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Conserved domains on  [gi|767913374|ref|XP_011508707|]
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arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 isoform X4 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
BAR super family cl12013
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
34-234 1.54e-113

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.


The actual alignment was detected with superfamily member cd07642:

Pssm-ID: 472257  Cd Length: 215  Bit Score: 348.56  E-value: 1.54e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  34 RNTVAAIEEvrrparrlrpqALDVDRMVLYKMKKSVKAINSSGLAHVENEEQYTQALEKFGGNCVCRDDPDLGSAFLKFS 113
Cdd:cd07642    1 RNTVVAIEE-----------ALDVDRTVLYKMKKSVKAIHTSGLAHVENEEQYTQALEKFGSNCVCRDDPDLGSAFLKFS 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 114 VFTKELTALFKNL-------------------------DLKKPFDKAWKDYETKITKIEKEKKEHAKLHGMIRTEISGAE 168
Cdd:cd07642   70 VFTKELTALFKNLvqnmnniitfpldsllkgdlkgvkgDLKKPFDKAWKDYETKVTKIEKEKKEHAKMHGMIRTEISGAE 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 169 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPSIETL 234
Cdd:cd07642  150 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVETLKPSIEKL 215
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
408-530 6.42e-90

ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2); The Arf GAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf , thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport.


:

Pssm-ID: 350074 [Multi-domain]  Cd Length: 123  Bit Score: 282.25  E-value: 6.42e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 408 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 487
Cdd:cd08849    1 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 767913374 488 EIMECCLPAEDSVKPNPGSDMNARKDYITAKYIERRYARKKHA 530
Cdd:cd08849   81 EIMEACLPAEDVVKPNPGSDMNARKDYITAKYIERRYARKKHA 123
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
286-392 2.59e-62

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) 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: 270071  Cd Length: 108  Bit Score: 206.44  E-value: 2.59e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 286 QPQGNKEHGTERNGSLYKKSDG-IRKVWQKRKCSVKNGFLTISHGTANRPPAKLNLLTCQVKTNPEEKKCFDLISHDRTY 364
Cdd:cd13251    1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                         90       100
                 ....*....|....*....|....*...
gi 767913374 365 HFQAEDEQECQIWMSVLQNSKEEALNNA 392
Cdd:cd13251   81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
937-992 5.35e-38

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: 135.47  E-value: 5.35e-38
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRKGAFPVSFVHF 992
Cdd:cd11966    1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPTRRGAFPVSFVHF 56
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
551-666 9.62e-14

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 73.06  E-value: 9.62e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 551 LLQAYADgVDLTEKiplaNGhepdETALHLAVRSVDrtsLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLL 630
Cdd:COG0666  139 LLEAGAD-VNAQDN----DG----NTPLHLAAANGN---LEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLL 206
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767913374 631 RGKASIEIANESGETPLDIAKRLKHEHCEELLTQAL 666
Cdd:COG0666  207 EAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAG 242
 
Name Accession Description Interval E-value
BAR_ASAP2 cd07642
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-234 1.54e-113

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP2 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2) is also known as DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. ASAP2 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 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. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153326  Cd Length: 215  Bit Score: 348.56  E-value: 1.54e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  34 RNTVAAIEEvrrparrlrpqALDVDRMVLYKMKKSVKAINSSGLAHVENEEQYTQALEKFGGNCVCRDDPDLGSAFLKFS 113
Cdd:cd07642    1 RNTVVAIEE-----------ALDVDRTVLYKMKKSVKAIHTSGLAHVENEEQYTQALEKFGSNCVCRDDPDLGSAFLKFS 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 114 VFTKELTALFKNL-------------------------DLKKPFDKAWKDYETKITKIEKEKKEHAKLHGMIRTEISGAE 168
Cdd:cd07642   70 VFTKELTALFKNLvqnmnniitfpldsllkgdlkgvkgDLKKPFDKAWKDYETKVTKIEKEKKEHAKMHGMIRTEISGAE 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 169 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPSIETL 234
Cdd:cd07642  150 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVETLKPSIEKL 215
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
408-530 6.42e-90

ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2); The Arf GAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf , thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport.


Pssm-ID: 350074 [Multi-domain]  Cd Length: 123  Bit Score: 282.25  E-value: 6.42e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 408 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 487
Cdd:cd08849    1 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 767913374 488 EIMECCLPAEDSVKPNPGSDMNARKDYITAKYIERRYARKKHA 530
Cdd:cd08849   81 EIMEACLPAEDVVKPNPGSDMNARKDYITAKYIERRYARKKHA 123
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
286-392 2.59e-62

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) 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: 270071  Cd Length: 108  Bit Score: 206.44  E-value: 2.59e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 286 QPQGNKEHGTERNGSLYKKSDG-IRKVWQKRKCSVKNGFLTISHGTANRPPAKLNLLTCQVKTNPEEKKCFDLISHDRTY 364
Cdd:cd13251    1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                         90       100
                 ....*....|....*....|....*...
gi 767913374 365 HFQAEDEQECQIWMSVLQNSKEEALNNA 392
Cdd:cd13251   81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
410-527 5.44e-45

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 157.77  E-value: 5.44e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  410 KEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEI 489
Cdd:pfam01412   1 KRVLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEF 80
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 767913374  490 MECCLPaeDSVKPNPGSDMNARKDYITAKYIERRYARK 527
Cdd:pfam01412  81 WEANLP--PSYKPPPSSDREKRESFIRAKYVEKKFAKP 116
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
937-992 5.35e-38

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: 135.47  E-value: 5.35e-38
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRKGAFPVSFVHF 992
Cdd:cd11966    1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPTRRGAFPVSFVHF 56
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
413-523 2.70e-31

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 118.60  E-value: 2.70e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374   413 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEC 492
Cdd:smart00105   1 LKLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80
                           90       100       110
                   ....*....|....*....|....*....|.
gi 767913374   493 CLPaEDSVKPNPGSDMNARKDYITAKYIERR 523
Cdd:smart00105  81 NLD-DFSLKPPDDDDQQKYESFIAAKYEEKL 110
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
409-523 1.95e-25

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 108.33  E-value: 1.95e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 409 TKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNE 488
Cdd:COG5347    7 DRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNSNANR 86
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 767913374 489 IMECCLPAEDSVKPNPGSDMNARKDYITAKYIERR 523
Cdd:COG5347   87 FYEKNLLDQLLLPIKAKYDSSVAKKYIRKKYELKK 121
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
295-382 2.55e-16

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: 75.28  E-value: 2.55e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374   295 TERNGSLYKKSDGIRKVWQKRKCSVKNGFLTI----SHGTANRPPAKLNLLTCQVKTNPE-----EKKCFDLISHDR-TY 364
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYykskKDKKSYKPKGSIDLSGCTVREAPDpdsskKPHCFEIKTSDRkTL 80
                           90
                   ....*....|....*...
gi 767913374   365 HFQAEDEQECQIWMSVLQ 382
Cdd:smart00233  81 LLQAESEEEREKWVEALR 98
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
934-990 1.91e-15

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: 1.91e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 767913374   934 KPKRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGdpGRKGAFPVSFV 990
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR--GKEGLFPSNYV 55
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
551-666 9.62e-14

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 73.06  E-value: 9.62e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 551 LLQAYADgVDLTEKiplaNGhepdETALHLAVRSVDrtsLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLL 630
Cdd:COG0666  139 LLEAGAD-VNAQDN----DG----NTPLHLAAANGN---LEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLL 206
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767913374 631 RGKASIEIANESGETPLDIAKRLKHEHCEELLTQAL 666
Cdd:COG0666  207 EAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAG 242
PH pfam00169
PH domain; PH stands for pleckstrin homology.
295-386 1.58e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 64.89  E-value: 1.58e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  295 TERNGSLYKKSDGIRKVWQKRKCSVKNGFLTI----SHGTANRPPAKLNLLTCQVKT-----NPEEKKCFDLISHD---- 361
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYykddKSGKSKEPKGSISLSGCEVVEvvasdSPKRKFCFELRTGErtgk 80
                          90       100
                  ....*....|....*....|....*
gi 767913374  362 RTYHFQAEDEQECQIWMSVLQNSKE 386
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSAIR 105
Ank_2 pfam12796
Ankyrin repeats (3 copies);
578-662 4.33e-11

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 60.13  E-value: 4.33e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  578 LHLAVRsvdRTSLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLLRgKASIEIANEsGETPLDIAKRLKH-E 656
Cdd:pfam12796   1 LHLAAK---NGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLE-HADVNLKDN-GRTALHYAARSGHlE 75

                  ....*.
gi 767913374  657 HCEELL 662
Cdd:pfam12796  76 IVKLLL 81
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
412-483 6.51e-11

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 65.65  E-value: 6.51e-11
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767913374 412 IISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGN 483
Cdd:PLN03114  12 VFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGN 83
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
168-252 1.81e-10

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 465256  Cd Length: 235  Bit Score: 62.19  E-value: 1.81e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  168 EIAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPSIETLSTDLHTIKQAQDE 247
Cdd:pfam16746 151 EADNELAATRKCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQGYELFKDLEPFMKDLQAQLQQTREDTRE 230

                  ....*
gi 767913374  248 ERRQL 252
Cdd:pfam16746 231 EKEEL 235
SH3_9 pfam14604
Variant SH3 domain;
940-990 5.41e-10

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 55.70  E-value: 5.41e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767913374  940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINT---GRTGLVPANYV 48
PHA03095 PHA03095
ankyrin-like protein; Provisional
574-649 7.93e-06

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 49.64  E-value: 7.93e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767913374 574 DETALHLAVRSVDRTSLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDN-AECLKLLLRGKASIEIANESGETPLDI 649
Cdd:PHA03095  47 GKTPLHLYLHYSSEKVKDIVRLLLEAGADVNAPERCGFTPLHLYLYNATtLDVIKLLIKAGADVNAKDKVGRTPLHV 123
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
609-638 2.01e-04

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 39.49  E-value: 2.01e-04
                           10        20        30
                   ....*....|....*....|....*....|
gi 767913374   609 KGSTALHYCCLTDNAECLKLLLRGKASIEI 638
Cdd:smart00248   1 DGRTPLHLAAENGNLEVVKLLLDKGADINA 30
 
Name Accession Description Interval E-value
BAR_ASAP2 cd07642
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-234 1.54e-113

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP2 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2) is also known as DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. ASAP2 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 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. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153326  Cd Length: 215  Bit Score: 348.56  E-value: 1.54e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  34 RNTVAAIEEvrrparrlrpqALDVDRMVLYKMKKSVKAINSSGLAHVENEEQYTQALEKFGGNCVCRDDPDLGSAFLKFS 113
Cdd:cd07642    1 RNTVVAIEE-----------ALDVDRTVLYKMKKSVKAIHTSGLAHVENEEQYTQALEKFGSNCVCRDDPDLGSAFLKFS 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 114 VFTKELTALFKNL-------------------------DLKKPFDKAWKDYETKITKIEKEKKEHAKLHGMIRTEISGAE 168
Cdd:cd07642   70 VFTKELTALFKNLvqnmnniitfpldsllkgdlkgvkgDLKKPFDKAWKDYETKVTKIEKEKKEHAKMHGMIRTEISGAE 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 169 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPSIETL 234
Cdd:cd07642  150 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVETLKPSIEKL 215
BAR_ASAPs cd07604
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-234 1.38e-93

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of ASAPs (ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) with similarity to ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins) in that they contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and ankyrin (ANK) repeats. However, ASAPs contain an additional C-terminal SH3 domain. ASAPs function in regulating cell growth, migration, and invasion. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3. ASAP1 and ASAP2 shows GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but is able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153288  Cd Length: 215  Bit Score: 295.48  E-value: 1.38e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  34 RNTVAAIEEvrrparrlrpqALDVDRMVLYKMKKSVKAINSSGLAHVENEEQYTQALEKFGGNCVCRDDPDLGSAFLKFS 113
Cdd:cd07604    1 RNTVGALEE-----------SLEGDRVGLQKLKKAVKAIHNSGLAHVENELQFAEALEKLGSKALSREEEDLGAAFLKFS 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 114 VFTKELTALFKNL-------------------------DLKKPFDKAWKDYETKITKIEKEKKEHAKLHGMIRTEISGAE 168
Cdd:cd07604   70 VFTKELAALFKNLmqnlnniimfpldsllkgdlkgskgDLKKPFDKAWKDYETKASKIEKEKKQLAKEAGMIRTEITGAE 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 169 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPSIETL 234
Cdd:cd07604  150 IAEEMEKERRMFQLQMCEYLIKVNEIKTKKGVDLLQHLVEYYHAQNSYFQDGLKVIEHFRPYIEKL 215
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
408-530 6.42e-90

ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2); The Arf GAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf , thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport.


