLEGKLQDIRCRLATQRQ-EIESTNKSRELrIAEithlqqqlqesqqMLGRLiPEkqILSDQLKQVQQNS 582
Cdd:PRK10929  210 -SELAKKRSQQLDAYLQALRNQLNSQRQrEAERALESTEL-LAE-------------QSGDL-PK--SIVAQFKINRELS 271

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  583 L------HRDSLLTLKRALEAKEL--ARQQL---REQ---------LDEVERETRSKLQEI---DVFNNQLKELR--EIH 637
Cdd:PRK10929  272 QalnqqaQRMDLIASQQRQAASQTlqVRQALntlREQsqwlgvsnaLGEALRAQVARLPEMpkpQQLDTEMAQLRvqRLR 351

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|.
gi 568997330  638 SKQQLQKQRSLEaarlKQKEQERKSLELEKQK-EDAQRRVQ 677
Cdd:PRK10929  352 YEDLLNKQPQLR----QIRQADGQPLTAEQNRiLDAQLRTQ 388

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212731 Cd Length: 50 Bit Score: 39.71 E-value: 3.81e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFP 814
Cdd:cd11797     1 YGVALYRFQALEPNELDFEVGDRIRI--IATLEDGWLEGELKGRRGIFP 47

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 39.99 E-value: 3.82e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLE-QQDMWWFGE-VQGQKGWFPKSYVKL 985
Cdd:cd11770     4 ALSDFQAEQEGDLSFKKGEVLRIISkRADGWWLAEnSKGNRGLVPKTYLKV 54

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 40.00 E-value: 3.88e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQD----MWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11954     3 VYALWDYEAQNADELSFQEGDAITILRRKDdsetEWWWARLNDKEGYVPKNLLGL 57

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212948 Cd Length: 53 Bit Score: 39.71 E-value: 3.93e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWW----EGELqargkkrqiGWFPANY 1149
Cdd:cd12015     4 VVADYKKQQPNEISLRAGDVVDVIEKNENGWWfvslEDEQ---------GWVPATY 50

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 40.01 E-value: 4.08e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILI-RKKNPGGWWEGELQARgkkrqIGWFPANYVK 1151
Cdd:cd11978     2 IAIARYDFCARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGR-----VGWFPSTYVE 54

Coiled-coil domain-containing protein 158; CCDC158 is a family of proteins found in eukaryotes. The function is not known.

Pssm-ID: 464943 [Multi-domain] Cd Length: 1112 Bit Score: 45.49 E-value: 4.11e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   353 LPEEPSSEDEQQP--EKKLPVTFEDKKREN--FERGSVELE----KRRQALLEQQRKEQERLAQLER----AEQE----R 416
Cdd:pfam15921  283 LTEKASSARSQANsiQSQLEIIQEQARNQNsmYMRQLSDLEstvsQLRSELREAKRMYEDKIEELEKqlvlANSElteaR 362

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   417 KERERQEQERKrqlELEKQLEKqrelerqreeerrkeierREAAKRELERQRQLEWERNRRqelLNQRNKEQEGTVvlka 496
Cdd:pfam15921  363 TERDQFSQESG---NLDDQLQK------------------LLADLHKREKELSLEKEQNKR---LWDRDTGNSITI---- 414

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   497 rrKTLEFELEALNDKKHQLEGKLQDIR--CRLATQRQ--EIESTNKSRElRIAEIThlqQQLQESQQMLGRLIPE----K 568
Cdd:pfam15921  415 --DHLRRELDDRNMEVQRLEALLKAMKseCQGQMERQmaAIQGKNESLE-KVSSLT---AQLESTKEMLRKVVEEltakK 488

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   569 QILSDQLKQVQQNSLhrdSLLTLKRALEAKELARQQLREQLDeveretrSKLQEIDVFNNQLKELREIhskqqlqkQRSL 648
Cdd:pfam15921  489 MTLESSERTVSDLTA---SLQEKERAIEATNAEITKLRSRVD-------LKLQELQHLKNEGDHLRNV--------QTEC 550

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   649 EAARLKQKEQERKSLELEKQKEDAQRRVQERDKQ----WLEHVQQEEQPRPRKPHEED----RLKREDSVRKKEAE 716
Cdd:pfam15921  551 EALKLQMAEKDKVIEILRQQIENMTQLVGQHGRTagamQVEKAQLEKEINDRRLELQEfkilKDKKDAKIRELEAR 626

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 44.75 E-value: 4.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  391 RRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQlELEKQLEKQRelerqreeerrkeierreaakrelERQRQL 470
Cdd:COG4942   136 RRLQYLKYLAPARREQAEELRADLAELAALRAELEAERA-ELEALLAELE------------------------EERAAL 190

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  471 EWERNRRQELLNQrnkeqegtvvLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSR 540
Cdd:COG4942   191 EALKAERQKLLAR----------LEKELAELAAELAELQQEAEELEALIARLEAEAAAAAERTPAAGFAA 250

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 39.76 E-value: 4.25e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKrqiGWFPANYVK 1151
Cdd:cd11785     3 RVIVPYPPQSEAELELKEGDIVFVHKKREDGWFKGTLQRTGKT---GLFPGSFVE 54

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 40.00 E-value: 4.25e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKK---DGDWWTGTVGDKSGVFPSNYVrlkDSEG 1079
Cdd:cd11977     4 VARYNFAARDMRELSLREGDVVRIYSRiggDQGWWKGETNGRIGWFPSTYV---EEEG 58

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 39.94 E-value: 4.29e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1021 GEEFIAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTV--GDKSGVFPSNYV 1072
Cdd:cd11918     1 RTPYKAVYQYRPQNEDELELREGDRVDVMQQcDDGWFVGVSrrTQKFGTFPGNYV 55

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 39.99 E-value: 4.40e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKK---DGDWW-----TGTVgdksGVFPSNYV 1072
Cdd:cd11767     3 VALYPFTGENDEELSFEKGERLEIIEKpedDPDWWkarnaLGTT----GLVPRNYV 54

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 39.70 E-value: 4.47e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGepgWLGGELKGKTGWFPANYAE 819
Cdd:cd11989     3 QALYPWRAKKDNHLNFNKNDVITVLEQQDM---WWFGEVQGQKGWFPKSYVK 51

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 39.76 E-value: 4.49e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKkrqIGWFPANYV 1150
Cdd:cd11784     4 ALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLSLVTGR---VGIFPSNYV 53

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 39.82 E-value: 4.89e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  933 LQAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11956     2 VEAVACFDYTGRTAQELSFKRGDVLLLHSKASSdWWRGEHNGMRGLIPHKYISV 55

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 39.91 E-value: 4.91e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLE---QQDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11952     5 ALWDYSAEFPDELSFKEGDMVTVLRkdgEGTDWWWASLCGREGYVPRNYFGL 56

Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a single domain protein that adopts a SH3 domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. MIA is a member of the recently identified family that also includes MIA-like (MIAL), MIA2, and MIA3 (also called TANGO); the biological functions of this family are not yet fully understood.

Pssm-ID: 212694 Cd Length: 76 Bit Score: 40.16 E-value: 4.93e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNK---EDPDWWKGEVSGQ---VGLFPSNYVK 1227
Cdd:cd11760    17 LEDYHGPDCRFLNFKKGDTIYVYSKlagERQDLWAGSVGGDaglFGYFPKNLVQ 70

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 39.56 E-value: 5.05e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  768 RALYPFESRSHDEITIQPGDIV----MVDESqtgepgWLGGELKGKTGWFPANYAEKI 821
Cdd:cd11919     4 RAKFDFKAQTLKELPLQKGDIVyiykQIDQN------WYEGEHHGRVGIFPRSYIELL 55

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 39.71 E-value: 5.18e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1095 IAQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGElqARGkkrQIGWFPANYVKL 1152
Cdd:cd11959     1 TAVALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGV--CRG---KYGLFPANYVEL 53

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 39.55 E-value: 5.31e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11995     5 GMYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGELNGQVGLFPSNYVK 53

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 39.39 E-value: 5.31e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11947     1 EARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAELNGEEGYVPKNFV 50

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 39.56 E-value: 5.39e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK-----DGDWWTGTVGDKSGVFPS 1069
Cdd:cd11895     4 ALYSYTGQSPEELSFPEGALIRLLPRaqdgvDDGFWRGEFGGRVGVFPS 52

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 42.34 E-value: 5.58e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   374 EDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLE------LEKQLEKQRELERQre 447
Cdd:pfam05672   25 EQREREEQERLEKEEEERLRKEELRRRAEEERARREEEARRLEEERRREEEERQRKAEeeaeerEQREQEEQERLQKQ-- 102

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   448 eerrkeierreaaKRELERQRQLEWERNRR-QELLNQRNkEQEGTvvlkARRKTLE 502
Cdd:pfam05672  103 -------------KEEAEAKAREEAERQRQeREKIMQQE-EQERL----ERKKRIE 140

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 39.30 E-value: 5.60e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGelqaRGKKRQIGWFPANYVKL 1152
Cdd:cd11960     2 ARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRG----TGPDGTYGLFPANYVEL 54

Flagellar biosynthesis chaperone FliJ [Cell motility];

Pssm-ID: 442129 [Multi-domain] Cd Length: 142 Bit Score: 41.81 E-value: 5.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  591 LKRALEAKELARQQLrEQLDEVERETRSKLQE-----IDV--------FNNQLKELREIHSKQQLQKQRSLEAAR--LKQ 655
Cdd:COG2882    25 LGQAQQALEQAEEQL-EQLEQYREEYEQRLQQklqqgLSAaqlrnyqqFIARLDEAIEQQQQQVAQAEQQVEQARqaWLE 103

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568997330  656 KEQERKSLE--LEKQKEDAQRRVQERDKQWL-EHVQQ 689
Cdd:COG2882   104 ARQERKALEklKERRREEERQEENRREQKELdELASR 140

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 44.91 E-value: 5.75e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  588 LLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHSKQQLQK----QRSLEAARLKQKEQERKSL 663
Cdd:COG4913   283 LWFAQRRLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQIRGNGGDRleqlEREIERLERELEERERRRA 362

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  664 ELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLkREDSVRKKEAEERAKPEMQDKQSRL 730
Cdd:COG4913   363 RLEALLAALGLPLPASAEEFAALRAEAAALLEALEEELEAL-EEALAEAEAALRDLRRELRELEAEI 428

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 39.40 E-value: 5.81e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANY 817
Cdd:cd11951     1 FVQAQYDFSAEDPSQLSFRRGDIIEVLDCP--DPNWWRGRISGRVGFFPRNY 50

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 39.63 E-value: 5.83e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKK---DGDWWTGTVGD-KSGVFPSNYV 1072
Cdd:cd11904     5 ALYPFSSSNDEELNFEKGEVMDVIEKpenDPEWWKCRKANgQVGLVPKNYV 55

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 41.02 E-value: 5.88e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1617 VNVVEGIELKpcrsHGKSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIR----DLEQEVLCITVFERDQFSPDDFL 1692
Cdd:cd04011     8 VRVIEARQLV----GGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHespdELFDKIIKISVYDSRSLRSDTLI 83

                          90
                  ....*....|
gi 568997330 1693 GRTEIRVADI 1702
Cdd:cd04011    84 GSFKLDVGTV 93

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 39.26 E-value: 5.91e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd11796     3 RVLQDLSAQLDEELDLREGDVVTI--TGILDKGWFRGELNGRRGIFPEGF 50

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 39.58 E-value: 5.92e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11996     5 AMYDYTANNEDELSFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVK 53

Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4) and similar proteins such as Formin Binding Protein 17 (FBP17) and FormiN Binding Protein 1-Like (FNBP1L), as well as yeast Bzz1 (or Bzz1p). CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. Bzz1 is also a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Members of this subfamily contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain as well as at least one C-terminal SH3 domain. Bzz1 contains a second SH3 domain at the C-terminus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212711 [Multi-domain] Cd Length: 55 Bit Score: 39.51 E-value: 5.93e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKKD-GDWWTGTVGDK--SGVFPSNYVRL 1074
Cdd:cd11777     1 ECKALYAFVGSSEGTISMTEGEKLSLVEEDkGDGWTRVRRDTgeEGYVPTSYIRI 55

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 39.66 E-value: 6.05e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVV-----TKKDGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd11800     2 YYALYTFEARSPGELSVTEGQVVTVlekhdLKGNPEWWLVEDRGKQGYVPSNYLA 56

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 44.91 E-value: 6.10e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  370 PVTFE--DKKRENFErgsvELEKRRQALLeqqrKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQrelerqre 447
Cdd:COG4913   221 PDTFEaaDALVEHFD----DLERAHEALE----DAREQIELLEPIRELAERYAAARERLAELEYLRAALRLW-------- 284

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  448 eerrkeierreaakrelERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKlqdircRLA 527
Cdd:COG4913   285 -----------------FAQRRLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQIRGNGGD------RLE 341

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  528 TQRQEIESTNKSRELRIAEITHLQQQLQESQQmlgRLIPEKQILSDQLKQVQQnslhrdSLLTLKRALEAKELARQQLRE 607
Cdd:COG4913   342 QLEREIERLERELEERERRRARLEALLAALGL---PLPASAEEFAALRAEAAA------LLEALEEELEALEEALAEAEA 412

                         250
                  ....*....|....*..
gi 568997330  608 QLDEVERETRSKLQEID 624
Cdd:COG4913   413 ALRDLRRELRELEAEIA 429

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 39.51 E-value: 6.13e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVL-EQQDMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11986     4 ALYRFKALEKDDLDFHPGERITVIdDSNEEWWRGKIGEKTGYFPMNFI 51

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 39.59 E-value: 6.34e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM--WWFG-EVQGQKGWFPKSYVKL 985
Cdd:cd11897     1 RARALYDFRSENPGEISLREHEVLSLCSEQDIegWLEGvNSRGDRGLFPASYVEV 55

Coiled-coil domain-containing protein 66; This protein family, named Coiled-coil domain-containing protein 66 (CCDC) refers to a protein domain found in eukaryotes, and is approximately 160 amino acids in length. CCDC66 protein is detected mainly in the inner segments of photoreceptors in many vertebrates including mice and humans. It has been found in dogs, that a mutation in the CCDC66 gene causes generalized progressive retinal atrophy (gPRA). This shows that the protein encoded for by this gene is vital for healthy vision and guards against photoreceptor cell degeneration. The structure of CCDC66 proteins includes a heptad repeat pattern which contains at least one coiled-coil domain. There are at least two or more alpha-helices which form a cable-like structure.

