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Conserved domains on  [gi|578824333|ref|XP_006719705|]
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rasGAP-activating-like protein 1 isoform X2 [Homo sapiens]

Protein Classification

RasGAP_RASAL and BTK domain-containing protein( domain architecture ID 10326087)

protein containing domains C2, RasGAP_RASAL, PH-like, and BTK

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RasGAP_RASAL cd05135
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
263-550 0e+00

Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like protein (RASAL) or RASAL1 is a member of the GAP1 family, and a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. It contains a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes.


:

Pssm-ID: 213337  Cd Length: 287  Bit Score: 572.14  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 263 PSQCYQPLMELLMESVQGPAEEDTASPLALLEELTLGDCRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLFR 342
Cdd:cd05135    1 PSQYYQPLIDLLVESVQSPAEAEDSTPLAMLEEVTTGESRQDVATKLVKIFLGQGLVVPFLDYLNTREVGRTTDPNTLFR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 343 SNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMDLGRTRRISFKGALSEEQMRETSLGLLTGYLGPI 422
Cdd:cd05135   81 SNSLASKSMEQFMKVVGMPYLHEVLKPVINRIFEEKKYVELDPCKIDLNRTRRISFKGSLSEAQVRESSLELLQGYLGSI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 423 VDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHqQDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLL 502
Cdd:cd05135  161 IDAIVGSVDQCPPVMRVAFKQLHKRVEERFPEAEH-QDVKYLAISGFLFLRFFAPAILTPKLFQLREQHADPRTSRTLLL 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 578824333 503 LAKAVQSIGNLGQQLGQGKELWMAPLHPFLLQCVSRVRDFLDRLVDVD 550
Cdd:cd05135  240 LAKAVQSIGNLGLQLGQGKEQWMAPLHPFILQSVARVKDFLDRLIDID 287
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
553-690 7.31e-93

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13369:

Pssm-ID: 473070  Cd Length: 138  Bit Score: 286.76  E-value: 7.31e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 553 EAGVPARALFPPSAIVREGYLLKRKEEPAGLATRFAFKKRYVWLSGETLSFSKSPEWQMCHSIPVSHIRAVERVDEGAFQ 632
Cdd:cd13369    1 ESEVPPRALFPPSVTVKEGYLHKRKAEGVGLVTRFTFKKRYFWLSSETLSYSKSPDWQVRSSIPVQRICAVERVDENAFQ 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 578824333 633 LPHVMQVVTQDGTGALHTTYLQCKNVNELNQWLSALRKASAPNPNKLAACHPGAFRSA 690
Cdd:cd13369   81 QPNVMQVVTQDGEGQVHTTYIQCKNVNELNQWLSALRKVSLSNERMLPACHPGAFRSA 138
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
134-255 1.04e-72

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


The actual alignment was detected with superfamily member cd04025:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 123  Bit Score: 233.15  E-value: 1.04e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 134 CLRCHVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLG 213
Cdd:cd04025    1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDFLG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 578824333 214 MVEFSPKTLQQ-KPPKGWFRLLPFPRAEEDSGGNLGALRVKVR 255
Cdd:cd04025   81 KVVFSIQTLQQaKQEEGWFRLLPDPRAEEESGGNLGSLRLKVR 123
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
6-126 3.14e-67

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


The actual alignment was detected with superfamily member cd04054:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 121  Bit Score: 218.15  E-value: 3.14e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   6 SLNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDTVGHDDIIG 85
Cdd:cd04054    1 SLYIRIVEGKNLPAKDITGSSDPYCIVKVDNEVIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDEDTLSRDDVIG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 578824333  86 KISLSREAITADPRGIDSWINLSRVDPDAEVQGEICLSVQM 126
Cdd:cd04054   81 KVSLTREVISAHPRGIDGWMNLTEVDPDEEVQGEIHLELSV 121
BTK pfam00779
BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found ...
682-710 4.16e-12

BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


:

Pssm-ID: 459937  Cd Length: 30  Bit Score: 61.00  E-value: 4.16e-12
                          10        20
                  ....*....|....*....|....*....
gi 578824333  682 CHPGAFRSARWTCCLQAERSAAGCSRTHS 710
Cdd:pfam00779   2 YHPGAFVDGKWLCCKQTDKNAPGCSPVTS 30
 
Name Accession Description Interval E-value
RasGAP_RASAL cd05135
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
263-550 0e+00

Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like protein (RASAL) or RASAL1 is a member of the GAP1 family, and a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. It contains a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes.


Pssm-ID: 213337  Cd Length: 287  Bit Score: 572.14  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 263 PSQCYQPLMELLMESVQGPAEEDTASPLALLEELTLGDCRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLFR 342
Cdd:cd05135    1 PSQYYQPLIDLLVESVQSPAEAEDSTPLAMLEEVTTGESRQDVATKLVKIFLGQGLVVPFLDYLNTREVGRTTDPNTLFR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 343 SNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMDLGRTRRISFKGALSEEQMRETSLGLLTGYLGPI 422
Cdd:cd05135   81 SNSLASKSMEQFMKVVGMPYLHEVLKPVINRIFEEKKYVELDPCKIDLNRTRRISFKGSLSEAQVRESSLELLQGYLGSI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 423 VDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHqQDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLL 502
Cdd:cd05135  161 IDAIVGSVDQCPPVMRVAFKQLHKRVEERFPEAEH-QDVKYLAISGFLFLRFFAPAILTPKLFQLREQHADPRTSRTLLL 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 578824333 503 LAKAVQSIGNLGQQLGQGKELWMAPLHPFLLQCVSRVRDFLDRLVDVD 550
Cdd:cd05135  240 LAKAVQSIGNLGLQLGQGKEQWMAPLHPFILQSVARVKDFLDRLIDID 287
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
243-605 4.97e-118

GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.


Pssm-ID: 214617  Cd Length: 344  Bit Score: 360.47  E-value: 4.97e-118
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   243 SGGNLGALRVKVRLIEDRVLPSQCYQPLMELLMESVQGPAeedtaspLALLEELTLGDCRQDLATKLVKLFLGRGLAGRF 322
Cdd:smart00323   2 KQGDLGSLRLKTVYTTDFILPSEYYEELLELLLFSLDLSL-------ASALSEVCSGLDKDELATKLVRLFLRRGRGHPF 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   323 LDYLTRREVARTMDPNTLFRSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMdlgrtrrisfkgal 402
Cdd:smart00323  75 LRALIDPEVERTDDPNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKL-------------- 140
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   403 sEEQMRETSLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAehqqDVKYLAISGFLFLRFFAPAILTP 482
Cdd:smart00323 141 -EGEDLETNLENLLQYVERLFDAIINSSDRLPYGLRDICKQLRQAAEKRFPDA----DVIYKAVSSFVFLRFFCPAIVSP 215
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   483 KLFDLRDQHADPQTSRSLLLLAKAVQSIGNLGQQlgQGKELWMAPLHPFLLQCVSRVRDFLDRLVDVDG--------DEA 554
Cdd:smart00323 216 KLFNLVDEHPDPTTRRTLTLIAKVLQNLANLSEF--GSKEPWMEPLNDFLLSHKDRVKDFLDELSSVPEilvdkvsdSTT 293
                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 578824333   555 GVPARALFPPSAIVREGYLLKRKEEPAGLATRFAFKKRYVWLSGETLSFSK 605
Cdd:smart00323 294 ISGRELSLLHSLLLENGDALKRELNNEDPLGKLLFKLRYFGLTTHELTYGK 344
PH_RASAL1 cd13369
Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the ...
553-690 7.31e-93

Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the GAP1 family of GTPase-activating proteins, along with GAP1(m), GAP1(IP4BP) and CAPRI. RASAL1 contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. RASAL1 contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL1 are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL1 differ in that CAPRI is an amplitude sensor while RASAL1 senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or 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: 270175  Cd Length: 138  Bit Score: 286.76  E-value: 7.31e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 553 EAGVPARALFPPSAIVREGYLLKRKEEPAGLATRFAFKKRYVWLSGETLSFSKSPEWQMCHSIPVSHIRAVERVDEGAFQ 632
Cdd:cd13369    1 ESEVPPRALFPPSVTVKEGYLHKRKAEGVGLVTRFTFKKRYFWLSSETLSYSKSPDWQVRSSIPVQRICAVERVDENAFQ 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 578824333 633 LPHVMQVVTQDGTGALHTTYLQCKNVNELNQWLSALRKASAPNPNKLAACHPGAFRSA 690
Cdd:cd13369   81 QPNVMQVVTQDGEGQVHTTYIQCKNVNELNQWLSALRKVSLSNERMLPACHPGAFRSA 138
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
134-255 1.04e-72

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 233.15  E-value: 1.04e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 134 CLRCHVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLG 213
Cdd:cd04025    1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDFLG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 578824333 214 MVEFSPKTLQQ-KPPKGWFRLLPFPRAEEDSGGNLGALRVKVR 255
Cdd:cd04025   81 KVVFSIQTLQQaKQEEGWFRLLPDPRAEEESGGNLGSLRLKVR 123
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
6-126 3.14e-67

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176018 [Multi-domain]  Cd Length: 121  Bit Score: 218.15  E-value: 3.14e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   6 SLNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDTVGHDDIIG 85
Cdd:cd04054    1 SLYIRIVEGKNLPAKDITGSSDPYCIVKVDNEVIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDEDTLSRDDVIG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 578824333  86 KISLSREAITADPRGIDSWINLSRVDPDAEVQGEICLSVQM 126
Cdd:cd04054   81 KVSLTREVISAHPRGIDGWMNLTEVDPDEEVQGEIHLELSV 121
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
322-512 1.04e-53

GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.


Pssm-ID: 459871  Cd Length: 207  Bit Score: 184.80  E-value: 1.04e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  322 FLDYLTRREVARTMDPNTLFRSNSLASKSMEQFMKL-VGMPYLHEVLKPVISRVFE-EKKYMELDPCKMDL-------GR 392
Cdd:pfam00616   1 LISELIEEEIESSDNPNDLLRGNSLVSKLLETYNRRpRGQEYLKKVLGPLVRKIIEdEDLDLESDPRKIYEslinqeeLK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  393 TRRISFKGALSEE---------QMRETSLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHQQdvKY 463
Cdd:pfam00616  81 TGRSDLPRDVSPEeaiedpevrQIFEDNLQKLRELADEFLDAIYSSLNQLPYGIRYICKQLYELLEEKFPDASEEE--IL 158
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 578824333  464 LAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLLLAKAVQSIGN 512
Cdd:pfam00616 159 NAIGGFLFLRFFCPAIVNPDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
C2 pfam00168
C2 domain;
135-233 3.42e-25

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 100.47  E-value: 3.42e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  135 LRCHVLQARDLAPRDISGTSDPFARVFW--GSQSLETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFL 212
Cdd:pfam00168   3 LTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDDFI 82
                          90       100
                  ....*....|....*....|..
gi 578824333  213 GMVEFSPKTLQQKPPK-GWFRL 233
Cdd:pfam00168  83 GEVRIPLSELDSGEGLdGWYPL 104
C2 pfam00168
C2 domain;
7-107 1.05e-22

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 93.54  E-value: 1.05e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333    7 LNVRVVEGRALPAKDVSGSSDPYCLVKV-DDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQ-LAFYVLDEDTVGHDDII 84
Cdd:pfam00168   3 LTVTVIEAKNLPPKDGNGTSDPYVKVYLlDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAvLEIEVYDYDRFGRDDFI 82
                          90       100
                  ....*....|....*....|...
gi 578824333   85 GKISLSREAItADPRGIDSWINL 107
Cdd:pfam00168  83 GEVRIPLSEL-DSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
135-231 3.05e-21

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 89.08  E-value: 3.05e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   135 LRCHVLQARDLAPRDISGTSDPFARVFWGSQSLE---TSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDF 211
Cdd:smart00239   2 LTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEkkkTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDDF 81
                           90       100
                   ....*....|....*....|
gi 578824333   212 LGMVEFSPKTLQQKPPKGWF 231
Cdd:smart00239  82 IGQVTIPLSDLLLGGRHEKL 101
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
6-99 3.06e-18

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 80.61  E-value: 3.06e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333     6 SLNVRVVEGRALPAKDVSGSSDPYCLVKVDDE--VVARTATVWRSLGPFWGEEYTVHL-PLDFHQLAFYVLDEDTVGHDD 82
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDpkEKKKTKVVKNTLNPVWNETFEFEVpPPELAELEIEVYDKDRFGRDD 80
                           90
                   ....*....|....*..
gi 578824333    83 IIGKISLSREAITADPR 99
Cdd:smart00239  81 FIGQVTIPLSDLLLGGR 97
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
567-673 3.39e-15

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: 71.81  E-value: 3.39e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   567 IVREGYLLKRKEepaglATRFAFKKRYVWLSGETLSFSKSPEWQM----CHSIPVSHIRAVERVDEGAFQLPHVMQVVTQ 642
Cdd:smart00233   1 VIKEGWLYKKSG-----GGKKSWKKRYFVLFNSTLLYYKSKKDKKsykpKGSIDLSGCTVREAPDPDSSKKPHCFEIKTS 75
                           90       100       110
                   ....*....|....*....|....*....|.
gi 578824333   643 DGtgalHTTYLQCKNVNELNQWLSALRKASA 673
Cdd:smart00233  76 DR----KTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
567-673 2.08e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 66.82  E-value: 2.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  567 IVREGYLLKRKEEPAGlatrfAFKKRYVWLSGETLSFSKS----PEWQMCHSIPVSHIRAVERVDEGAFQLPHVMQVVTQ 642
Cdd:pfam00169   1 VVKEGWLLKKGGGKKK-----SWKKRYFVLFDGSLLYYKDdksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTG 75
                          90       100       110
                  ....*....|....*....|....*....|.
gi 578824333  643 DGTGAlHTTYLQCKNVNELNQWLSALRKASA 673
Cdd:pfam00169  76 ERTGK-RTYLLQAESEEERKDWIKAIQSAIR 105
BTK pfam00779
BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found ...
682-710 4.16e-12

BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 459937  Cd Length: 30  Bit Score: 61.00  E-value: 4.16e-12
                          10        20
                  ....*....|....*....|....*....
gi 578824333  682 CHPGAFRSARWTCCLQAERSAAGCSRTHS 710
Cdd:pfam00779   2 YHPGAFVDGKWLCCKQTDKNAPGCSPVTS 30
IQG1 COG5261
Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and ...
322-555 3.78e-09

Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and chromosome partitioning / Signal transduction mechanisms];


Pssm-ID: 227586 [Multi-domain]  Cd Length: 1054  Bit Score: 60.28  E-value: 3.78e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  322 FLDYLTRREVARTMDPNTLFRSNSLASKSMEQ-FMKLVGMPYLHEVLKPVISRVfEEKKYMELDPCKMDLGR----TRRI 396
Cdd:COG5261   440 LFQMLLRTEVEATSLVQSLLRGNLPVHRNMTNyFRRSQGQAALREIRYQIINDV-AIHEDLEVDINPLLVYRallnKGQL 518
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  397 SFKGALSEEQMRET--------------SLGLLtgYLGP--IVDAIVGSVGRCPPAMRLaFKQLHRRVEERFPQAEHQ-- 458
Cdd:COG5261   519 SPDKDLELLTSNEEvseflavmnavqesSAKLL--ELSTerILDAVYNSLDEIGYGIRF-VCELIRVVFELTPNRLFPsi 595
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  459 QDVKYL------------AISGFLFLRFFAPAILTPKLFDLRDQHADpQTSRSLLLLAKAVQSIGNlgqqlGQGKELWMA 526
Cdd:COG5261   596 SDSRCLrticfaeidslgLIGGFFFLRFVNEALVSPQTSMLKDSCPS-DNVRKLATLSKILQSVFE-----ITSSDKFDV 669
                         250       260       270
                  ....*....|....*....|....*....|
gi 578824333  527 PLHPFLLQCVSRVRDFLDRLVDV-DGDEAG 555
Cdd:COG5261   670 PLQPFLKEYKEKVHNLLRKLGNVgDFEEYF 699
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
4-90 7.18e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 56.31  E-value: 7.18e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333    4 SSSLNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFH-QLAFYVLDEDTVGHDD 82
Cdd:COG5038  1039 SGYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKdVLTINVNDWDSGEKND 1118

                  ....*...
gi 578824333   83 IIGKISLS 90
Cdd:COG5038  1119 LLGTAEID 1126
BTK smart00107
Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and ...
675-706 4.32e-05

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 128417  Cd Length: 36  Bit Score: 41.21  E-value: 4.32e-05
                           10        20        30
                   ....*....|....*....|....*....|..
gi 578824333   675 NPNKLAACHPGAFRSARWTCCLQAERSAAGCS 706
Cdd:smart00107   1 NNNLLQKYHPSFWVDGKWLCCQQSEKNAPGCT 32
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
142-244 7.31e-05

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 46.68  E-value: 7.31e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  142 ARDLAPRDISGTSDPFARVFWGSQSL-ETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLGMVEFSPK 220
Cdd:COG5038  1049 GENLPSSDENGYSDPFVKLFLNEKSVyKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLS 1128
                          90       100
                  ....*....|....*....|....
gi 578824333  221 TLQQKPPKGWFRLLPFPRAEEDSG 244
Cdd:COG5038  1129 KLEPGGTTNSNIPLDGKTFIVLDG 1152
PLN03008 PLN03008
Phospholipase D delta
25-165 3.63e-04

Phospholipase D delta


Pssm-ID: 178585 [Multi-domain]  Cd Length: 868  Bit Score: 44.31  E-value: 3.63e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  25 SSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDTVGHdDIIGKISLSREAITADPRgIDSW 104
Cdd:PLN03008  76 TSDPYVTVVVPQATLARTRVLKNSQEPLWDEKFNISIAHPFAYLEFQVKDDDVFGA-QIIGTAKIPVRDIASGER-ISGW 153
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 578824333 105 ---INLSRVDPDAEVQgeICLSVQMLEDGQGRCLRCHVlqARDLAPRDISGTSDPFARvfwGSQ 165
Cdd:PLN03008 154 fpvLGASGKPPKAETA--IFIDMKFTPFDQIHSYRCGI--AGDPERRGVRRTYFPVRK---GSQ 210
 
Name Accession Description Interval E-value
RasGAP_RASAL cd05135
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
263-550 0e+00

Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like protein (RASAL) or RASAL1 is a member of the GAP1 family, and a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. It contains a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes.


Pssm-ID: 213337  Cd Length: 287  Bit Score: 572.14  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 263 PSQCYQPLMELLMESVQGPAEEDTASPLALLEELTLGDCRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLFR 342
Cdd:cd05135    1 PSQYYQPLIDLLVESVQSPAEAEDSTPLAMLEEVTTGESRQDVATKLVKIFLGQGLVVPFLDYLNTREVGRTTDPNTLFR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 343 SNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMDLGRTRRISFKGALSEEQMRETSLGLLTGYLGPI 422
Cdd:cd05135   81 SNSLASKSMEQFMKVVGMPYLHEVLKPVINRIFEEKKYVELDPCKIDLNRTRRISFKGSLSEAQVRESSLELLQGYLGSI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 423 VDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHqQDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLL 502
Cdd:cd05135  161 IDAIVGSVDQCPPVMRVAFKQLHKRVEERFPEAEH-QDVKYLAISGFLFLRFFAPAILTPKLFQLREQHADPRTSRTLLL 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 578824333 503 LAKAVQSIGNLGQQLGQGKELWMAPLHPFLLQCVSRVRDFLDRLVDVD 550
Cdd:cd05135  240 LAKAVQSIGNLGLQLGQGKEQWMAPLHPFILQSVARVKDFLDRLIDID 287
RasGAP_GAP1_like cd05128
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
265-549 1.97e-120

Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras GTPase-activating proteins includes GAP1(m) (or RASA2), GAP1_IP4BP (or RASA3), Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), and Ras GTPase activating-like proteins (RASAL) or RASAL1. The members are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin homology domain that is associated with a Bruton's tyrosine kinase motif. While this domain structure is conserved, a small change in the function of each individual domain and the interaction between domains has a marked effect on the regulation of each protein.


Pssm-ID: 213330  Cd Length: 269  Bit Score: 363.49  E-value: 1.97e-120
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 265 QCYQPLMELLMESVQGPaeEDTASPLALLEELTLGDcRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLFRSN 344
Cdd:cd05128    1 QYYEPLLNLLLESLDVP--PFTASAVYLLEELVKVD-KDDVARPLVRIFLHHGQIVPLLRALASREISKTQDPNTLFRGN 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 345 SLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMDLGrtrrisfkgalseeQMRETSLGLLTGYLGPIVD 424
Cdd:cd05128   78 SLASKCMDEFMKLVGMQYLHETLKPVIDEIFSEKKSCEIDPSKLKDG--------------EVLETNLANLRGYVERVFK 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 425 AIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEhqqDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLLLA 504
Cdd:cd05128  144 AITSSARRCPTLMCEIFSDLRESAAQRFPDNE---DVPYTAVSGFIFLRFFAPAILNPKLFGLREEHPDPQTARTLTLIS 220
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 578824333 505 KAVQSIGNLGQQLG--QGKELWMAPL--HPFLLQCVSRVRDFLDRLVDV 549
Cdd:cd05128  221 KTIQTLGNLGSSSSglGVKEAYMSPLyeRFTDEQHVDAVKKFLDRISSV 269
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
243-605 4.97e-118

GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.


Pssm-ID: 214617  Cd Length: 344  Bit Score: 360.47  E-value: 4.97e-118
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   243 SGGNLGALRVKVRLIEDRVLPSQCYQPLMELLMESVQGPAeedtaspLALLEELTLGDCRQDLATKLVKLFLGRGLAGRF 322
Cdd:smart00323   2 KQGDLGSLRLKTVYTTDFILPSEYYEELLELLLFSLDLSL-------ASALSEVCSGLDKDELATKLVRLFLRRGRGHPF 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   323 LDYLTRREVARTMDPNTLFRSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMdlgrtrrisfkgal 402
Cdd:smart00323  75 LRALIDPEVERTDDPNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKL-------------- 140
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   403 sEEQMRETSLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAehqqDVKYLAISGFLFLRFFAPAILTP 482
Cdd:smart00323 141 -EGEDLETNLENLLQYVERLFDAIINSSDRLPYGLRDICKQLRQAAEKRFPDA----DVIYKAVSSFVFLRFFCPAIVSP 215
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   483 KLFDLRDQHADPQTSRSLLLLAKAVQSIGNLGQQlgQGKELWMAPLHPFLLQCVSRVRDFLDRLVDVDG--------DEA 554
Cdd:smart00323 216 KLFNLVDEHPDPTTRRTLTLIAKVLQNLANLSEF--GSKEPWMEPLNDFLLSHKDRVKDFLDELSSVPEilvdkvsdSTT 293
                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 578824333   555 GVPARALFPPSAIVREGYLLKRKEEPAGLATRFAFKKRYVWLSGETLSFSK 605
Cdd:smart00323 294 ISGRELSLLHSLLLENGDALKRELNNEDPLGKLLFKLRYFGLTTHELTYGK 344
RasGAP_RASA4 cd05395
Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also ...
263-550 2.38e-108

Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also known as Ca2+ -promoted Ras inactivator (CAPRI), is a member of the GAP1 family. Members of the GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL4, like RASAL, is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to a receptor-mediated elevation in the concentration of intracellular free Ca2+ ([Ca2+]i). However, unlike RASAL, RASAL4 does not sense oscillations in [Ca2+]i.


Pssm-ID: 213343 [Multi-domain]  Cd Length: 287  Bit Score: 332.99  E-value: 2.38e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 263 PSQCYQPLMELLMESVQGPAEEDTASPLALLEELTLGDCRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLFR 342
Cdd:cd05395    1 PSSHYQPLVQLLCQEVKLGHQAGPVQLISLIDETTTAECRQEVATNLVKLFLGQGLAKEFLDLLFQLELDKTTEPNTLFR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 343 SNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMDLGRTRRISFKGALSEEQMRETSLGLLTGYLGPI 422
Cdd:cd05395   81 SNSLASKSMESFLKVAGMQYLHSVLGPTINRVFEEKKYVELDPSKVEIKDVGCSGLHRIQTESEVIEQSAQLLQSYLGEL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 423 VDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHqQDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLL 502
Cdd:cd05395  161 LSAISKSVKYCPAVIRATFRQLFKRVQERFPENQH-QNVKFIAVTSFLCLRFFSPAIMSPKLFHLREKHADARTSRTLLL 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 578824333 503 LAKAVQSIGNLGQQLGQGKELWMAPLHPFLLQCVSRVRDFLDRLVDVD 550
Cdd:cd05395  240 LAKAVQNVGNMDTLASRAKEAWMAPLQPAIQQGVAQLKDFITKLVDIE 287
PH_RASAL1 cd13369
Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the ...
553-690 7.31e-93

Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the GAP1 family of GTPase-activating proteins, along with GAP1(m), GAP1(IP4BP) and CAPRI. RASAL1 contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. RASAL1 contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL1 are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL1 differ in that CAPRI is an amplitude sensor while RASAL1 senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or 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: 270175  Cd Length: 138  Bit Score: 286.76  E-value: 7.31e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 553 EAGVPARALFPPSAIVREGYLLKRKEEPAGLATRFAFKKRYVWLSGETLSFSKSPEWQMCHSIPVSHIRAVERVDEGAFQ 632
Cdd:cd13369    1 ESEVPPRALFPPSVTVKEGYLHKRKAEGVGLVTRFTFKKRYFWLSSETLSYSKSPDWQVRSSIPVQRICAVERVDENAFQ 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 578824333 633 LPHVMQVVTQDGTGALHTTYLQCKNVNELNQWLSALRKASAPNPNKLAACHPGAFRSA 690
Cdd:cd13369   81 QPNVMQVVTQDGEGQVHTTYIQCKNVNELNQWLSALRKVSLSNERMLPACHPGAFRSA 138
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
134-255 1.04e-72

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 233.15  E-value: 1.04e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 134 CLRCHVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLG 213
Cdd:cd04025    1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDFLG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 578824333 214 MVEFSPKTLQQ-KPPKGWFRLLPFPRAEEDSGGNLGALRVKVR 255
Cdd:cd04025   81 KVVFSIQTLQQaKQEEGWFRLLPDPRAEEESGGNLGSLRLKVR 123
RasGAP cd04519
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
265-548 2.95e-69

Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is bound to Ras-GTPases. Proteins having a RasGAP domain include p120GAP, IQGAP, Rab5-activating protein 6, and Neurofibromin, among others. Although the Rho (Ras homolog) GTPases are most closely related to members of the Ras family, RhoGAP and RasGAP exhibit no similarity at their amino acid sequence level. RasGTPases function as molecular switches in a large number of signaling pathways. They are in the on state when bound to GTP, and in the off state when bound to GDP. The RasGAP domain speeds up the hydrolysis of GTP in Ras-like proteins acting as a negative regulator.