Pssm-ID: 350074 [Multi-domain]  Cd Length: 123  Bit Score: 282.25  E-value: 6.42e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 408 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 487
Cdd:cd08849    1 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 767913374 488 EIMECCLPAEDSVKPNPGSDMNARKDYITAKYIERRYARKKHA 530
Cdd:cd08849   81 EIMEACLPAEDVVKPNPGSDMNARKDYITAKYIERRYARKKHA 123
BAR_ASAP1 cd07641
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-234 4.03e-75

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1) is also known as DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. ASAP1 is 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. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153325  Cd Length: 215  Bit Score: 246.12  E-value: 4.03e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  34 RNTVAAIEEvrrparrlrpqALDVDRMVLYKMKKSVKAINSSGLAHVENEEQYTQALEKFGGNCVCRDDPDLGSAFLKFS 113
Cdd:cd07641    1 RNTVNVLEE-----------ALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQALDKFGSNFLSRDNPDLGTAFVKFS 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 114 VFTKELTALFKNL-------------------------DLKKPFDKAWKDYETKITKIEKEKKEHAKLHGMIRTEISGAE 168
Cdd:cd07641   70 TLTKELSTLLKNLlqglshnviftldsllkgdlkgvkgDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAE 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 169 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPSIETL 234
Cdd:cd07641  150 IAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 215
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
408-526 1.47e-73

ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation factor GTPase-activating proteins; The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. Both ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350063 [Multi-domain]  Cd Length: 117  Bit Score: 237.89  E-value: 1.47e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 408 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 487
Cdd:cd08834    1 LTKSIIAEVKRLPGNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFN 80
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 767913374 488 EIMECCLPaeDSVKPNPGSDMNARKDYITAKYIERRYAR 526
Cdd:cd08834   81 EIMEANLP--PGYKPTPNSDMEERKDFIRAKYVEKKFVV 117
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
408-531 1.58e-70

ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP1 and ASAP2, ASAP3 do not have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350087 [Multi-domain]  Cd Length: 124  Bit Score: 229.73  E-value: 1.58e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 408 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 487
Cdd:cd17900    1 LTKLLIAEVKSRPGNSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDLLSTSELLLAVSMGNTRFN 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 767913374 488 EIMECCLPAEDSVKPNPGSDMNARKDYITAKYIERRYARKKHAD 531
Cdd:cd17900   81 EVMEATLPAHGGPKPSAESDMGTRKDYIMAKYVEHRFVRKRCTP 124
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
408-527 5.18e-66

ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.


Pssm-ID: 350073 [Multi-domain]  Cd Length: 122  Bit Score: 217.21  E-value: 5.18e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 408 LTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFN 487
Cdd:cd08848    1 LTKAIIDDVQRLPGNEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFN 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 767913374 488 EIMECCLPAEdSVKPNPGSDMNARKDYITAKYIERRYARK 527
Cdd:cd08848   81 DIMEGNLPSP-SPKPSPSSDMTARKEYITAKYVEHRFSRK 119
BAR_ASAP3 cd07640
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
34-234 2.55e-63

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP3 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 3) is also known as ACAP4 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 4), DDEFL1 (Development and Differentiation Enhancing Factor-Like 1), or centaurin beta-6. It is an Arf6-specific GTPase activating protein (GAP) and is co-localized with Arf6 in ruffling membranes upon EGF stimulation. ASAP3 is implicated in the pathogenesis of hepatocellular carcinoma and plays a role in regulating cell migration and invasion. ASAP3 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. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153324  Cd Length: 213  Bit Score: 213.32  E-value: 2.55e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  34 RNTVAAIEEVrrparrlrpqaLDVDRMVLYKMKKSVKAINSSGLAHVENEEQYTQALEKFGGNCVCRDDPDLGSAFLKFS 113
Cdd:cd07640    1 RSTAAALEES-----------LEGDQASLQRIKKIVKAIHNSGLNHVENEEQYTEALENLGNSHLSQNNHELSTGFLNLA 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 114 VFTKELTALFKNL-------------------------DLKKPFDKAWKDYETKITKIEKEKKEHAKLHGMIRTEIsgAE 168
Cdd:cd07640   70 VFTREVTALFKNLvqnlnnivsfpldsllkgqlrdgrlESKKQMEKAWKDYEAKIGKLEKERREKQKQHGLIRLDM--TD 147
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 169 IAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPSIETL 234
Cdd:cd07640  148 TAEDMQRERRNFQLHMCEYLLKAQESQMKQGPDFLQSLIKFFHAQHNFFQDGWKAAQNLGPFIEKL 213
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
286-392 2.59e-62

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) 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: 270071  Cd Length: 108  Bit Score: 206.44  E-value: 2.59e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 286 QPQGNKEHGTERNGSLYKKSDG-IRKVWQKRKCSVKNGFLTISHGTANRPPAKLNLLTCQVKTNPEEKKCFDLISHDRTY 364
Cdd:cd13251    1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                         90       100
                 ....*....|....*....|....*...
gi 767913374 365 HFQAEDEQECQIWMSVLQNSKEEALNNA 392
Cdd:cd13251   81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
413-519 4.27e-45

GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide-binding protein Arf, a member of the Ras superfamily of GTPases. Like all GTP-binding proteins, Arf proteins function as molecular switches, cycling between GTP (active-membrane bound) and GDP (inactive-cytosolic) form. Conversion to the GTP-bound form requires a guanine nucleotide exchange factor (GEF), whereas conversion to the GDP-bound form is catalyzed by a GTPase activating protein (GAP). In that sense, ArfGAPs were originally proposed to function as terminators of Arf signaling, which is mediated by regulating Arf family GTP-binding proteins. However, recent studies suggest that ArfGAPs can also function as Arf effectors, independently of their GAP enzymatic activity to transduce signals in cells. The ArfGAP domain contains a C4-type zinc finger motif and a conserved arginine that is required for activity, within a specific spacing (CX2CX16CX2CX4R). ArfGAPs, which have multiple functional domains, regulate the membrane trafficking and actin cytoskeleton remodeling via specific interactions with signaling lipids such as phosphoinositides and trafficking proteins, which consequently affect cellular events such as cell growth, migration, and cancer invasion. The ArfGAP family, which includes 31 human ArfGAP-domain containing proteins, is divided into 10 subfamilies based on domain structure and sequence similarity. The ArfGAP nomenclature is mainly based on the protein domain structure. For example, ASAP1 contains ArfGAP, SH3, ANK repeat and PH domains; ARAPs contain ArfGAP, Rho GAP, ANK repeat and PH domains; ACAPs contain ArfGAP, BAR (coiled coil), ANK repeat and PH domains; and AGAPs contain Arf GAP, GTP-binding protein-like, ANK repeat and PH domains. Furthermore, the ArfGAPs can be classified into two major types of subfamilies, according to the overall domain structure: the ArfGAP1 type includes 6 subfamilies (ArfGAP1, ArfGAP2/3, ADAP, SMAP, AGFG, and GIT), which contain the ArfGAP domain at the N-terminus of the protein; and the AZAP type includes 4 subfamilies (ASAP, ACAP, AGAP, and ARAP), which contain an ArfGAP domain between the PH and ANK repeat domains.


Pssm-ID: 350058 [Multi-domain]  Cd Length: 106  Bit Score: 157.66  E-value: 4.27e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 413 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEC 492
Cdd:cd08204    1 LEELLKLPGNKVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDSWTPEQVELMKAIGNARANAYYEA 80
                         90       100
                 ....*....|....*....|....*..
gi 767913374 493 CLPAeDSVKPNPGSDMNARKDYITAKY 519
Cdd:cd08204   81 NLPP-GFKKPTPDSSDEEREQFIRAKY 106
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
410-527 5.44e-45

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 157.77  E-value: 5.44e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  410 KEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEI 489
Cdd:pfam01412   1 KRVLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEF 80
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 767913374  490 MECCLPaeDSVKPNPGSDMNARKDYITAKYIERRYARK 527
Cdd:pfam01412  81 WEANLP--PSYKPPPSSDREKRESFIRAKYVEKKFAKP 116
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
412-525 5.69e-41

ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP domain is an essential part of ACAP proteins that play important role in endocytosis, actin remodeling and receptor tyrosine kinase-dependent cell movement. ACAP subfamily of ArfGAPs are composed of coiled coils (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. In addition, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350064 [Multi-domain]  Cd Length: 116  Bit Score: 146.25  E-value: 5.69e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 412 IISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLgTSELL-LAKNIGNAGFNEIM 490
Cdd:cd08835    3 ALEQVLSVPGNAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDSW-EPELLkVMLELGNDVVNRIY 81
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 767913374 491 ECCLPAEDSVKPNPGSDMNARKDYITAKYIERRYA 525
Cdd:cd08835   82 EANVPDDGSVKPTPDSSRQEREAWIRAKYVEKKFV 116
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
937-992 5.35e-38

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: 135.47  E-value: 5.35e-38
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRKGAFPVSFVHF 992
Cdd:cd11966    1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPTRRGAFPVSFVHF 56
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
412-524 2.23e-36

ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. It has been shown that ACAP3 positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) also have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages.


Pssm-ID: 350075 [Multi-domain]  Cd Length: 116  Bit Score: 133.15  E-value: 2.23e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 412 IISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIME 491
Cdd:cd08850    3 ILQRVQSIAGNDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDSWEPELLKLMCELGNSTVNQIYE 82
                         90       100       110
                 ....*....|....*....|....*....|...
gi 767913374 492 CCLPAEDSVKPNPGSDMNARKDYITAKYIERRY 524
Cdd:cd08850   83 AQCEELGLKKPTASSSRQDKEAWIKAKYVEKKF 115
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
413-524 5.09e-33

ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350076 [Multi-domain]  Cd Length: 116  Bit Score: 123.56  E-value: 5.09e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 413 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEC 492
Cdd:cd08851    4 LQRVQCIPGNASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYEA 83
                         90       100       110
                 ....*....|....*....|....*....|..
gi 767913374 493 CLPAEDSVKPNPGSDMNARKDYITAKYIERRY 524
Cdd:cd08851   84 RVEKMGAKKPQPGGQRQEKEAYIRAKYVERKF 115
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
411-519 9.70e-33

ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350065 [Multi-domain]  Cd Length: 108  Bit Score: 122.40  E-value: 9.70e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 411 EIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIM 490
Cdd:cd08836    1 AALQAIRNVRGNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVW 80
                         90       100
                 ....*....|....*....|....*....
gi 767913374 491 ECCLPAEdsVKPNPGSDMNARKDYITAKY 519
Cdd:cd08836   81 EGNTQGR--TKPTPDSSREEKERWIRAKY 107
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
937-989 3.16e-32

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: 118.96  E-value: 3.16e-32
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRKGAFPVSF 989
Cdd:cd11821    1 RVRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGDPSRRGVFPVSF 53
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
410-527 5.29e-32

ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.


Pssm-ID: 350077 [Multi-domain]  Cd Length: 120  Bit Score: 120.83  E-value: 5.29e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 410 KEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEI 489
Cdd:cd08852    1 GHAVAQVQSVDGNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDSWEPELVKLMCELGNVIINQI 80
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767913374 490 MECCLPAEDSVKPNPGSDMNARKDYITAKYIERRYARK 527
Cdd:cd08852   81 YEARIEAMAIKKPGPSSSRQEKEAWIRAKYVEKKFITK 118
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
413-523 2.70e-31

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 118.60  E-value: 2.70e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374   413 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEC 492
Cdd:smart00105   1 LKLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80
                           90       100       110
                   ....*....|....*....|....*....|.
gi 767913374   493 CLPaEDSVKPNPGSDMNARKDYITAKYIERR 523
Cdd:smart00105  81 NLD-DFSLKPPDDDDQQKYESFIAAKYEEKL 110
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
413-519 8.79e-29

ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350079 [Multi-domain]  Cd Length: 109  Bit Score: 111.26  E-value: 8.79e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 413 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEC 492
Cdd:cd08854    4 IQAIRNAKGNSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSIWES 83
                         90       100
                 ....*....|....*....|....*..
gi 767913374 493 ClpAEDSVKPNPGSDMNARKDYITAKY 519
Cdd:cd08854   84 C--TQGRTKPAPDSSREERESWIRAKY 108
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
406-519 6.37e-28

ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350061 [Multi-domain]  Cd Length: 113  Bit Score: 108.89  E-value: 6.37e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 406 QELTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAG 485
Cdd:cd08832    1 AERNKKRLLELLKLPGNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDNWDDSQVEFMEENGNEK 80
                         90       100       110
                 ....*....|....*....|....*....|....
gi 767913374 486 FNEIMECCLPAeDSVKPNPGSDMNARKDYITAKY 519
Cdd:cd08832   81 AKAKYEAHVPA-FYRRPTPTDPQVLREQWIRAKY 113
SH3_ASAP1 cd11965
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
937-993 3.13e-27

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: 105.09  E-value: 3.13e-27
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRKGAFPVSFVHFI 993
Cdd:cd11965    1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 57
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
413-519 6.49e-27

ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion.