Pssm-ID: 434558 [Multi-domain] Cd Length: 154 Bit Score: 42.09 E-value: 6.40e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   387 ELEKRRQALLE------QQRKEQERLAQLERaEQERKERERQEQERKRQLELE---------KQLEKQRELERQREEERR 451
Cdd:pfam15236   46 ERERKRQKALEhqnaikKQLEEKERQKKLEE-ERRRQEEQEEEERLRREREEEqkqfeeerrKQKEKEEAMTRKTQALLQ 124

                           90       100
                   ....*....|....*....|....*
gi 568997330   452 KEIERREAAKRELERQRQLEWERNR 476
Cdd:pfam15236  125 AMQKAQELAQRLKQEQRIRELAEKG 149

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 44.73 E-value: 6.56e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   334 RVRSGSGMSVISSSSVDQRLPEEPSSEDEQQPEKKLPVTFEDKKRENFERgsvELEKRRQALLEQQRK------------ 401
Cdd:pfam17380  450 RVRLEEQERQQQVERLRQQEEERKRKKLELEKEKRDRKRAEEQRRKILEK---ELEERKQAMIEEERKrkllekemeerq 526

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   402 ------EQERLAQLER-AEQERKERERQEQERKRQLELEKQLEkqrelerqreeerrkeierreAAKRELERQRQLEWER 474
Cdd:pfam17380  527 kaiyeeERRREAEEERrKQQEMEERRRIQEQMRKATEERSRLE---------------------AMEREREMMRQIVESE 585


                   ....*.
gi 568997330   475 NRRQEL 480
Cdd:pfam17380  586 KARAEY 591

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 39.24 E-value: 6.74e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQTGEpGWLGGELKGKTGWFPANYAE 819
Cdd:cd11946     5 AKYDFKATADDELSFKRGDILKVLNEECDQ-NWYKAELNGKDGFIPKNYIE 54

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 39.72 E-value: 6.75e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGEL-----KGKTGWFPANYAE 819
Cdd:cd11993     7 QVIASYTATGPEQLTLAPGQLILIRKKNPG--GWWEGELqargkKRQIGWFPANYVK 61

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 39.40 E-value: 6.80e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKGKTGWFPANYAE 819
Cdd:cd12046     4 ALFSYEASQPEDLEFQKGDVILVLSKVNED--WLEGQCKGKIGIFPSAFVE 52

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

Pssm-ID: 274303 [Multi-domain] Cd Length: 346 Bit Score: 44.07 E-value: 6.89e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   351 QRLPEEPSSEDEQQPEKKLPvtfEDKKRENFERgsvELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL 430
Cdd:TIGR02794   55 IQQQKKPAAKKEQERQKKLE---QQAEEAEKQR---AAEQARQKELEQRAAAEKAAKQAEQAAKQAEEKQKQAEEAKAKQ 128

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   431 ELEKqlekqrelerqreeerrkeierreAAKRELERQRQLEWERNRRQElLNQRNKEQEgtvvlKARRKTLEFELEALND 510
Cdd:TIGR02794  129 AAEA------------------------KAKAEAEAERKAKEEAAKQAE-EEAKAKAAA-----EAKKKAEEAKKKAEAE 178


                   ..
gi 568997330   511 KK 512
Cdd:TIGR02794  179 AK 180

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 44.65 E-value: 7.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  373 FEDKKRENFERGSVELEKRRQALlEQQRKEQErlAQLERAEQERkereRQEQERKRQLE--LEKQLEKQrelerQREEER 450
Cdd:PRK02224  189 LDQLKAQIEEKEEKDLHERLNGL-ESELAELD--EEIERYEEQR----EQARETRDEADevLEEHEERR-----EELETL 256

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  451 RKEIERREAAKRELERQR-----QLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCR 525
Cdd:PRK02224  257 EAEIEDLRETIAETEREReelaeEVRDLRERLEELEEERDDLLAEAGLDDADAEAVEARREELEDRDEELRDRLEECRVA 336

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  526 LATQRQEIESTNKS---RELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLkqvqqnslhRDSLLTLKRALEAKELAR 602
Cdd:PRK02224  337 AQAHNEEAESLREDaddLEERAEELREEAAELESELEEAREAVEDRREEIEEL---------EEEIEELRERFGDAPVDL 407

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  603 QQLREQLDEVERE---TRSKLQEIDVfnnQLKELRE-IHSKQQLQK-----------QRSLEAARLKQKEQERKSLELEK 667
Cdd:PRK02224  408 GNAEDFLEELREErdeLREREAELEA---TLRTARErVEEAEALLEagkcpecgqpvEGSPHVETIEEDRERVEELEAEL 484

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  668 QK-EDAQRRVQERDKQWLEHVQQEEQprprkphEEDRLKREDSVRKKEAEERAKPEmqDKQSRLFHPHQEPAKLATQA 744
Cdd:PRK02224  485 EDlEEEVEEVEERLERAEDLVEAEDR-------IERLEERREDLEELIAERRETIE--EKRERAEELRERAAELEAEA 553

Second Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212864 Cd Length: 55 Bit Score: 39.13 E-value: 7.21e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1179 GMYDYTAQNDDE----LAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11931     4 ALYDFEIKDKDQdkdcLTFTKDEILTVIRRVDENWAEGMLGDKIGIFPILYV 55

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 39.44 E-value: 7.21e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKK--DGDWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12053     1 EYIVEYDYDAVHEDELTIRVGEIIRNVKKleEEGWLEGELNGRRGMFPDNFVK 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 39.23 E-value: 7.26e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11982     3 FMAVKPYQSQAEGEISLSKGEKIkVLSVGEGGFWEGQVKGRVGWFPSDCV 52

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 39.16 E-value: 7.28e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPAN 816
Cdd:cd11984     5 AVKAYSPQGEGEIQLNRGERVKV--LSIGEGGFWEGTVKGRTGWFPAD 50

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176046 [Multi-domain] Cd Length: 121 Bit Score: 41.27 E-value: 7.51e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1615 LMVNVVEGIELKPcRSHGKS--NPYCEVTMgSQCHI--TKTIQDTLNPKWNSNCQFFI-RDLEQevLCITVFERDQFSPD 1689
Cdd:cd08401     2 LKIKIGEAKNLPP-RSGPNKmrDCYCTVNL-DQEEVfrTKTVEKSLCPFFGEDFYFEIpRTFRH--LSFYIYDRDVLRRD 77

                          90
                  ....*....|....*....
gi 568997330 1690 DFLGRTEIRVADIKKDQGS 1708
Cdd:cd08401    78 SVIGKVAIKKEDLHKYYGK 96

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 44.17 E-value: 7.61e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   351 QRLPEEPSSEDEQQPEKKLPVTFEDkkrenfERGSVELEKRRQALLEQQRKEQERLAQLERAEQER-KERERQ-EQERKR 428
Cdd:pfam15709  394 QRLEEERQRQEEEERKQRLQLQAAQ------ERARQQQEEFRRKLQELQRKKQQEEAERAEAEKQRqKELEMQlAEEQKR 467

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 568997330   429 QLEL--EKQLEKQRElerqreeerrkeierreaaKRELERQRQLEWERNRRQE 479
Cdd:pfam15709  468 LMEMaeEERLEYQRQ-------------------KQEAEEKARLEAEERRQKE 501

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 43.74 E-value: 7.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  410 ERAEQERKERERQEQERKRQLELEKQLEKQRELERQREEERRKEierREAAKRELERQRQlewERNRRQELLNQRNKeqe 489
Cdd:COG4372     3 RLGEKVGKARLSLFGLRPKTGILIAALSEQLRKALFELDKLQEE---LEQLREELEQARE---ELEQLEEELEQARS--- 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  490 gtvvlkarrktlefELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEIThlqqqlqesqqmlgRLIPEKQ 569
Cdd:COG4372    74 --------------ELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELE--------------ELQKERQ 125

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  570 ILSDQLKQVQQNSLHRDSLLTLKRAlEAKELARQ--QLREQLDEVERETRSklQEIDVFNNQLKELREIHSKQQLQKQRS 647
Cdd:COG4372   126 DLEQQRKQLEAQIAELQSEIAEREE-ELKELEEQleSLQEELAALEQELQA--LSEAEAEQALDELLKEANRNAEKEEEL 202

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  648 LEAARL---KQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQ 724
Cdd:COG4372   203 AEAEKLiesLPRELAEELLEAKDSLEAKLGLALSALLDALELEEDKEELLEEVILKEIEELELAILVEKDTEEEELEIAA 282


                  ....*.
gi 568997330  725 DKQSRL 730
Cdd:COG4372   283 LELEAL 288

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 39.17 E-value: 7.89e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGG--ELKGKTGWFPANY 817
Cdd:cd11918     4 YKAVYQYRPQNEDELELREGDRVDV--MQQCDDGWFVGvsRRTQKFGTFPGNY 54

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 44.40 E-value: 7.90e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   387 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQ-EQERKR----------QLELEK------QLEKQRELERQREEE 449
Cdd:pfam01576   58 EAEEMRARLAARKQELEEILHELESRLEEEEERSQQlQNEKKKmqqhiqdleeQLDEEEaarqklQLEKVTTEAKIKKLE 137

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   450 RRKEIERREAAKRELERQ----------RQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKL 519
Cdd:pfam01576  138 EDILLLEDQNSKLSKERKlleeriseftSNLAEEEEKAKSLSKLKNKHEAMISDLEERLKKEEKGRQELEKAKRKLEGES 217

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   520 QDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQN----SLHRDSLLTLKRAL 595
Cdd:pfam01576  218 TDLQEQIAELQAQIAELRAQLAKKEEELQAALARLEEETAQKNNALKKIRELEAQISELQEDleseRAARNKAEKQRRDL 297

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   596 -EAKELARQQLREQLDE--VERETRSKLQ------------EIDVFNNQLKELREIHSKQQLQKQRSLEAA-RLKQK-EQ 658
Cdd:pfam01576  298 gEELEALKTELEDTLDTtaAQQELRSKREqevtelkkaleeETRSHEAQLQEMRQKHTQALEELTEQLEQAkRNKANlEK 377

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330   659 ERKSLELEKQKEDAQRRVQERDKQWLEHvqqeeqprpRKPHEEDRLKrEDSVRKKEAeERAKPEMQDKQSRL 730
Cdd:pfam01576  378 AKQALESENAELQAELRTLQQAKQDSEH---------KRKKLEGQLQ-ELQARLSES-ERQRAELAEKLSKL 438

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 44.27 E-value: 8.01e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   360 EDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERE--------RQEQERKRQLE 431
Cdd:TIGR00606  478 QELRKAERELSKAEKNSLTETLKKEVKSLQNEKADLDRKLRKLDQEMEQLNHHTTTRTQMEmltkdkmdKDEQIRKIKSR 557

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   432 LEKQLEKQRELERQREEERRKEIERREAAKRELERQRQLEWERNRRQELLNQRNKEQegtvvlkarrKTLEFELEALNDK 511
Cdd:TIGR00606  558 HSDELTSLLGYFPNKKQLEDWLHSKSKEINQTRDRLAKLNKELASLEQNKNHINNEL----------ESKEEQLSSYEDK 627

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   512 KHQLEGKlQDIRCRLATQRQEIESTNKSRELRIAE-------ITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNS-L 583
Cdd:TIGR00606  628 LFDVCGS-QDEESDLERLKEEIEKSSKQRAMLAGAtavysqfITQLTDENQSCCPVCQRVFQTEAELQEFISDLQSKLrL 706

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   584 HRDSLLTLKRALEAKELARQQL-------REQLDEVER---ETRSKLQEIdvfNNQLKELREIHSKQQLQ------KQRS 647
Cdd:TIGR00606  707 APDKLKSTESELKKKEKRRDEMlglapgrQSIIDLKEKeipELRNKLQKV---NRDIQRLKNDIEEQETLlgtimpEEES 783

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   648 LEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEH-VQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKpEMQDK 726
Cdd:TIGR00606  784 AKVCLTDVTIMERFQMELKDVERKIAQQAAKLQGSDLDRtVQQVNQEKQEKQHELDTVVSKIELNRKLIQDQQE-QIQHL 862

                          410
                   ....*....|....*...
gi 568997330   727 QSRLFHPHQEPAKLATQA 744
Cdd:TIGR00606  863 KSKTNELKSEKLQIGTNL 880

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 39.15 E-value: 8.38e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMV--DESQTGEPGWlGGELKGKTGWFPANYAE 819
Cdd:cd11894     1 FVKALYDYEGQTDDELSFPEGAIIRIlnKENQDDDGFW-EGEFNGRIGVFPSVLVE 55

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212693 [Multi-domain] Cd Length: 57 Bit Score: 39.01 E-value: 8.52e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1093 PEIAQVIASYA--ATGPEQLTLAPGQLILIRKKNPGGWWEGELqaRGKKrqiGWFPANYVKL 1152
Cdd:cd11759     1 PAYARVIQKRVpnAYDKTALALEVGDLVKVTKINVSGQWEGEL--NGKV---GHFPFTHVEL 57

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 38.96 E-value: 8.64e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPA 815
Cdd:cd11832     1 YFIAVKSYSPQEEGEISLHKGDRVKV--LSIGEGGFWEGSVRGRTGWFPS 48

Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442298 [Multi-domain] Cd Length: 485 Bit Score: 43.87 E-value: 8.82e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  372 TFEDKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELerqreeerr 451
Cdd:COG3064     4 ALEEKAAEAAAQERLEQAEAEKRAAAEAEQKAKEEAEEERLAELEAKRQAEEEAREAKAEAEQRAAELAAE--------- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  452 keierreAAKRELERQRQLEWERNRRQELLNQRNKEQEGTvvLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQ 531
Cdd:COG3064    75 -------AAKKLAEAEKAAAEAEKKAAAEKAKAAKEAEAA--AAAEKAAAAAEKEKAEEAKRKAEEEAKRKAEEERKAAE 145

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  532 EIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDE 611
Cdd:COG3064   146 AEAAAKAEAEAARAAAAAAAAAAAAAARAAAGAAAALVAAAAAAVEAADTAAAAAAALAAAAAAAAADAALLALAVAARA 225

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  612 VERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQEE 691
Cdd:COG3064   226 AAASREAALAAVEATEEAALGGAEEAADLAAVGVLGAALAAAAAGAAALSSGLVVVAAALAGLAAAAAGLVLDDSAALAA 305

                         330       340
                  ....*....|....*....|
gi 568997330  692 QPRPRKPHEEDRLKREDSVR 711
Cdd:COG3064   306 ELLGAVAAEEAVLAAAAAAG 325

Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; LARG (also called RhoGEF12) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. LARG contains a N-terminal extension, followed by Dbl homology (DH)-PH domains which bind and catalyze the exchange of GDP for GTP on RhoA in addition to a RGS domain. The active site of RhoA adopts two distinct GDP-excluding conformations among the four unique complexes in the asymmetric unit. The LARG PH domain also contains a potential protein-docking site. LARG forms a homotetramer via its DH domains. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 275425 Cd Length: 138 Bit Score: 41.51 E-value: 8.98e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1475 LGPRKFLHSGKL-YKAKSNK--ELYGFLFNDFLLLTQ----------ITKPLGSSGTDK-VFSPKsnlqykmyktpIFLN 1540
Cdd:cd13390    21 LTKRKMIHEGPLtWKVNRDKtiDLYTLLLEDILVLLQkqddrlvlrcHSKILASTADSKhTFSPV-----------IKLN 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 568997330 1541 EVLVK-LPTDpsgDEPIFHISHID---RVYTLRAESINERTAW 1579
Cdd:cd13390    90 TVLVRqVATD---NKAFFVISMSEngaQIYELVAQTVSEKTVW 129

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 38.86 E-value: 9.00e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLG-GELKGKTGWFPANY 817
Cdd:cd11904     4 QALYPFSSSNDEELNFEKGEVMDVIEKPENDPEWWKcRKANGQVGLVPKNY 54

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

Pssm-ID: 274303 [Multi-domain] Cd Length: 346 Bit Score: 43.68 E-value: 9.02e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   573 DQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEidvfnnQLKElREIHSKQQLQKQRSLEAAR 652
Cdd:TIGR02794   53 NRIQQQKKPAAKKEQERQKKLEQQAEEAEKQRAAEQARQKELEQRAAAEK------AAKQ-AEQAAKQAEEKQKQAEEAK 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   653 LKQKEQERKSLELE---KQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEE-RAKPEMQDKQS 728
Cdd:TIGR02794  126 AKQAAEAKAKAEAEaerKAKEEAAKQAEEEAKAKAAAEAKKKAEEAKKKAEAEAKAKAEAEAKAKAEEaKAKAEAAKAKA 205

                          170
                   ....*....|....*.
gi 568997330   729 RlfhphQEPAKLATQA 744
Cdd:TIGR02794  206 A-----AEAAAKAEAE 216

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 39.03 E-value: 9.48e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11876     4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsgdEGWWTGKIGDKVGIFPSNYV 56

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 38.91 E-value: 9.49e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKS--GVFPSNYV 1072
Cdd:cd11858     2 YKALYDFAGSVANELSLKKDDIVYIVQKEDNgWWLAKKLDESkeGWVPAAYL 53

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442439 [Multi-domain] Cd Length: 687 Bit Score: 43.85 E-value: 9.53e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  414 QERKERERQEQERKRQLELEKQLEKqrelerqreeerrkeierreaAKRELERQRQlewernRRQELlnqrnKEQEGTVV 493
Cdd:COG3206   162 LEQNLELRREEARKALEFLEEQLPE---------------------LRKELEEAEA------ALEEF-----RQKNGLVD 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  494 LKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEithlqqqlqesqqmlgrliPEKQILSD 573
Cdd:COG3206   210 LSEEAKLLLQQLSELESQLAEARAELAEAEARLAALRAQLGSGPDALPELLQS-------------------PVIQQLRA 270