Pssm-ID: 213328  Cd Length: 256  Bit Score: 228.92  E-value: 2.95e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 265 QCYQPLMELLMESvqgpaeedtasPLALLEELT---LGDCRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLF 341
Cdd:cd04519    1 EEYRLLSLLLTES-----------PLALLRELSqvlPVKDKEEVATALLRIFESRGLALEFLRYLVRSEVKNTKNPNTLF 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 342 RSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCkmdlgrtrrisfkgaLSEEQMRETSLGLLTGYLGP 421
Cdd:cd04519   70 RGNSLATKLLDQYMKLVGQEYLKETLSPLIREILESKESCEIDTK---------------LPVGEDLEENLENLLELVNK 134
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 422 IVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHQQdvkYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLL 501
Cdd:cd04519  135 LVDRILSSLDRLPPELRYVFKILREFLAERFPEEPDEA---YQAVSGFLFLRFICPAIVSPELFGLVPDEPSEQARRNLT 211
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 578824333 502 LLAKAVQSIGNLGQqlGQGKELWMAPLHPFLLQCVSRVRDFLDRLVD 548
Cdd:cd04519  212 LISKVLQSLANGVE--FGDKEPFMKPLNDFIKSNKPKLKQFLDELSS 256
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
6-126 3.14e-67

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176018 [Multi-domain]  Cd Length: 121  Bit Score: 218.15  E-value: 3.14e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   6 SLNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDTVGHDDIIG 85
Cdd:cd04054    1 SLYIRIVEGKNLPAKDITGSSDPYCIVKVDNEVIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDEDTLSRDDVIG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 578824333  86 KISLSREAITADPRGIDSWINLSRVDPDAEVQGEICLSVQM 126
Cdd:cd04054   81 KVSLTREVISAHPRGIDGWMNLTEVDPDEEVQGEIHLELSV 121
RasGAP_RASA3 cd05134
Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family ...
264-544 1.39e-58

Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family and has been shown to specifically bind 1,3,4,5-tetrakisphosphate (IP4). Thus, RASA3 may function as an IP4 receptor. The members of GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. Purified RASA3 stimulates GAP activity on Ras with about a five-fold lower potency than p120RasGAP, but shows no GAP-stimulating activity at all against Rac or Rab3A.


Pssm-ID: 213336  Cd Length: 269  Bit Score: 200.64  E-value: 1.39e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 264 SQCYQPLMELLMESvqGPAEEDTASPLALLEELtlgdCR--QDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLF 341
Cdd:cd05134    1 SEYYSPLRDLLLKS--ADVEPVSASAAHILGEV----CRekQEAAIPLVRLFLHYGKIVPFISAIASAEVNRTQDPNTIF 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 342 RSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMdlgrtrrisfKGALSEEQMRETslglLTGYLGP 421
Cdd:cd05134   75 RGNSLTSKCIDETMKLAGMHYLQVTLKPIIDEICQEHKPCEIDPVKL----------KDGENLENNREN----LRQYVDR 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 422 IVDAIVGSVGRCPPAMRLAFKQLHRRVEERFpqaEHQQDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLL 501
Cdd:cd05134  141 IFRVITKSGVSCPTVMCDIFFSLRESAAKRF---QVDPDVRYTAVSSFIFLRFFAPAILSPNLFQLTPHHPDPQTSRTLT 217
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 578824333 502 LLAKAVQSIGNLGQQLGQG-KELWMAPLHPFL--LQCVSRVRDFLD 544
Cdd:cd05134  218 LISKTIQTLGSLSKSKSANfKESYMAAFYDYFneQKYADAVKNFLD 263
RasGAP_CLA2_BUD2 cd05137
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein ...
253-545 4.09e-57

Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein (GAP) for BUD1/RSR1 and is necessary for proper bud-site selection in yeast. BUD2 has sequence similarity to the catalytic domain of RasGAPs, and stimulates the hydrolysis of BUD1-GTP to BUD1-GDP. Elimination of Bud2p activity by mutation causes a random budding pattern with no growth defect. Overproduction of Bud2p also alters the budding pattern.


Pssm-ID: 213339 [Multi-domain]  Cd Length: 356  Bit Score: 199.33  E-value: 4.09e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 253 KVRLIEDRVLPSQCYQPLMELLMEsvqgpaeeDTASPLALLEELTLGDCRQDLATKLVKLFLGRGLAGRFLDYLTRREVA 332
Cdd:cd05137    1 KVRLDENVVLPSKNYKPLEELLHN--------FDLGLTLQIAELVPGDKLERLSEILLDIFQASGREDEWFMALVEDEID 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 333 ---------------RTMDPNTLFRSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPckmdlgrtRRIS 397
Cdd:cd05137   73 gidkstsknkdmgksSNNEANLLFRGNSLLTKSLEKYMRRIGKEYLEKSIGDVIRKICEENKDCEVDP--------SRVK 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 398 FKGALSEEQMRETSLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPqaEHQQDVKYLAISGFLFLRFFAP 477
Cdd:cd05137  145 ESDSIEKEEDLEENWENLISLTEEIWNSIYITSNDCPPELRKILKHIRAKVEDRYG--DFLRTVTLNSVSGFLFLRFFCP 222
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578824333 478 AILTPKLFDLRDQHADPQTSRSLLLLAKAVQSIGNLgQQLGQgKELWMAPLHPFLLQCVSRVRDFLDR 545
Cdd:cd05137  223 AILNPKLFGLLKDHPRPRAQRTLTLIAKVLQNLANL-TTFGQ-KEPWMEPMNEFLTTHREELKDYIDK 288
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
322-512 1.04e-53

GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.


Pssm-ID: 459871  Cd Length: 207  Bit Score: 184.80  E-value: 1.04e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  322 FLDYLTRREVARTMDPNTLFRSNSLASKSMEQFMKL-VGMPYLHEVLKPVISRVFE-EKKYMELDPCKMDL-------GR 392
Cdd:pfam00616   1 LISELIEEEIESSDNPNDLLRGNSLVSKLLETYNRRpRGQEYLKKVLGPLVRKIIEdEDLDLESDPRKIYEslinqeeLK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  393 TRRISFKGALSEE---------QMRETSLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHQQdvKY 463
Cdd:pfam00616  81 TGRSDLPRDVSPEeaiedpevrQIFEDNLQKLRELADEFLDAIYSSLNQLPYGIRYICKQLYELLEEKFPDASEEE--IL 158
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 578824333  464 LAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLLLAKAVQSIGN 512
Cdd:pfam00616 159 NAIGGFLFLRFFCPAIVNPDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
569-679 2.06e-53

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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: 269950  Cd Length: 107  Bit Score: 180.18  E-value: 2.06e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 569 REGYLLKRKEEPAGLATRFAFKKRYVWLSGETLSFSKSPEWQMCHSIPVSHIRAVERVDEGAFQLPHVMQVVTQDgtgal 648
Cdd:cd01244    1 KEGYLIKRAQGRKKKFGRKNFKKRYFRLTNEALSYSKSKGKQPLCSIPLEDILAVERVEEESFKMKNMFQIVQPD----- 75
                         90       100       110
                 ....*....|....*....|....*....|.
gi 578824333 649 HTTYLQCKNVNELNQWLSALRKASAPNPNKL 679
Cdd:cd01244   76 RTLYLQAKNVVELNEWLSALRKVCLCNPNRL 106
RasGAP_p120GAP cd05391
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
259-549 1.18e-45

Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates hydrolysis of bound GTP to GDP. Once the Ras regulator p120GAP, a member of the GAP protein family, is recruited to the membrane, it is transiently immobilized to interact with Ras-GTP. The down-regulation of Ras by p120GAP is a critical step in the regulation of many cellular processes, which is disrupted in approximately 30% of human cancers. p120GAP contains SH2, SH3, PH, calcium- and lipid-binding domains, suggesting its involvement in a complex network of cellular interactions in vivo.


Pssm-ID: 213340  Cd Length: 328  Bit Score: 166.51  E-value: 1.18e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 259 DRVLPSQCYQPLMELLMESvqgpaEEDTASPLALLeeltlgdCRQD---LATKLVKLFLGRGLAGRFLDYLTRREVARTM 335
Cdd:cd05391    2 EKIMPEEEYSELKELILQK-----ELHVVYALAHV-------CGQDrtlLASILLRIFRHEKLESLLLRTLNDREISMED 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 336 DPNTLFRSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMDLGRTrrisfkgalseeqmRETSLGLL 415
Cdd:cd05391   70 EATTLFRATTLASTLMEQYMKATATPFVHHALKDTILKILESKQSCELNPSKLEKNED--------------VNTNLEHL 135
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 416 TGYLGPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPqaeHQQDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQ 495
Cdd:cd05391  136 LNILSELVEKIFMAAEILPPTLRYIYGCLQKSVQQKWP---TNTTVRTRVVSGFVFLRLICPAILNPRMFNIISETPSPT 212
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 578824333 496 TSRSLLLLAKAVQSIGNLgQQLGqGKELWMAPLHPFLLQCVSRVRDFLDRLVDV 549
Cdd:cd05391  213 AARTLTLVAKSLQNLANL-VEFG-AKEPYMEGVNPFIKKNKERMIMFLDELGNV 264
RasGAP_RASA2 cd05394
Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of ...
264-546 1.63e-45

Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of Ras GTPase-activating proteins that includes GAP1_IP4BP (or RASA3), CAPRI, and RASAL. In vitro, RASA2 has been shown to bind inositol 1,3,4,5-tetrakisphosphate (IP4), the water soluble inositol head group of the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3). In vivo studies also demonstrated that RASA2 binds PIP3, and it is recruited to the plasma membrane following agonist stimulation of PI 3-kinase. Furthermore, the membrane translocation is a consequence of the ability of its pleckstrin homology (PH) domain to bind PIP3.


Pssm-ID: 213342  Cd Length: 272  Bit Score: 164.30  E-value: 1.63e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 264 SQCYQPLMELLMESVQgpAEEDTASPLALLEELtlgdCRQ--DLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLF 341
Cdd:cd05394    1 SACYTSLRNLLLKSPD--VKPISASAAHILGEI----CRDkyDAVLPLVRLLLHHNKLVPFVAAVAALDLKDTQEANTIF 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 342 RSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKmdlgrtrrisfkgaLSEEQMRETSLGLLTGYLGP 421
Cdd:cd05394   75 RGNSLATRCLDEMMKIVGKHYLKVTLKPVLDEICESPKPCEIDPIK--------------LKEGDNVENNKENLRYYVDK 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 422 IVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHqqdVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLL 501
Cdd:cd05394  141 VFFSIVKSSMSCPTLMCDVFRSLRHLAVKRFPNDPH---VQYSAVSSFVFLRFFAVAVVSPHTFQLRPHHPDAQTSRTLT 217
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 578824333 502 LLAKAVQSIGNLG----QQLGQGKELWMAPLHPFLLQ--CVSRVRDFLDRL 546
Cdd:cd05394  218 LISKTIQTLGSWGslskSKLSSFKETFMCDFFKMFQEekYIEKVKKFLDEI 268
RasGAP_Neurofibromin_like cd05392
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
284-568 1.11e-44

Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins include the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2, the closest homolog of neurofibromin, which is responsible for the human autosomal dominant disease neurofibromatosis type I (NF1). The RasGAP Ira1/2 proteins are negative regulators of the Ras-cAMP signaling pathway and conserved from yeast to human. In yeast Ras proteins are activated by GEFs, and inhibited by two GAPs, Ira1 and Ira2. Ras proteins activate the cAMP/protein kinase A (PKA) pathway, which controls metabolism, stress resistance, growth, and meiosis. Recent studies showed that the kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with Ira1 and Ira2. Gpb1/2 bind to a conserved C-terminal domain of Ira1/2, and loss of Gpb1/2 results in a destabilization of Ira1 and Ira2, leading to elevated levels of Ras2-GTP and uninhibited cAMP-PKA signaling. Since the Gpb1/2 binding domain on Ira1/2 is conserved in the human neurofibromin protein, the studies suggest that an analogous signaling mechanism may contribute to the neoplastic development of NF1.


Pssm-ID: 213341  Cd Length: 317  Bit Score: 163.61  E-value: 1.11e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 284 EDTASPLALLEELTlGDCRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLFRSNSLASKSMEQFMKLVGMPYL 363
Cdd:cd05392   15 EDPQLLLAIAEVCP-SSEVDLLAQSLLNLFETRNRLLPLISWLIEDEISHTSRAADLFRRNSVATRLLTLYAKSVGNKYL 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 364 HEVLKPVISRVFEEKKYMELDpcKMDLGrtrrisfkgalsEEQMREtSLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQ 443
Cdd:cd05392   94 RKVLRPLLTEIVDNKDYFEVE--KIKPD------------DENLEE-NADLLMKYAQMLLDSITDSVDQLPPSFRYICNT 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 444 LHRRVEERFPqaehqqDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLLLAKAVQSIGNlgQQLGQGKEL 523
Cdd:cd05392  159 IYESVSKKFP------DAALIAVGGFLFLRFICPAIVSPESENLLDPPPTPEARRSLILIAKVLQNIAN--GVLFSLKEP 230
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 578824333 524 WMAPLHPFLLQCVSRVRDFLDRLVDVDGDEagvPARALFPPSAIV 568
Cdd:cd05392  231 YLESLNEFLKKNSDRIQQFLSEVSTIPPTD---PIFDESDEEPIT 272
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
260-545 1.38e-43

Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.