Pssm-ID: 350080 [Multi-domain]  Cd Length: 110  Bit Score: 105.91  E-value: 6.49e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 413 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEC 492
Cdd:cd08855    5 IQSIRNVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSVWEG 84
                         90       100
                 ....*....|....*....|....*..
gi 767913374 493 CLpaEDSVKPNPGSDMNARKDYITAKY 519
Cdd:cd08855   85 AL--DGYSKPGPDSTREEKERWIRAKY 109
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
409-523 1.95e-25

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 108.33  E-value: 1.95e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 409 TKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNE 488
Cdd:COG5347    7 DRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNSNANR 86
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 767913374 489 IMECCLPAEDSVKPNPGSDMNARKDYITAKYIERR 523
Cdd:COG5347   87 FYEKNLLDQLLLPIKAKYDSSVAKKYIRKKYELKK 121
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
409-493 2.71e-24

Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350059 [Multi-domain]  Cd Length: 115  Bit Score: 98.72  E-value: 2.71e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 409 TKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNE 488
Cdd:cd08830    1 ARAVLRELQKLPGNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDSWSEKQLKKMELGGNAKLRE 80

                 ....*
gi 767913374 489 IMECC 493
Cdd:cd08830   81 FFESY 85
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
413-519 7.04e-24

Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350068 [Multi-domain]  Cd Length: 103  Bit Score: 96.96  E-value: 7.04e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 413 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEC 492
Cdd:cd08839    1 LAKLLREEDNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDSWTPEQVQSMQEMGNARANAYYEA 80
                         90       100
                 ....*....|....*....|....*..
gi 767913374 493 CLPaEDSVKPNPGSDMNArkdYITAKY 519
Cdd:cd08839   81 NLP-DGFRRPQTDSALEN---FIRDKY 103
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
413-519 3.98e-22

ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.


Pssm-ID: 350078 [Multi-domain]  Cd Length: 109  Bit Score: 92.38  E-value: 3.98e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 413 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEC 492
Cdd:cd08853    4 LQSIRNMRGNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDDWPVELRKVMSSIGNELANSIWEG 83
                         90       100
                 ....*....|....*....|....*..
gi 767913374 493 clPAEDSVKPNPGSDMNARKDYITAKY 519
Cdd:cd08853   84 --SSQGQTKPSSDSTREEKERWIRAKY 108
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
409-488 4.22e-22

ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350084 [Multi-domain]  Cd Length: 115  Bit Score: 92.19  E-value: 4.22e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 409 TKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNE 488
Cdd:cd08959    1 TRAVFKKLRSKPENKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDKWTEEQLRKMKVGGNANARE 80
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
411-524 4.44e-22

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics.


Pssm-ID: 350066 [Multi-domain]  Cd Length: 116  Bit Score: 92.44  E-value: 4.44e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 411 EIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDV-LGTSELL-LAKNIGNAGFNE 488
Cdd:cd08837    2 EVAEKIWSNPANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTkVWTEELVeLFLKLGNDRANR 81
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767913374 489 IMECCLPAEDSVKPNpgSDMNARKDYITAKYIERRY 524
Cdd:cd08837   82 FWAANLPPSEALHPD--ADSEQRREFITAKYREGKY 115
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
422-519 5.63e-22

The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350062 [Multi-domain]  Cd Length: 109  Bit Score: 91.59  E-value: 5.63e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 422 NDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMECCLP---AED 498
Cdd:cd08833    8 ARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSLLdpsQSG 87
                         90       100
                 ....*....|....*....|..
gi 767913374 499 SVKPNPGSDMNARK-DYITAKY 519
Cdd:cd08833   88 KRKPIPPDPVHPTKeEFIKAKY 109
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
409-488 8.62e-22

Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350060 [Multi-domain]  Cd Length: 116  Bit Score: 91.45  E-value: 8.62e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 409 TKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNE 488
Cdd:cd08831    2 RDAIFKKLRSKPENKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDSWTPEQLRRMKVGGNAKARE 81
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
422-528 2.80e-18

Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.


Pssm-ID: 350083 [Multi-domain]  Cd Length: 107  Bit Score: 81.19  E-value: 2.80e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 422 NDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMECCLPaEDSVK 501
Cdd:cd08859   10 NKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAFLP-ENFRR 88
                         90       100
                 ....*....|....*....|....*..
gi 767913374 502 PnpgsdmnaRKDYITAKYIERRYARKK 528
Cdd:cd08859   89 P--------QTDQAVEGFIRDKYEKKK 107
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
417-519 3.87e-18

GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350072 [Multi-domain]  Cd Length: 111  Bit Score: 80.84  E-value: 3.87e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 417 QRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMECCLPA 496
Cdd:cd08847    3 KRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSLLD 82
                         90       100
                 ....*....|....*....|....*....
gi 767913374 497 EDSV-----KPNPGSDMNARK-DYITAKY 519
Cdd:cd08847   83 PASImsgkrKANPQDKVHPNKaEFIRAKY 111
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
406-519 9.75e-18

ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350069 [Multi-domain]  Cd Length: 112  Bit Score: 79.66  E-value: 9.75e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 406 QELTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGvHYSRMQSLTLDVLGTSELLLAKNIGNAG 485
Cdd:cd08843    1 GKERRRAVLELLQRPGNARCADCGAPDPDWASYTLGVFICLSCSGIHRNIP-QVSKVKSVRLDAWEEAQVEFMASHGNDA 79
                         90       100       110
                 ....*....|....*....|....*....|....
gi 767913374 486 FNEIMECCLPAEdSVKPNPGSDMNARKDYITAKY 519
Cdd:cd08843   80 ARARFESKVPSF-YYRPTPSDCQLLREQWIRAKY 112
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
422-524 3.31e-17

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.


Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 78.41  E-value: 3.31e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 422 NDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTS----ELLLAknIGNAGFNEIMECCLPAE 497
Cdd:cd08856   18 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDASIWSneliELFIV--VGNKPANLFWAANLFSE 95
                         90       100
                 ....*....|....*....|....*..
gi 767913374 498 DSVkpNPGSDMNARKDYITAKYIERRY 524
Cdd:cd08856   96 EDL--HMDSDVEQRTPFITQKYKEGKF 120
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
299-390 2.45e-16

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. 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: 270070  Cd Length: 98  Bit Score: 75.33  E-value: 2.45e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 299 GSLYKKSDGIRKVWQKRKCSVKNGFLTISHGTANRPPAKL--NLLTCQVK--TNPEEKKCFDLISHDRTYHFQAEDEQEC 374
Cdd:cd13250    3 GYLFKRSSNAFKTWKRRWFSLQNGQLYYQKRDKKDEPTVMveDLRLCTVKptEDSDRRFCFEVISPTKSYMLQAESEEDR 82
                         90
                 ....*....|....*.
gi 767913374 375 QIWMSVLQNSKEEALN 390
Cdd:cd13250   83 QAWIQAIQSAIASALN 98
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
295-382 2.55e-16

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: 75.28  E-value: 2.55e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374   295 TERNGSLYKKSDGIRKVWQKRKCSVKNGFLTI----SHGTANRPPAKLNLLTCQVKTNPE-----EKKCFDLISHDR-TY 364
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSWKKRYFVLFNSTLLYykskKDKKSYKPKGSIDLSGCTVREAPDpdsskKPHCFEIKTSDRkTL 80
                           90
                   ....*....|....*...
gi 767913374   365 HFQAEDEQECQIWMSVLQ 382
Cdd:smart00233  81 LLQAESEEEREKWVEALR 98
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
411-524 1.39e-15

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP3 possesses a unique dual-specificity GAP activity for Arf6 and RhoA regulated by PI(3,4,5)P3 and a small GTPase Rap1-GTP. The RhoGAP activity of ARAP3 is enhanced by direct binding of Rap1-GTP to the Ras-association (RA) domain. ARAP3 is involved in regulation of cell shape and adhesion.


Pssm-ID: 350089 [Multi-domain]  Cd Length: 116  Bit Score: 73.79  E-value: 1.39e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 411 EIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDV-LGTSELL-LAKNIGNAGFNE 488
Cdd:cd17902    2 EVAEKIWSNKANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTsVWSNEIVqLFIVLGNDRANR 81
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767913374 489 IMECCLPAEDSVKPNpgSDMNARKDYITAKYIERRY 524
Cdd:cd17902   82 FWAARLPASEALHPD--ATPEQRREFISRKYREGRF 115
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
410-519 1.48e-15

ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.


Pssm-ID: 350070 [Multi-domain]  Cd Length: 112  Bit Score: 73.65  E-value: 1.48e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 410 KEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGvHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEI 489
Cdd:cd08844    5 KKRLLELLKLPGNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNLP-DISRVKSIRLDFWEDELVEFMKENGNLKAKAK 83
                         90       100       110
                 ....*....|....*....|....*....|
gi 767913374 490 MECCLPAEdSVKPNPGSDMNARKDYITAKY 519
Cdd:cd08844   84 FEAFVPPF-YYRPQANDCDVLKEQWIRAKY 112
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
411-524 1.87e-15

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP1 localizes to the plasma membrane, the Golgi complex, and endosomal compartments. It displays PI(3,4,5)P3-dependent ArfGAP activity that regulates Arf-, RhoA-, and Cdc42-dependent cellular events. For example, ARAP1 inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome.


Pssm-ID: 350088 [Multi-domain]  Cd Length: 116  Bit Score: 73.31  E-value: 1.87e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 411 EIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLD-VLGTSELL-LAKNIGNAGFNE 488
Cdd:cd17901    2 EVAEKIWSVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKMDrKVWTEELIeLFLLLGNGKANQ 81
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767913374 489 IMECCLPAEDSVKPNpgSDMNARKDYITAKYIERRY 524
Cdd:cd17901   82 FWAANVPPSEALCPS--SSSEERRHFITAKYKEGKY 115
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
934-990 1.91e-15

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: 1.91e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 767913374   934 KPKRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGdpGRKGAFPVSFV 990
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR--GKEGLFPSNYV 55
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
937-989 2.51e-15

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: 70.95  E-value: 2.51e-15
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGdpGRKGAFPVSF 989
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNG--GREGLFPANY 51
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
411-526 4.34e-15

ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350067 [Multi-domain]  Cd Length: 113  Bit Score: 72.23  E-value: 4.34e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 411 EIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGvHysRMQSLTLDVLGTSELLLAKNIGNAGFNEIM 490
Cdd:cd08838    2 KILRELLKLPENKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN-H--RVKSISMSTFTPEEVEFLQAGGNEVARKIW 78
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767913374 491 ECCLPAEDSVKPNPGsDMNARKDYITAKYIERRYAR 526
Cdd:cd08838   79 LAKWDPRTDPEPDSG-DDQKIREFIRLKYVDKRWYD 113
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
412-468 6.41e-14

Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350085 [Multi-domain]  Cd Length: 120  Bit Score: 69.32  E-value: 6.41e-14
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767913374 412 IISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLD 468
Cdd:cd09028    9 IFKRLRSVPTNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTELD 65
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
297-381 7.93e-14

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: 67.95  E-value: 7.93e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 297 RNGSLYKKSDGIRKVWQKRKCSVKNGFLTIS---HGTANRPPAKLNL---LTCQVKTNPEEKKCFDLI-SHDRTYHFQAE 369
Cdd:cd00821    1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYkskKDSSYKPKGSIPLsgiLEVEEVSPKERPHCFELVtPDGRTYYLQAD 80
                         90
                 ....*....|..
gi 767913374 370 DEQECQIWMSVL 381
Cdd:cd00821   81 SEEERQEWLKAL 92
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
551-666 9.62e-14

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 73.06  E-value: 9.62e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 551 LLQAYADgVDLTEKiplaNGhepdETALHLAVRSVDrtsLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLL 630
Cdd:COG0666  139 LLEAGAD-VNAQDN----DG----NTPLHLAAANGN---LEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLL 206
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767913374 631 RGKASIEIANESGETPLDIAKRLKHEHCEELLTQAL 666
Cdd:COG0666  207 EAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAG 242
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
508-662 1.64e-13

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 72.29  E-value: 1.64e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 508 MNARKDYITAKYIERRYARKKHADNAAKLHSLCEAVKTRDIFGLLQAYADGVDLTEKIplanghEPDETALHLAVRSVDr 587
Cdd:COG0666   60 AAALAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARD------KDGETPLHLAAYNGN- 132
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 588 tsLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLLRGKASIEIANESGETPLDIAKRLKHEHCEELL 662
Cdd:COG0666  133 --LEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLL 205
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
422-468 2.06e-13

Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.