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  574 QLKQVQQNslhRDSLLT--------LKRALEAKELARQQLREQLDEVERETRSklqEIDVFNNQLKELReihskQQLQKQ 645
Cdd:COG3206   271 QLAELEAE---LAELSArytpnhpdVIALRAQIAALRAQLQQEAQRILASLEA---ELEALQAREASLQ-----AQLAQL 339

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 568997330  646 RSlEAARLKQKEQERKSLE-----LEKQKEDAQRRVQE 678
Cdd:COG3206   340 EA-RLAELPELEAELRRLErevevARELYESLLQRLEE 376

Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. Vertebrates contain two SLAPs, named SLAP (or SLA1) and SLAP2 (or SLA2). SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, among others, while SLAP2 interacts with CSF1R. Both SLAPs interact with c-Cbl, LAT, CD247, and Zap70. SLAP modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212782 Cd Length: 55 Bit Score: 38.71 E-value: 9.55e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNkEDPDWWK--GEVSGQVGLFPSNYV 1226
Cdd:cd11848     5 LGDYPSGGPAELSLRLGEPLTIVS-DEGDWWKvlSEVTGRESYIPSVHV 52

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 38.98 E-value: 9.65e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQ------DMWWFGEVQGQKGWFPKSYV 983
Cdd:cd12059     4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsgdEGWWTGKINDRVGIFPSNYV 56

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176013 [Multi-domain] Cd Length: 120 Bit Score: 40.63 E-value: 9.65e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1633 KSNPYCEVTMGSQCHI-------TKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPD----DFLGRTEIRVAD 1701
Cdd:cd04048    20 KSDPFVVVYVKTGGSGqwveigrTEVIKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSKSKDlsdhDFLGEAECTLGE 99

                          90       100
                  ....*....|....*....|...
gi 568997330 1702 IkkdQGSKGPVTKCLLLHEVPTG 1724
Cdd:cd04048   100 I---VSSPGQKLTLPLKGGKGKG 119

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 38.82 E-value: 9.68e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1180 MYDYTAQNDDELAFSKGQIINVLNKEDPD-WWKGEVS-GQVGLFPSNYVKL 1228
Cdd:cd11897     5 LYDFRSENPGEISLREHEVLSLCSEQDIEgWLEGVNSrGDRGLFPASYVEV 55

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 38.84 E-value: 9.74e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  768 RALYPFESRSHDEITIQPGDIV--MVDESQTGepgWLGGEL--KGKTGWFPANYAEK 820
Cdd:cd11779     4 KALYPHAAGGETQLSFEEGDVItlLGPEPRDG---WHYGENerSGRRGWFPIAYTEP 57

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 38.84 E-value: 9.81e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd11977     3 AVARYNFAARDMRELSLREGDVVRIYSRiggDQGWWKGETNGRIGWFPSTYVE 55

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 38.77 E-value: 1.01e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEV--SGQVGLFPSNYVK 1227
Cdd:cd11939     1 QVQCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGERlhDQERGWFPSSVVE 54

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 38.83 E-value: 1.02e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1028 YTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTVGDKSGVFPSNYV 1072
Cdd:cd11902     7 FAYVAEREDELSLVKGSRVTVMEKCSDgWWRGSYNGQIGWFPSNYV 52

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212742 [Multi-domain] Cd Length: 53 Bit Score: 38.62 E-value: 1.05e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQKGWFPKSYVK 984
Cdd:cd11808     4 ALYDYQEKSPREVSMKKGDILTLLNSSNKdWWKVEVNDRQGFVPAAYVK 52

Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that were originally characterized in silico. They are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC2, also called Iporin, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212744 Cd Length: 50 Bit Score: 38.58 E-value: 1.07e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNY 1225
Cdd:cd11810     2 VRALCHHVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTKGLVPLSY 50

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 38.82 E-value: 1.09e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  768 RALYPFESRSHDEITIQPGDIV-MVDESqtgEPGWLGGELKGKTGWFPANY 817
Cdd:cd12055     3 QVAFSYLPQNEDELELKVGDIIeVVGEV---EEGWWEGVLNGKTGMFPSNF 50

chromosome partition protein MukB;

Pssm-ID: 235316 [Multi-domain] Cd Length: 1486 Bit Score: 44.18 E-value: 1.10e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  374 EDKKRENFERgSVELEKRRQALLEQQRKEQERLAQLERAEQERKERER----------------------QEQERKRQ-- 429
Cdd:PRK04863  278 ANERRVHLEE-ALELRRELYTSRRQLAAEQYRLVEMARELAELNEAESdleqdyqaasdhlnlvqtalrqQEKIERYQad 356

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  430 -LELEKQLEKQRELERQREEERRKEIERREAAKRELER-QRQLEwERNRRQELLNQRNKEQEGTVVLKARRKTL----EF 503
Cdd:PRK04863  357 lEELEERLEEQNEVVEEADEQQEENEARAEAAEEEVDElKSQLA-DYQQALDVQQTRAIQYQQAVQALERAKQLcglpDL 435

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  504 ELEALNDKKHQLEGKLQDircrLATQRQEIEstnksRELRIAEITHLqqqlqesqqmlgrlIPEK--QILSDQLKQVQQN 581
Cdd:PRK04863  436 TADNAEDWLEEFQAKEQE----ATEELLSLE-----QKLSVAQAAHS--------------QFEQayQLVRKIAGEVSRS 492

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  582 SLHRDSLLTLKRALEAKELA--RQQLREQLDEVERETRSKlqeidvfNNQLKELREIHSKQQLQKQRSLEAARLkQKEQE 659
Cdd:PRK04863  493 EAWDVARELLRRLREQRHLAeqLQQLRMRLSELEQRLRQQ-------QRAERLLAEFCKRLGKNLDDEDELEQL-QEELE 564

                         330       340       350
                  ....*....|....*....|....*....|..
gi 568997330  660 RKSLELEKQKEDA-QRRVQERDKQwlEHVQQE 690
Cdd:PRK04863  565 ARLESLSESVSEArERRMALRQQL--EQLQAR 594

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 38.60 E-value: 1.10e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKKDGDWW---TGTVGDKSGVFPSNYV 1072
Cdd:cd11784     2 CVALHSYSAHRPEELELQKGEGVRVLGKFQEGWlrgLSLVTGRVGIFPSNYV 53

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 38.65 E-value: 1.10e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQiGWFPANYV 1150
Cdd:cd11812     8 YTANRSDELTIHRGDIIRVLYKDNDNWWFGSL---VNGQQ-GYFPANYV 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 43.98 E-value: 1.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  350 DQRLPEE--PSSEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQallEQQRKEQE-RLAQLERAEQERKERERQEQER 426
Cdd:PTZ00121 1673 DKKKAEEakKAEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKKA---EELKKAEEeNKIKAEEAKKEAEEDKKKAEEA 1749

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  427 KRQLELEKQLEKQRELERQREEERRKEIERREAAK-RELERQRQLEWERNRRQELLNQRNKEQ---EGTVVLKARRKTLE 502
Cdd:PTZ00121 1750 KKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVIEEElDEEDEKRRMEVDKKIKDIFDNFANIIEggkEGNLVINDSKEMED 1829

                         170
                  ....*....|.
gi 568997330  503 FELEALNDKKH 513
Cdd:PTZ00121 1830 SAIKEVADSKN 1840

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212932 [Multi-domain] Cd Length: 56 Bit Score: 38.77 E-value: 1.16e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  765 VYYRALYPFESRSHDEITIQPGDIVMVDESQTgEPGWLGG-ELKGKTGWFPANYAE 819
Cdd:cd11999     2 VRVRAVYDYTGQEPDELSFKAGEELLKVEDED-EQGWCKGvTDGGAVGLYPANYVE 56

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 38.60 E-value: 1.18e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1183 YTAQNDDELAFSKGQIINVLNKEDPDWWKG--EVSGQVGLFPSNYVK 1227
Cdd:cd11785     8 YPPQSEAELELKEGDIVFVHKKREDGWFKGtlQRTGKTGLFPGSFVE 54

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 38.51 E-value: 1.19e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVL----EQQDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11807     2 VVYALFDYEAENGDELSFREGDELTVLrkgdDDETEWWWARLNDKEGYVPRNLLGL 57

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 42.95 E-value: 1.19e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  639 KQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQWLEHVQQ------EEQPRPRKPHE---EDRLKREDS 709
Cdd:cd16269   191 QALTEKEKEIEAERAKAEAAEQERKLLEEQQRELEQKLEDQERSYEEHLRQlkekmeEERENLLKEQEralESKLKEQEA 270

                          90       100
                  ....*....|....*....|.
gi 568997330  710 VRKKEAEERAKpEMQDKQSRL 730
Cdd:cd16269   271 LLEEGFKEQAE-LLQEEIRSL 290

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 38.53 E-value: 1.21e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQtgEPGWLGGE--LKGKTGWFPANY 817
Cdd:cd11783     2 YVALYPYKPQKPDELELRKGEMYTVTEKC--QDGWFKGTslRTGQSGVFPGNY 52

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 38.77 E-value: 1.21e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997330   248 KYRQLFNSHDKTMSGHLT----GPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAM 307
Cdd:pfam13499    3 KLKEAFKLLDSDGDGYLDveelKKLLRKLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 38.47 E-value: 1.26e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGK-TGWFPANYAEK 820
Cdd:cd11825     3 KALYDYRAQRPDELSFCKHAIITNVEKEDG--GWWRGDYGGKkQKWFPANYVEE 54

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 38.53 E-value: 1.27e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGE--VQGQKGWFPKSYVKL 985
Cdd:cd11783     4 ALYPYKPQKPDELELRKGEMYTVTEKcQDGWFKGTslRTGQSGVFPGNYVQP 55

Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212970 Cd Length: 59 Bit Score: 38.78 E-value: 1.29e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1181 YDYTAQNDD-------ELAFSKGQIINVLNKEDPDWWKG--EVSGQVGLFPS 1223
Cdd:cd12037     6 FDYDPSSDSlipckeaGLKFRAGDLLQIVNQEDPNWWQAchVEGGSAGLIPS 57

HOOK protein coiled-coil region; This family consists of several HOOK1, 2 and 3 proteins from different eukaryotic organizms. The different members of the human gene family are HOOK1, HOOK2 and HOOK3. Different domains have been identified in the three human HOOK proteins, and it was demonstrated that the highly conserved NH2-domain mediates attachment to microtubules, whereas this central coiled-coil motif mediates homodimerization and the more divergent C-terminal domains are involved in binding to specific organelles (organelle-binding domains). It has been demonstrated that endogenous HOOK3 binds to Golgi membranes, whereas both HOOK1 and HOOK2 are localized to discrete but unidentified cellular structures. In mice the Hook1 gene is predominantly expressed in the testis. Hook1 function is necessary for the correct positioning of microtubular structures within the haploid germ cell. Disruption of Hook1 function in mice causes abnormal sperm head shape and fragile attachment of the flagellum to the sperm head. This entry includes the central coiled-coiled domain and the divergent C-terminal domain.

Pssm-ID: 461694 [Multi-domain] Cd Length: 528 Bit Score: 43.52 E-value: 1.30e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   383 RGSVELEKRRQALLEQQRKEQERLAQLERaeQERKERERQEQERKRQLELEKQLEKqrelerqreeerrkeierREAAKR 462
Cdd:pfam05622  124 RESSDKVKKLEATVETYKKKLEDLGDLRR--QVKLLEERNAEYMQRTLQLEEELKK------------------ANALRG 183

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   463 ELERQ-RQLewernrrQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHqlegklqdircRLATQRQEIESTNKsrE 541
Cdd:pfam05622  184 QLETYkRQV-------QELHGKLSEESKKADKLEFEYKKLEEKLEALQKEKE-----------RLIIERDTLRETNE--E 243

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   542 LRIAeithlqqqlqesqqmlgrlipekqilsdqlkQVQQNSLHRDSLLTLKRALE----AKELARQQLREQLDEVERETR 617
Cdd:pfam05622  244 LRCA-------------------------------QLQQAELSQADALLSPSSDPgdnlAAEIMPAEIREKLIRLQHENK 292

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   618 S-KLQEIDVFNNQLKELreihsKQQL-QKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERD---------KQWLEh 686
Cdd:pfam05622  293 MlRLGQEGSYRERLTEL-----QQLLeDANRRKNELETQNRLANQRILELQQQVEELQKALQEQGskaedssllKQKLE- 366

                          330       340
                   ....*....|....*....|.
gi 568997330   687 vqqEEQPRPRKPHEEDRLKRE 707
Cdd:pfam05622  367 ---EHLEKLHEAQSELQKKKE 384

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 38.59 E-value: 1.31e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568997330 1182 DYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd12017     7 EFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYI 51

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 40.85 E-value: 1.33e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTM---GSQCHITKTI--QDTLNPKWNSNCQFFI--RDLEQEVLCITVFERDQ 1685
Cdd:cd08402    15 GKLTVVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTikKRTLNPYYNESFSFEVpfEQIQKVHLIVTVLDYDR 94


                  ....*....
gi 568997330 1686 FSPDDFLGR 1694
Cdd:cd08402    95 IGKNDPIGK 103

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 38.39 E-value: 1.35e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVTKKDGD--WWTGTV-GDKSGVFPSNYV 1072
Cdd:cd11998     5 ALYDYDGQEQDELSFKAGDELTKLEDEDEqgWCKGRLdSGQVGLYPANYV 54

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 38.33 E-value: 1.36e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGE--VQGQKGWFPKSY 982
Cdd:cd11845     4 ALYDYEARTDDDLSFKKGDRLQILDDsDGDWWLARhlSTGKEGYIPSNY 52

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175998 [Multi-domain] Cd Length: 127 Bit Score: 40.32 E-value: 1.36e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1611 GIGRLMVNVVegielkpcRSHG-------KSNPYCEVTMGSQCHITKTIQDTLNPKWNSNCQFFIRDLEQ-EVLCITVFE 1682
Cdd:cd04032    26 GLATLTVTVL--------RATGlwgdyftSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFGSVELSPgGKLRFEVWD 97

                          90       100
                  ....*....|....*....|....*
gi 568997330 1683 RDQFSPDDFLGRTEIRV-ADIKKDQ 1706
Cdd:cd04032    98 RDNGWDDDLLGTCSVVPeAGVHEDS 122

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 38.10 E-value: 1.38e-03

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 568997330 1037 DLTFQQGDVIVVTK-KDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11796    15 ELDLREGDVVTITGiLDKGWFRGELNGRRGIFPEGFV 51

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 38.35 E-value: 1.38e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  769 ALYPFESRSHDEITIQPGDIVMVDESQ--TGEPGWLGGELKGKTGWFPANY 817
Cdd:cd11941     4 AAYPFTARSKHEVSLQAGQPVTVLEPHdkKGSPEWSLVEVNGQRGYVPSSY 54

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212871 Cd Length: 55 Bit Score: 38.29 E-value: 1.40e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  773 FESRSHDEITIQPGDIVMVdeSQTGEPGWLGGEL--KGKTGWFPANYAE 819
Cdd:cd11938     8 YTAKQPDELSLQQADVVLV--LQTESDGWYYGERlrDGERGWFPSSCAK 54

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 38.43 E-value: 1.42e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI--VVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd12065     4 AVYPCEAEHSSELSFEVGAIFedVTLSREPGWLEGTLNGKRGLIPENYVEI 54

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 38.40 E-value: 1.42e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQGQ---KGWFPKSYV 983
Cdd:cd11966     1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKeWWIGHIDGEptrRGAFPVSFV 54

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212955 [Multi-domain] Cd Length: 53 Bit Score: 38.28 E-value: 1.43e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKK--DGdWWTGTVGDKSGVFPSNYV 1072
Cdd:cd12022     2 YITIKAYTAVEEDELTLLEGEAIEVIHKllDG-WWVVRKGEVTGYFPSMYL 51

flagellar export protein FliJ; Members of this family are the FliJ protein found, in nearly every case, in the midst of other flagellar biosynthesis genes in bacgterial genomes. Typically the fliJ gene is found adjacent to the gene for the flagellum-specific ATPase FliI. Sequence scoring in the gray zone between trusted and noise cutoffs include both probable FliJ proteins and components of bacterial type III secretion systems.