Pssm-ID: 213338  Cd Length: 324  Bit Score: 160.44  E-value: 1.38e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 260 RVLPSQCYQPLMELLmesvqgpaEEDTASPLALLEELTLGDCRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNT 339
Cdd:cd05136    6 DILPLEVYKEFLEYL--------TNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRLDDEHL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 340 LFRSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFEEKKYMELDPCKMdlgrtrriSFKGALSEEQmretslGLLTGYL 419
Cdd:cd05136   78 IFRGNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKC--------PPSASLSRNQ------ANLRRSV 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 420 GPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERfpqaeHQQDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRS 499
Cdd:cd05136  144 ELAWCKILSSHCVFPRELREVFSSWRERLEER-----GREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARN 218
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 578824333 500 LLLLAKAVQSIGNLgqQLGQGKELWMAPLHPFLLQCVSRVRDFLDR 545
Cdd:cd05136  219 LTLIAKVIQNLANF--TRFGGKEEYMEFMNDFVEQEWPNMKQFLQE 262
PH_CAPRI cd13372
Ca2+ promoted Ras inactivator pleckstrin homology (PH) domain; CAPRI (also called RASA4/RAS ...
542-681 1.07e-40

Ca2+ promoted Ras inactivator pleckstrin homology (PH) domain; CAPRI (also called RASA4/RAS p21 protein activator (GTPase activating protein) 4/GAPL/FLJ59070/KIAA0538/MGC131890) is a member of the GAP1 family of GTPase-activating proteins. CAPRI contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL differ in that CAPRI is an amplitude sensor while RASAL senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or 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: 241523  Cd Length: 140  Bit Score: 146.17  E-value: 1.07e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 542 FLDRLVDVDGDEAGVPARALFPPSAIVREGYLLKRKEEPAGLATRFAFKKRYVWLSGETLSFSKSPEWQMCHSIPVSHIR 621
Cdd:cd13372    1 FITKLVDIEEEDELDLTRMLLLQAPMVKEGFLFIHRTKGKGPLMASSFKKLYFTLTKDALSFAKTPHSKKSSSISLAKIR 80
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 622 AVERVDEGAFQLPHVMQVVTQDGTGALHTTYLQCKNVNELNQWLSALRKASAPNPNKLAA 681
Cdd:cd13372   81 AAEKVEEKCFGSSNVMQIIYTDDAGQQETLYLQCKSVNELNQWLSALRKVCSNNTNLLSS 140
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
6-126 4.51e-40

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


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 143.17  E-value: 4.51e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   6 SLNVRVVEGRALPAKdvsGSSDPYCLVKVDDEVVARTATVWRsLGPFWGEEYTVHLP---LDFHQLAFYVLDEDTVGHDD 82
Cdd:cd08383    1 SLRLRILEAKNLPSK---GTRDPYCTVSLDQVEVARTKTVEK-LNPFWGEEFVFDDPppdVTFFTLSFYNKDKRSKDRDI 76
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 578824333  83 IIGKISLSREAItadPRGIDSWINLSRVDPDAEVQGEICLSVQM 126
Cdd:cd08383   77 VIGKVALSKLDL---GQGKDEWFPLTPVDPDSEVQGSVRLRARY 117
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
135-250 1.10e-39

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


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 142.90  E-value: 1.10e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRdISGTSDPFARVFWG----SQSLETSTIKKTRFPHWDEVLELREMPG---------------APSP 195
Cdd:cd08675    1 LSVRVLECRDLALK-SNGTCDPFARVTLNysskTDTKRTKVKKKTNNPRFDEAFYFELTIGfsyekksfkveeedlEKSE 79
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 578824333 196 LRVELWDWDMVGKNDFLGMVEFSPKTLQQ-KPPKGWFRLLPF--PRAEEDSGGNLGAL 250
Cdd:cd08675   80 LRVELWHASMVSGDDFLGEVRIPLQGLQQaGSHQAWYFLQPReaPGTRSSNDGSLGSL 137
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
9-126 2.05e-27

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176046 [Multi-domain]  Cd Length: 121  Bit Score: 107.52  E-value: 2.05e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   9 VRVVEGRA---LPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDTVGHDDIIG 85
Cdd:cd08401    2 LKIKIGEAknlPPRSGPNKMRDCYCTVNLDQEEVFRTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDRDVLRRDSVIG 81
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 578824333  86 KISLSREAITADpRGIDSWINLSRVDPDAEVQGEICLSVQM 126
Cdd:cd08401   82 KVAIKKEDLHKY-YGKDTWFPLQPVDADSEVQGKVHLELRL 121
C2 pfam00168
C2 domain;
135-233 3.42e-25

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 100.47  E-value: 3.42e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  135 LRCHVLQARDLAPRDISGTSDPFARVFW--GSQSLETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFL 212
Cdd:pfam00168   3 LTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDDFI 82
                          90       100
                  ....*....|....*....|..
gi 578824333  213 GMVEFSPKTLQQKPPK-GWFRL 233
Cdd:pfam00168  83 GEVRIPLSELDSGEGLdGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
7-107 1.21e-23

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 95.98  E-value: 1.21e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQ-LAFYVLDEDTVGHDDIIG 85
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFPVLDPESDtLTVEVWDKDRFSKDDFLG 80
                         90       100
                 ....*....|....*....|..
gi 578824333  86 KISLSREAITADPRGIDSWINL 107
Cdd:cd00030   81 EVEIPLSELLDSGKEGELWLPL 102
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
135-233 1.90e-23

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 96.46  E-value: 1.90e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVL--ELREMPGAPSPLR-------VELWDWDM 205
Cdd:cd04017    3 LRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLifDEVELYGSPEEIAqnpplvvVELFDQDS 82
                         90       100       110
                 ....*....|....*....|....*....|....
gi 578824333 206 VGKNDFLG------MVEFSPKTLqQKPPKGWFRL 233
Cdd:cd04017   83 VGKDEFLGrsvakpLVKLDLEED-FPPKLQWFPI 115
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
135-233 1.95e-23

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 95.21  E-value: 1.95e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARV-FWGSQSLETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLG 213
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVsLGGKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFLG 80
                         90       100
                 ....*....|....*....|..
gi 578824333 214 MVEFSPKTL--QQKPPKGWFRL 233
Cdd:cd00030   81 EVEIPLSELldSGKEGELWLPL 102
RasGAP_GAPA cd05132
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
330-550 2.95e-23

Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to bind to small GTPases, which are yet to be identified. IQGAP proteins are integral components of cytoskeletal regulation. Results from truncated GAPAs indicated that almost the entire region of GAPA homologous to IQGAP is required for cytokinesis in Dictyostelium. More members of the IQGAP family are emerging, and evidence suggests that there are both similarities and differences in their function.


Pssm-ID: 213334  Cd Length: 352  Bit Score: 102.05  E-value: 2.95e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 330 EVARTMDPNTLFRSNSLASKSMEQFMKLV-GMPYLHEVLKPVISRVFEEKKY-MELDPCKM----------DLGRT---- 393
Cdd:cd05132   37 EFDETTEFGSLLRANTAVSRMMTTYTRRGpGQSYLKTVLADRINDLISLKDLnLEINPLKVyeqmindielDTGLPsnlp 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 394 RRISFKGALSEEQMR---ETSLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAehQQDVKYLAISGFL 470
Cdd:cd05132  117 RGITPEEAAENPAVQniiEPRLEMLEEITNSFLEAIINSLDEVPYGIRWICKQIRSLTRRKFPDA--SDETICSLIGGFF 194
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 471 FLRFFAPAILTPKLFDLRDQHADPQTSRSLLLLAKAVQSIGNLGQqlgQGKELWMAPLHPFLLQCVSRVRDFLDRLVDVD 550
Cdd:cd05132  195 LLRFINPAIVSPQAYMLVDGKPSDNTRRTLTLIAKLLQNLANKPS---YSKEPYMAPLQPFVEENKERLNKFLNDLCEVD 271
C2 pfam00168
C2 domain;
7-107 1.05e-22

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 93.54  E-value: 1.05e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333    7 LNVRVVEGRALPAKDVSGSSDPYCLVKV-DDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQ-LAFYVLDEDTVGHDDII 84
Cdd:pfam00168   3 LTVTVIEAKNLPPKDGNGTSDPYVKVYLlDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAvLEIEVYDYDRFGRDDFI 82
                          90       100
                  ....*....|....*....|...
gi 578824333   85 GKISLSREAItADPRGIDSWINL 107
Cdd:pfam00168  83 GEVRIPLSEL-DSGEGLDGWYPL 104
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
569-708 1.22e-22

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.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: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 94.60  E-value: 1.22e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 569 REGYLLKR---KEepagLATRFAFKKRYVWLSGETLS-FSKSPEWQMCH--SIPVSHIRAVERVDEGA-FQLPHVMQVVT 641
Cdd:cd01238    1 LEGLLVKRsqgKK----RFGPVNYKERWFVLTKSSLSyYEGDGEKRGKEkgSIDLSKVRCVEEVKDEAfFERKYPFQVVY 76
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578824333 642 QDGTgalhtTYLQCKNVNELNQWLSALRKASAPNPNKLAACHPGAFRSARWTCCLQAERSAAGCSRT 708
Cdd:cd01238   77 DDYT-----LYVFAPSEEDRDEWIAALRKVCRNNSNLHDKYHPGFWTGGKWSCCGQTSKSAPGCQPA 138
RasGAP_Neurofibromin cd05130
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
300-555 3.08e-22

Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the neurofibromatosis type 1 gene (NF1) and shares a region of similarity with catalytic domain of the mammalian p120RasGAP protein and an extended similarity with the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2. Neurofibromin has been shown to function as a GAP (GTPase-activating protein) which inhibits low molecular weight G proteins such as Ras by stimulating their intrinsic GTPase activity. NF1 is a common genetic disorder characterized by various symptoms ranging from predisposition for the development of tumors to learning disability or mental retardation. Loss of neurofibromin activity can be correlated to the increase in Ras-GTP concentration in neurofibromas of NF1 of patients, supporting the notion that unregulated Ras signaling may contribute to their development.


Pssm-ID: 213332 [Multi-domain]  Cd Length: 332  Bit Score: 98.55  E-value: 3.08e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 300 DCRQDLATKLVKLFLGRGLAGRFLDYLTRREVARTMDPNTLFRSNSLASKSMEQFMKLVGMPYLHEVLKPVISRVFE--E 377
Cdd:cd05130   37 SQMDELARVLVTLFDSKHLLYQLLWNMFSKEVELADSMQTLFRGNSLASKIMTFCFKVYGATYLQSLLEPLLRTMITssE 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 378 KKYMELDPCKMDlgrtrrisfkgalSEEQMRETSLGLLTGYLGpIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEh 457
Cdd:cd05130  117 WVSYEVDPTRLE-------------GNENLEENQRNLLQLTEK-FFHAIISSSDEFPPQLRSVCHCLYQVVSHRFPNSG- 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 458 qqdvkYLAISGFLFLRFFAPAILTPKLFDLRDQHADPQTSRSLLLLAKAVQSIGNlgqQLGQGKELWMAPLHPFLLQCVS 537
Cdd:cd05130  182 -----LGAVGSAIFLRFINPAIVSPYEYGILDREPPPRVKRGLKLMSKILQNIAN---HVLFTKEAHMLPFNDFLRNHFE 253
                        250
                 ....*....|....*...
gi 578824333 538 RVRDFLDRLVDVDGDEAG 555
Cdd:cd05130  254 AGRRFFSSIASDCGAVDG 271
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
135-231 3.05e-21

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 89.08  E-value: 3.05e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   135 LRCHVLQARDLAPRDISGTSDPFARVFWGSQSLE---TSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDF 211
Cdd:smart00239   2 LTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEkkkTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDDF 81
                           90       100
                   ....*....|....*....|
gi 578824333   212 LGMVEFSPKTLQQKPPKGWF 231
Cdd:smart00239  82 IGQVTIPLSDLLLGGRHEKL 101
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
118-234 5.46e-19

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 83.85  E-value: 5.46e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 118 GEICLSVQMLEDGqgrcLRCHVLQARDLAPRDISGTSDPFARVFW-----GSQSLETSTIKKTRFPHWDEVLELREMPGA 192
Cdd:cd04026    2 GRIYLKISVKDNK----LTVEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDLKPAD 77
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 578824333 193 PSP-LRVELWDWDMVGKNDFLGMVEFSPKTLQQKPPKGWFRLL 234
Cdd:cd04026   78 KDRrLSIEVWDWDRTTRNDFMGSLSFGVSELIKMPVDGWYKLL 120
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
6-99 3.06e-18

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 80.61  E-value: 3.06e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333     6 SLNVRVVEGRALPAKDVSGSSDPYCLVKVDDE--VVARTATVWRSLGPFWGEEYTVHL-PLDFHQLAFYVLDEDTVGHDD 82
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDpkEKKKTKVVKNTLNPVWNETFEFEVpPPELAELEIEVYDKDRFGRDD 80
                           90
                   ....*....|....*..
gi 578824333    83 IIGKISLSREAITADPR 99
Cdd:smart00239  81 FIGQVTIPLSDLLLGGR 97
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
135-233 1.97e-17

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


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 79.00  E-value: 1.97e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDIS--GTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLE-LREMPGAPSpLRVELWDWDMVGKNDF 211
Cdd:cd04024    3 LRVHVVEAKDLAAKDRSgkGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEfPIFSAQNQL-LKLILWDKDRFAGKDY 81
                         90       100
                 ....*....|....*....|....*.
gi 578824333 212 LGMVEFSPKTLQQKPPKG----WFRL 233
Cdd:cd04024   82 LGEFDIALEEVFADGKTGqsdkWITL 107
PH_GAP1m_mammal-like cd13370
GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS ...
565-687 1.37e-16

GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS p21 protein activator (GTPase activating protein) 2) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(IP4BP), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(m) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1IP4BP, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(m) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(m) binds inositol tetrakisphosphate (IP4). 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: 241521  Cd Length: 133  Bit Score: 76.91  E-value: 1.37e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 565 SAIVREGYLLKRKEEPAGLATRfAFKKRYVWLSGETLSFSKSPEWQMCHSIPVSHIRAVERVDEGAFQLPHVMQVvtqdg 644
Cdd:cd13370   14 SVHLKEGEMHKRAQGRTRIGKK-NFKKRWFCLTSRELTYHKQKGKEAIFTIPVKNILAVEKLEESAFNKKNMFQV----- 87
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 578824333 645 tgaLHTT---YLQCKNVNELNQWLSALRKASAPNPNKLAACHPGAF 687
Cdd:cd13370   88 ---IHSEkplYVQANNCVEANEWIEVLSRVSRCNQKRLSFYHPSAY 130
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
135-225 1.45e-16

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


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 76.56  E-value: 1.45e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDIS------GTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLE--LREMPGapSPLRVELWDWDmV 206
Cdd:cd08391    3 LRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEavVDEVPG--QELEIELFDED-P 79
                         90
                 ....*....|....*....
gi 578824333 207 GKNDFLGMVEFSPKTLQQK 225
Cdd:cd08391   80 DKDDFLGRLSIDLGSVEKK 98
RasGAP_IQGAP_like cd05127
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
342-554 7.19e-16

Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family represents IQ motif containing GTPase activating protein (IQGAP) which associated with the Ras GTP-binding protein. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.