Pssm-ID: 350086 [Multi-domain]  Cd Length: 120  Bit Score: 67.78  E-value: 2.06e-13
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 767913374 422 NDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLD 468
Cdd:cd09029   19 NKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTELD 65
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
423-519 1.43e-12

GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350071 [Multi-domain]  Cd Length: 111  Bit Score: 65.12  E-value: 1.43e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 423 DVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMECCL--PAE--- 497
Cdd:cd08846    9 EVCADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEHSLldPAQvqs 88
                         90       100
                 ....*....|....*....|...
gi 767913374 498 DSVKPNPGSDMNARK-DYITAKY 519
Cdd:cd08846   89 GRRKANPQDKVHPTKsEFIRAKY 111
PH pfam00169
PH domain; PH stands for pleckstrin homology.
295-386 1.58e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 64.89  E-value: 1.58e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  295 TERNGSLYKKSDGIRKVWQKRKCSVKNGFLTI----SHGTANRPPAKLNLLTCQVKT-----NPEEKKCFDLISHD---- 361
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYykddKSGKSKEPKGSISLSGCEVVEvvasdSPKRKFCFELRTGErtgk 80
                          90       100
                  ....*....|....*....|....*
gi 767913374  362 RTYHFQAEDEQECQIWMSVLQNSKE 386
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSAIR 105
BAR cd07307
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
55-230 4.96e-12

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.


Pssm-ID: 153271 [Multi-domain]  Cd Length: 194  Bit Score: 65.93  E-value: 4.96e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  55 LDVDRMVLYKMKKSVKAINSSGLAHVENEEQYTQALEKFGGNCVCRDDPDLGSAFLKFSVFTKELTALFKNL-------- 126
Cdd:cd07307    2 LDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELPDLSNTDLGEALEKFGKIQKELEEFRDQLeqklenkv 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 127 ----------------DLKKPFDKAWKDYETKITKIEKEKKEHAKLHGMIRTEisgaeiaEEMEKERRFFQLQMCEYLLK 190
Cdd:cd07307   82 ieplkeylkkdlkeikKRRKKLDKARLDYDAAREKLKKLRKKKKDSSKLAEAE-------EELQEAKEKYEELREELIED 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 767913374 191 VNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPS 230
Cdd:cd07307  155 LNKLEEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLLPY 194
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
937-990 3.40e-11

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: 59.35  E-value: 3.40e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11840    1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELN---GQTGLFPSNYV 51
Ank_2 pfam12796
Ankyrin repeats (3 copies);
578-662 4.33e-11

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 60.13  E-value: 4.33e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  578 LHLAVRsvdRTSLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLLRgKASIEIANEsGETPLDIAKRLKH-E 656
Cdd:pfam12796   1 LHLAAK---NGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLE-HADVNLKDN-GRTALHYAARSGHlE 75

                  ....*.
gi 767913374  657 HCEELL 662
Cdd:pfam12796  76 IVKLLL 81
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
412-483 6.51e-11

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 65.65  E-value: 6.51e-11
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767913374 412 IISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGN 483
Cdd:PLN03114  12 VFKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGN 83
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
168-252 1.81e-10

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 465256  Cd Length: 235  Bit Score: 62.19  E-value: 1.81e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  168 EIAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKPSIETLSTDLHTIKQAQDE 247
Cdd:pfam16746 151 EADNELAATRKCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQGYELFKDLEPFMKDLQAQLQQTREDTRE 230

                  ....*
gi 767913374  248 ERRQL 252
Cdd:pfam16746 231 EKEEL 235
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
296-390 2.57e-10

Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. SIP3 contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a PH domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. 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: 270098  Cd Length: 105  Bit Score: 58.42  E-value: 2.57e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 296 ERNGSLY---KKSDGIRKVWQKRKCSVKN---GFLTIS-HGTANRPPAKLNLLTCQVKTNPEE--KKCFDL-ISHDRTYH 365
Cdd:cd13280    1 EKSGWLYmktSVGKPNRTIWVRRWCFVKNgvfGMLSLSpSKTYVEETDKFGVLLCSVRYAPEEdrRFCFEVkIFKDISII 80
                         90       100
                 ....*....|....*....|....*
gi 767913374 366 FQAEDEQECQIWMSVLQNSKEEALN 390
Cdd:cd13280   81 LQAETLKELKSWLTVFENAKRYALQ 105
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
507-650 4.30e-10

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 61.89  E-value: 4.30e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 507 DMNARKDYITAKYIERRYARKKHADNAAKLHSLCEAVKTRDIFGLLQAYADGVDLTEKIPLANGHEPD--------ETAL 578
Cdd:COG0666   12 LAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADinakddggNTLL 91
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767913374 579 HLAVRSVDrtsLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLLRGKASIEIANESGETPLDIA 650
Cdd:COG0666   92 HAAARNGD---LEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLA 160
SH3_9 pfam14604
Variant SH3 domain;
940-990 5.41e-10

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 55.70  E-value: 5.41e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767913374  940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINT---GRTGLVPANYV 48
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
936-990 7.07e-10

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: 55.40  E-value: 7.07e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 936 KRVKALYNCVADNPDELTFSEGD-VIIVDGEEDQEWWIGHIDgDPGRKGAFPVSFV 990
Cdd:cd11775    1 KRGKVLYDFDAQSDDELTVKEGDvVYILDDKKSKDWWMVENV-STGKEGVVPASYI 55
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
937-990 8.51e-10

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: 8.51e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11805    1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELR---GRVGIFPANYV 51
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
938-991 1.01e-09

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: 55.01  E-value: 1.01e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFVH 991
Cdd:cd11877    2 VRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLN---GKTGWFPSNYVK 52
SH3_Bbc1 cd11887
Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces ...
935-990 1.39e-09

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: 54.66  E-value: 1.39e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 935 PKRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRK--GAFPVSFV 990
Cdd:cd11887    1 PFKVKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYVDSNGNTkeGIFPKNFV 58
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
939-987 1.86e-09

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: 1.86e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 767913374  939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGdpGRKGAFPV 987
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKG--GKEGLIPS 47
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
939-990 1.96e-09

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: 54.19  E-value: 1.96e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11803    4 RALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVN---GQSGFFPVNYV 52
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
937-990 2.33e-09

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: 53.89  E-value: 2.33e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11823    1 RCKALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELN---GKKGIFPATYV 51
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
937-990 2.34e-09

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: 53.89  E-value: 2.34e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEE--DQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11875    1 KARVLFDYEAENEDELTLREGDIVTILSKDceDKGWWKGELN---GKRGVFPDNFV 53
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
937-990 2.42e-09

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: 53.86  E-value: 2.42e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11826    1 KVVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLN---GVTGLFPGNYV 51
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
937-989 3.56e-09

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: 53.87  E-value: 3.56e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIV---DGEEDQE--WWIGHIDGDpGRKGAFPVSF 989
Cdd:cd11790    4 KVRATHDYTAEDTDELTFEKGDVILVipfDDPEEQDegWLMGVKEST-GCRGVFPENF 60
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
937-991 3.60e-09

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: 53.51  E-value: 3.60e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIdgdPGRKGAFPVSFVH 991
Cdd:cd11782    1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRI---GGRQGIFPVSYVQ 52
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
937-992 6.21e-09

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: 52.68  E-value: 6.21e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIvDGEEDQE--WWIGHIDgdpGRKGAFPVSFVHF 992
Cdd:cd11882    1 RARALYACKAEDESELSFEPGQIIT-NVQPSDEpgWLEGTLN---GRTGLIPENYVEF 54
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
937-990 7.85e-09

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: 52.36  E-value: 7.85e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11796    1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELN---GRRGIFPEGFV 51
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
937-990 1.15e-08

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: 51.98  E-value: 1.15e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQE--WWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11836    1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAEpgWLAGELK---GKTGWFPANYV 53
SH3_SH3RF2_1 cd11929
First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
937-990 1.65e-08

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: 51.48  E-value: 1.65e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11929    2 RAKALCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEIN---GVSGIFPASSV 52
PLN03131 PLN03131
hypothetical protein; Provisional
406-531 1.67e-08

hypothetical protein; Provisional


Pssm-ID: 178677 [Multi-domain]  Cd Length: 705  Bit Score: 58.64  E-value: 1.67e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 406 QELTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELgVHysRMQSLTLDVLGTSELLLAKNIGNAG 485
Cdd:PLN03131   7 EERNEKIIRGLMKLPPNRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF-TH--RVKSVSMSKFTSQDVEALQNGGNQR 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 767913374 486 FNEIMECCLPAEDSVKPNpGSDMNARKDYITAKYIERRYARKKHAD 531
Cdd:PLN03131  84 AREIYLKDWDQQRQRLPD-NSKVDKIREFIKDIYVDKKYAGGKTHD 128
SH3_Noxa1_C cd12047
C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox ...
937-990 2.05e-08

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: 51.36  E-value: 2.05e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12047    1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCD---GRIGIFPKCFA 51
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
937-990 2.32e-08

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: 51.18  E-value: 2.32e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11874    1 RCKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLN---GKVGVFPSNFV 51
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
938-990 2.40e-08

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: 51.15  E-value: 2.40e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11772    2 FRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCG---GKTGLIPSNYV 51
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
937-990 2.77e-08

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: 50.77  E-value: 2.77e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGhiDGDPGRKGAFPVSFV 990
Cdd:cd11819    1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLG--VNAKGQKGLFPANYV 52
Ank_2 pfam12796
Ankyrin repeats (3 copies);
567-640 3.29e-08

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 52.04  E-value: 3.29e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  567 LANGHEPD------ETALHLAVRsvdRTSLHIVDFLVQNsGNLDKQTgKGSTALHYCCLTDNAECLKLLLRGKASIEIAN 640
Cdd:pfam12796  17 LENGADANlqdkngRTALHLAAK---NGHLEIVKLLLEH-ADVNLKD-NGRTALHYAARSGHLEIVKLLLEKGADINVKD 91
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
938-990 3.45e-08

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: 3.45e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11828    2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIR---DEEGWFPASFV 51
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
937-990 4.75e-08

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: 50.11  E-value: 4.75e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11827    1 QCKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLR---GKEGLFPGNYV 51
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
937-990 4.82e-08

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: 50.10  E-value: 4.82e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11816    1 RCVARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELN---GKIGIFPLNFV 51
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
938-986 6.11e-08

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: 50.09  E-value: 6.11e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIV----DGEEDQEWWIGHIDgdpGRKGAFP 986
Cdd:cd11762    2 VRALYDYEAQSDEELSFPEGAIIRIlrkdDNGVDDGWWEGEFN---GRVGVFP 51
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
938-990 6.21e-08

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: 49.80  E-value: 6.21e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12046    2 VVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCK---GKIGIFPSAFV 51
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
406-535 6.75e-08

putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional


Pssm-ID: 178666  Cd Length: 648  Bit Score: 56.39  E-value: 6.75e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 406 QELTKEIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGvhySRMQSLTLDVLGTSELLLAKNIGNAG 485
Cdd:PLN03119   7 EERNEKIIRGLMKLPPNRRCINCNSLGPQYVCTTFWTFVCMACSGIHREFT---HRVKSVSMSKFTSKEVEVLQNGGNQR 83
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 486 FNEIMeccLPAEDSVKPNPGSDMNAR--KDYITAKYIERRYARKKHADNAAK 535
Cdd:PLN03119  84 AREIY---LKNWDHQRQRLPENSNAErvREFIKNVYVQKKYAGANDADKPSK 132
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
939-990 7.22e-08

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: 49.67  E-value: 7.22e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11786    3 KALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECN---GKQGFFPASYV 51
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
936-990 8.72e-08

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: 49.39  E-value: 8.72e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHidgDPGRKGAFPVSFV 990
Cdd:cd11820    1 RKVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGS---NHRGEGLFPANFV 52
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
937-990 9.28e-08

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: 49.59  E-value: 9.28e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11996    2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEIN---GVTGLFPSNYV 52
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
940-990 1.03e-07

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: 49.24  E-value: 1.03e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDgEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11992    4 ALYPYSSSEPGDLTFNEGEEILVT-QKDGEWWTGSIE---DRTGIFPSNYV 50
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
938-990 1.24e-07

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: 49.30  E-value: 1.24e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12061    2 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHN---GRTGWFPSNYV 51
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
551-666 1.35e-07

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 54.19  E-value: 1.35e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 551 LLQAYADgVDLTEKIplanghepDETALHLAVRSVDrtsLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLL 630
Cdd:COG0666  172 LLEAGAD-VNARDND--------GETPLHLAAENGH---LEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLL 239
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767913374 631 RGKASIEIANESGETPLDIAKRLKHEHCEELLTQAL 666
Cdd:COG0666  240 EAGADLNAKDKDGLTALLLAAAAGAALIVKLLLLAL 275
SH3_PACSIN_like cd11999
Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C ...
937-990 1.43e-07