Pssm-ID: 131526 [Multi-domain] Cd Length: 141 Bit Score: 40.76 E-value: 1.45e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   573 DQLKQVQQNSLHRdSLLTLKRALEAKELARQQLRE---QLDEVERETRSK---------LQEIDVFNNQLKELREIHSKQ 640
Cdd:TIGR02473    5 QKLLDLREKEEEQ-AKLELAKAQAEFERLETQLQQlikYREEYEQQALEKvgagtsaleLSNYQRFIRQLDQRIQQQQQE 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 568997330   641 QLQKQRSLEAAR--LKQKEQERKSLELEKQKEDAQRRVQE 678
Cdd:TIGR02473   84 LALLQQEVEAKRerLLEARRELKALEKLKEKKQKEYRAEE 123

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 42.56 E-value: 1.45e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQALLEQQRKEQERlaQLERAEQERKERERQEQERKRQLEleKQLEKqrelerqreeerrkeierreaakrelER 466
Cdd:cd16269   201 EAERAKAEAAEQERKLLEE--QQRELEQKLEDQERSYEEHLRQLK--EKMEE--------------------------ER 250

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 568997330  467 QRQL-EWERNRRQELLNQRNKEQEGtvvLKARRKTLEFELEAL 508
Cdd:cd16269   251 ENLLkEQERALESKLKEQEALLEEG---FKEQAELLQEEIRSL 290

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 38.41 E-value: 1.50e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTV--GDKSGVFPSNYV 1072
Cdd:cd11926     2 YVAIYPYTPRKEDELELRKGEMFLVFERCQDgWFKGTSmhTSKIGVFPGNYV 53

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 42.22 E-value: 1.54e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  595 LEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREIHS---KQQLQKQRSLEAARLKQKEQERKSLE------- 664
Cdd:COG1579    12 LQELDSELDRLEHRLKELPAELAELEDELAALEARLEAAKTELEdleKEIKRLELEIEEVEARIKKYEEQLGNvrnnkey 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  665 --LEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRL-KREDSVRKKEAE-ERAKPEMQDKQSRL 730
Cdd:COG1579    92 eaLQKEIESLKRRISDLEDEILELMERIEELEEELAELEAELaELEAELEEKKAElDEELAELEAELEEL 161

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 38.20 E-value: 1.55e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1099 IASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYV 1150
Cdd:cd12017     5 IGEFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKE-----GWAPSSYI 51

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 38.46 E-value: 1.59e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWEGElqargKKRQIGWFPANYV 1150
Cdd:cd11963    10 FEAVEDNELTFKHGEIIIVLDDSDANWWKGE-----NHRGVGLFPSNFV 53

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 38.32 E-value: 1.59e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVK 984
Cdd:cd11815     1 HAVVLHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYrGKCKNTTGIFPANHVK 52

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 42.87 E-value: 1.61e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  593 RALEAKELARQQLREQLDEVERETRSKLQeidvfnnQLKElreihskqqlQKQRSLEAARLKQKEQERKSLELEKQ-KED 671
Cdd:PRK09510  104 KQLEKERLAAQEQKKQAEEAAKQAALKQK-------QAEE----------AAAKAAAAAKAKAEAEAKRAAAAAKKaAAE 166

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  672 AQRRVQErdkqwlEHVQQEEQPRPRKPHEEDRLKREDSVRKK---EAEERAKPEMQDK 726
Cdd:PRK09510  167 AKKKAEA------EAAKKAAAEAKKKAEAEAAAKAAAEAKKKaeaEAKKKAAAEAKKK 218

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212844 [Multi-domain] Cd Length: 55 Bit Score: 38.01 E-value: 1.63e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWW----KGEvsGQVGLFPSNYVKL 1228
Cdd:cd11911     1 TCTALYDFDGTSEGTLSMEEGEILLVLEEDGGDGWtrvrKNN--GDEGYVPTSYIEV 55

Src Homology 3 domain of Sorting nexin 9; Sorting nexin 9 (SNX9), also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX9 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212831 Cd Length: 57 Bit Score: 38.30 E-value: 1.64e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1180 MYDYTAQ-NDDELAFSKGQIINVLNKE-DPDWWKGEVS-GQVGLFPSNYVKL 1228
Cdd:cd11898     5 LYDFAAEpGNNELTVKEGEIITVTNPNvGGGWIEAKNSqGERGLVPTDYVEI 56

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212708 [Multi-domain] Cd Length: 52 Bit Score: 38.21 E-value: 1.66e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDW-WTGTVGDKSGVFPSNYV 1072
Cdd:cd11774     4 ALYDYDKQTEEELSFNEGDTLdVYDDSDSDWiLVGFNGTQFGFVPANYI 52

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212709 [Multi-domain] Cd Length: 57 Bit Score: 38.07 E-value: 1.66e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1094 EIAQVIASYAATGPEQLTLAPGQ-LILIRKKNPGGWWEGELQARGKKrqiGWFPANYVKL 1152
Cdd:cd11775     1 KRGKVLYDFDAQSDDELTVKEGDvVYILDDKKSKDWWMVENVSTGKE---GVVPASYIEI 57

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 38.01 E-value: 1.66e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGD-VIVVTKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11984     3 FIAVKAYSPQGEGEIQLNRGErVKVLSIGEGGFWEGTVKGRTGWFPADCV 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 38.33 E-value: 1.69e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGE-PGWLGGELKGKTGWFPANYAEKIPE 823
Cdd:cd12003     4 KALYDNAAESPEELSFRRGDVLMVLKREHGSlPGWWLCSLHGQQGIAPANRLRLLPT 60

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 43.09 E-value: 1.73e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   356 EPSSEDEQQPEKKLPVTFEDKKRENFERGSVELEKRRQALlEQQRKEQERLAQleraeqerkererQEQERKRQLELEKQ 435
Cdd:TIGR04523  357 ENSEKQRELEEKQNEIEKLKKENQSYKQEIKNLESQINDL-ESKIQNQEKLNQ-------------QKDEQIKKLQQEKE 422

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   436 -LEKQRelerqreeerrkeierreaakrelerqrqlewernrrQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQ 514
Cdd:TIGR04523  423 lLEKEI-------------------------------------ERLKETIIKNNSEIKDLTNQDSVKELIIKNLDNTRES 465

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   515 LEGKLQDIRCRLATQRQEIESTNKSRELRIAEIThlqqqlqesqqmlgRLIPEKQILSDQLKQVQQNSlhrDSLLTLKRA 594
Cdd:TIGR04523  466 LETQLKVLSRSINKIKQNLEQKQKELKSKEKELK--------------KLNEEKKELEEKVKDLTKKI---SSLKEKIEK 528

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   595 LEA----KELARQQLREQLDEVERE-TRSKLQ-EIDVFNNQLKELREiHSKQQLQKQRSLEaARLKQKEQERKslELEKQ 668
Cdd:TIGR04523  529 LESekkeKESKISDLEDELNKDDFElKKENLEkEIDEKNKEIEELKQ-TQKSLKKKQEEKQ-ELIDQKEKEKK--DLIKE 604

                          330       340
                   ....*....|....*....|..
gi 568997330   669 KEDAQRRVQERDKQwLEHVQQE 690
Cdd:TIGR04523  605 IEEKEKKISSLEKE-LEKAKKE 625

Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full length form of the previously-identified tumor supressor, p53-binding protein 2 (p53BP2). ASPP2 activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). It plays a central role in regulating apoptosis and cell growth; ASPP2-deficient mice show postnatal death. Downregulated expression of ASPP2 is frequently found in breast tumors, lung cancer, and diffuse large B-cell lymphoma where it is correlated with a poor clinical outcome. ASPP2 contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP2 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212886 [Multi-domain] Cd Length: 57 Bit Score: 38.39 E-value: 1.73e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGD---WWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11953     5 ALWDYEGESDDELSFKEGDCMtILRREDEDeteWWWARLNDKEGYVPRNLLGL 57

DNA polymerase III subunits gamma and tau; Provisional

Pssm-ID: 237865 [Multi-domain] Cd Length: 618 Bit Score: 43.16 E-value: 1.75e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  129 QPVAISSAPAfgigGIASMPPLTAVAPVPMGSIPVVGMSPPLVSSVPPAAVPPLANGAPPVIQPLPAFAHPAATLPKSSS 208
Cdd:PRK14951  383 RPEAAAPAAA----PVAQAAAAPAPAAAPAAAASAPAAPPAAAPPAPVAAPAAAAPAAAPAAAPAAVALAPAPPAQAAPE 458

                          90       100       110
                  ....*....|....*....|....*....|
gi 568997330  209 FSRSGPGSQLNTKLQKAQSfDVASAPPAAE 238
Cdd:PRK14951  459 TVAIPVRVAPEPAVASAAP-APAAAPAAAR 487

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 38.05 E-value: 1.76e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVK 1151
Cdd:cd12055     3 QVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGK-----TGMFPSNFIK 52

DDRGK domain; This is a family of proteins of approximately 300 residues, found in plants and vertebrates. They contain a highly conserved DDRGK motif.

Pssm-ID: 370664 [Multi-domain] Cd Length: 188 Bit Score: 41.18 E-value: 1.81e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   389 EKRRQALLEQQRKEQERLAQleraEQERKERERQEQERKRQLELEKqlekqrelerqreeerrkeierreaAKRELERQR 468
Cdd:pfam09756    5 AKKRAKLELKEAKRQQREAE----EEEREEREKLEEKREEEYKERE-------------------------EREEEAEKE 55

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330   469 QLEWERNRRQEllnQRNKEQEGTVVLKArrktlEFELEALNDKKHQLEGKLQDIRC 524
Cdd:pfam09756   56 KEEEERKQEEE---QERKEQEEYEKLKS-----QFVVEEEGTDKLSAEDESQLLED 103

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 37.86 E-value: 1.82e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQD-MWWFGEVQ--GQKGWFPKSYV 983
Cdd:cd11889     2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDgSWWSGKLRrnGAEGIFPSNFV 53

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 38.12 E-value: 1.83e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGElqargKKRQIGWFPANYVKL 1152
Cdd:cd11824     2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVE-----RNGQKGLVPGTYLEK 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 38.04 E-value: 1.83e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQ--QDMWWFGEVQGQKGWFPKSYVKL 985
Cdd:cd11882     1 RARALYACKAEDESELSFEPGQIITNVQPsdEPGWLEGTLNGRTGLIPENYVEF 54

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 38.45 E-value: 1.84e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1099 IASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQArgkkrQIGWFPANYVKLLS 1154
Cdd:cd11972     8 IYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNG-----VTGLFPGNYVESIM 58

First Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212913 Cd Length: 60 Bit Score: 38.38 E-value: 1.85e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568997330 1038 LTFQQGDVIVVTKKDGD--WWTGTV--GDKSGVFPSNYVR 1073
Cdd:cd11980    20 LTFQTGDVIELLRGDPDspWWEGRLlqTKKSGYFPSSSVK 59

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 38.09 E-value: 1.89e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330  771 YPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANY 817
Cdd:cd11901     8 FNYTAEREDELSLVKGTKVIVMEKCSD--GWWRGSYNGQVGWFPSNY 52

Src Homology 3 domain of Amphiphysin I; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213016 Cd Length: 72 Bit Score: 38.72 E-value: 1.89e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  770 LYPFESRSHDEITIQPGDIVMVDESQTG---EPGWLGG----------ELKGKTGWFPANYAEKI 821
Cdd:cd12140     8 LHDFEAANSDELELKRGDIVLVVPSETAadqDAGWLTGvkesdwlqyrDASAYKGLFPENFTRRL 72

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 42.21 E-value: 1.90e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  407 AQLERAEQERKE-RERQEQERKRQLELEKQLEKqrelerqreeerrkeierrEAAKRELERQrQLEWERNRRQELLNQRN 485
Cdd:COG1340     8 SSLEELEEKIEElREEIEELKEKRDELNEELKE-------------------LAEKRDELNA-QVKELREEAQELREKRD 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  486 KEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCR---LATQRQEIE-----------STNKSREL--RIAEITH 549
Cdd:COG1340    68 ELNEKVKELKEERDELNEKLNELREELDELRKELAELNKAggsIDKLRKEIErlewrqqtevlSPEEEKELveKIKELEK 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  550 LQQQLQESQQMLGRLIpEKQILSDQLKqVQQNSLHRDSLLTLKRALEAKELaRQQLREQLDEVERETRSKLQEIDVFNNQ 629
Cdd:COG1340   148 ELEKAKKALEKNEKLK-ELRAELKELR-KEAEEIHKKIKELAEEAQELHEE-MIELYKEADELRKEADELHKEIVEAQEK 224

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  630 LKELREihskQQLQKQRSLEAAR--LKQKEQERKSLELEKQKEDAQRRVQE 678
Cdd:COG1340   225 ADELHE----EIIELQKELRELRkeLKKLRKKQRALKREKEKEELEEKAEE 271

Src Homology 3 domain of Sorting nexin 9; Sorting nexin 9 (SNX9), also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX9 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212831 Cd Length: 57 Bit Score: 37.92 E-value: 1.98e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1096 AQVIASYAA-TGPEQLTLAPGQLILIRKKNPGGWWegeLQARGKKRQIGWFPANYVKLL 1153
Cdd:cd11898     2 ARVLYDFAAePGNNELTVKEGEIITVTNPNVGGGW---IEAKNSQGERGLVPTDYVEIV 57

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 38.03 E-value: 2.00e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESqtGEPGWLGGEL--KGKTGWFPANY 817
Cdd:cd11926     2 YVAIYPYTPRKEDELELRKGEMFLVFER--CQDGWFKGTSmhTSKIGVFPGNY 52

RNase Y N-terminal region;

Pssm-ID: 463456 [Multi-domain] Cd Length: 201 Bit Score: 41.41 E-value: 2.00e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330   375 DKKRENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKER-ER-----QEQERKRQL-ELEKQLEK 438
Cdd:pfam12072   95 DRKDESLEKKEESLEKKEKELEAQQQQLEEKEEELEELIEEQRQElERisgltSEEAKEILLdEVEEELRH 165

First Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck2 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212832 [Multi-domain] Cd Length: 58 Bit Score: 38.19 E-value: 2.01e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNkEDPDWWK-GEVSGQVGLFPSNYVK 1227
Cdd:cd11899     6 VIAKWDYTAQQDQELDIKKNERLWLLD-DSKTWWRvRNAANRTGYVPSNYVE 56

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 37.97 E-value: 2.04e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-----WWFGEVQGQKGWFPKSYV 983
Cdd:cd11941     1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDKkgspeWSLVEVNGQRGYVPSSYL 55

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 40.16 E-value: 2.07e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997330  236 AAEWAVPQSSRLKYRQLFNSHDKTMSGHLTGPQARTILMQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMH 308
Cdd:COG5126    58 GMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEFVAAVR 130

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 43.00 E-value: 2.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  378 RENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEkqrelerqrEEERRKEIERR 457
Cdd:COG1196   643 AGRLREVTLEGEGGSAGGSLTGGSRRELLAALLEAEAELEELAERLAEEELELEEALLAE---------EEEERELAEAE 713

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  458 EAAKRELERQRQLEWERNR-RQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDI------------RC 524
Cdd:COG1196   714 EERLEEELEEEALEEQLEAeREELLEELLEEEELLEEEALEELPEPPDLEELERELERLEREIEALgpvnllaieeyeEL 793

                         170       180
                  ....*....|....*....|....*...
gi 568997330  525 R-----LATQRQEIESTNKSRELRIAEI 547
Cdd:COG1196   794 EerydfLSEQREDLEEARETLEEAIEEI 821

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 37.85 E-value: 2.15e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGEVQ---GQKGWFPKSYVKL 985
Cdd:cd11940     1 QVQCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGVRlsdGERGWFPQSHVEE 55

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 37.75 E-value: 2.17e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1102 YAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKL 1152
Cdd:cd11828     8 HVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDE-----EGWFPASFVRL 53

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 38.06 E-value: 2.23e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  932 GLQAQALYPWRAKKDNHLNFNKSDVITVLEQQDM-WWFGEVQ--GQKGWFPKSYVKLI 986
Cdd:cd11933     1 GKSFRAMYDYRAADDDEVSFKDGDTIVNVQTIDEgWMYGTVQrtGKTGMLPANYVEAI 58

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176012 [Multi-domain] Cd Length: 110 Bit Score: 39.47 E-value: 2.25e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1620 VEGIELKPCRSHGKSNPYCEVTMGS------QCHITKTIQDTLNPKWNsncQFFIR-------DLEQEVLcITVFERDQF 1686
Cdd:cd04047     7 FSGKKLDKKDFFGKSDPFLEISRQSedgtwvLVYRTEVIKNTLNPVWK---PFTIPlqklcngDYDRPIK-IEVYDYDSS 82

                          90       100
                  ....*....|....*....|.
gi 568997330 1687 SPDDFLGRTEIRVADIKKDQG 1707
Cdd:cd04047    83 GKHDLIGEFETTLDELLKSSP 103

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 43.00 E-value: 2.27e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  119 PSTLPPVMKQQPVAISSAPAFGIGGIASMPPLTAVAPVPMGSIPVVGmSPPLVSSvPPAAVPPLANGAPPviqplpafaH 198
Cdd:PHA03247 2712 PHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPA-RPPTTAG-PPAPAPPAAPAAGP---------P 2780

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  199 PAATLPKSSSFSRSGPGSQLntklqKAQSFDVASAPPAAEWAVPQSSR 246
Cdd:PHA03247 2781 RRLTRPAVASLSESRESLPS-----PWDPADPPAAVLAPAAALPPAAS 2823

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 38.08 E-value: 2.39e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVL------EQQDMWWFG--EVQGQKGWFPKSYVKLI 986
Cdd:cd11790     5 VRATHDYTAEDTDELTFEKGDVILVIpfddpeEQDEGWLMGvkESTGCRGVFPENFTERI 64

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212946 Cd Length: 61 Bit Score: 37.74 E-value: 2.40e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1025 IAMYTYESSE-------QGDLTFQQGDVIVV---TKKDGdWWTGTVGDKSGVFPSNYVR 1073
Cdd:cd12013     3 VALFDYDPREsspnvdaEVELSFRAGDIITVfgeMDEDG-FYYGELNGQRGLVPSNFLE 60

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 37.61 E-value: 2.40e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVV----TKKDGDWWTGTVGDKSGVFPS 1069
Cdd:cd11894     4 ALYDYEGQTDDELSFPEGAIIRIlnkeNQDDDGFWEGEFNGRIGVFPS 51

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 442330 [Multi-domain] Cd Length: 1470 Bit Score: 43.02 E-value: 2.42e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  397 EQQRKEQERLAQLERAEQerKERERQEQERKRQLELEKQLEKQrelerqrEEERRKEIERREAAKRELER----QRQLEW 472
Cdd:COG3096   278 NERRELSERALELRRELF--GARRQLAEEQYRLVEMARELEEL-------SARESDLEQDYQAASDHLNLvqtaLRQQEK 348

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  473 ERNRRQEL--LNQRNKEQEGTVV-LKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQ-------RQEIESTNKSREL 542
Cdd:COG3096   349 IERYQEDLeeLTERLEEQEEVVEeAAEQLAEAEARLEAAEEEVDSLKSQLADYQQALDVQqtraiqyQQAVQALEKARAL 428

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  543 -RIAEIThlqqqlqeSQQMLGRLipekQILSDQLKQVQQnslhrdSLLTLKRALEAKELARQQLREQL-------DEVER 614
Cdd:COG3096   429 cGLPDLT--------PENAEDYL----AAFRAKEQQATE------EVLELEQKLSVADAARRQFEKAYelvckiaGEVER 490

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  615 ETRSKlqeidvfnnQLKELREIHSKQQLQKQR--SLEA--ARLKQKEQERKSLElEKQKEDAQRRVQERDKQW-LEHVQQ 689
Cdd:COG3096   491 SQAWQ---------TARELLRRYRSQQALAQRlqQLRAqlAELEQRLRQQQNAE-RLLEEFCQRIGQQLDAAEeLEELLA 560

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  690 EeqprprkpHEEDRLKREDSVRkKEAEERAKPEMQDKQSRlfhphQEPAKLATQAP-W 746
Cdd:COG3096   561 E--------LEAQLEELEEQAA-EAVEQRSELRQQLEQLR-----ARIKELAARAPaW 604

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442439 [Multi-domain] Cd Length: 687 Bit Score: 42.70 E-value: 2.47e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  378 RENFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKER-------ERQEQERKRQLELEKQLEKqrelerqreeer 450
Cdd:COG3206   163 EQNLELRREEARKALEFLEEQLPELRKELEEAEAALEEFRQKnglvdlsEEAKLLLQQLSELESQLAE------------ 230

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  451 rkEIERREAAKRELER-QRQLEWERNRRQELLNQRNKEQegtvvLKARRKTLEFELEALNDK---KH----QLEGKLQDI 522
Cdd:COG3206   231 --ARAELAEAEARLAAlRAQLGSGPDALPELLQSPVIQQ-----LRAQLAELEAELAELSARytpNHpdviALRAQIAAL 303

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  523 RCRLATQRQEIESTNKSR----ELRIAEIthlqqqlqesqqmlgrlipeKQILSDQLKQVQQNSLHRDSLLTLKRALEAK 598
Cdd:COG3206   304 RAQLQQEAQRILASLEAElealQAREASL--------------------QAQLAQLEARLAELPELEAELRRLEREVEVA 363

                         250
                  ....*....|....*
gi 568997330  599 ELARQQLREQLDEVE 613
Cdd:COG3206   364 RELYESLLQRLEEAR 378

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

Pssm-ID: 464768 [Multi-domain] Cd Length: 374 Bit Score: 42.33 E-value: 2.47e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   416 RKERERQEQERKRQLELEKQLEKqrelerqreeerrkeierreaakrelERQRQLEWERNRRQELL-NQRNKEQEgtvvL 494
Cdd:pfam15558   18 KEEQRMRELQQQAALAWEELRRR--------------------------DQKRQETLERERRLLLQqSQEQWQAE----K 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   495 KARRKTLEFELEALNDKKhQLEGKLQDIRCRLATQRQEiestnKSRELRIaeithlqqqlqesqqmlgrlipEKQILSDQ 574
Cdd:pfam15558   68 EQRKARLGREERRRADRR-EKQVIEKESRWREQAEDQE-----NQRQEKL----------------------ERARQEAE 119

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   575 LKQVQQnslhrdslltlKRALEAKELARQQLREQldevERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLK 654
Cdd:pfam15558  120 QRKQCQ-----------EQRLKEKEEELQALREQ----NSLQLQERLEEACHKRQLKEREEQKKVQENNLSELLNHQARK 184

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 568997330   655 Q---------KEQERKSLELEKQK--EDAQRRVQERDKQWLEHVQQEEQ 692
Cdd:pfam15558  185 VlvdcqakaeELLRRLSLEQSLQRsqENYEQLVEERHRELREKAQKEEE 233

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 38.05 E-value: 2.50e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQK--GWFPKSYVK 984
Cdd:cd11917     8 QALYNYMPRNEDELELREGDVIDVMEKCDDGWFvGTSRRTKffGTFPGNYVK 59

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 37.91 E-value: 2.53e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997330  248 KYRQLFNSHDKTMSGHLTGPQARTIL--MQSSLPQAQLASIWNLSDIDQDGKLTAEEFILAMH 308
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALksLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 42.73 E-value: 2.54e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   393 QALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKqLEKQRELERQREEERRKEIERREAAKRELERQRQLEW 472
Cdd:TIGR00606  690 EAELQEFISDLQSKLRLAPDKLKSTESELKKKEKRRDEMLGL-APGRQSIIDLKEKEIPELRNKLQKVNRDIQRLKNDIE 768

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   473 ERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRiaeithlqq 552
Cdd:TIGR00606  769 EQETLLGTIMPEEESAKVCLTDVTIMERFQMELKDVERKIAQQAAKLQGSDLDRTVQQVNQEKQEKQHELD--------- 839

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   553 qlqeSQQMLGRLIpeKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKE 632
Cdd:TIGR00606  840 ----TVVSKIELN--RKLIQDQQEQIQHLKSKTNELKSEKLQIGTNLQRRQQFEEQLVELSTEVQSLIREIKDAKEQDSP 913

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   633 LRE------------IHSKQQLQKQRSLE----AARLKQKEQERKSLELEKQK-EDAQRRVQERDKQWLEHVQQEEQPRP 695
Cdd:TIGR00606  914 LETflekdqqekeelISSKETSNKKAQDKvndiKEKVKNIHGYMKDIENKIQDgKDDYLKQKETELNTVNAQLEECEKHQ 993

                          330       340
                   ....*....|....*....|.
gi 568997330   696 RKPHEEDRLKREDSVRKKEAE 716
Cdd:TIGR00606  994 EKINEDMRLMRQDIDTQKIQE 1014

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 37.68 E-value: 2.56e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQ---QDMWWFGE-VQGQKGWFPKSYVKL 985
Cdd:cd11767     2 VVALYPFTGENDEELSFEKGERLEIIEKpedDPDWWKARnALGTTGLVPRNYVEV 56

Chromosome segregation protein NDC80, interacts with SMC proteins [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 444066 [Multi-domain] Cd Length: 594 Bit Score: 42.64 E-value: 2.58e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  354 PEEPSSEDEQQPEK-KLPVTFEDKKRENFERGSVELEKRrqalLEQQRKEQERlaQLERAEQERKERERQEQERKRQLEL 432
Cdd:COG5185   241 PESELEDLAQTSDKlEKLVEQNTDLRLEKLGENAESSKR----LNENANNLIK--QFENTKEKIAEYTKSIDIKKATESL 314

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  433 EKQLEKQRELERQreeerrkeierreaAKRELERQRQLeweRNRRQELLNQRNKEQEGTVVLKARRKTLEFEL------E 506
Cdd:COG5185   315 EEQLAAAEAEQEL--------------EESKRETETGI---QNLTAEIEQGQESLTENLEAIKEEIENIVGEVelskssE 377

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  507 ALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQNSLHRD 586
Cdd:COG5185   378 ELDSFKDTIESTKESLDEIPQNQRGYAQEILATLEDTLKAADRQIEELQRQIEQATSSNEEVSKLLNELISELNKVMREA 457

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  587 SLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELREiHSKQQLQKQRSLE---AARLKQKEQERKsL 663
Cdd:COG5185   458 DEESQSRLEEAYDEINRSVRSKKEDLNEELTQIESRVSTLKATLEKLRA-KLERQLEGVRSKLdqvAESLKDFMRARG-Y 535

                         330       340       350
                  ....*....|....*....|....*....|....
gi 568997330  664 ELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPRK 697
Cdd:COG5185   536 AHILALENLIPASELIQASNAKTDGQAANLRTAV 569

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 37.76 E-value: 2.60e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVV-TKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11806     1 EYVAIADFVATDDSQLSFESGDKLLVlRKPSVDWWWAEHNGCCGYIPASHL 51

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 39.87 E-value: 2.63e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHITKT-----IQDTLNPKWNSNCQFFI--RDLEQEVLCITVFERDQ 1685
Cdd:cd08410    14 GRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTkktscMRGTIDPFYNESFSFKVpqEELENVSLVFTVYGHNV 93

                          90
                  ....*....|..
gi 568997330 1686 FSPDDFLGRTEI 1697
Cdd:cd08410    94 KSSNDFIGRIVI 105

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 41.82 E-value: 2.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQL--ELEKQLEKqrelerqreeerrkeierreaaKREL 464
Cdd:COG1340    12 ELEEKIEELREEIEELKEKRDELNEELKELAEKRDELNAQVKELreEAQELREK----------------------RDEL 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  465 -ERQRQLeweRNRRQELLNQRN----------KEQEGTVVLKARRKTLEFELEALN----------DKKHQLEGKLQDIR 523
Cdd:COG1340    70 nEKVKEL---KEERDELNEKLNelreeldelrKELAELNKAGGSIDKLRKEIERLEwrqqtevlspEEEKELVEKIKELE 146

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  524 CRLATQRQEIESTNKSRELRiAEITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQnslHRDSLLtlKRALEAKElARQ 603
Cdd:COG1340   147 KELEKAKKALEKNEKLKELR-AELKELRKEAEEIHKKIKELAEEAQELHEEMIELYK---EADELR--KEADELHK-EIV 219

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330  604 QLREQLDEVEretrsklQEIDVFNNQLKELREihskqQLQKQRSLEAARLKQKEQErkslELEKQKEDA 672
Cdd:COG1340   220 EAQEKADELH-------EEIIELQKELRELRK-----ELKKLRKKQRALKREKEKE----ELEEKAEEI 272

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 37.46 E-value: 2.72e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  773 FESRSHDEITIQPGDIVMVdeSQTGEPGWLGGEL--KGKTGWFPANYAE 819
Cdd:cd11940     8 YKAQENDELTLEKADIIMV--RQQSSDGWLEGVRlsDGERGWFPQSHVE 54

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 37.51 E-value: 2.74e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVI-TVLEQQDMWWFGEVQGQ-KGWFPKSYVK 984
Cdd:cd11969     3 KALYDYRAKRSDELSFCKGALIhNVSKETGGWWKGDYGGKvQHYFPSNYVE 53

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212858 Cd Length: 57 Bit Score: 37.67 E-value: 2.80e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVTKKDGD-WWTGTV--GDKSGVFPSNYV 1072
Cdd:cd11925     3 YLALYAYKPQKNDELELRKGEMYRVIEKCQDgWFKGTSlrTGVSGVFPGNYV 54

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 39.45 E-value: 2.82e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1632 GKSNPYCEVTM-----GSQC-HITKTIQD-TLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSpDDFLGRTEIRVADIKK 1704
Cdd:cd00275    23 SIVDPYVEVEIhglpaDDSAkFKTKVVKNnGFNPVWNETFEFDVTVPELAFLRFVVYDEDSGD-DDFLGQACLPLDSLRQ 101

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 42.25 E-value: 2.86e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   360 EDEQQPEKKLPVTFEDKKRENFErgSVELEKRRQALLEQQRKEQERLAQL-ERAEQERKERERQEQERK-RQLELEKQLE 437
Cdd:pfam15709  365 QEQLERAEKMREELELEQQRRFE--EIRLRKQRLEEERQRQEEEERKQRLqLQAAQERARQQQEEFRRKlQELQRKKQQE 442

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330   438 K----QRELERQREEERRKEIERRE----AAKRELERQRQ-LEWERNRRQELLNQRNKEQE 489
Cdd:pfam15709  443 EaeraEAEKQRQKELEMQLAEEQKRlmemAEEERLEYQRQkQEAEEKARLEAEERRQKEEE 503

Second Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the second SH3 domain, located C-terminal of the first SH3 domain at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212863 Cd Length: 55 Bit Score: 37.66 E-value: 2.92e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQND----DELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNYV 1226
Cdd:cd11930     1 QCKALYDFEVKDKeadkDCLPFAKDDILTVIRRVDENWAEGMLGDKIGIFPISYV 55

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 37.44 E-value: 2.93e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMVDESQTgePGWLGGELKGKTGWFPANYAEK 820
Cdd:cd12016     3 YITTQAYKAENEDEIGFETGVVVEVIQKNL--DGWWKIRYQGKEGWAPATYLKK 54

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 37.71 E-value: 2.98e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGEpgWLGGELKG-----KTGWFPANYAEK 820
Cdd:cd11887     5 KALYPYESDHEDDLNFDVGQLITVTEEEDAD--WYFGEYVDsngntKEGIFPKNFVEV 60