Pssm-ID: 213329 [Multi-domain]  Cd Length: 331  Bit Score: 79.55  E-value: 7.19e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 342 RSNSLASKSMEQFMK-LVGMPYLHEVLKPVISRVFEEKK-YMELDPckMDLGRTRR----------------ISFKGALS 403
Cdd:cd05127   34 TGNPTVIKLVVNYNRgPRGQKYLRELLGPVVKEILDDDDlDLETDP--VDIYKAWInqeesrtgepsklpydVTREQALK 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 404 EEQMRET---SLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEhqQDVKYLAISGFLFLRFFAPAIL 480
Cdd:cd05127  112 DPEVRKRlieHLEKLRAITDKFLTAITESLDKMPYGMRYIAKVLKEALREKFPDAP--EEEILKIVGNLLYYRYMNPAIV 189
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578824333 481 TPKLFDL----RDQHADPQTSRSLLLLAKAVQSIGNlGQQLGqGKELWMAPLHPFLLQCVSRVRDFLDRLVDVDGDEA 554
Cdd:cd05127  190 APEAFDIidlsVGGQLSPLQRRNLGSIAKVLQQAAS-GKLFG-GENPYLSPLNPYISESHEKFKKFFLEACTVPEAEE 265
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
7-136 3.31e-15

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


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 72.22  E-value: 3.31e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQ-LAFYVLDEDTVGHDDIIG 85
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAvLKVEVYDWDRGGKDDLLG 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 578824333  86 KISlsreaitadprgidswINLSRVDPDAEVQGEICLSVQMLEDGQGRCLR 136
Cdd:cd04040   81 SAY----------------IDLSDLEPEETTELTLPLDGQGGGKLGAVFLP 115
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
567-673 3.39e-15

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: 71.81  E-value: 3.39e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   567 IVREGYLLKRKEepaglATRFAFKKRYVWLSGETLSFSKSPEWQM----CHSIPVSHIRAVERVDEGAFQLPHVMQVVTQ 642
Cdd:smart00233   1 VIKEGWLYKKSG-----GGKKSWKKRYFVLFNSTLLYYKSKKDKKsykpKGSIDLSGCTVREAPDPDSSKKPHCFEIKTS 75
                           90       100       110
                   ....*....|....*....|....*....|.
gi 578824333   643 DGtgalHTTYLQCKNVNELNQWLSALRKASA 673
Cdd:smart00233  76 DR----KTLLLQAESEEEREKWVEALRKAIA 102
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
135-253 7.34e-15

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


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 71.45  E-value: 7.34e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARVFW-GSQSLETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLG 213
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDLLG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 578824333 214 MVEFSPKTLQQKPPKGWfrLLPFpraEEDSGGNLGALRVK 253
Cdd:cd04040   81 SAYIDLSDLEPEETTEL--TLPL---DGQGGGKLGAVFLP 115
PH pfam00169
PH domain; PH stands for pleckstrin homology.
567-673 2.08e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 66.82  E-value: 2.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  567 IVREGYLLKRKEEPAGlatrfAFKKRYVWLSGETLSFSKS----PEWQMCHSIPVSHIRAVERVDEGAFQLPHVMQVVTQ 642
Cdd:pfam00169   1 VVKEGWLLKKGGGKKK-----SWKKRYFVLFDGSLLYYKDdksgKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTG 75
                          90       100       110
                  ....*....|....*....|....*....|.
gi 578824333  643 DGTGAlHTTYLQCKNVNELNQWLSALRKASA 673
Cdd:pfam00169  76 ERTGK-RTYLLQAESEEERKDWIKAIQSAIR 105
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
4-90 2.31e-13

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 67.83  E-value: 2.31e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   4 SSSLNVRVVEGRALPAKDVSGSSDPYclVKV-----DDEVVAR-TATVWRSLGPFWGEEYTVHLPLDF---HQLAFYVLD 74
Cdd:cd08405   14 ANRITVNIIKARNLKAMDINGTSDPY--VKVwlmykDKRVEKKkTVIKKRTLNPVFNESFIFNIPLERlreTTLIITVMD 91
                         90
                 ....*....|....*.
gi 578824333  75 EDTVGHDDIIGKISLS 90
Cdd:cd08405   92 KDRLSRNDLIGKIYLG 107
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
121-215 2.58e-13

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


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 67.27  E-value: 2.58e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 121 CLSVQMLEDGQGRCLRCHVLQARDLAPRDISGTSDPFARVFW------GSQSlETSTIKKTRFPHWDEVLelrEMPGAPS 194
Cdd:cd04031    4 RIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLlpdrseKSKR-RTKTVKKTLNPEWNQTF---EYSNVRR 79
                         90       100
                 ....*....|....*....|....*..
gi 578824333 195 P------LRVELWDWDMVGKNDFLGMV 215
Cdd:cd04031   80 EtlkertLEVTVWDYDRDGENDFLGEV 106
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
135-218 4.39e-13

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


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 67.35  E-value: 4.39e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDIsGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELrEMPGAPSPLRVELWDWDMVGKNDFLGM 214
Cdd:cd04038    4 LKVRVVRGTNLAVRDF-TSSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTL-SVPNPMAPLKLEVFDKDTFSKDDSMGE 81

                 ....
gi 578824333 215 VEFS 218
Cdd:cd04038   82 AEID 85
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
7-111 1.27e-12

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


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 65.01  E-value: 1.27e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKD------VSGSSDPYCLVKVDDEVVaRTATVWRSLGPFWGEEYTVHL-PLDFHQLAFYVLDEDtVG 79
Cdd:cd08391    3 LRIHVIEAQDLVAKDkfvgglVKGKSDPYVIVRVGAQTF-KSKVIKENLNPKWNEVYEAVVdEVPGQELEIELFDED-PD 80
                         90       100       110
                 ....*....|....*....|....*....|..
gi 578824333  80 HDDIIGKISLSREAITADpRGIDSWINLSRVD 111
Cdd:cd08391   81 KDDFLGRLSIDLGSVEKK-GFIDEWLPLEDVK 111
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
7-90 1.66e-12

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


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 65.07  E-value: 1.66e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVAR------TATVWRSLGPFWGEEYT--VHlPLDfHQLAFYVLDEDTV 78
Cdd:cd04033    2 LRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNGeidsvqTKTIKKTLNPKWNEEFFfrVN-PRE-HRLLFEVFDENRL 79
                         90
                 ....*....|..
gi 578824333  79 GHDDIIGKISLS 90
Cdd:cd04033   80 TRDDFLGQVEVP 91
BTK pfam00779
BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found ...
682-710 4.16e-12

BTK motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains. The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 459937  Cd Length: 30  Bit Score: 61.00  E-value: 4.16e-12
                          10        20
                  ....*....|....*....|....*....
gi 578824333  682 CHPGAFRSARWTCCLQAERSAAGCSRTHS 710
Cdd:pfam00779   2 YHPGAFVDGKWLCCKQTDKNAPGCSPVTS 30
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
135-216 5.90e-12

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


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 63.53  E-value: 5.90e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARV-FWGSQ------SLETSTIKKTRFPHWDEVLELREMPGApSPLRVELWDWDMVG 207
Cdd:cd04033    2 LRVKVLAGIDLAKKDIFGASDPYVKIsLYDPDgngeidSVQTKTIKKTLNPKWNEEFFFRVNPRE-HRLLFEVFDENRLT 80

                 ....*....
gi 578824333 208 KNDFLGMVE 216
Cdd:cd04033   81 RDDFLGQVE 89
PH_GAP1_mammal-like cd13371
GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras ...
567-680 7.00e-12

GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras GTPase-activating protein 3, and RAS p21 protein activator (GTPase activating protein) 3/GAPIII/MGC46517/MGC47588)) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(m), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(IP4BP) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1M, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(IP4BP) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and PIP2 (phosphatidylinositol 4,5-bisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(IP4BP) binds tyrosine-protein kinase, HCK. Members here include humans, chickens, frogs, and fish. 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: 241522  Cd Length: 125  Bit Score: 63.13  E-value: 7.00e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 567 IVREGYLLKRKEEpaglATRFA---FKKRYVWLSGETLSFSKSPEWQMCHSIPVSHIRAVERVDEGAFQLPHVMQVVTQD 643
Cdd:cd13371   16 LLKEGFMIKRAQG----RKRFGmknFKKRWFRLTNHEFTYHKSKGDHPLCSIPIENILAVERLEEESFKMKNMFQVIQPE 91
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 578824333 644 gtgalHTTYLQCKNVNELNQWLSALRKASAPNPNKLA 680
Cdd:cd13371   92 -----RALYIQANNCVEAKDWIDILTKVSQCNKKRLT 123
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
136-213 1.72e-11

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 62.18  E-value: 1.72e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 136 RCHVLQARDLAPRDISGTSDPFARVFWGSQSLETS--TIKKTRFPHWDEVLELR-EMPGApSPLRVELWDWDMVGKNDFL 212
Cdd:cd04037    3 RVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRdnYIPNTLNPVFGKMFELEaTLPGN-SILKISVMDYDLLGSDDLI 81

                 .
gi 578824333 213 G 213
Cdd:cd04037   82 G 82
RasGAP_IQGAP1 cd05133
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a ...
359-549 2.04e-11

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a homodimeric protein that is widely expressed among vertebrate cell types from early embryogenesis. Mammalian IQGAP1 protein is the best characterized member of the IQGAP family, and contains several protein-interacting domains. Human IQGAP1 is most similar to mouse Iqgap1 (94% identity) and has 62% identity to human IQGAP2. IQGAP1 binds and cross-links actin filaments in vitro and has been implicated in Ca2+/calmodulin signaling, E-cadherin-dependent cell adhesion, cell motility, and invasion. Yeast IQGAP homologs have a role in the recruitment of actin filaments, are components of the spindle pole body, and are required for actomyosin ring assembly and cytokinesis. Furthermore, IQGAP1 over-expression has also been detected in gastric and colorectal carcinomas and gastric cancer cell lines.


Pssm-ID: 213335  Cd Length: 380  Bit Score: 66.61  E-value: 2.04e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 359 GMPYLHEVLKPVISRVFEEKKY-MELDPCKM----------DLGRTRRISF----KGALSEEQMR---ETSLGLLTGYLG 420
Cdd:cd05133   62 GQNALRQILAPVVKEIMDDKSLnIKTDPVDIykswvnqmesQTGEASKLPYdvtpEQAMSHEEVRtrlDASIKNMRMVTD 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 421 PIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHQQDVKylAISGFLFLRFFAPAILTPKLFDLRDQHADPQTS--- 497
Cdd:cd05133  142 KFLSAIISSVDKIPYGMRFIAKVLKDTLHEKFPDAGEDELLK--IVGNLLYYRYMNPAIVAPDAFDIIDLSAGGQLTtdq 219
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 578824333 498 -RSLLLLAKAVQSIGNLGQQLGQGKELwmAPLHPFLLQCVSRVRDFLDRLVDV 549
Cdd:cd05133  220 rRNLGSIAKMLQHAASNKMFLGDNAHL--SPINEYLSQSYQKFRRFFQAACDV 270
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
6-85 2.83e-11

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


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 61.14  E-value: 2.83e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   6 SLNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTvhLPLD--FHQLAFYVLDEDTVGHDDI 83
Cdd:cd04042    1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYGGKTVYKSKTIYKNLNPVWDEKFT--LPIEdvTQPLYIKVFDYDRGLTDDF 78

                 ..
gi 578824333  84 IG 85
Cdd:cd04042   79 MG 80
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
7-88 3.97e-11

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


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 60.78  E-value: 3.97e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVaRTATVWRSLGPFWGEEYTVHLPlDFHQ-LAFYVLDEDTVGHDDIIG 85
Cdd:cd08377    3 LQVKVIRASGLAAADIGGKSDPFCVLELVNARL-QTHTIYKTLNPEWNKIFTFPIK-DIHDvLEVTVYDEDKDKKPEFLG 80

                 ...
gi 578824333  86 KIS 88
Cdd:cd08377   81 KVA 83
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
569-668 5.29e-11

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: 59.48  E-value: 5.29e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 569 REGYLLKRKEepaglATRFAFKKRYVWLSGETLSFSKSPEWQM---CHSIPVSHIRAVERVDEGAFqlPHVMQVVTQDGt 645
Cdd:cd00821    1 KEGYLLKRGG-----GGLKSWKKRWFVLFEGVLLYYKSKKDSSykpKGSIPLSGILEVEEVSPKER--PHCFELVTPDG- 72
                         90       100
                 ....*....|....*....|...
gi 578824333 646 galHTTYLQCKNVNELNQWLSAL 668
Cdd:cd00821   73 ---RTYYLQADSEEERQEWLKAL 92
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
121-213 6.90e-11

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 60.71  E-value: 6.90e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 121 CLSVQMLEDGQGRCLRCHVLQARDLAPRDISGTSDPFARV-------FWGSQSLETSTIKKTRFPHWDEVLelrEMPGAP 193
Cdd:cd04009    4 VLTVKAYYRASEQSLRVEILNARNLLPLDSNGSSDPFVKVellprhlFPDVPTPKTQVKKKTLFPLFDESF---EFNVPP 80
                         90       100
                 ....*....|....*....|....*..
gi 578824333 194 SPLRVE-------LWDWDMVGKNDFLG 213
Cdd:cd04009   81 EQCSVEgalllftVKDYDLLGSNDFEG 107
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
118-216 8.67e-11