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: 49.17  E-value: 1.43e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVII-VDGEEDQEWWIGHIDGdpGRKGAFPVSFV 990
Cdd:cd11999    3 RVRAVYDYTGQEPDELSFKAGEELLkVEDEDEQGWCKGVTDG--GAVGLYPANYV 55
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
937-990 1.67e-07

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: 48.75  E-value: 1.67e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 767913374  937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:pfam07653   1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETG---GRVGLVPSTAV 51
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
937-990 2.28e-07

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: 48.41  E-value: 2.28e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11995    2 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELN---GQVGLFPSNYV 52
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
938-990 2.84e-07

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: 47.90  E-value: 2.84e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11961    2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECH---GSRGLFPSNYV 51
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
296-387 3.30e-07

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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: 270073  Cd Length: 94  Bit Score: 49.31  E-value: 3.30e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 296 ERNGSLYKKS-DGIRKVWQKRkcSVKNGFLTISHGTANRPPAKLNL--LTCQVKTNPEEKKCFDLISHDRTYHFQAEDEQ 372
Cdd:cd13253    1 IKSGYLDKQGgQGNNKGFQKR--WVVFDGLSLRYFDSEKDAYSKRIipLSAISTVRAVGDNKFELVTTNRTFVFRAESDD 78
                         90
                 ....*....|....*
gi 767913374 373 ECQIWMSVLQNSKEE 387
Cdd:cd13253   79 ERNLWCSTLQAAISE 93
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
938-990 3.88e-07

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: 47.69  E-value: 3.88e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12060    4 VKARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLN---GKTGWFPSNYV 53
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
936-990 5.00e-07

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: 5.00e-07
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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIdgdPGRKGAFPVSFV 990
Cdd:cd11964    1 RKVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGET---PQGTGLFPSNFV 52
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
938-990 5.60e-07

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: 5.60e-07
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                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11950    2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLH---GKLGLFPANYV 51
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
937-990 5.71e-07

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: 47.03  E-value: 5.71e-07
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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWI-GHIDgdpGRKGAFPVSFV 990
Cdd:cd11843    1 PVRALYDYEGQESDELSFKAGDILTKLEEEDEQGWCkGRLD---GRVGLYPANYV 52
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
939-993 5.75e-07

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: 47.20  E-value: 5.75e-07
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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEE--DQEWWIGHIDgdpGRKGAFPVSFVHFI 993
Cdd:cd12057    3 KVLFPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELN---GRRGVFPDNFVKLL 56
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
938-989 5.89e-07

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: 47.09  E-value: 5.89e-07
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                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSF 989
Cdd:cd11817    2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLN---GREGIFPRAF 50
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
938-991 6.11e-07

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: 47.10  E-value: 6.11e-07
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                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFVH 991
Cdd:cd11951    2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRIS---GRVGFFPRNYVH 52
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
937-990 6.29e-07

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: 6.29e-07
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                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDgEEDQEWWIGHIDGdpGRKGAFPVSFV 990
Cdd:cd11837    1 TATALYPWRAKKENHLSFAKGDIITVL-EQQEMWWFGELEG--GEEGWFPKSYV 51
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
937-990 6.55e-07

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: 47.12  E-value: 6.55e-07
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                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGdpGRKGAFPVSFV 990
Cdd:cd11812    1 TVVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLVN--GQQGYFPANYV 52
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
938-990 7.58e-07

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: 46.88  E-value: 7.58e-07
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gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11873    2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLN---GKRGMFPDNFV 51
SH3_p67phox-like_C cd11870
C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; ...
937-990 8.07e-07

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: 46.75  E-value: 8.07e-07
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gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11870    1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSD---GRVGIFPKCFV 51
SH3_CAS cd11844
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins ...
939-986 1.02e-06

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: 46.57  E-value: 1.02e-06
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                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIV---DGEEDQEWWIGHIdgdPGRKGAFP 986
Cdd:cd11844    3 RALYDNVAESPDELAFRRGDILTVleqNTAGLEGWWLCSL---RGRQGIAP 50
Ank_5 pfam13857
Ankyrin repeats (many copies);
596-650 1.09e-06

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 46.57  E-value: 1.09e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374  596 LVQN-SGNLDKQTGKGSTALHYCCLTDNAECLKLLLRGKASIEIANESGETPLDIA 650
Cdd:pfam13857   1 LLEHgPIDLNRLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
940-990 1.10e-06

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: 46.25  E-value: 1.10e-06
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                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDgEEDQEWWIGHIdGDpgRKGAFPVSFV 990
Cdd:cd11838    4 ALYPYESNEPGDLTFNAGDVILVT-KKDGEWWTGTI-GD--RTGIFPSNYV 50
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
938-990 1.12e-06

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: 46.56  E-value: 1.12e-06
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gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIghidGDPG--RKGAFPVSFV 990
Cdd:cd11825    2 VKALYDYRAQRPDELSFCKHAIITNVEKEDGGWWR----GDYGgkKQKWFPANYV 52
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
936-990 1.12e-06

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: 46.55  E-value: 1.12e-06
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gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWighiDGDPGRK-GAFPVSFV 990
Cdd:cd11963    2 RKVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWW----KGENHRGvGLFPSNFV 53
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
939-990 1.17e-06

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: 46.30  E-value: 1.17e-06
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gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGE--EDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12142    3 RVLFDYNPVAPDELALKKGDVIEVISKetEDEGWWEGELN---GRRGFFPDNFV 53
SH3_SH3RF1_1 cd11927
First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ...
939-991 1.33e-06

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: 46.10  E-value: 1.33e-06
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gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFVH 991
Cdd:cd11927    4 KALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVN---GIHGFFPTNFVQ 53
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
525-662 1.46e-06

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 51.11  E-value: 1.46e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 525 ARKKHADNAAKLHSLCEAVKTRDIFGLLQAYADGVDLTEKIPLANGHEPDETALHLAVRSVDRtsLHIVDFLVQNSGNLD 604
Cdd:COG0666    4 LLLLLLLLLAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGD--LLVALLLLAAGADIN 81
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 605 KQTGKGSTALHYCCLTDNAECLKLLLRGKASIEIANESGETPLDIAKRLKHEHCEELL 662
Cdd:COG0666   82 AKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLL 139
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
937-990 1.68e-06

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: 45.88  E-value: 1.68e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVI-IVDGEEDQE-WWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11842    1 KAVALYDFAGEQPGDLAFQKGDIItILKKSDSQNdWWTGRIG---GREGIFPANYV 53
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
946-990 2.28e-06

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: 45.66  E-value: 2.28e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 767913374 946 ADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12052   10 AQHEDELTITVGDIITKIKKDDGGWWEGEIK---GRRGLFPDNFV 51
SH3_PACSIN1-2 cd11998
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) ...
937-990 2.35e-06

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: 45.71  E-value: 2.35e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWI-GHIDGdpGRKGAFPVSFV 990
Cdd:cd11998    2 RVRALYDYDGQEQDELSFKAGDELTKLEDEDEQGWCkGRLDS--GQVGLYPANYV 54
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
937-989 2.64e-06

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: 45.17  E-value: 2.64e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSF 989
Cdd:cd11818    1 KARALYDFTGENEDELSFKAGDIITELESIDEEWMSGELR---GKSGIFPKNF 50
SH3_Irsp53_BAIAP2L cd11779
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific ...
936-990 2.75e-06

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: 45.39  E-value: 2.75e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQE-WWIGHIDGDpGRKGAFPVSFV 990
Cdd:cd11779    1 PRVKALYPHAAGGETQLSFEEGDVITLLGPEPRDgWHYGENERS-GRRGWFPIAYT 55
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
939-990 3.12e-06

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: 3.12e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11920    4 RAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHH---GRVGIFPISYV 52
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
939-990 3.14e-06

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: 45.02  E-value: 3.14e-06
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                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHidgDPGRKGAFPVSFV 990
Cdd:cd11781    3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGE---HNGRVGIFPASYV 51
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
939-990 3.23e-06

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: 45.20  E-value: 3.23e-06
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                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEE--DQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12056    5 KALFHYEGTNEDELDFKEGEIILIISKDtgEPGWWKGELN---GKEGVFPDNFV 55
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
940-980 3.28e-06

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: 45.11  E-value: 3.28e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 767913374 940 ALYNCVADNPDELTFSEGDVI-IVDGEED-QEWWIGHIDGDPG 980
Cdd:cd11866    4 GLWDCSGNEPDELSFKRGDLIyIISKEYDsFGWWVGELNGKVG 46
Ank_4 pfam13637
Ankyrin repeats (many copies);
576-630 3.50e-06

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 44.96  E-value: 3.50e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374  576 TALHLAVRSvdrTSLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLL 630
Cdd:pfam13637   3 TALHAAAAS---GHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVLKLLL 54
SH3_Sorbs2_2 cd11923
Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
940-993 3.76e-06

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: 44.91  E-value: 3.76e-06
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                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGdPGRKGAFPVSFVHFI 993
Cdd:cd11923    5 AKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPG-TNRQGIFPVSYVEVI 57
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
939-980 3.90e-06

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: 44.85  E-value: 3.90e-06
                         10        20        30        40
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gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQE--WWIGHIDGDPG 980
Cdd:cd12044    3 QGLWDCFGDNPDELSFQRGDLIYILSKEYNMygWWVGELNGIVG 46
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
937-990 4.14e-06

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: 44.99  E-value: 4.14e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12055    1 RCQVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLN---GKTGMFPSNFI 51
SH3_Bem1p_2 cd11879
Second Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this ...
941-992 4.48e-06

Second 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: 212812 [Multi-domain]  Cd Length: 56  Bit Score: 44.63  E-value: 4.48e-06
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                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 941 LYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRKGAFPVSFVHF 992
Cdd:cd11879    5 LYDFKAERPDELDAKAGDAIIICAHSNYEWFVAKPIGRLGGPGLIPVSFVEI 56
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
937-990 4.49e-06

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: 44.66  E-value: 4.49e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWigHIDGDPGRKGAFPVSFV 990
Cdd:cd11758    2 YVRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWW--NARNSEGKTGMIPVPYV 53
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
936-990 4.67e-06

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: 44.57  E-value: 4.67e-06
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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12054    1 RQCKVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLN---GKSGLFPSNFV 52
SH3_SKAP2 cd12045
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called ...
939-980 4.88e-06

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: 44.51  E-value: 4.88e-06
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gi 767913374 939 KALYNCVADNPDELTFSEGDVI-IVDGEEDQ-EWWIGHIDGDPG 980
Cdd:cd12045    3 QGLWDCTGDQPDELSFKRGDTIyILSKEYNRfGWWVGEMKGTIG 46
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
937-990 4.95e-06

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: 44.70  E-value: 4.95e-06
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gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHidGDPGRKGAFPVSFV 990
Cdd:cd11960    1 RARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGT--GPDGTYGLFPANYV 52
PHA03095 PHA03095
ankyrin-like protein; Provisional
574-649 7.93e-06

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 49.64  E-value: 7.93e-06
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gi 767913374 574 DETALHLAVRSVDRTSLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDN-AECLKLLLRGKASIEIANESGETPLDI 649
Cdd:PHA03095  47 GKTPLHLYLHYSSEKVKDIVRLLLEAGADVNAPERCGFTPLHLYLYNATtLDVIKLLIKAGADVNAKDKVGRTPLHV 123
SH3_DOCK_AB cd11872
Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are ...
940-991 1.09e-05

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: 43.73  E-value: 1.09e-05
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gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDgEEDQEWWIGHIDGDPGRKGAFPVSFVH 991
Cdd:cd11872    4 AIYNFQGDGEHQLSLQVGDTVQIL-EECEGWYRGFSLRNKSLKGIFPKSYVH 54
SH3_SH3RF3_1 cd11928
First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
939-991 1.15e-05

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: 43.76  E-value: 1.15e-05
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gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDpgrKGAFPVSFVH 991
Cdd:cd11928    4 KALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGC---HGFLPASYIQ 53
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
937-971 1.19e-05

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: 43.52  E-value: 1.19e-05
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gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIV---DGEEDQEWW 971
Cdd:cd11807    2 VVYALFDYEAENGDELSFREGDELTVlrkGDDDETEWW 39
SH3_SNX18 cd11897
Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal ...
937-990 1.34e-05

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: 43.44  E-value: 1.34e-05
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gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDpGRKGAFPVSFV 990
Cdd:cd11897    1 RARALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNSR-GDRGLFPASYV 53
SH3_Stac_1 cd11833
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) ...
940-991 1.71e-05

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: 42.87  E-value: 1.71e-05
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gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIdGDpgRKGAFPVSFVH 991
Cdd:cd11833    4 ALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKI-ED--RVGFFPANFVQ 52
SH3_PACSIN3 cd11997
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); ...
937-990 2.04e-05