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212972 Cd Length: 62 Bit Score: 37.63 E-value: 3.02e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1180 MYDYTAQNDDE-------LAFSKGQIINVLNKEDPDWWK----GEVSGQVGLFPS 1223
Cdd:cd12039     5 LFDYNPYEDRAipcqeagLPFKRRDILEVVSQDDPTWWQakrvGDTNLRAGLIPS 59

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 37.57 E-value: 3.04e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQ-DM--WWFGEVQGQKGWFPKSYV 983
Cdd:cd12045     3 QGLWDCTGDQPDELSFKRGDTIYILSKEyNRfgWWVGEMKGTIGLVPKAYI 53

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212871 Cd Length: 55 Bit Score: 37.52 E-value: 3.05e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKrqiGWFPANYVK 1151
Cdd:cd11938     3 EIIKAYTAKQPDELSLQQADVVLVLQTESDGWYYGERLRDGER---GWFPSSCAK 54

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

Pssm-ID: 402959 [Multi-domain] Cd Length: 164 Bit Score: 40.44 E-value: 3.17e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330   652 RLKQKEQERKSLELEKQKEDAQRRV-QERDKQWLEHVQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQ 727
Cdd:pfam11600    5 KSVQSQEEKEKQRLEKDKERLRRQLkLEAEKEEKERLKEEAKAEKERAKEEARRKKEEEKELKEKERREKKEKDEKE 81

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 37.47 E-value: 3.21e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 986
Cdd:cd11869     1 RAEALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLeGTVRGATGIFPLSFVKII 54

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212856 [Multi-domain] Cd Length: 57 Bit Score: 37.59 E-value: 3.27e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1023 EFIAMYTYESSEQGDLTFQQGDVIVVTKK-DGDWWTGTV--GDKSGVFPSNYVRL 1074
Cdd:cd11923     2 EAVAKYNFNADTNVELSLRKGDRVVLLKQvDQNWYEGKIpgTNRQGIFPVSYVEV 56

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 39.71 E-value: 3.27e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTM---GSQCHITKTI--QDTLNPKWNSNCQF-----FIRDLEqevLCITVFE 1682
Cdd:cd08405    15 NRITVNIIKARNLKAMDINGTSDPYVKVWLmykDKRVEKKKTVikKRTLNPVFNESFIFnipleRLRETT---LIITVMD 91

                          90
                  ....*....|..
gi 568997330 1683 RDQFSPDDFLGR 1694
Cdd:cd08405    92 KDRLSRNDLIGK 103

Alpha helical coiled-coil rod protein (HCR); This family consists of several mammalian alpha helical coiled-coil rod HCR proteins. The function of HCR is unknown but it has been implicated in psoriasis in humans and is thought to affect keratinocyte proliferation.

Pssm-ID: 284517 [Multi-domain] Cd Length: 749 Bit Score: 42.43 E-value: 3.27e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   462 RELERQRQLEWE-RNRRQELLNQrnkeqegtvvlKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQ---RQEIESTN 537
Cdd:pfam07111   70 RQLQELRRLEEEvRLLRETSLQQ-----------KMRLEAQAMELDALAVAEKAGQAEAEGLRAALAGAemvRKNLEEGS 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   538 KsRELRIAEITHLQQQLQesqqmlgrLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELARQQ-----LREQLDEV 612
Cdd:pfam07111  139 Q-RELEEIQRLHQEQLSS--------LTQAHEEALSSLTSKAEGLEKSLNSLETKRAGEAKQLAEAQkeaelLRKQLSKT 209

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   613 ERETRSKLQEIDVFNNQLKE--LREIHSKQ-QLQKQRSLEAarLKQKEQERKSleLEKQKEDAQRRVQErdkqwLEHV-- 687
Cdd:pfam07111  210 QEELEAQVTLVESLRKYVGEqvPPEVHSQTwELERQELLDT--MQHLQEDRAD--LQATVELLQVRVQS-----LTHMla 280

                          250
                   ....*....|..
gi 568997330   688 -QQEEQPRPRKP 698
Cdd:pfam07111  281 lQEEELTRKIQP 292

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 37.33 E-value: 3.34e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQTGepgWLGGELKGKTGWFPANY 817
Cdd:cd11990     3 QALCSWTAKKDNHLNFSKNDIITVLEQQEN---WWFGEVHGGRGWFPKSY 49

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 37.33 E-value: 3.37e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGgWWEGELqaRGKKrqiGWFPANYVKL 1152
Cdd:cd11990     2 AQALCSWTAKKDNHLNFSKNDIITVLEQQEN-WWFGEV--HGGR---GWFPKSYVKL 52

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 213001 Cd Length: 55 Bit Score: 37.16 E-value: 3.39e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1177 VIGMYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGEVSGQVGLFPSNYVKL 1228
Cdd:cd12068     2 VVALRSYITDDKSLLSFHRGDLIKLLPMAglEPGWQFGSTGGRSGLFPADIVQP 55

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 37.30 E-value: 3.51e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1096 AQVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKLL 1153
Cdd:cd11920     3 ARAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGR-----VGIFPISYVEKL 55

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 37.31 E-value: 3.53e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330  763 KVVyyrALYPFESRSHDEITIQPGDIVMVdeSQTGEPGWLGGELKGKTGWFPANYAEKI 821
Cdd:cd11971     1 KVV---AIYDYSKDKDDELSFMEGAIIYV--IKKNDDGWYEGVCNGVTGLFPGNYVESI 54

DNA polymerase III subunit gamma/tau;

Pssm-ID: 237057 [Multi-domain] Cd Length: 700 Bit Score: 42.17 E-value: 3.56e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  140 GIGGIASMPPLTA---VAPVPMGSIPVVGMSPPLVSSVPPAAVPPLANGAPPVIQPLPAFAHPAATLPKSSSFSRSGPGS 216
Cdd:PRK12323  367 QSGGGAGPATAAAapvAQPAPAAAAPAAAAPAPAAPPAAPAAAPAAAAAARAVAAAPARRSPAPEALAAARQASARGPGG 446

                          90       100
                  ....*....|....*....|....*.
gi 568997330  217 qlntklqkaqsfdvASAPPAAEWAVP 242
Cdd:PRK12323  447 --------------APAPAPAPAAAP 458

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 37.22 E-value: 3.59e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  764 VVYyrALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd11952     2 VVY--ALWDYSAEFPDELSFKEGDMVTVLRKDGEGTDWWWASLCGREGYVPRNY 53

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 42.06 E-value: 3.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   114 QGYQLPSTLPPV----MKQQPVAISSAPAfgiggiaSMPPLTAvaPVPMGSIPVVGMSPPLVSSVPPAAVPPLANGAPPV 189
Cdd:pfam03154  308 QVPPGPSPAAPGqsqqRIHTPPSQSQLQS-------QQPPREQ--PLPPAPLSMPHIKPPPTTPIPQLPNPQSHKHPPHL 378

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   190 IQP----LPAFAHPAATLPKSSSFSRSGPGSQLNTKLQKAQSFDVASAPPAAEWAVPQSSrlkyrqlfnSHDKTMSGHLT 265
Cdd:pfam03154  379 SGPspfqMNSNLPPPPALKPLSSLSTHHPPSAHPPPLQLMPQSQQLPPPPAQPPVLTQSQ---------SLPPPAASHPP 449

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   266 GPQARTILMQSSLPQAQLasiwnlsdidqdgkltaeefilamhlidvaMSGQPlPPVLPPEYIPPSFRRVRSGSGMSVIS 345
Cdd:pfam03154  450 TSGLHQVPSQSPFPQHPF------------------------------VPGGP-PPITPPSGPPTSTSSAMPGIQPPSSA 498

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   346 SSSVDQRLP-------------EEPSSEDEQqPEKKLP-----------------VTFEDKKRENFERGSVELEKRRQAL 395
Cdd:pfam03154  499 SVSSSGPVPaavscplppvqikEEALDEAEE-PESPPPpprspspeptvvntpshASQSARFYKHLDRGYNSCARTDLYF 577

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 568997330   396 --LEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQ 439
Cdd:pfam03154  578 mpLAGSKLAKKREEALEKAKREAEQKAREEKEREKEKEKERERERE 623

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 42.36 E-value: 3.65e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  392 RQAL-LEQQRKEQERLAQLERAEQERKER-----ERQEQERKRQLELEKQLEKQRELERQREEERRKEIERREAAKRELE 465
Cdd:PRK03918  152 RQILgLDDYENAYKNLGEVIKEIKRRIERlekfiKRTENIEELIKEKEKELEEVLREINEISSELPELREELEKLEKEVK 231

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  466 RqrqLEwernRRQELLNQrnkeqegtvvlkarrktLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTnKSRELRIA 545
Cdd:PRK03918  232 E---LE----ELKEEIEE-----------------LEKELESLEGSKRKLEEKIRELEERIEELKKEIEEL-EEKVKELK 286

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  546 EITHLQQQLQESQQMLGRLIPEKQILSDQLKQVQQnslHRDSLLTLKRALEAKELARQQLREQLDEVER-----ETRSKL 620
Cdd:PRK03918  287 ELKEKAEEYIKLSEFYEEYLDELREIEKRLSRLEE---EINGIEERIKELEEKEERLEELKKKLKELEKrleelEERHEL 363

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  621 -QEIDVFNNQLKELREIHSKQQLQK-QRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQwLEHVQQEEQP----- 693
Cdd:PRK03918  364 yEEAKAKKEELERLKKRLTGLTPEKlEKELEELEKAKEEIEEEISKITARIGELKKEIKELKKA-IEELKKAKGKcpvcg 442

                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 568997330  694 RPRKPHEEDRLKREDSVRKKEAEERAKpEMQDKQSRL 730
Cdd:PRK03918  443 RELTEEHRKELLEEYTAELKRIEKELK-EIEEKERKL 478

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 42.05 E-value: 3.73e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1610 TGIGRLMVNVVEGIELKPCRSH--GKSNPYCEVTMGSQCH-ITKTIQDTLNPKWNSNCQFFIRDLEQEvLCITVFERDQF 1686
Cdd:COG5038   433 TAIGVVEVKIKSAEGLKKSDSTinGTVDPYITVTFSDRVIgKTRVKKNTLNPVWNETFYILLNSFTDP-LNLSLYDFNSF 511

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330 1687 SPDDFLGRTEIRVADIKKDQGSKGPVTKcLLLHEVPTGEIVvrLDLQLF 1735
Cdd:COG5038   512 KSDKVVGSTQLDLALLHQNPVKKNELYE-FLRNTKNVGRLT--YDLRFF 557

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 37.29 E-value: 3.81e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330  771 YPFESRSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANY 817
Cdd:cd11902     7 FAYVAEREDELSLVKGSRVTVMEKCSD--GWWRGSYNGQIGWFPSNY 51

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 37.28 E-value: 3.82e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  934 QAQALYPWRAKKDNHLNFNKSDVITVL-EQQDMWWFGEVQGQKGWFPKSYVK 984
Cdd:cd12055     1 RCQVAFSYLPQNEDELELKVGDIIEVVgEVEEGWWEGVLNGKTGMFPSNFIK 52

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 41.41 E-value: 3.83e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  362 EQQPEKKLPVTFEDKKReNFERGSVELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLE 437
Cdd:cd16269   217 LEEQQRELEQKLEDQER-SYEEHLRQLKEKMEEERENLLKEQERALESKLKEQEALLEEGFKEQAELLQEEIRSLK 291

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 37.22 E-value: 3.99e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKD------GdWWTGTVGD-KSGVFPSNYVRL 1074
Cdd:cd11864     3 RAEYDFVAESEDELSFRAGDKLRLAPKElqprvrG-WLLATVDGqKIGLVPANYVKI 58

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 36.94 E-value: 4.30e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  768 RALYPFESRSHDEITIQPGDIVM----VDESqtgepgWLGGELKGKTGWFPANYAE 819
Cdd:cd11782     3 RAKYNFNADTGVELSFRKGDVITltrrVDEN------WYEGRIGGRQGIFPVSYVQ 52

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 37.25 E-value: 4.39e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330 1097 QVIASYAATG--PEQLTLAPGQLI-LIRKKNpGGWWEGELQARGKKrqiGWFPANYVKL 1152
Cdd:cd11924     2 EAVAQYTFKGdlEVELSFRKGEHIcLIRKVN-ENWYEGRITGTGRQ---GIFPASYVQV 56

DNA polymerase III subunit gamma/tau;

Pssm-ID: 237874 [Multi-domain] Cd Length: 614 Bit Score: 41.68 E-value: 4.49e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  119 PSTLPPVMKQQP-VAISSAPAFGIGGIASMPPLTAVAPVPMGSIPVVGMSPPLVSSVPPAAVPPLANGAPPVIQPLPafa 197
Cdd:PRK14971  381 PVFTQPAAAPQPsAAAAASPSPSQSSAAAQPSAPQSATQPAGTPPTVSVDPPAAVPVNPPSTAPQAVRPAQFKEEKK--- 457

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568997330  198 hpaATLPKSSSFSRSGPGSQLNTKLQKAQSFDVASAPPAAE 238
Cdd:PRK14971  458 ---IPVSKVSSLGPSTLRPIQEKAEQATGNIKEAPTGTQKE 495

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 36.96 E-value: 4.62e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997330 1093 PEIAQVIASYAATGPEQLTLAPGQLI-LIRKKNPGGWwegeLQARGKKRQIGWFPANYVKL 1152
Cdd:cd11761     1 PVTCKVLYSYEAQRPDELTITEGEELeVIEDGDGDGW----VKARNKSGEVGYVPENYLQF 57

Domain of unknown function (DUF4686); This family of proteins is found in eukaryotes. Proteins in this family are typically between 498 and 775 amino acids in length. There is a conserved DLK sequence motif.