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


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 60.11  E-value: 8.67e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 118 GEICLSVQMleDGQGRCLRCHVLQARDLAPRDISGTSDPFARVFW---GSQSLETSTIKKTRFPHWDE--VLELREMPGA 192
Cdd:cd08387    3 GELHFSLEY--DKDMGILNVKLIQARNLQPRDFSGTADPYCKVRLlpdRSNTKQSKIHKKTLNPEFDEsfVFEVPPQELP 80
                         90       100
                 ....*....|....*....|....
gi 578824333 193 PSPLRVELWDWDMVGKNDFLGMVE 216
Cdd:cd08387   81 KRTLEVLLYDFDQFSRDECIGVVE 104
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
7-94 1.03e-10

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


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 60.42  E-value: 1.03e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVsGSSDPYCLVKVDDEVVaRTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDTVGHDDIIGK 86
Cdd:cd04038    4 LKVRVVRGTNLAVRDF-TSSDPYVVLTLGNQKV-KTRVIKKNLNPVWNEELTLSVPNPMAPLKLEVFDKDTFSKDDSMGE 81

                 ....*...
gi 578824333  87 ISLSREAI 94
Cdd:cd04038   82 AEIDLEPL 89
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
135-244 1.18e-10

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


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 59.60  E-value: 1.18e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARVFWGSQSLETS-TIKKTRFPHWDEVLELR-EMPGApsPLRVELWDWDMVGKNDFL 212
Cdd:cd04042    2 LDIHLKEGRNLAARDRGGTSDPYVKFKYGGKTVYKSkTIYKNLNPVWDEKFTLPiEDVTQ--PLYIKVFDYDRGLTDDFM 79
                         90       100       110
                 ....*....|....*....|....*....|..
gi 578824333 213 GMVEFSPKTLQQKPPKGWFRLLPFPRAEEDSG 244
Cdd:cd04042   80 GSAFVDLSTLELNKPTEVKLKLEDPNSDEDLG 111
RasGAP_IQGAP2 cd05131
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
359-553 3.16e-10

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a member of the IQGAP family that contains a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeat, a single WW domain, four IQ motifs which mediate interactions with calmodulin, and a Ras-GTPase-activating protein (GAP)-related domain that binds Rho family GTPases. IQGAP2 and IQGAP3 play important roles in the regulation of the cytoskeleton for axon outgrowth in hippocampal neurons and are thought to stay in a common regulatory pathway. The results of RNA interference studies indicated that IQGAP3 partially compensates functions of IQGAP2, but has lesser ability than IQGAP2 to promote axon outgrowth in hippocampal neuron. Moreover, IQGAP2 is required for the cadherin-mediated cell-to-cell adhesion in Xenopus laevis embryos.


Pssm-ID: 213333 [Multi-domain]  Cd Length: 359  Bit Score: 62.71  E-value: 3.16e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 359 GMPYLHEVLKPVISRVFEEKKY-MELDPC----------KMDLGRTRRISF----KGALSEEQMR---ETSLGLLTGYLG 420
Cdd:cd05131   62 GQNTLRQLLAPVVKEIIEDKSLiINTNPVevykawvnqlETATGEASKLPYdvttEQALTHPEVVnklESSIQSLRSVTD 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 421 PIVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAEHQQDVKYlaISGFLFLRFFAPAILTPKLFDLRDQHADPQT---- 496
Cdd:cd05131  142 KVLGSIFSSLDLIPYGMRYIAKVLKNSLHEKFPDATEDELLKI--VGNLLYYRYMNPAIVAPDGFDIIDMTAGGQIhseq 219
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 578824333 497 SRSLLLLAKAVQSIGNlgQQLGQGKELWMAPLHPFLLQCVSRVRDFLDRLVDVDGDE 553
Cdd:cd05131  220 RRNLGSVAKVLQHAAS--NKLFEGENAHLSSMNSYLSQTYQKFRKFFQAACDVPEPE 274
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
4-107 4.38e-10

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175981 [Multi-domain]  Cd Length: 132  Bit Score: 58.44  E-value: 4.38e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   4 SSSLNVRVVEGRALPAKDVS--------GSS--DPYCLVKVDDEVVARTATVWRSLGPFWGEEYT--VHlplDFHQLAFY 71
Cdd:cd04014    3 TGTLKIKICEAVDLKPTDWStrhavpkkGSQllDPYVSIDVDDTHIGKTSTKPKTNSPVWNEEFTteVH---NGRNLELT 79
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 578824333  72 VLDEDTVGHDDIIGKISLS-REAITADPRGIDSWINL 107
Cdd:cd04014   80 VFHDAAIGPDDFVANCTISfEDLIQRGSGSFDLWVDL 116
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
7-122 6.79e-10

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


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 57.43  E-value: 6.79e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGS--SDPYCLVKVDDEVVaRTATVWRSLGPFWgeEYTVHLPLDFHQ---LAFYVLDEDTVGHD 81
Cdd:cd04024    3 LRVHVVEAKDLAAKDRSGKgkSDPYAILSVGAQRF-KTQTIPNTLNPKW--NYWCEFPIFSAQnqlLKLILWDKDRFAGK 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 578824333  82 DIIGKISLSREAITADP--RGIDSWINL--SRVDPDAEVQGEICL 122
Cdd:cd04024   80 DYLGEFDIALEEVFADGktGQSDKWITLksTRPGKTSVVSGEIHL 124
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
135-217 7.52e-10

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


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 57.31  E-value: 7.52e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLE--LREMpgaPSPLRVELWDWDMVGKNDFL 212
Cdd:cd08377    3 LQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTfpIKDI---HDVLEVTVYDEDKDKKPEFL 79

                 ....*
gi 578824333 213 GMVEF 217
Cdd:cd08377   80 GKVAI 84
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
4-89 9.20e-10

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 56.95  E-value: 9.20e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   4 SSSLNVRVVEGRALPAKDVSGSSDPYclVKV----DDEVVARTATVWRSLGPFWGEEYTVH-LPLD-FHQLAFY--VLDE 75
Cdd:cd08386   15 ESTLTLKILKAVELPAKDFSGTSDPF--VKIyllpDKKHKLETKVKRKNLNPHWNETFLFEgFPYEkLQQRVLYlqVLDY 92
                         90
                 ....*....|....
gi 578824333  76 DTVGHDDIIGKISL 89
Cdd:cd08386   93 DRFSRNDPIGEVSL 106
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
139-233 1.10e-09

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 57.08  E-value: 1.10e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 139 VLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELrEMPGAPSP------LRVELWDWDMVGKNDFL 212
Cdd:cd08682    5 VLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSF-ELPGLLSGngnratLQLTVMHRNLLGLDKFL 83
                         90       100
                 ....*....|....*....|....
gi 578824333 213 GMVEFSPKTL---QQKPPKGWFRL 233
Cdd:cd08682   84 GQVSIPLNDLdedKGRRRTRWFKL 107
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
134-228 1.22e-09

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 56.52  E-value: 1.22e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 134 CLRCHVLQARDLAPRDISGTSDPFARVFW-----GSQSLETSTIKKTRFPHWDEVLE---LREMPGAPSPLRVELWDWDM 205
Cdd:cd04035   16 ALHCTIIRAKGLKAMDANGLSDPYVKLNLlpgasKATKLRTKTVHKTRNPEFNETLTyygITEEDIQRKTLRLLVLDEDR 95
                         90       100
                 ....*....|....*....|...
gi 578824333 206 VGkNDFLGMVEFSPKTLQQKPPK 228
Cdd:cd04035   96 FG-NDFLGETRIPLKKLKPNQTK 117
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
7-104 1.23e-09

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 56.82  E-value: 1.23e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYclVKV----DDEVVA--RTATVWRSLGPFWGEEYTVHLPLDFHQ---LAFYVLDEDT 77
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPY--VKVsllqGGKKLKkkKTSVKKGTLNPVFNEAFSFDVPAEQLEevsLVITVVDKDS 93
                         90       100
                 ....*....|....*....|....*..
gi 578824333  78 VGHDDIIGKISLSREaitADPRGIDSW 104
Cdd:cd00276   94 VGRNEVIGQVVLGPD---SGGEELEHW 117
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
131-237 1.98e-09

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


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 56.59  E-value: 1.98e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 131 QGRCLRCHVLQARDLAPRDISGTSDPFARVFW----GSQSLETSTIKK-TRFPHWDEVL--ELREMPGAPSPLRVELWDW 203
Cdd:cd08384   11 QRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLkpdaGKKSKHKTQVKKkTLNPEFNEEFfyDIKHSDLAKKTLEITVWDK 90
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 578824333 204 DMVGKNDFLGMVEFSPKT----LQQkppkgWFRLLPFP 237
Cdd:cd08384   91 DIGKSNDYIGGLQLGINAkgerLRH-----WLDCLKNP 123
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
118-216 2.20e-09

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 56.18  E-value: 2.20e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 118 GEICLSVQMleDGQGRCLRCHVLQARDLAPRDISGTSDPFARVFW---GSQSLETSTIKKTRFPHWDEVLELREMPGAPS 194
Cdd:cd08386    3 GRIQFSVSY--DFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFEGFPYEKL 80
                         90       100
                 ....*....|....*....|....*
gi 578824333 195 PLRV---ELWDWDMVGKNDFLGMVE 216
Cdd:cd08386   81 QQRVlylQVLDYDRFSRNDPIGEVS 105
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
139-217 3.18e-09

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 55.34  E-value: 3.18e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578824333 139 VLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLGMVEF 217
Cdd:cd08376    6 LVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDEFIGRCEI 84
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
9-126 3.34e-09

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 55.73  E-value: 3.34e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   9 VRVVEGRALPAKDVSGSSDPYcLVKVDD---EVVARTATVWRSLGPFWGEEYTVHLPLDFHQ-LAFYVLDEDTVGHDDII 84
Cdd:cd04043    5 IRIVRAENLKADSSNGLSDPY-VTLVDTngkRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLwISATVWDRSFVGKHDLC 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 578824333  85 GKISLsreaiTADPR-----GI--DSWINLsrvDPdaevQGEICLSVQM 126
Cdd:cd04043   84 GRASL-----KLDPKrfgddGLprEIWLDL---DT----QGRLLLRVSM 120
IQG1 COG5261
Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and ...
322-555 3.78e-09

Protein involved in regulation of cellular morphogenesis/cytokinesis [Cell division and chromosome partitioning / Signal transduction mechanisms];


Pssm-ID: 227586 [Multi-domain]  Cd Length: 1054  Bit Score: 60.28  E-value: 3.78e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  322 FLDYLTRREVARTMDPNTLFRSNSLASKSMEQ-FMKLVGMPYLHEVLKPVISRVfEEKKYMELDPCKMDLGR----TRRI 396
Cdd:COG5261   440 LFQMLLRTEVEATSLVQSLLRGNLPVHRNMTNyFRRSQGQAALREIRYQIINDV-AIHEDLEVDINPLLVYRallnKGQL 518
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  397 SFKGALSEEQMRET--------------SLGLLtgYLGP--IVDAIVGSVGRCPPAMRLaFKQLHRRVEERFPQAEHQ-- 458
Cdd:COG5261   519 SPDKDLELLTSNEEvseflavmnavqesSAKLL--ELSTerILDAVYNSLDEIGYGIRF-VCELIRVVFELTPNRLFPsi 595
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  459 QDVKYL------------AISGFLFLRFFAPAILTPKLFDLRDQHADpQTSRSLLLLAKAVQSIGNlgqqlGQGKELWMA 526
Cdd:COG5261   596 SDSRCLrticfaeidslgLIGGFFFLRFVNEALVSPQTSMLKDSCPS-DNVRKLATLSKILQSVFE-----ITSSDKFDV 669
                         250       260       270
                  ....*....|....*....|....*....|
gi 578824333  527 PLHPFLLQCVSRVRDFLDRLVDV-DGDEAG 555
Cdd:COG5261   670 PLQPFLKEYKEKVHNLLRKLGNVgDFEEYF 699
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
135-236 3.97e-09

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


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 54.96  E-value: 3.97e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDI-SGTSDPFARVFW---GSQSLETSTIKKTRFPHWDE---VLELREMPGAPSPLRVELWDWDMVG 207
Cdd:cd04041    3 LVVTIHRATDLPKADFgTGSSDPYVTASFakfGKPLYSTRIIRKDLNPVWEEtwfVLVTPDEVKAGERLSCRLWDSDRFT 82
                         90       100
                 ....*....|....*....|....*....
gi 578824333 208 KNDFLGMVEFSPKTLQQKPPKGWFRLLPF 236
Cdd:cd04041   83 ADDRLGRVEIDLKELIEDRNWMGRREDGF 111
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
140-230 6.53e-09

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 54.11  E-value: 6.53e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 140 LQARDLAPRDISGTSDPFARVFWGSQS------LETSTIKKTRFPHWDEV-LELREMPGAP--SPLRVELWDWDMVGKND 210
Cdd:cd04047    7 FSGKKLDKKDFFGKSDPFLEISRQSEDgtwvlvYRTEVIKNTLNPVWKPFtIPLQKLCNGDydRPIKIEVYDYDSSGKHD 86
                         90       100
                 ....*....|....*....|
gi 578824333 211 FLGMVEFSPKTLQQKPPKGW 230
Cdd:cd04047   87 LIGEFETTLDELLKSSPLEF 106
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
7-124 1.54e-08

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 53.73  E-value: 1.54e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVdDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDtvghDDIIGK 86
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYVTVQV-GKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDED----DDIKSR 77
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 578824333  87 I--SLSREA------ITADPRGI----DSWINLSRVDPDAEVQGEICLSV 124
Cdd:cd04027   78 LkqKFTRESddflgqTIIEVRTLsgemDVWYNLEKRTDKSAVSGAIRLHI 127
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
135-244 1.54e-08