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: 2.04e-05
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gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWI-GHIDGdpGRKGAFPVSFV 990
Cdd:cd11997    3 RVRALYDYTGQEADELSFKAGEELLKIGEEDEQGWCkGRLLS--GRIGLYPANYV 55
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
940-990 2.25e-05

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: 42.88  E-value: 2.25e-05
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gi 767913374 940 ALYNCVADNPDELTFSEGDVI-IVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11948    4 ALYSFQATESDELPFQKGDILkILNMEDDQNWYKAELQ---GREGYIPKNYI 52
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
299-384 2.36e-05

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. 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: 270108  Cd Length: 103  Bit Score: 44.38  E-value: 2.36e-05
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gi 767913374 299 GSLYKKSDGI----RKVWQKRKCSVKNGFLTI--SHGTANRPPAKLNLLTCQVKT-NPEEKKCFDLISHDRTYHFQAEDE 371
Cdd:cd13296    3 GWLTKKGGGSstlsRRNWKSRWFVLRDTVLKYyeNDQEGEKLLGTIDIRSAKEIVdNDPKENRLSITTEERTYHLVAESP 82
                         90
                 ....*....|...
gi 767913374 372 QECQIWMSVLQNS 384
Cdd:cd13296   83 EDASQWVNVLTRV 95
PHA03100 PHA03100
ankyrin repeat protein; Provisional
575-656 2.56e-05

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 47.74  E-value: 2.56e-05
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gi 767913374 575 ETALHLAVRSVdRTSLHIVDFLVQNSGNLDKQTG----------------KGSTALHYCCLTDNAECLKLLLRGKASIEI 638
Cdd:PHA03100 142 ENLLHLYLESN-KIDLKILKLLIDKGVDINAKNRvnyllsygvpinikdvYGFTPLHYAVYNNNPEFVKYLLDLGANPNL 220
                         90
                 ....*....|....*...
gi 767913374 639 ANESGETPLDIAKRLKHE 656
Cdd:PHA03100 221 VNKYGDTPLHIAILNNNK 238
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
938-990 4.15e-05

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: 41.99  E-value: 4.15e-05
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gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQ--EWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11841    2 VTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRLR---GRVGIFPANYV 53
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
304-382 4.15e-05

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. 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: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 43.08  E-value: 4.15e-05
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gi 767913374 304 KSDGIRKVWQKRKCSV-KNGFLTISHGTANRPPAKLNLLTC---QVKTNPEEKKCFDLISHDRTYHFQAEDEQECQIWMS 379
Cdd:cd10573   11 KLGGIVKNWKTRWFVLrRNELKYFKTRGDTKPIRVLDLRECssvQRDYSQGKVNCFCLVFPERTFYMYANTEEEADEWVK 90

                 ...
gi 767913374 380 VLQ 382
Cdd:cd10573   91 LLK 93
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
285-382 4.50e-05

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but 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: 275402  Cd Length: 116  Bit Score: 43.76  E-value: 4.50e-05
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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 285 HQPqgNKEHGTERNGSLYKKSDgIRKVWQKRKCSVKNGFLTIsHGTANRP--PA---KLNLLT--CQVKTNPEEKKCFDL 357
Cdd:cd13215   13 YLP--KRSGAVIKSGYLSKRSK-RTLRYTRYWFVLKGDTLSW-YNSSTDLyfPAgtiDLRYATsiELSKSNGEATTSFKI 88
                         90       100
                 ....*....|....*....|....*
gi 767913374 358 ISHDRTYHFQAEDEQECQIWMSVLQ 382
Cdd:cd13215   89 VTNSRTYKFKADSETSADEWVKALK 113
SH3_MYO15 cd11884
Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to ...
938-990 4.75e-05

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: 4.75e-05
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gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEE---DQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11884    2 VVAVRAYITRDQTLLSFHKGDVIKLLPKEgplDPGWLFGTLD---GRSGAFPKEYV 54
SH3_Lasp1_C cd11934
C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic ...
936-993 5.00e-05

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: 41.91  E-value: 5.00e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgDPGRKGAFPVSFVHFI 993
Cdd:cd11934    3 KRYRAVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGTVE-RTGDTGMLPANYVEAI 59
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
938-992 5.03e-05

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: 41.94  E-value: 5.03e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDpGRKGAFPVSFVHF 992
Cdd:cd11793    2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERLRD-GERGWFPSSYTEE 55
SH3_SGSM3 cd11813
Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called ...
937-990 5.40e-05

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: 41.72  E-value: 5.40e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11813    1 RAKALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELN---GLRGWFPAKFV 51
SH3_BCAR1 cd12001
Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, ...
939-986 5.54e-05

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: 41.95  E-value: 5.54e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQ---EWWIGHIDgdpGRKGAFP 986
Cdd:cd12001    6 KALYDNVAESPDELSFRKGDIMTVLERDTQgldGWWLCSLH---GRQGIVP 53
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
937-990 5.75e-05

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: 41.54  E-value: 5.75e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQE-WWIGHidGDPGRKGAFPVSFV 990
Cdd:cd11763    1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDgWLEGR--NSRGEVGLFPSSYV 53
SH3_Nebulin_C cd11933
C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 ...
936-993 6.19e-05

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: 41.53  E-value: 6.19e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgDPGRKGAFPVSFVHFI 993
Cdd:cd11933    2 KSFRAMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVQ-RTGKTGMLPANYVEAI 58
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
938-989 7.62e-05

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: 41.33  E-value: 7.62e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVI-IVDGEEDQEWWIGHIDGDpgrKGAFPVSF 989
Cdd:cd11778    2 VEALYDYEAQGDDEISIRVGDRIaVIRGDDGSGWTYGEINGV---KGLFPTSY 51
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
937-990 8.57e-05

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: 41.18  E-value: 8.57e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDgEEDQEWWIGHIDGDpgrKGAFPVSFV 990
Cdd:cd11990    1 KAQALCSWTAKKDNHLNFSKNDIITVL-EQQENWWFGEVHGG---RGWFPKSYV 50
BAR_ACAP3 cd07637
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
79-229 8.76e-05

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3), also called centaurin beta-5, is presumed to be an Arf GTPase activating protein (GAP) based on its similarity to the Arf6-specific GAPs ACAP1 and ACAP2. The specific function of ACAP3 is still unknown. ACAP3 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153321  Cd Length: 200  Bit Score: 44.61  E-value: 8.76e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  79 HVENEEQYTQALEKFGGNC-------VCRDDPDLGSAFLKFSVFTKELTALFKnlDLKKPFDKAWKDyetkiTKIEKEKK 151
Cdd:cd07637   52 QCKKDEMISECLDKFGDSLqemvnyhMILFDQAQRSVRQQLHSFVKEDVRKFK--ETKKQFDKVRED-----LEIALVKN 124
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 152 EHAKLHGMIRTEisgaEIAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESLKP 229
Cdd:cd07637  125 AQAPRHKPHEVE----EATSTLTITRKCFRHLALDYVLQINVLQAKKKFEILDSMLSFMHAQYTFFQQGYSLLHELDP 198
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
939-990 9.40e-05

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: 41.08  E-value: 9.40e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 939 KALYNCVADNPDELTFSEGDVI-IVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11830    3 KARYDFCARDMRELSLKEGDVVkIYNKKGQQGWWRGEIN---GRIGWFPSTYV 52
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
938-990 1.11e-04

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: 40.98  E-value: 1.11e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWighiDGDPGRKGA--FPVSFV 990
Cdd:cd11969    2 VKALYDYRAKRSDELSFCKGALIHNVSKETGGWW----KGDYGGKVQhyFPSNYV 52
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
938-989 1.24e-04

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: 40.73  E-value: 1.24e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGR--KGAFPVSF 989
Cdd:cd11883    2 VVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKvkRGWFPSNY 55
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
421-524 1.33e-04

ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG2 is a member of the HIV-1 Rev binding protein (HRB) family and contains one Arf-GAP zinc finger domain, several Phe-Gly (FG) motifs, and four Asn-Pro-Phe (NPF) motifs. AGFG2 interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350090 [Multi-domain]  Cd Length: 116  Bit Score: 42.28  E-value: 1.33e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 421 GNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYsRMQSLTLDVLGTSELLLAKNIGNAGFNEIMECCLPAEDSV 500
Cdd:cd17903   13 ANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPH-RVKSISMTTFTEPEVLFLQARGNEVCRKIWLGLFDARTSL 91
                         90       100
                 ....*....|....*....|....
gi 767913374 501 KPNpGSDMNARKDYITAKYIERRY 524
Cdd:cd17903   92 IPD-SRDPQKVKEFLQEKYEKKRW 114
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
940-990 1.40e-04

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: 40.42  E-value: 1.40e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 940 ALYNCVADNPDELTFSEGDVI-IVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11804    4 AKHDFKATAEDELSFKKGSILkVLNMEDDPNWYKAELD---GKEGLIPKNYI 52
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
411-524 1.46e-04

ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG1 is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG1 plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG1 promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.


Pssm-ID: 350082 [Multi-domain]  Cd Length: 116  Bit Score: 42.33  E-value: 1.46e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 411 EIISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYsRMQSLTLDVLGTSELLLAKNIGNAGFNEIM 490
Cdd:cd08857    3 KMLREMTSLPHNRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPPH-RVKSISMTTFTQQEIEFLQKHGNEVCKQIW 81
                         90       100       110
                 ....*....|....*....|....*....|....
gi 767913374 491 ECCLPAEDSVKPNpGSDMNARKDYITAKYIERRY 524
Cdd:cd08857   82 LGLFDDRSSAIPD-FRDPQKVKEFLQEKYEKKRW 114
SH3_Nebulette_C cd11935
C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a ...
939-993 1.64e-04

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: 40.37  E-value: 1.64e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgDPGRKGAFPVSFVHFI 993
Cdd:cd11935    4 RAMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGTVQ-RTGRTGMLPANYIEFV 57
PHA03095 PHA03095
ankyrin-like protein; Provisional
457-674 1.81e-04

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 45.02  E-value: 1.81e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 457 VHYSRMQSLTLDVLgtsELLLAK--NI---GNAGFNEIMECClpAEDSVKP-------NPGSDMNARKDY---------- 514
Cdd:PHA03095  87 LHLYLYNATTLDVI---KLLIKAgaDVnakDKVGRTPLHVYL--SGFNINPkvirlllRKGADVNALDLYgmtplavllk 161
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 515 ---ITAKYIerRYARKKHADNAAK-------LHSLCEAVKTR-DIFGLLQAYadGVDLTEKIPLANghepdeTALHLAVR 583
Cdd:PHA03095 162 srnANVELL--RLLIDAGADVYAVddrfrslLHHHLQSFKPRaRIVRELIRA--GCDPAATDMLGN------TPLHSMAT 231
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 584 SVDRTSLHIVDFLVQNSGnLDKQTGKGSTALHYCCLTDNAE-CLKLLLRGkASIEIANESGETPLDIAKRLKHEHCeelL 662
Cdd:PHA03095 232 GSSCKRSLVLPLLIAGIS-INARNRYGQTPLHYAAVFNNPRaCRRLIALG-ADINAVSSDGNTPLSLMVRNNNGRA---V 306
                        250
                 ....*....|..
gi 767913374 663 TQALSGRFNSHV 674
Cdd:PHA03095 307 RAALAKNPSAET 318
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
938-990 1.90e-04

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: 40.21  E-value: 1.90e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11949    2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACH---GQTGMFPRNYV 51
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
938-990 1.91e-04

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: 40.31  E-value: 1.91e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIV---DGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11894    2 VKALYDYEGQTDDELSFPEGAIIRIlnkENQDDDGFWEGEFN---GRIGVFPSVLV 54
SH3_ASEF2 cd11974
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also ...
939-990 2.01e-04

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: 40.05  E-value: 2.01e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11974    4 EALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNE---DREAWFPASFV 52
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
609-638 2.01e-04

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 39.49  E-value: 2.01e-04
                           10        20        30
                   ....*....|....*....|....*....|
gi 767913374   609 KGSTALHYCCLTDNAECLKLLLRGKASIEI 638
Cdd:smart00248   1 DGRTPLHLAAENGNLEVVKLLLDKGADINA 30
SH3_Bem1p_1 cd11878
First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this ...
938-989 2.09e-04

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: 39.96  E-value: 2.09e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRKGAFPVSF 989
Cdd:cd11878    2 IRALYDYRAQTPGELSFSKGDFFHVIGEEDQGEWYEATNPVTGKRGLVPKSY 53
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
940-990 2.56e-04

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: 39.58  E-value: 2.56e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDgEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11991    4 AMYTYESNEQGDLTFQQGDVILVT-KKDGDWWTGTVG---DKTGVFPSNYV 50
SH3_Sorbs_3 cd11780
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) ...
937-990 2.58e-04