Pssm-ID: 464838 [Multi-domain] Cd Length: 384 Bit Score: 41.20 E-value: 4.68e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   390 KRRQALLEQQRKEQERLAQ-LER-------AEQE-RKERER-----------QEQERKRQLELeKQLEKQRELERQREEE 449
Cdd:pfam15742    2 SSGEKLKYQQQEEVQQLRQnLQRlqilctsAEKElRYERGKnldlkqhnsllQEENIKIKAEL-KQAQQKLLDSTKMCSS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   450 RRKEIERREAAKRELE----RQRQLEWERNRRQELLNQrnkeqEGTVVLKARRKTLEFE-----------LEALNDKKHQ 514
Cdd:pfam15742   81 LTAEWKHCQQKIRELElevlKQAQSIKSQNSLQEKLAQ-----EKSRVADAEEKILELQqklehahkvclTDTCILEKKQ 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   515 LEGKLQDIRCRLATQRQEIESTNKSREL---RIAEITHLQQQLQESQQMLGRLIPEKQI----LSDQLKQVQQNSLHRDS 587
Cdd:pfam15742  156 LEERIKEASENEAKLKQQYQEEQQKRKLldqNVNELQQQVRSLQDKEAQLEMTNSQQQLriqqQEAQLKQLENEKRKSDE 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   588 LLTLKRALEAKELARQQLREQLDEverETRSKLQEIDVFNNQLKElREIHSKQQLQKQRSLEAARLKQKEQERKslELEK 667
Cdd:pfam15742  236 HLKSNQELSEKLSSLQQEKEALQE---ELQQVLKQLDVHVRKYNE-KHHHHKAKLRRAKDRLVHEVEQRDERIK--QLEN 309

                          330       340
                   ....*....|....*....|....*
gi 568997330   668 QKEDAQRRVqERDKQWLEHVQQEEQ 692
Cdd:pfam15742  310 EIGILQQQS-EKEKAFQKQVTAQNE 333

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 41.70 E-value: 4.69e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   360 EDEQQPEK----KLPVTFEDKKrENFERgsvELEKRRQALLEQQRKEQERLAQLE-RAEQERKERErQEQERKRQLELE- 433
Cdd:pfam01576  705 EDELQATEdaklRLEVNMQALK-AQFER---DLQARDEQGEEKRRQLVKQVRELEaELEDERKQRA-QAVAAKKKLELDl 779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   434 KQLEKQRELERQREEERRKEIERREAAKRELerQRQLEWERNRRQELLNQ-RNKE-------------QEGTVVLKARRK 499
Cdd:pfam01576  780 KELEAQIDAANKGREEAVKQLKKLQAQMKDL--QRELEEARASRDEILAQsKESEkklknleaellqlQEDLAASERARR 857

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   500 TLEFELE--------------ALNDKKHQLEGKLQDIRCRLATQRQEIESTN---KSRELRIAEITH--LQQQLQESQQM 560
Cdd:pfam01576  858 QAQQERDeladeiasgasgksALQDEKRRLEARIAQLEEELEEEQSNTELLNdrlRKSTLQVEQLTTelAAERSTSQKSE 937

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   561 LGRLIPEKQILSDQLKQVQQNSLHRDSLLTLKRALEAKELarqQLREQLDEVERETRSKLQEIDVFNNQLKEL-----RE 635
Cdd:pfam01576  938 SARQQLERQNKELKAKLQEMEGTVKSKFKSSIAALEAKIA---QLEEQLEQESRERQAANKLVRRTEKKLKEVllqveDE 1014

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 568997330   636 IHSKQQLQKQRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERD 680
Cdd:pfam01576 1015 RRHADQYKDQAEKGNSRMKQLKRQLEEAEEEASRANAARRKLQRE 1059

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 36.82 E-value: 4.86e-03

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 568997330 1037 DLTFQQGDVIVVTKK-DGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11921    16 ELTLQKGDIVYIHKEvDKNWLEGEHHGRVGIFPANYVEV 54

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 37.40 E-value: 4.87e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330  935 AQALYPWRAKKDNHLNFNKSDVITVLEQQ-DMWWFGEVQG-----QKGWFPKSYVKLIS 987
Cdd:cd11993     6 AQVIASYTATGPEQLTLAPGQLILIRKKNpGGWWEGELQArgkkrQIGWFPANYVKLLS 64

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 213001 Cd Length: 55 Bit Score: 36.78 E-value: 4.88e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDG---DWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd12068     3 VALRSYITDDKSLLSFHRGDLIKLLPMAGlepGWQFGSTGGRSGLFPADIVQP 55

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 36.74 E-value: 4.90e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1097 QVIA--SYAATGPEQLTLAPGQLILIRKKNPGGWWEGElqARGKkrqIGWFPANYVK 1151
Cdd:cd11870     1 QVVAlhRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGH--SDGR---VGIFPKCFVV 52

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 36.91 E-value: 4.91e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568997330 1104 ATGPEQLTLAPGQLILIRKKNPGGWWEGELQarGKKRQIGWFPANY 1149
Cdd:cd11821    10 ADNDDELTFSEGEIIVVTGEEDDEWWEGHIE--GDPSRRGVFPVSF 53

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 36.64 E-value: 4.95e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  936 QALYPWRAKKDNHLNFNKSDVITVLEQQ---DMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11866     3 MGLWDCSGNEPDELSFKRGDLIYIISKEydsFGWWVGELNGKVGLVPKDYL 53

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 442330 [Multi-domain] Cd Length: 1470 Bit Score: 41.86 E-value: 5.09e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  393 QALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQrelerqreeerrkeIERREAAKRELERQrQLEW 472
Cdd:COG3096   498 RELLRRYRSQQALAQRLQQLRAQLAELEQRLRQQQNAERLLEEFCQR--------------IGQQLDAAEELEEL-LAEL 562

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997330  473 ERnRRQELLNQRNKEQEgtvvlkaRRKTLEFELEALNDKKHQLEGK------LQDIRCRLATQ 529
Cdd:COG3096   563 EA-QLEELEEQAAEAVE-------QRSELRQQLEQLRARIKELAARapawlaAQDALERLREQ 617

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 36.90 E-value: 5.24e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGE--VQGQKGWFPKSYV 983
Cdd:cd12004     4 ALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARslTTKKEGFIPSNYV 52

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 41.67 E-value: 5.32e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1613 GRLMVNVVEGIELKPCRSHGKSNPYCEVTM-GSQCHITKTIQDTLNPKWNSNCQFFIRDLEQEVLCITVFERDQFSPDDF 1691
Cdd:COG5038  1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFLnEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDL 1119

                          90       100
                  ....*....|....*....|....
gi 568997330 1692 LGRTEIRVADIK--KDQGSKGPVT 1713
Cdd:COG5038  1120 LGTAEIDLSKLEpgGTTNSNIPLD 1143

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 41.33 E-value: 5.44e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  384 GSVELEKRRQallEQQRKEQERLAQLERAEQERKERERQEQERKRQLELeKQLEKQrelerqreeerrkeierreaakRE 463
Cdd:PRK09510   58 GAVVEQYNRQ---QQQQKSAKRAEEQRKKKEQQQAEELQQKQAAEQERL-KQLEKE----------------------RL 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330  464 LERQRQLEWERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIRCRLATQRQEIESTNKSRE 541
Cdd:PRK09510  112 AAQEQKKQAEEAAKQAALKQKQAEEAAAKAAAAAKAKAEAEAKRAAAAAKKAAAEAKKKAEAEAAKKAAAEAKKKAEA 189

Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunits; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. They play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation, and apoptosis. They are classified according to their substrate specificity, regulation, and domain structure. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit. The R subunit down-regulates PI3K basal activity, stabilizes the C subunit, and plays a role in the activation downstream of tyrosine kinases. All R subunits contain two SH2 domains that flank an intervening helical domain (iSH2), which binds to the N-terminal adaptor-binding domain (ABD) of the catalytic subunit. In vertebrates, there are three genes (PIK3R1, PIK3R2, and PIK3R3) that encode for different Class IA PI3K R subunits.

Pssm-ID: 214016 [Multi-domain] Cd Length: 152 Bit Score: 39.13 E-value: 5.45e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  375 DKKRENFERGSVELEKRRQAL---------LEQQRKEQERLaQLERAEQER---KERERQEQERKRQLE-----LEKQLE 437
Cdd:cd12923    25 DELYEKYNKLSQEIQLKRQALeafeeavkmFEEQLRTQEKF-QKEAQPHEKqrlMENNELLKSRLKELEeskeqLEEDLR 103

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  438 KQRelerqreeerrkeierreAAKRELERQR--------QLEWERNRRQELLNQRNKEQE 489
Cdd:cd12923   104 KQV------------------AYNRELEREMnslkpelmQLRKQKDQYLRWLKRKGVSQE 145

hypothetical protein; Provisional

Pssm-ID: 237178 [Multi-domain] Cd Length: 508 Bit Score: 41.23 E-value: 5.49e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  574 QLKQVQQNSLHRDSLLTLKRAlEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKelREIhsKQQLQKQRSLEAARL 653
Cdd:PRK12705   24 LLKKRQRLAKEAERILQEAQK-EAEEKLEAALLEAKELLLRERNQQRQEARREREELQ--REE--ERLVQKEEQLDARAE 98

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997330  654 KQKEQERKSLELEKQKEDAQRRVQERDKQW---LEHVQQEEQPRPRKP---HEEDRLKREDSVRKKEAEERAK 720
Cdd:PRK12705   99 KLDNLENQLEEREKALSARELELEELEKQLdneLYRVAGLTPEQARKLllkLLDAELEEEKAQRVKKIEEEAD 171

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 41.70 E-value: 5.51e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   416 RKERERQEQERKRQLELEKQLEKQRELerqreeerrkeierreaakRELE-RQRQLEWERNRRQEllnQRNKEQEgtvvl 494
Cdd:pfam01576    2 RQEEEMQAKEEELQKVKERQQKAESEL-------------------KELEkKHQQLCEEKNALQE---QLQAETE----- 54

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   495 karrktlefelealndkkhqLEGKLQDIRCRLATQRQEIESTNKSRELRIAEITHLQqqlqesqqmlgrlipekQILSDQ 574
Cdd:pfam01576   55 --------------------LCAEAEEMRARLAARKQELEEILHELESRLEEEEERS-----------------QQLQNE 97

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   575 LKQVQQNslhrdsLLTLKRALEAKELARQQLreQLDEVERETRSKLQEIDVFnnqlkELREIHSKqqLQKQRSLEAARLK 654
Cdd:pfam01576   98 KKKMQQH------IQDLEEQLDEEEAARQKL--QLEKVTTEAKIKKLEEDIL-----LLEDQNSK--LSKERKLLEERIS 162

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 568997330   655 Q-----KEQERKSLELEKQK-------EDAQRRVQERDKQWLE 685
Cdd:pfam01576  163 EftsnlAEEEEKAKSLSKLKnkheamiSDLEERLKKEEKGRQE 205

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

Pssm-ID: 402959 [Multi-domain] Cd Length: 164 Bit Score: 39.67 E-value: 5.57e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   613 ERETRSKLQEIDVFNNQLKELREIHSKQQLQKQRSLEAARLKQkEQERKSLELEKQKEDAQRRVQERD------KQWLEH 686
Cdd:pfam11600   12 EKEKQRLEKDKERLRRQLKLEAEKEEKERLKEEAKAEKERAKE-EARRKKEEEKELKEKERREKKEKDekekaeKLRLKE 90

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   687 VQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEmQDKQSRLFHPHQEPAKLATQAPW 746
Cdd:pfam11600   91 EKRKEKQEALEAKLEEKRKKEEEKRLKEEEKRIKAE-KAEITRFLQKPKTQQAPKTLAGS 149

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 36.92 E-value: 5.62e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWW---KGEVSGQVGLFPSNYVK 1227
Cdd:cd11779     2 RVKALYPHAAGGETQLSFEEGDVITLLGPEPRDGWhygENERSGRRGWFPIAYTE 56

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 36.62 E-value: 5.65e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQ-QDMWWFGEVQGQKGWFPKSYV 983
Cdd:cd11816     4 ARFDFEGEQEDELSFSEGDVITLKEYvGEEWAKGELNGKIGIFPLNFV 51

Src Homology 3 domain of the p85beta regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85beta binds CD28 and may be involved in the activation and differentiation of antigen-stimulated T cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212842 Cd Length: 74 Bit Score: 37.12 E-value: 5.73e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  767 YRALYPFESRSHDEITIQPGDIVMV-------------DESQTGEPGWLGG--ELKGKTGWFPANYAEKI 821
Cdd:cd11909     3 YRALYPYRKEREEDIDLLPGDVLTVsraalqalgvkegGEQCPQSIGWILGlnERTKQRGDFPGTYVEFL 72

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212984 [Multi-domain] Cd Length: 56 Bit Score: 36.72 E-value: 5.74e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1025 IAMYTYESSEQGDLTFQQGDVIVVTKKDGDWWTG-TVGDKS--GVFPSNYVRLK 1075
Cdd:cd12051     3 VAIYNYDARGPDELSLQIGDTVHILETYEGWYRGyTLRKKSkkGIFPASYIHLK 56

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 36.82 E-value: 5.77e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGkkrqiGWFPANYVKL 1152
Cdd:cd11928     4 KALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCH-----GFLPASYIQC 54

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 36.71 E-value: 5.80e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVI-VVTKKDGDWWTGTVGDKSGVFPSNYVRL 1074
Cdd:cd11813     4 ALLDFERHDDDELGFRKNDIItIISQKDEHCWVGELNGLRGWFPAKFVEL 53

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 36.66 E-value: 5.82e-03

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 568997330  949 LNFNKSDVITVLEQQ-DMWWFGEVQGQKGWFPKSYV 983
Cdd:cd12017    16 ISFQKGQKVEVIDKNpSGWWYVKIDGKEGWAPSSYI 51

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 36.48 E-value: 5.83e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568997330 1097 QVIA--SYAATGPEQLTLAPGQ-LILIRKKNPGgWWegelQARGKKRQIGWFPANYVK 1151
Cdd:cd11768     1 IVVAlyDFQPIEPGDLPLEKGEeYVVLDDSNEH-WW----RARDKNGNEGYIPSNYVT 53

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 41.44 E-value: 5.87e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  387 ELEKRRQAL--LEQQRKEQERLAQLERA----EQERKE-----------RERQEQERKRQLELEKQLEKQRELERQREEE 449
Cdd:COG4913   642 ALQERREALqrLAEYSWDEIDVASAEREiaelEAELERldassddlaalEEQLEELEAELEELEEELDELKGEIGRLEKE 721

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  450 RRKEIERREAAKRELERQRQLewERNRRQELLNQRNKEQEGTVVLKARRKTLEFELEALNDKKHQLEGKLQDIR------ 523
Cdd:COG4913   722 LEQAEEELDELQDRLEAAEDL--ARLELRALLEERFAAALGDAVERELRENLEERIDALRARLNRAEEELERAMrafnre 799

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  524 --CRLATQRQEIESTNKSRELRiAEITHLQqqlqesqqmlgrlIPEKQilsDQLKQvQQNSLHRDSLLTLKRALEAkelA 601
Cdd:COG4913   800 wpAETADLDADLESLPEYLALL-DRLEEDG-------------LPEYE---ERFKE-LLNENSIEFVADLLSKLRR---A 858

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  602 RQQLREQLDEVERE----------------TRSKLQEIDVFNNQLKELRE 635
Cdd:COG4913   859 IREIKERIDPLNDSlkripfgpgrylrleaRPRPDPEVREFRQELRAVTS 908

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 36.42 E-value: 5.88e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd12045     1 FYQGLWDCTGDQPDELSFKRGDTIYILSKEYNRFGWWVGEMKGTIGLVPKAY 52

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

Pssm-ID: 274303 [Multi-domain] Cd Length: 346 Bit Score: 40.98 E-value: 5.90e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   387 ELEKRRQALLEQQRKEQERLAQLERAEQERKERERQEQERKRQLELEKQLEKQRELERQreeerrkeierreAAKRELER 466
Cdd:TIGR02794   51 QANRIQQQKKPAAKKEQERQKKLEQQAEEAEKQRAAEQARQKELEQRAAAEKAAKQAEQ-------------AAKQAEEK 117

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   467 QRQLEwernrrqELLNQRNKEQegtvvlKARrktlefeLEALNDKKHQLEgklqdircrlATQRQEIESTNKSRElriae 546
Cdd:TIGR02794  118 QKQAE-------EAKAKQAAEA------KAK-------AEAEAERKAKEE----------AAKQAEEEAKAKAAA----- 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   547 ithlqqqlqesqqmlgrlipekqilsdqlkqvqqnslhrdslltlKRALEAKELARQQLREQLDEVERETRSKLQEIDVF 626
Cdd:TIGR02794  163 ---------------------------------------------EAKKKAEEAKKKAEAEAKAKAEAEAKAKAEEAKAK 197

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   627 NNQLKELREIHSKQQLQKQRSL-EAARLKQKEQE---------RKSLELEKQKEDAQRRVQERDKQWLEHVQQEEQPRPR 696
Cdd:TIGR02794  198 AEAAKAKAAAEAAAKAEAEAAAaAAAEAERKADEaelgdifglASGSNAEKQGGARGAAAGSEVDKYAAIIQQAIQQNLY 277


                   ..
gi 568997330   697 KP 698
Cdd:TIGR02794  278 DD 279

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 36.52 E-value: 5.98e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDEsqTGEPGWLGGELKGK---TGWFPANY 817
Cdd:cd11821     3 RALYDCQADNDDELTFSEGEIIVVTG--EEDDEWWEGHIEGDpsrRGVFPVSF 53

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 36.92 E-value: 6.08e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330 1026 AMYTYESSEQGDLTFQQGDVIVVT------KKDGDWWTGTVGD--KSGVFPSNYVR 1073
Cdd:cd11790     7 ATHDYTAEDTDELTFEKGDVILVIpfddpeEQDEGWLMGVKEStgCRGVFPENFTE 62

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 2; Shank2, also called ProSAP1 (Proline-rich synapse-associated protein 1) or CortBP1 (Cortactin-binding protein 1), is found in neurons, glia, endocrine cells, liver, and kidney. It plays a role in regulating dendritic spine volume and branching and postsynaptic clustering. Mutations in the Shank2 gene are associated with autism spectrum disorder and mental retardation. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212916 Cd Length: 52 Bit Score: 36.44 E-value: 6.09e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGelQARGkkrQIGWFPANYV 1150
Cdd:cd11983     5 VVKSYQPQVEGEIPLHKGDRVKVLSIGEGGFWEG--SARG---HVGWFPAECV 52

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175988 [Multi-domain] Cd Length: 125 Bit Score: 38.41 E-value: 6.29e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1620 VEGIELKPCRSHGKSNPYCEVTMGSQcHITKT--IQDTLNPKWNSncQFFIRDLEQEVLCITVFERDQFSPDDFLGRTEI 1697
Cdd:cd04021     8 VESAKLKSNSKSFKPDPYVEVTVDGQ-PPKKTevSKKTSNPKWNE--HFTVLVTPQSTLEFKVWSHHTLKADVLLGEASL 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1698 RVADI-KKDQGskgpvtKC----LLLH--------EVPTGEIVVRLD 1731
Cdd:cd04021    85 DLSDIlKNHNG------KLenvkLTLNlssenkgsSVKVGELTVILD 125

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.