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176018 [Multi-domain]  Cd Length: 121  Bit Score: 53.67  E-value: 1.54e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARVFWGSQSL-ETSTIKKTRFPHWDEVLELReMPGAPSPLRVELWDWDMVGKNDFLG 213
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYCIVKVDNEVIiRTATVWKTLNPFWGEEYTVH-LPPGFHTVSFYVLDEDTLSRDDVIG 80
                         90       100       110
                 ....*....|....*....|....*....|...
gi 578824333 214 MVEFSPKTLQQKPP--KGWFRLLPFPRAEEDSG 244
Cdd:cd04054   81 KVSLTREVISAHPRgiDGWMNLTEVDPDEEVQG 113
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
7-93 2.71e-08

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 52.64  E-value: 2.71e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVaRTATVWRSLGPFWGEEYTVHLPLDFHQ-LAFYVLDEDTVGHDDIIG 85
Cdd:cd08376    2 VTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKY-KSKVCSKTLNPQWLEQFDLHLFDDQSQiLEIEVWDKDTGKKDEFIG 80

                 ....*...
gi 578824333  86 KISLSREA 93
Cdd:cd08376   81 RCEIDLSA 88
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
7-87 4.06e-08

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 51.92  E-value: 4.06e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKD-VSGSSDPYCLVKVDDeVVARTATVWRSLGPFWG-EEYTVHLPLDFHQ---LAFYVLDEDTVGHD 81
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGS-TTYKTDVVKKSLNPVWNsEWFRFEVDDEELQdepLQIRVMDHDTYSAN 79

                 ....*.
gi 578824333  82 DIIGKI 87
Cdd:cd08688   80 DAIGKV 85
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
8-86 4.75e-08

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 52.17  E-value: 4.75e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   8 NVRVVEGRALPAKDVSGSSDPYCLVKV-DDEVVARTATVWRSLGPFWGE--EYTVHLPLDfHQLAFYVLDEDTVGHDDII 84
Cdd:cd04037    3 RVYVVRARNLQPKDPNGKSDPYLKIKLgKKKINDRDNYIPNTLNPVFGKmfELEATLPGN-SILKISVMDYDLLGSDDLI 81

                 ..
gi 578824333  85 GK 86
Cdd:cd04037   82 GE 83
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
3-107 5.21e-08

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 52.26  E-value: 5.21e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   3 KSSSLNVRVVEGRALPAKDVSGSSDPYclVKV------DDEVVARTATVWRSLGPFWGEEYTVHL-PLDFHQ-LAFYVLD 74
Cdd:cd04026   11 KDNKLTVEVREAKNLIPMDPNGLSDPY--VKLklipdpKNETKQKTKTIKKTLNPVWNETFTFDLkPADKDRrLSIEVWD 88
                         90       100       110
                 ....*....|....*....|....*....|...
gi 578824333  75 EDTVGHDDIIGKISLSREAITADPrgIDSWINL 107
Cdd:cd04026   89 WDRTTRNDFMGSLSFGVSELIKMP--VDGWYKL 119
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
133-233 5.92e-08

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 52.76  E-value: 5.92e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 133 RCLRCHVLQARDLAPRDISGTSDPFA----------RVFWGSQSLE-------------------TSTIKKTRFPHWDE- 182
Cdd:cd08676   28 FVLKVTVIEAKGLLAKDVNGFSDPYCmlgivpasreRNSEKSKKRKshrkkavlkdtvpaksikvTEVKPQTLNPVWNEt 107
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578824333 183 -VLELREMPGApsPLRVELWDWDmvgkNDFLGMVEFSPKTLqqkPPKG---WFRL 233
Cdd:cd08676  108 fRFEVEDVSND--QLHLDIWDHD----DDFLGCVNIPLKDL---PSCGldsWFKL 153
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
155-213 6.96e-08

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 52.25  E-value: 6.96e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 155 DPFARVFWGSQSLETSTIKKTRFPHWDEVLELREM-PGAPSPLRVELWDWDMVGKNDFLG 213
Cdd:cd04018   36 DPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMfPPLCERIKIQIRDWDRVGNDDVIG 95
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
4-90 7.18e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 56.31  E-value: 7.18e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333    4 SSSLNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFH-QLAFYVLDEDTVGHDD 82
Cdd:COG5038  1039 SGYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKdVLTINVNDWDSGEKND 1118

                  ....*...
gi 578824333   83 IIGKISLS 90
Cdd:COG5038  1119 LLGTAEID 1126
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
6-90 8.07e-08

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 51.85  E-value: 8.07e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   6 SLNVRVVEGRALPAKDVSGSSDPYclVKVD--------DEVVARTATVWRSLGPFWGEEYTVHLPLDFHQ-----LAFYV 72
Cdd:cd04009   17 SLRVEILNARNLLPLDSNGSSDPF--VKVEllprhlfpDVPTPKTQVKKKTLFPLFDESFEFNVPPEQCSvegalLLFTV 94
                         90
                 ....*....|....*...
gi 578824333  73 LDEDTVGHDDIIGKISLS 90
Cdd:cd04009   95 KDYDLLGSNDFEGEAFLP 112
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
129-216 8.73e-08

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


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 51.62  E-value: 8.73e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 129 DGQGRcLRCHVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDE-----VLELREmpgapSPLRVELWDW 203
Cdd:cd08375   12 SGIGR-LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSsmqffVKDLEQ-----DVLCITVFDR 85
                         90
                 ....*....|...
gi 578824333 204 DMVGKNDFLGMVE 216
Cdd:cd08375   86 DFFSPDDFLGRTE 98
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
7-98 8.97e-08

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


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 51.11  E-value: 8.97e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKD-VSGSSDPYCLV--KVDDEVVARTATVWRSLGPFWGEEYTV-----HLPLDFhQLAFYVLDEDTV 78
Cdd:cd04041    3 LVVTIHRATDLPKADfGTGSSDPYVTAsfAKFGKPLYSTRIIRKDLNPVWEETWFVlvtpdEVKAGE-RLSCRLWDSDRF 81
                         90       100
                 ....*....|....*....|
gi 578824333  79 GHDDIIGKISLSREAITADP 98
Cdd:cd04041   82 TADDRLGRVEIDLKELIEDR 101
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
7-109 9.53e-08

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


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 51.25  E-value: 9.53e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKV--DDEVVARTATVWRSLGPFWGEEYTVHLP---LDFHQLAFYVLDEDTVGHD 81
Cdd:cd08387   18 LNVKLIQARNLQPRDFSGTADPYCKVRLlpDRSNTKQSKIHKKTLNPEFDESFVFEVPpqeLPKRTLEVLLYDFDQFSRD 97
                         90       100
                 ....*....|....*....|....*...
gi 578824333  82 DIIGKISLSREAITADPRgIDSWINLSR 109
Cdd:cd08387   98 ECIGVVELPLAEVDLSEK-LDLWRKIQS 124
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
139-221 1.57e-07

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 50.88  E-value: 1.57e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 139 VLQARDLAPRDISGTSDPFARVF--WGSQSLE---TSTIKKTRFPHWDEVLE-------LREMpgapsPLRVELWDWDMV 206
Cdd:cd08405   21 IIKARNLKAMDINGTSDPYVKVWlmYKDKRVEkkkTVIKKRTLNPVFNESFIfniplerLRET-----TLIITVMDKDRL 95
                         90
                 ....*....|....*
gi 578824333 207 GKNDFLGMVEFSPKT 221
Cdd:cd08405   96 SRNDLIGKIYLGWKS 110
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
2-107 3.02e-07

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 50.83  E-value: 3.02e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   2 AKSSSLNVRVVEGRALPAKDVSGSSDPYCLVKVDD----------------------------EVVARTATVWRSLGPFW 53
Cdd:cd08676   25 PPIFVLKVTVIEAKGLLAKDVNGFSDPYCMLGIVPasrernsekskkrkshrkkavlkdtvpaKSIKVTEVKPQTLNPVW 104
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 578824333  54 GEeytvHLPLDF-----HQLAFYVLDEDtvghDDIIGKISLSREAITADprGIDSWINL 107
Cdd:cd08676  105 NE----TFRFEVedvsnDQLHLDIWDHD----DDFLGCVNIPLKDLPSC--GLDSWFKL 153
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
566-676 4.23e-07

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: 48.95  E-value: 4.23e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 566 AIVREGYLLKRKEEpaglatRFAFKKRYVWLSGETLSFSKS-PEWQMCHSIPVSHIRAVERVDEGafQLPHVMQVVTQDg 644
Cdd:cd13255    5 AVLKAGYLEKKGER------RKTWKKRWFVLRPTKLAYYKNdKEYRLLRLIDLTDIHTCTEVQLK--KHDNTFGIVTPA- 75
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 578824333 645 tgalHTTYLQCKNVNELNQWLSA-------LRKASAPNP 676
Cdd:cd13255   76 ----RTFYVQADSKAEMESWISAinlarqaLRATITPNT 110
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
4-89 4.70e-07

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 49.19  E-value: 4.70e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   4 SSSLNVRVVEGRALPAKDVSGSSDPYclVKV----DDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQ---LAFYVLDED 76
Cdd:cd08385   15 SNQLTVGIIQAADLPAMDMGGTSDPY--VKVyllpDKKKKFETKVHRKTLNPVFNETFTFKVPYSELGnktLVFSVYDFD 92
                         90
                 ....*....|...
gi 578824333  77 TVGHDDIIGKISL 89
Cdd:cd08385   93 RFSKHDLIGEVRV 105
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
7-124 4.73e-07

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 49.26  E-value: 4.73e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVaRTATVWRSLGPFWGE--EYTVHLPLDFHQLAF--YVLDE--DTVGH 80
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKK-RTRTKPKDLNPVWNEklVFNVSDPSRLSNLVLevYVYNDrrSGRRR 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578824333  81 dDIIGKISLSREAI-----------TADPRGIDSWinlsrvdpdaeVQGEICLSV 124
Cdd:cd04022   81 -SFLGRVRISGTSFvppseavvqryPLEKRGLFSR-----------VRGEIGLKV 123
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
7-99 5.28e-07

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 49.71  E-value: 5.28e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYclVKV----DDEVVAR--TATVWRSLGPFWGEEYTVHLPldFHQ-----LAFYVLDE 75
Cdd:cd08402   17 LTVVILEAKNLKKMDVGGLSDPY--VKIhlmqNGKRLKKkkTTIKKRTLNPYYNESFSFEVP--FEQiqkvhLIVTVLDY 92
                         90       100
                 ....*....|....*....|....
gi 578824333  76 DTVGHDDIIGKISLSREAITADPR 99
Cdd:cd08402   93 DRIGKNDPIGKVVLGCNATGAELR 116
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
117-216 8.75e-07

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 48.58  E-value: 8.75e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 117 QGEICLSVQMleDGQGRCLRCHVLQARDLAPRDI-SGTSDPFARVFW----GSQS-LETSTIKKTRFPHWDEVLELR--- 187
Cdd:cd08393    1 QGSVQFALDY--DPKLRELHVHVIQCQDLAAADPkKQRSDPYVKTYLlpdkSNRGkRKTSVKKKTLNPVFNETLRYKver 78
                         90       100       110
                 ....*....|....*....|....*....|
gi 578824333 188 -EMPGapSPLRVELWDWDMVGKNDFLGMVE 216
Cdd:cd08393   79 eELPT--RVLNLSVWHRDSLGRNSFLGEVE 106
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
7-108 8.98e-07

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 48.96  E-value: 8.98e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYclVKV----DDEVVA--RTATVWRSLGPFWGEEYTVHLP---LDFHQLAFYVLDEDT 77
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLADPY--VKVnlyyGKKRISkkKTHVKKCTLNPVFNESFVFDIPseeLEDISVEFLVLDSDR 94
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 578824333  78 VGHDDIIGKISLSREAITADP-----------RGIDSWINLS 108
Cdd:cd08404   95 VTKNEVIGRLVLGPKASGSGGhhwkevcnpprRQIAEWHMLC 136
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
139-220 9.14e-07

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 48.41  E-value: 9.14e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 139 VLQARDLAPRDISGTSDPFARVFWGSQSLE---TSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLG-- 213
Cdd:cd04043    7 IVRAENLKADSSNGLSDPYVTLVDTNGKRRiakTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDLCGra 86

                 ....*..
gi 578824333 214 MVEFSPK 220
Cdd:cd04043   87 SLKLDPK 93
RasGAP_IQGAP3 cd12207
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
422-549 9.17e-07

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family represents the IQ motif containing GTPase activating protein 3 (IQGAP3), which associates with Ras GTP-binding proteins. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.