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: 39.59  E-value: 2.58e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGhIDGDPGRKGAFPVSFV 990
Cdd:cd11780    1 RYRALYSYTPQNEDELELREGDIVYVMEKCDDGWFVG-TSERTGLFGTFPGNYV 53
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
936-994 2.77e-04

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: 39.99  E-value: 2.77e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFVHFIA 994
Cdd:cd11972    3 EKVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMN---GVTGLFPGNYVESIM 58
PHA03100 PHA03100
ankyrin repeat protein; Provisional
574-641 2.81e-04

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 44.66  E-value: 2.81e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 574 DETALHLAVRSVdrtSLHIVDFLVQNSGNLDKQTGKGSTALHYCCLTDNAECLKLLLRGKASIEIANE 641
Cdd:PHA03100 192 GFTPLHYAVYNN---NPEFVKYLLDLGANPNLVNKYGDTPLHIAILNNNKEIFKLLLNNGPSIKTIIE 256
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
940-991 2.87e-04

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: 39.68  E-value: 2.87e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDpgrKGAFPVSFVH 991
Cdd:cd11806    4 AIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGC---CGYIPASHLH 52
SH3_ARHGEF9 cd11975
Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also ...
939-992 2.90e-04

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: 40.08  E-value: 2.90e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDpgrKGAFPVSFVHF 992
Cdd:cd11975    8 EAVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDE---EGWFPASFVRL 58
SH3_Vinexin_1 cd11921
First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3) ...
936-993 2.93e-04

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: 39.52  E-value: 2.93e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 936 KRVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHidgDPGRKGAFPVSFVHFI 993
Cdd:cd11921    1 KAARLKFDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGE---HHGRVGIFPANYVEVL 55
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
939-990 3.08e-04

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: 39.54  E-value: 3.08e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 939 KALYNCVADNPDELTFSEGDVI-IVDGEEDQEWWIGHIdgdPGRKGAFPVSFV 990
Cdd:cd11976    3 KARYDFCARDRSELSLKEGDIIkILNKKGQQGWWRGEI---YGRVGWFPANYV 52
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
938-989 3.18e-04

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: 39.53  E-value: 3.18e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIV---DGEEDQEWWIGHIdgdpGRKGAFPVSF 989
Cdd:cd11952    3 VYALWDYSAEFPDELSFKEGDMVTVlrkDGEGTDWWWASLC----GREGYVPRNY 53
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
938-980 3.32e-04

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: 39.72  E-value: 3.32e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPG 980
Cdd:cd11773    2 YKALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKVKLKVNSS 44
SH3_ASEF cd11973
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ...
939-992 3.60e-04

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: 40.00  E-value: 3.60e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHI-DGDpgrkGAFPVSFVHF 992
Cdd:cd11973   21 EALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVlDSE----GWFPASFVRL 71
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
940-980 3.60e-04

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: 39.28  E-value: 3.60e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPG 980
Cdd:cd11824    4 VLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKG 44
SH3_Vinexin_2 cd11924
Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 ...
940-991 4.17e-04

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: 39.18  E-value: 4.17e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGdPGRKGAFPVSFVH 991
Cdd:cd11924    5 AQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITG-TGRQGIFPASYVQ 55
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
940-989 4.47e-04

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: 39.10  E-value: 4.47e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIG-HIdgDPGRKGAFPVSF 989
Cdd:cd11845    4 ALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLArHL--STGKEGYIPSNY 52
SH3_FCHSD1_2 cd11895
Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain ...
938-986 4.51e-04

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: 39.18  E-value: 4.51e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIV----DGEEDQEWWIGHIDgdpGRKGAFP 986
Cdd:cd11895    2 ARALYSYTGQSPEELSFPEGALIRLlpraQDGVDDGFWRGEFG---GRVGVFP 51
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
940-980 4.84e-04

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: 39.05  E-value: 4.84e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPG 980
Cdd:cd11956    6 ACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRG 46
SH3_Cyk3p-like cd11889
Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 ...
937-990 5.85e-04

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: 38.63  E-value: 5.85e-04
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                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDpGRKGAFPVSFV 990
Cdd:cd11889    1 KVKAVYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLRRN-GAEGIFPSNFV 53
BAR_ACAP1 cd07639
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
38-227 6.08e-04

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 1), also called centaurin beta-1, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP1 also participates in the cargo sorting and recycling of the transferrin receptor and integrin beta1. It may also play a role in innate immune responses. ACAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153323  Cd Length: 200  Bit Score: 42.21  E-value: 6.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374  38 AAIEEVRRPARRLRPQaldvdrmvLYKMKKSVKAINSSGLAHVENEEQYTQALEKFGGNCvcRDDPDLGSAFLKFSV--- 114
Cdd:cd07639    2 AAIEEVEAEVSELETR--------LEKLVKLGSGMLEGGRHYCAASRAFVDGLCDLAHHG--PKDPMMAECLEKFSDgln 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 115 ----------------FTKELTALFKNlDLKKpFDKAWKDYETKITKIEKEKKEHAKLHGMIRTEISGAEIAeeMEKERR 178
Cdd:cd07639   72 hildshaelleatqfsFKQQLQLLVKE-DLRG-FRDARKEFERGAESLEAALQHNAETPRRKAQEVEEAAAA--LLGARA 147
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 767913374 179 FFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVESL 227
Cdd:cd07639  148 TFRDRALDYALQINVIEDKKKFDILEFMLQLMEAQASFFQQGHEALSAL 196
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
294-388 6.54e-04

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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: 270118  Cd Length: 113  Bit Score: 40.47  E-value: 6.54e-04
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gi 767913374 294 GTERNGSLYKK--SDGIRKVWQKRKCSVKNGFLT-ISHGTANRPPAKLNLLTCQVKTNPE----EKKCFDLIS---HDRT 363
Cdd:cd13308    8 DVIHSGTLTKKggSQKTLQNWQLRYVIIHQGCVYyYKNDQSAKPKGVFSLNGYNRRAAEErtskLKFVFKIIHlspDHRT 87
                         90       100
                 ....*....|....*....|....*
gi 767913374 364 YHFQAEDEQECQIWMSVLQNSKEEA 388
Cdd:cd13308   88 WYFAAKSEDEMSEWMEYIRREIDHY 112
SH3_Intersectin1_2 cd11989
Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
937-990 6.76e-04

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: 38.54  E-value: 6.76e-04
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gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQeWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11989    1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQ---GQKGWFPKSYV 50
SH3_BAIAP2L2 cd11914
Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; ...
936-990 7.54e-04

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: 38.64  E-value: 7.54e-04
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gi 767913374 936 KRVKALYNCVA-DNPDELTFSEGDVIIVDGEEDQEWWI-GHIDGDPgRKGAFPVSFV 990
Cdd:cd11914    1 RRVRAIVSHPAgSNPTLLRFNRGDIITVLVPEARNGWLyGKLEGSS-RQGWFPEAYV 56
SH3_EFS cd12003
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
939-980 7.57e-04

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: 38.72  E-value: 7.57e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQE---WWIGHIDGDPG 980
Cdd:cd12003    4 KALYDNAAESPEELSFRRGDVLMVLKREHGSlpgWWLCSLHGQQG 48
SH3_ASPP1 cd11954
Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates ...
938-971 7.87e-04

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: 38.46  E-value: 7.87e-04
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQ---EWW 971
Cdd:cd11954    3 VYALWDYEAQNADELSFQEGDAITILRRKDDsetEWW 39
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
304-383 8.12e-04

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. 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: 241436  Cd Length: 96  Bit Score: 39.59  E-value: 8.12e-04
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gi 767913374 304 KSDGIRKVWQKRKCSVKNGFLTI---SHGTANRPPAKLNLLT-CQVkTNPEEKKCFDLISHDRTYHFQAEDEQECQIWMS 379
Cdd:cd13282    7 KLGGKVKTWKRRWFVLKNGELFYyksPNDVIRKPQGQIALDGsCEI-ARAEGAQTFEIVTEKRTYYLTADSENDLDEWIR 85

                 ....
gi 767913374 380 VLQN 383
Cdd:cd13282   86 VIQN 89
SH3_ASPP2 cd11953
Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full ...
938-971 8.58e-04

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: 8.58e-04
                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIV----DGEEDQEWW 971
Cdd:cd11953    3 VYALWDYEGESDDELSFKEGDCMTIlrreDEDETEWWW 40
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
937-990 8.74e-04

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: 38.45  E-value: 8.74e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIvDGEEDQEWWIGHIDGDPGRKGAFPVSFV 990
Cdd:cd11789    1 RYRAMYDYAAADDDEVSFQEGDVII-NVEIIDDGWMEGTVQRTGQSGMLPANYV 53
SH3_Stac3_1 cd11986
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 ...
940-990 9.82e-04

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: 37.97  E-value: 9.82e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIdgdpGRK-GAFPVSFV 990
Cdd:cd11986    4 ALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKI----GEKtGYFPMNFI 51
BAR_APPL2 cd07632
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
167-224 9.88e-04

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. Both APPL proteins interact with the transcriptional repressor Reptin, acting as activators of beta-catenin/TCF-mediated trancription. APPL2 is essential for cell proliferation. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153316  Cd Length: 215  Bit Score: 41.55  E-value: 9.88e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 167 AEIAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAV 224
Cdd:cd07632  142 AEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGYTHGQINFFKKGAELF 199
SH3_Sorbs1_2 cd11922
Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ...
940-994 1.02e-03

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: 38.05  E-value: 1.02e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDpGRKGAFPVSFVHFIA 994
Cdd:cd11922    5 AKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGT-SRQGIFPITYVDVIK 58
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
940-990 1.11e-03

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: 38.26  E-value: 1.11e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEE-----DQEWWIGHIdgdPGRKGAFPVSFV 990
Cdd:cd11876    4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsgDEGWWTGKI---GDKVGIFPSNYV 56
BAR_APPL1 cd07631
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
153-243 1.43e-03

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. APPL1 interacts with diverse receptors (e.g. NGF receptor TrkA, FSHR, adiponectin receptors) and signaling proteins (e.g. Akt, PI3K), and may function as an adaptor linked to many distinct signaling pathways. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153315  Cd Length: 215  Bit Score: 41.23  E-value: 1.43e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 153 HAKLHGMIRTEISGAEIAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGlkaVESLKPSIE 232
Cdd:cd07631  128 YSRLSKRRENEKVKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMG---SENLNEQLE 204
                         90
                 ....*....|.
gi 767913374 233 TLSTDLHTIKQ 243
Cdd:cd07631  205 EFLTNIGTSVQ 215
SH3_RUSC1_like cd11810
Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that ...
937-970 1.58e-03

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: 37.42  E-value: 1.58e-03
                         10        20        30
                 ....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEW 970
Cdd:cd11810    1 VVRALCHHVATDSGQLSFRKGDILRVIARVDDDW 34
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
339-381 1.68e-03

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. 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: 270110  Cd Length: 106  Bit Score: 39.15  E-value: 1.68e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 767913374 339 NLLTCQVKTNPEEKKCFDLISHDRTYHFQAEDEQECQIWMSVL 381
Cdd:cd13298   53 ELLAVAPLKDKKRKNVFGIYTPSKNLHFRATSEKDANEWVEAL 95
SH3_SH3TC cd11885
Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins ...
937-990 1.73e-03

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: 37.30  E-value: 1.73e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGE--EDQEWWIGHIDGDpGRKGAFPVSFV 990
Cdd:cd11885    1 SCTAKMDFEGVEPGELSFRQGDSIEIIGDliPGLQWFVGRSKSS-GRVGFVPTNHF 55
SH3_RasGAP cd11788
Src Homology 3 domain of Ras GTPase-Activating Protein 1; RasGAP, also called Ras p21 protein ...
935-971 1.76e-03

Src Homology 3 domain of Ras GTPase-Activating Protein 1; RasGAP, also called Ras p21 protein activator, RASA1, or p120RasGAP, is part of the GAP1 family of GTPase-activating proteins. It is a 120kD cytosolic protein containing an SH3 domain flanked by two SH2 domains at the N-terminal end, a pleckstrin homology (PH) domain, a calcium dependent phospholipid binding domain (CaLB/C2), and a C-terminal catalytic GAP domain. It stimulates the GTPase activity of normal RAS p21. It acts as a positive effector of Ras in tumor cells. It also functions as a regulator downstream of tyrosine receptors such as those of PDGF, EGF, ephrin, and insulin, among others. The SH3 domain of RasGAP is unable to bind proline-rich sequences but have been shown to interact with protein partners such as the G3BP protein, Aurora kinases, and the Calpain small subunit 1. The RasGAP SH3 domain is necessary for the downstream signaling of Ras and it also influences Rho-mediated cytoskeletal reorganization. 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: 212722  Cd Length: 59  Bit Score: 37.36  E-value: 1.76e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 767913374 935 PKRVKAL--YNCVADNpDELTFSEGDVIIVDGEEDQEW-W 971
Cdd:cd11788    1 RRRVRAIlpYNKVPDT-DELSFQKGDIFVVHNELEDGWlW 39
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
295-414 1.98e-03