Pssm-ID: 431111 [Multi-domain] Cd Length: 766 Bit Score: 41.35 E-value: 6.35e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   382 ERGSVELEKRRQALLEQQRKEQERLAQLER-----------------------AEQER------KERERQEQERKRQLE- 431
Cdd:pfam10174  393 ERKINVLQKKIENLQEQLRDKDKQLAGLKErvkslqtdssntdtalttleealSEKERiierlkEQREREDRERLEELEs 472

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   432 -------LEKQL-----EKQRELERQREEERRKEIERREAAKRElERQRQLEWERNRRQE----LLNQRNKEQEGTVVLK 495
Cdd:pfam10174  473 lkkenkdLKEKVsalqpELTEKESSLIDLKEHASSLASSGLKKD-SKLKSLEIAVEQKKEecskLENQLKKAHNAEEAVR 551

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   496 A------RRKTLEFELEALNDKKHQLEGKLQdircRLATQRQEIESTNKSRELRIAEIthlqqqlqesQQMLGRLIPEKQ 569
Cdd:pfam10174  552 TnpeindRIRLLEQEVARYKEESGKAQAEVE----RLLGILREVENEKNDKDKKIAEL----------ESLTLRQMKEQN 617

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   570 ILSDQLKQVQQnSLHRDSLLTLKRALEAKE-LARQQLREQLDEVERETRSKLQEIDVFNNQLKelreihSKQQL--QKQR 646
Cdd:pfam10174  618 KKVANIKHGQQ-EMKKKGAQLLEEARRREDnLADNSQQLQLEELMGALEKTRQELDATKARLS------STQQSlaEKDG 690

                          330       340
                   ....*....|....*....|..
gi 568997330   647 SLEAARLKQKEQERKSLELEKQ 668
Cdd:pfam10174  691 HLTNLRAERRKQLEEILEMKQE 712

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212769 [Multi-domain] Cd Length: 54 Bit Score: 36.66 E-value: 6.41e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997330 1030 YESSEQGDLTFQQGDVIVV----TKKDGDWWTGTVGDKSGVFPSNYV 1072
Cdd:cd11835     8 YTAQAPDELSLEVGDIVSVidmpPPEESTWWRGKKGFQVGFFPSECV 54

Src homology 3 domain of DBL's Big Sister (DBS), a guanine nucleotide exchange factor; DBS, also called MCF2L (MCF2-transforming sequence-like protein) or OST, is a Rho GTPase guanine nucleotide exchange factor (RhoGEF), facilitating the exchange of GDP and GTP. It was originally isolated from a cDNA screen for sequences that cause malignant growth. It plays roles in regulating clathrin-mediated endocytosis and cell migration through its activation of Rac1 and Cdc42. Depending on cell type, DBS can also activate RhoA and RhoG. DBS contains a Sec14-like domain, spectrin-like repeats, a RhoGEF [or Dbl homology (DH)] domain, a Pleckstrin homology (PH) domain, and an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212791 Cd Length: 55 Bit Score: 36.50 E-value: 6.48e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  767 YRALYPFESRSHDEITIQPGDIV-MVDESQTGEpgWLGGEL-KGKTGWFPAN 816
Cdd:cd11857     2 YTVVADYEKGGPDDLTVKSGDLVqLIHEGDEGQ--WLVKNLsTRKEGWVPAA 51

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 36.48 E-value: 6.53e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568997330 1097 QVIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQARgkkrqIGWFPANYVKLL 1153
Cdd:cd12054     4 KVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGK-----SGLFPSNFVKEL 55

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 36.29 E-value: 6.59e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 568997330 1109 QLTLAPGQLILIRKKNPGGWWEGELQargkkRQIGWFPANYVK 1151
Cdd:cd11820    16 ELTFKAGEIITVLDDSDPNWWKGSNH-----RGEGLFPANFVT 53

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 41.35 E-value: 6.67e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  603 QQLREQLDEVERETRSKLQEIDVFNNQLKELreihsKQQLQKQRSLEAARLKQKEQERksleLEKQKEDAQRRVQERDKq 682
Cdd:PRK00409  526 EELERELEQKAEEAEALLKEAEKLKEELEEK-----KEKLQEEEDKLLEEAEKEAQQA----IKEAKKEADEIIKELRQ- 595

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  683 wlehvQQEEQPRPRKPHEEDRLKREDSVRKKEAEERAKPEMQDKQSrlFHPHQE 736
Cdd:PRK00409  596 -----LQKGGYASVKAHELIEARKRLNKANEKKEKKKKKQKEKQEE--LKVGDE 642

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 36.52 E-value: 6.71e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568997330 1098 VIASYAATGPEQLTLAPGQLILIRKKNPGGWWEGElQARGKKrqiGWFPANYVKL 1152
Cdd:cd11770     4 ALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAE-NSKGNR---GLVPKTYLKV 54

peptidoglycan -binding protein;

Pssm-ID: 181619 [Multi-domain] Cd Length: 343 Bit Score: 40.72 E-value: 6.74e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  563 RLIPEKQILSDQLKQVQQNSLH-RDSLLTLKRALEAKELARQQLR---------------------EQLDEVERETRSKL 620
Cdd:PRK09039   57 RLNSQIAELADLLSLERQGNQDlQDSVANLRASLSAAEAERSRLQallaelagagaaaegragelaQELDSEKQVSARAL 136

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  621 QEIDVFNNQLKELREihskqQLQK-QRSLEAARLKQKEQERKSLELEKQKEDA-QRRVQE 678
Cdd:PRK09039  137 AQVELLNQQIAALRR-----QLAAlEAALDASEKRDRESQAKIADLGRRLNVAlAQRVQE 191

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 39.91 E-value: 7.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  566 PEKQilsDQLKQVQQNSLHRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDV----FNNQLKELRE-I-HSK 639
Cdd:COG1579     3 PEDL---RALLDLQELDSELDRLEHRLKELPAELAELEDELAALEARLEAAKTELEDLEKeikrLELEIEEVEArIkKYE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  640 QQLQKQRS----------LEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQwLEHVQQEeqprprkpHEEDRLKREDS 709
Cdd:COG1579    80 EQLGNVRNnkeyealqkeIESLKRRISDLEDEILELMERIEELEEELAELEAE-LAELEAE--------LEEKKAELDEE 150

                         170
                  ....*....|
gi 568997330  710 VRKKEAEERA 719
Cdd:COG1579   151 LAELEAELEE 160

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 36.56 E-value: 7.11e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330  768 RALYPFESRSHDEITIQPGDIVMVDESQT-GEPGWLGGELKGKTGWFPAN 816
Cdd:cd11844     3 RALYDNVAESPDELAFRRGDILTVLEQNTaGLEGWWLCSLRGRQGIAPGN 52

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 36.34 E-value: 7.24e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDMWWFGE--VQGQKGWFPKSYV 983
Cdd:cd12005     4 ALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAQslTTGQEGFIPFNFV 52

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 36.54 E-value: 7.84e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997330 1099 IASYAATGPEQLTLAPGQLILIRKKNPGGWWEGELQargkkRQIGWFPANYVK 1151
Cdd:cd11971     5 IYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCN-----GVTGLFPGNYVE 52

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 36.26 E-value: 8.10e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd11866     1 WYMGLWDCSGNEPDELSFKRGDLIYIISKEYDSFGWWVGELNGKVGLVPKDY 52

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212977 Cd Length: 53 Bit Score: 36.37 E-value: 8.14e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568997330  766 YYRALYPFESRSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANY 817
Cdd:cd12044     1 YYQGLWDCFGDNPDELSFQRGDLIYILSKEYNMYGWWVGELNGIVGIVPKDY 52

Guanylate-binding protein, C-terminal domain; Transcription of the anti-viral guanylate-binding protein (GBP) is induced by interferon-gamma during macrophage induction. This family contains GBP1 and GPB2, both GTPases capable of binding GTP, GDP and GMP.

Pssm-ID: 460721 [Multi-domain] Cd Length: 297 Bit Score: 40.35 E-value: 8.37e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   586 DSLLTLKRALEAKELARQQLREQLDEVERETRSkLQEIDVFNNQLKELREIHSKQQL-QKQRSLEAAR----------LK 654
Cdd:pfam02841  190 EAILQTDQALTAKEKAIEAERAKAEAAEAEQEL-LREKQKEEEQMMEAQERSYQEHVkQLIEKMEAEReqllaeqermLE 268

                           90       100
                   ....*....|....*....|....
gi 568997330   655 QKEQERKSLELEKQKEDAQRRVQE 678
Cdd:pfam02841  269 HKLQEQEELLKEGFKTEAESLQKE 292

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 36.54 E-value: 8.40e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568997330  937 ALYPWRAKKDNHLNFNKSDVITVLEQQDMWWF-GEVQGQKGWFPKSYVKLI 986
Cdd:cd11971     4 AIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYeGVCNGVTGLFPGNYVESI 54

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 40.79 E-value: 8.51e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  376 KKRENFERgsvELEKRRQALLEQQRKEQERLAQ--LERAEQERKERERQEQERKRQlELEKQLEKQRELERQREEErrke 453
Cdd:PRK02224  272 REREELAE---EVRDLRERLEELEEERDDLLAEagLDDADAEAVEARREELEDRDE-ELRDRLEECRVAAQAHNEE---- 343

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  454 ierreaAKRELERQRQLEwernrrqellnQRNKEqegtvvLKARRKTLEFELE----ALNDKKHQ---LEGKLQDIRCRL 526
Cdd:PRK02224  344 ------AESLREDADDLE-----------ERAEE------LREEAAELESELEeareAVEDRREEieeLEEEIEELRERF 400

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  527 A---TQRQEIESTNKSRELRIAEITHLQQQLQESQQMLGRLIPEKQILSDQLK-----QVQQNSLH-------RDSLLTL 591
Cdd:PRK02224  401 GdapVDLGNAEDFLEELREERDELREREAELEATLRTARERVEEAEALLEAGKcpecgQPVEGSPHvetieedRERVEEL 480

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330  592 KRALEAKELARQQLREQLD------EVERETrsklqeidvfnNQLKELREIHSKQQLQKQRSLEAARLKQKEQERKSLEL 665
Cdd:PRK02224  481 EAELEDLEEEVEEVEERLEraedlvEAEDRI-----------ERLEERREDLEELIAERRETIEEKRERAEELRERAAEL 549

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997330  666 E---KQKEDAQRRVQERDKQWLEHVQQEEQPRPRKPHEEDRLKR-EDSVRKKEAEERAKPEMQDKQSRL 730
Cdd:PRK02224  550 EaeaEEKREAAAEAEEEAEEAREEVAELNSKLAELKERIESLERiRTLLAAIADAEDEIERLREKREAL 618

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212948 Cd Length: 53 Bit Score: 36.24 E-value: 8.92e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568997330 1176 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGEVSGQVGLFPSNY 1225
Cdd:cd12015     1 QYVVVADYKKQQPNEISLRAGDVVDVIEKNENGWWFVSLEDEQGWVPATY 50

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 36.14 E-value: 9.04e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1026 AMYTYESSEQGDLTFQQGDV-IVVTKKDGDWW-----TGTVgdksGVFPSNYVR 1073
Cdd:cd11849     4 ALYDFKSAEPNTLSFSEGETfLLLERSNAHWWlvtnhSGET----GYVPANYVK 53

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 36.14 E-value: 9.40e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330  767 YRALYPFESRSHDEITIQPGDI-VMVDESQtgEPGWLGGELKGKTGWFPANYAE 819
Cdd:cd11849     2 YRALYDFKSAEPNTLSFSEGETfLLLERSN--AHWWLVTNHSGETGYVPANYVK 53

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 36.08 E-value: 9.45e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568997330  768 RALYPFESRSHDEITIQPGDIVM----VDESqtgepgWLGGELKGKTGWFPANYAE 819
Cdd:cd11927     4 KALYNYEGKEPGDLKFSKGDIIIlrrqVDEN------WYHGEVNGIHGFFPTNFVQ 53

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 37.88 E-value: 9.69e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330 1615 LMVNVVEGIELKPCRSHGKSNPYCEVTMGSQCHI-TKTIQDTLNPKWNSNCQFFIrDLEQEVLCITVFERDQFSPDDFLG 1693
Cdd:cd04054     2 LYIRIVEGKNLPAKDITGSSDPYCIVKVDNEVIIrTATVWKTLNPFWGEEYTVHL-PPGFHTVSFYVLDEDTLSRDDVIG 80


                  ....
gi 568997330 1694 RTEI 1697
Cdd:cd04054    81 KVSL 84

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

Pssm-ID: 466641 [Multi-domain] Cd Length: 120 Bit Score: 37.98 E-value: 9.77e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   567 EKQILSDQLKQVQqnslhrdslltlkralEAKELARQQLREQLDEVER--ETRSKLQEidvfnnQLKELREIHSKQQLQK 644
Cdd:pfam20492    7 EKQELEERLKQYE----------------EETKKAQEELEESEETAEEleEERRQAEE------EAERLEQKRQEAEEEK 64

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 568997330   645 QRSLEAARLKQKEQERKSLELEKQKEDAQRRVQERDKQ 682
Cdd:pfam20492   65 ERLEESAEMEAEEKEQLEAELAEAQEEIARLEEEVERK 102

Cortexillin I, coiled coil; Members of this family are predominantly found in the actin-bundling protein Cortexillin I from Dictyostelium discoideum. They adopt a structure consisting of an 18-heptad-repeat alpha-helical coiled-coil, and are a prerequisite for the assembly of Cortexillin I.

Pssm-ID: 312712 [Multi-domain] Cd Length: 107 Bit Score: 37.68 E-value: 9.89e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997330   577 QVQQNSLhRDSLLTLKRALEAKELARQQLREQLDEVERETRSKLQEIDVFNNQLKELR----EIHSKQQLQKQRSLE-AA 651
Cdd:pfam09304    8 EASKNSL-ANKLAGLENSLESEKTSREQLIKQKDELESLLASLEQENAEREKRLRELEakldEALKNLELEKLARMElES 86

                           90
                   ....*....|....*
gi 568997330   652 RLKQKEQERKSLELE 666
Cdd:pfam09304   87 RLSKTEKDKAILELK 101

Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins and similar domains; This subfamily is composed of vertebrate SH3TC proteins and hypothetical fungal proteins containing BAR and SH3 domains. Mammals contain two SH3TC proteins, SH3TC1 and SH3TC2. The function of SH3TC1 is unknown. SH3TC2 is localized in Schwann cells in the peripheral nervous system, where it interacts with Rab11 and plays a role in peripheral nerve myelination. Mutations in SH3TC2 are associated with Charcot-Marie-Tooth disease type 4C, a severe hereditary peripheral neuropathy with symptoms that include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212818 Cd Length: 55 Bit Score: 36.14 E-value: 9.99e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997330 1024 FIAMYTYESSEQGDLTFQQGDVIVVT---KKDGDWWTGTVGDKS--GVFPSNYV 1072
Cdd:cd11885     2 CTAKMDFEGVEPGELSFRQGDSIEIIgdlIPGLQWFVGRSKSSGrvGFVPTNHF 55