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single 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: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 39.14  E-value: 1.98e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 295 TERNGSLYKKSDgIRKVWQKRKCSVKNGFLTISHGTANRPPAKLNLLT-CQVK-TNPEEKKCFDLISH---DRTYHFQAE 369
Cdd:cd13288    8 VDKEGYLWKKGE-RNTSYQKRWFVLKGNLLFYFEKKGDREPLGVIVLEgCTVElAEDAEPYAFAIRFDgpgARSYVLAAE 86
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 767913374 370 DEQECQIWMSVLQNSKEEALnnafkgddntgeNNIVQELTKEIIS 414
Cdd:cd13288   87 NQEDMESWMKALSRASYDYL------------RLTVEELEKQLEE 119
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
940-990 2.28e-03

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: 37.12  E-value: 2.28e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd12073    5 ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCH---GHRGLFPANYV 52
SH3_DNMBP_C2_like cd11800
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
940-991 2.44e-03

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: 36.97  E-value: 2.44e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIV----DGEEDQEWWIGHidgDPGRKGAFPVSFVH 991
Cdd:cd11800    4 ALYTFEARSPGELSVTEGQVVTVlekhDLKGNPEWWLVE---DRGKQGYVPSNYLA 56
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
303-388 2.47e-03

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. 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: 241446  Cd Length: 103  Bit Score: 38.44  E-value: 2.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 303 KKSDGIRKVWQKRKCSVKNGFLTI-----SHGTANRppAKLNLLTCQVKTNPEEKKCFDLISHDRT---YHFQAEDEQEC 374
Cdd:cd13292    9 KKWTNYAKGYKTRWFVLEDGVLSYyrhqdDEGSACR--GSINMKNARLVSDPSEKLRFEVSSKTSGspkWYLKANHPVEA 86
                         90
                 ....*....|....
gi 767913374 375 QIWMSVLQNSKEEA 388
Cdd:cd13292   87 ARWIQALQKAIEWA 100
Ank_4 pfam13637
Ankyrin repeats (many copies);
610-659 2.52e-03

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 36.87  E-value: 2.52e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 767913374  610 GSTALHYCCLTDNAECLKLLLRGKASIEIANESGETPLDIAkrLKHEHCE 659
Cdd:pfam13637   1 ELTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFA--ASNGNVE 48
SH3_Sorbs1_1 cd11919
First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; ...
934-993 2.54e-03

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: 36.86  E-value: 2.54e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 934 KPKRVKalYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHidgDPGRKGAFPVSFVHFI 993
Cdd:cd11919    1 RPARAK--FDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGE---HHGRVGIFPRSYIELL 55
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
940-992 2.56e-03

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: 37.00  E-value: 2.56e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFVHF 992
Cdd:cd11809    4 AQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLN---GQDGLVPHKYITL 53
SH3_NEDD9 cd12002
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
939-986 2.63e-03

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: 36.89  E-value: 2.63e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIV---DGEEDQEWWIGHIDgdpGRKGAFP 986
Cdd:cd12002    3 RALYDNVPECAEELAFRKGDILTVieqNTGGLEGWWLCSLH---GRQGIAP 50
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
935-990 2.73e-03

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: 36.86  E-value: 2.73e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 935 PKRVKalYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIdgdPGRKGAFPVSFV 990
Cdd:cd11766    1 PAVVK--FNYEAQREDELSLRKGDRVLVLEKSSDGWWRGEC---NGQVGWFPSNYV 51
SH3_Amphiphysin_I cd12140
Src Homology 3 domain of Amphiphysin I; Amphiphysins function primarily in endocytosis and ...
937-989 2.83e-03

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: 37.57  E-value: 2.83e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIV---DGEEDQE--W--------WIGHIDGDpGRKGAFPVSF 989
Cdd:cd12140    4 KVETLHDFEAANSDELELKRGDIVLVvpsETAADQDagWltgvkesdWLQYRDAS-AYKGLFPENF 68
SH3_JIP2 cd11942
Src homology 3 domain of JNK-interacting protein 2; JNK-interacting protein 2 (JIP2) is also ...
939-991 3.23e-03

Src homology 3 domain of JNK-interacting protein 2; JNK-interacting protein 2 (JIP2) is also called Mitogen-activated protein kinase 8-interacting protein 2 (MAPK8IP2) or Islet-brain-2 (IB2). It is widely expressed in the brain, where it forms complexes with fibroblast growth factor homologous factors (FHFs), which facilitates activation of the p38delta MAPK. JIP2 is enriched in postsynaptic densities and may play a role in motor and cognitive function. In addition to a JNK binding domain, JIP2 also contains SH3 and Phosphotyrosine-binding (PTB) domains. The SH3 domain of the related protein JIP1 homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212875  Cd Length: 55  Bit Score: 36.83  E-value: 3.23e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHiDGDPGRKGAFPVSFVH 991
Cdd:cd11942    3 RAVFRFIPRHEDELELDVDDPLLVEAEEDDYWYRGY-NMRTGERGIFPAFYAH 54
SH3_VAV2_2 cd11977
C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and ...
940-990 3.29e-03

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: 36.91  E-value: 3.29e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGE--EDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11977    5 ARYNFAARDMRELSLREGDVVRIYSRigGDQGWWKGETN---GRIGWFPSTYV 54
SH3_Stac2_C cd11985
C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); ...
940-991 3.31e-03

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: 36.46  E-value: 3.31e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIdGDpgRKGAFPVSFVH 991
Cdd:cd11985    4 ALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKS-GD--RVGFFPANFVQ 52
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
937-993 3.38e-03

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: 36.92  E-value: 3.38e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFVHFI 993
Cdd:cd11971    1 KVVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCN---GVTGLFPGNYVESI 54
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
939-990 3.78e-03

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: 36.39  E-value: 3.78e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQE--WWIGHIDGDpgrKGAFPVSFV 990
Cdd:cd11988    5 RALYPFEARNHDEMSFNAGDIIQVDEKTVGEpgWLYGSFQGN---FGWFPCNYV 55
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
338-386 3.95e-03

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). 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: 269939  Cd Length: 103  Bit Score: 37.96  E-value: 3.95e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767913374 338 LNLLTCQVKTNPEEKK------CFDLISHDRTYHFQAEDEQECQIWMSVLQNSKE 386
Cdd:cd01233   49 INLSTARVEYSPDQEAllgrpnVFAVYTPTNSYLLQARSEKEMQDWLYAIDPLLA 103
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
937-990 4.43e-03

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: 36.24  E-value: 4.43e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDgdpGRKGAFPVSFV 990
Cdd:cd11959    1 TAVALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCR---GKYGLFPANYV 51
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
296-389 4.66e-03

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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: 270078  Cd Length: 123  Bit Score: 38.07  E-value: 4.66e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 296 ERNGSLYKKSDGIRKVWqkrkCSVKNGFL----TISHGTANRPPAKLNLLTCQVKTNPEEKKCFDL-ISH----DRTYHF 366
Cdd:cd13258   24 ERQMGGPKKSEVFKERW----FKLKGNLLfyfrTNEFGDCSEPIGAIVLENCRVQMEEITEKPFAFsIVFndepEKKYIF 99
                         90       100
                 ....*....|....*....|...
gi 767913374 367 QAEDEQECQIWMSVLQNSKEEAL 389
Cdd:cd13258  100 SCRSEEQCEQWIEALRQASYEYL 122
SH3_DNMBP_N1 cd11794
First N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
938-990 4.80e-03

First 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: 212728  Cd Length: 51  Bit Score: 35.95  E-value: 4.80e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 938 VKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIGHIDGDPGRkgaFPVSFV 990
Cdd:cd11794    2 VRAIFDFCPSVSEELPLFAGDVIEVLKVVDEFWLLGTKEGVTGQ---FPSSFV 51
SH3_CASS4 cd12000
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; ...
939-986 5.11e-03

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: 36.40  E-value: 5.11e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGE---EDQEWWIGHIDgdpGRKGAFP 986
Cdd:cd12000    4 RALYDNKADCSDELAFRRGDILTVLEQnvpGSEGWWKCLLH---GRQGLAP 51
SH3_PEX13_eumet cd11864
Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and ...
939-990 5.24e-03

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: 36.07  E-value: 5.24e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767913374 939 KALYNCVADNPDELTFSEGDVIIVDGEEDQE----WWIGHIDGDpgRKGAFPVSFV 990
Cdd:cd11864    3 RAEYDFVAESEDELSFRAGDKLRLAPKELQPrvrgWLLATVDGQ--KIGLVPANYV 56
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
297-387 5.25e-03

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. 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: 270075  Cd Length: 110  Bit Score: 37.78  E-value: 5.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 297 RNGSLYKKSdGIRKVWQKRKCSVKNGFLTISHGTANRPPAKLNLLT-------CQVKTNPEekkCFDLISHDRTYHFQAE 369
Cdd:cd13255    8 KAGYLEKKG-ERRKTWKKRWFVLRPTKLAYYKNDKEYRLLRLIDLTdihtcteVQLKKHDN---TFGIVTPARTFYVQAD 83
                         90
                 ....*....|....*...
gi 767913374 370 DEQECQIWMSVLQNSKEE 387
Cdd:cd13255   84 SKAEMESWISAINLARQA 101
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
940-990 6.15e-03

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: 36.13  E-value: 6.15e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767913374 940 ALYNCVADNPDELTFSEGDVI-IVDGEEDQEWWIG-HIDgdpGRKGAFPVSFV 990
Cdd:cd11769    6 AKYNFNGASEEDLPFKKGDILtIVAVTKDPNWYKAkNKD---GREGMIPANYV 55
SH3_DOCK1_5_A cd12051
Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called ...
940-991 6.27e-03

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: 35.95  E-value: 6.27e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767913374 940 ALYNCVADNPDELTFSEGDVIIVDgEEDQEWWIGHIDGDPGRKGAFPVSFVH 991
Cdd:cd12051    4 AIYNYDARGPDELSLQIGDTVHIL-ETYEGWYRGYTLRKKSKKGIFPASYIH 54
SH3_Bzz1_1 cd11912
First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
937-990 6.69e-03

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: 35.66  E-value: 6.69e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767913374 937 RVKALYNCVADNPDELTFSEGDVIIVDGEEDQEWWIgHIDGDPGRKGAFPVSFV 990
Cdd:cd11912    1 TAKVLYDYTASGDDEVSISEGEEVTVLEPDDGSGWT-KVRNGSGEEGLVPTSYI 53
Ank pfam00023
Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the ...
609-641 7.76e-03

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities. Repeats 13-24 are especially active, with known sites of interaction for the Na/K ATPase, Cl/HCO(3) anion exchanger, voltage-gated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. The ANK repeats are found to form a contiguous spiral stack such that ion transporters like the anion exchanger associate in a large central cavity formed by the ANK repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.


Pssm-ID: 459634 [Multi-domain]  Cd Length: 34  Bit Score: 34.96  E-value: 7.76e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 767913374  609 KGSTALHYCCL-TDNAECLKLLLRGKASIEIANE 641
Cdd:pfam00023   1 DGNTPLHLAAGrRGNLEIVKLLLSKGADVNARDK 34
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
297-379 7.77e-03

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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: 270095  Cd Length: 106  Bit Score: 36.91  E-value: 7.77e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767913374 297 RNGSLYKKSDGIrKVWQKRKCSVKNG----FLTISHGTANRPPAKLNLLTCQVKTNPEEK----KCFDLISHDRTYHFQA 368
Cdd:cd13276    1 KAGWLEKQGEFI-KTWRRRWFVLKQGklfwFKEPDVTPYSKPRGVIDLSKCLTVKSAEDAtnkeNAFELSTPEETFYFIA 79
                         90
                 ....*....|.
gi 767913374 369 EDEQECQIWMS 379
Cdd:cd13276   80 DNEKEKEEWIG 90
PHA02859 PHA02859
ankyrin repeat protein; Provisional
575-647 9.79e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165195 [Multi-domain]  Cd Length: 209  Bit Score: 38.65  E-value: 9.79e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767913374 575 ETALHLAVRSvDRTSLHIVDFLVQNSGNLDKQT-GKGSTALHYCcLTDNA----ECLKLLLRGKASIEIANESGETPL 647
Cdd:PHA02859  52 ETPIFSCLEK-DKVNVEILKFLIENGADVNFKTrDNNLSALHHY-LSFNKnvepEILKILIDSGSSITEEDEDGKNLL 127
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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