Pssm-ID: 213346 [Multi-domain]  Cd Length: 350  Bit Score: 51.75  E-value: 9.17e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 422 IVDAIVGSVGRCPPAMRLAFKQLHRRVEERFPQAehQQDVKYLAISGFLFLRFFAPAILTPKLFDLRDQHA----DPQTS 497
Cdd:cd12207  143 FLSAITSSVDKIPYGMRYVAKVLRDSLQEKFPGA--SEDEVYKVVGNLLYYRFMNPAVVAPDGFDIVDCSAggalQPEQR 220
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 578824333 498 RSLLLLAKAVQSIGNLGQQLGQGKELWMapLHPFLLQCVSRVRDFLDRLVDV 549
Cdd:cd12207  221 RMLGSVAKVLQHAAANKHFQGDSEHLQA--LNQYLEETHVKFRKFILQACCV 270
PH_Cla4_Ste20 cd13279
Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), ...
567-665 1.34e-06

Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), Cla4 and Ste20. The yeast Ste20 protein kinase is involved in pheromone response, though the function of Ste20 mammalian homologs is unknown. Cla4 is involved in budding and cytokinesis and interacts with Cdc42, a GTPase required for polarized cell growth as is Pak. Cla4 and Ste20 kinases share a function in localizing cell growth with respect to the septin ring. They both contain a PH domain, a Cdc42/Rac interactive binding (CRIB) domain, and a C-terminal Protein Kinase catalytic (PKc) 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: 270097  Cd Length: 92  Bit Score: 47.24  E-value: 1.34e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 567 IVREGYLlKRKEEpaGLATrFAFKKRYVWLSGETLSFSKS-PEWQMCHSIPVSHIRAVERVDEGafqlPHVMQVVTQDGT 645
Cdd:cd13279    1 VVKSGWV-SVKED--GLLS-FRWSKRYLVLREQSLDFYKNeSSSSASLSIPLKDISNVSRTDLK----PYCFEIVRKSST 72
                         90       100
                 ....*....|....*....|
gi 578824333 646 galHTTYLQCKNVNELNQWL 665
Cdd:cd13279   73 ---KSIYISVKSDDELYDWM 89
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
134-229 1.43e-06

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 47.97  E-value: 1.43e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 134 CLRCHVLQARDLAPRDISGTSDPFARVFW-GSQSLETSTIKKTRFPHWDEVLElrempgAP--SP---LRVELWDWDMVG 207
Cdd:cd04045    2 VLRLHIRKANDLKNLEGVGKIDPYVRVLVnGIVKGRTVTISNTLNPVWDEVLY------VPvtSPnqkITLEVMDYEKVG 75
                         90       100
                 ....*....|....*....|..
gi 578824333 208 KNDFLGMVEFSPKTLQQKPPKG 229
Cdd:cd04045   76 KDRSLGSVEINVSDLIKKNEDG 97
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
138-254 1.78e-06

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 47.66  E-value: 1.78e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 138 HVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDE-VLELREMPGapSPLRVELWDWDMVgKNDFLGMVE 216
Cdd:cd04046    8 HVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTqAIFYRKKPR--SPIKIQVWNSNLL-CDEFLGQAT 84
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 578824333 217 FSPKTLQQKPPkgwfRLLP-FPRAEEDSGGNLGALRVKV 254
Cdd:cd04046   85 LSADPNDSQTL----RTLPlRKRGRDAAGEVPGTISVKV 119
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
9-125 1.80e-06

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 47.83  E-value: 1.80e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   9 VRVVEGRALPAKDVSGSSDPYCLVKVDDEVVaRTATVWRSLGPFWGEEYTVHLPL------DFHQLAFYVLDEDTVGHDD 82
Cdd:cd08682    3 VTVLQARGLLCKGKSGTNDAYVIIQLGKEKY-STSVKEKTTSPVWKEECSFELPGllsgngNRATLQLTVMHRNLLGLDK 81
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 578824333  83 IIGKISLS-REAITADPRGIDSWINL-SRVDPDAEVQGEICLSVQ 125
Cdd:cd08682   82 FLGQVSIPlNDLDEDKGRRRTRWFKLeSKPGKDDKERGEIEVDIQ 126
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
135-220 2.23e-06

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175998 [Multi-domain]  Cd Length: 127  Bit Score: 47.64  E-value: 2.23e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPrDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELRE---MPGapSPLRVELWDWDMVGKNDF 211
Cdd:cd04032   30 LTVTVLRATGLWG-DYFTSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFGSvelSPG--GKLRFEVWDRDNGWDDDL 106

                 ....*....
gi 578824333 212 LGMVEFSPK 220
Cdd:cd04032  107 LGTCSVVPE 115
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
567-672 2.27e-06

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: 46.85  E-value: 2.27e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 567 IVREGYLLKRKEepaglATRFaFKKRYVWLSGETLSFSK-SPEWQMCHSIPVSHIRAVERVDEGAFqlPHVMQVVTQDgt 645
Cdd:cd13298    6 VLKSGYLLKRSR-----KTKN-WKKRWVVLRPCQLSYYKdEKEYKLRRVINLSELLAVAPLKDKKR--KNVFGIYTPS-- 75
                         90       100
                 ....*....|....*....|....*..
gi 578824333 646 galHTTYLQCKNVNELNQWLSALRKAS 672
Cdd:cd13298   76 ---KNLHFRATSEKDANEWVEALREEF 99
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
118-238 3.88e-06

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 47.12  E-value: 3.88e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 118 GEICLSVQMLEDGqGRcLRCHVLQARDLAPRDISGTSDPFARVFWGSQ-----SLETSTIKKTRFPHWDEVLELREMPGA 192
Cdd:cd08403    1 GELMFSLCYLPTA-GR-LTLTIIKARNLKAMDITGFSDPYVKVSLMCEgrrlkKKKTSVKKNTLNPTYNEALVFDVPPEN 78
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 578824333 193 PS--PLRVELWDWDMVGKNDFLGMVEFSPKTlqqkPPKG---WFRLLPFPR 238
Cdd:cd08403   79 VDnvSLIIAVVDYDRVGHNELIGVCRVGPNA----DGQGrehWNEMLANPR 125
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
14-128 4.85e-06

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 46.77  E-value: 4.85e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  14 GRALPAKDVSGSSDPYCLVKVDDEvVARTATVWRSLGPFWGEeyTvhlpLDFHQLAFY----------------VLDEDT 77
Cdd:cd04017   10 ARDLLAADKSGLSDPFARVSFLNQ-SQETEVIKETLSPTWDQ--T----LIFDEVELYgspeeiaqnpplvvveLFDQDS 82
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 578824333  78 VGHDDIIGKISLSREAITADPRGIDS---WINLSRVDpdaEVQGEICLSVQMLE 128
Cdd:cd04017   83 VGKDEFLGRSVAKPLVKLDLEEDFPPklqWFPIYKGG---QSAGELLAAFELIE 133
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
118-215 5.42e-06

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 46.63  E-value: 5.42e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 118 GEICLSVQMLEDGqGRcLRCHVLQARDLAPRDISGTSDPFARVFW--GSQSLE---TSTIKKTRFPHWDEVLELrEMPG- 191
Cdd:cd08402    2 GDICFSLRYVPTA-GK-LTVVILEAKNLKKMDVGGLSDPYVKIHLmqNGKRLKkkkTTIKKRTLNPYYNESFSF-EVPFe 78
                         90       100
                 ....*....|....*....|....*.
gi 578824333 192 --APSPLRVELWDWDMVGKNDFLGMV 215
Cdd:cd08402   79 qiQKVHLIVTVLDYDRIGKNDPIGKV 104
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
6-93 5.51e-06

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


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 46.57  E-value: 5.51e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   6 SLNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVV----ARTATVWRSLGPFWGEEYTVHLPldFHQLA-----FYVLDED 76
Cdd:cd08384   14 GLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGkkskHKTQVKKKTLNPEFNEEFFYDIK--HSDLAkktleITVWDKD 91
                         90
                 ....*....|....*..
gi 578824333  77 TVGHDDIIGKISLSREA 93
Cdd:cd08384   92 IGKSNDYIGGLQLGINA 108
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
139-249 5.53e-06

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176024 [Multi-domain]  Cd Length: 121  Bit Score: 46.15  E-value: 5.53e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 139 VLQARDLAPrdisGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLEL-REMPGAPSpLRVELWDWDMVgKNDFLGMVEF 217
Cdd:cd08378    6 VVKARGLPA----NSNDPVVEVKLGNYKGSTKAIERTSNPEWNQVFAFsKDRLQGST-LEVSVWDKDKA-KDDFLGGVCF 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 578824333 218 S----PKtlqQKPPKG-----WFRLlpfpraeEDSGGNLGA 249
Cdd:cd08378   80 DlsevPT---RVPPDSplapqWYRL-------EDKKGGRVG 110
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
7-104 6.15e-06

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 46.35  E-value: 6.15e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYclVKVD-----DEVVARTATVWRS-LGPFWGEEYTVHLP---LDFHQLAFYVLDEDT 77
Cdd:cd08403   16 LTLTIIKARNLKAMDITGFSDPY--VKVSlmcegRRLKKKKTSVKKNtLNPTYNEALVFDVPpenVDNVSLIIAVVDYDR 93
                         90       100
                 ....*....|....*....|....*..
gi 578824333  78 VGHDDIIGKISLSREaitADPRGIDSW 104
Cdd:cd08403   94 VGHNELIGVCRVGPN---ADGQGREHW 117
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
118-216 6.24e-06

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 46.09  E-value: 6.24e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 118 GEICLSVQMLEDGQgrCLRCHVLQARDLAPRDIS-GTSDPFARVFW-----GSQSLETSTIKKTRFPHWDEVL------- 184
Cdd:cd08521    1 GEIEFSLSYNYKTG--SLEVHIKECRNLAYADEKkKRSNPYVKVYLlpdksKQSKRKTSVKKNTTNPVFNETLkyhisks 78
                         90       100       110
                 ....*....|....*....|....*....|..
gi 578824333 185 ELREmpgapSPLRVELWDWDMVGKNDFLGMVE 216
Cdd:cd08521   79 QLET-----RTLQLSVWHHDRFGRNTFLGEVE 105
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
2-91 6.68e-06

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 46.12  E-value: 6.68e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   2 AKSSSLNVRVVEGRALPAKDVSGSSDPYC----LVKVDDEVVARTATVWRSLGPFWGEEYTVH--LPLDFHQ--LAFYVL 73
Cdd:cd04035   12 PANSALHCTIIRAKGLKAMDANGLSDPYVklnlLPGASKATKLRTKTVHKTRNPEFNETLTYYgiTEEDIQRktLRLLVL 91
                         90       100
                 ....*....|....*....|
gi 578824333  74 DEDTVGHdDIIG--KISLSR 91
Cdd:cd04035   92 DEDRFGN-DFLGetRIPLKK 110
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
139-219 1.12e-05

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 45.65  E-value: 1.12e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 139 VLQARDLAPRDISGTSDPFARV--FWGSQSLE---TSTIKKTRFPHWDEVL--ELREMPGAPSPLRVELWDWDMVGKNDF 211
Cdd:cd00276   20 VLKARNLPPSDGKGLSDPYVKVslLQGGKKLKkkkTSVKKGTLNPVFNEAFsfDVPAEQLEEVSLVITVVDKDSVGRNEV 99

                 ....*...
gi 578824333 212 LGMVEFSP 219
Cdd:cd00276  100 IGQVVLGP 107
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
7-122 1.21e-05

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176063 [Multi-domain]  Cd Length: 118  Bit Score: 45.32  E-value: 1.21e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVdDEVVARTATVWRS-LGPFWGEE--YTVHlPLDFHQLAFYVLDEDTvGHDDI 83
Cdd:cd08681    3 LVVVVLKARNLPNKRKLDKQDPYCVLRI-GGVTKKTKTDFRGgQHPEWDEElrFEIT-EDKKPILKVAVFDDDK-RKPDL 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 578824333  84 IGK--ISLSrEAITADprGIDSWINLSRvdpDAEVQGEICL 122
Cdd:cd08681   80 IGDteVDLS-PALKEG--EFDDWYELTL---KGRYAGEVYL 114
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
135-231 1.26e-05

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 44.99  E-value: 1.26e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRD-ISGTSDPFARVFWGSQSLETSTIKKTRFPHWD------EV--LELREmpgapSPLRVELWDWDM 205
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNsewfrfEVddEELQD-----EPLQIRVMDHDT 75
                         90       100       110
                 ....*....|....*....|....*....|
gi 578824333 206 VGKNDFLGMVEFSPKTLQQKPP----KGWF 231
Cdd:cd08688   76 YSANDAIGKVYIDLNPLLLKDSvsqiSGWF 105
RasGAP_RAP6 cd05129
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is ...
323-557 1.30e-05

Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is an endosomal protein with a role in the regulation of receptor-mediated endocytosis. RAP6 contains a Vps9 domain, which is involved in the activation of Rab5, and a Ras GAP domain (RGD). Rab5 is a small GTPase required for the control of the endocytic route, and its activity is regulated by guanine nucleotide exchange factor, such as Rabex5, and GAPs, such as RN-tre. Human Rap6 protein is localized on the plasma membrane and on the endosome. RAP6 binds to Rab5 and Ras through the Vps9 and RGD domains, respectively.


Pssm-ID: 213331  Cd Length: 365  Bit Score: 48.11  E-value: 1.30e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 323 LDYLTRREVARTMDPNTLFRSNSLA-SKSMEQFMKLV--GMPYLHEVL-KPVISRVFEEKKYMELDPCKM---------- 388
Cdd:cd05129   70 LRELMELQLKKSDNPRRLLRKGSCAfSRVFKLFTELLfsAKLYLTAALhKPIMQVLVDDEIFLETDPQKAlcrfspaeqe 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 389 -DLGRTRRISFKGALseEQMRETSLGLLTGYLGPIVDAIVGSVGRCPPAMRLAFKQLHR--RVEERFPQAEHQQDVKYLa 465
Cdd:cd05129  150 kRFGEEGTPEQQRKL--QQYRAEFLSRLVALVNKFISSLRQSVYCFPQSLRWIVRQLRKilTRSGDDEEAEARALCTDL- 226
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 466 isgfLFLRFFAPAILTPKLFDLRDQHADPQTSRS-LLLLAKAVQSIGNLGQQLGQG--KELWMAplhpFLLQCVSRvrdF 542
Cdd:cd05129  227 ----LFTNFICPAIVNPEQYGIISDAPISEVARHnLMQVAQILQVLALTEFESPDPrlKELLSK----FDKDCVSA---F 295
                        250
                 ....*....|....*
gi 578824333 543 LDRLVDVDGDEAGVP 557
Cdd:cd05129  296 LDVVIVGRAVETPPP 310
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
135-254 1.96e-05

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 45.47  E-value: 1.96e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPrdISGTSDPFARV--FWGSQSLETS---TIKKTRFPHWDEV----------------------LELR 187
Cdd:cd04010    2 LSVRVIECSDLAL--KNGTCDPYASVtlIYSNKKQDTKrtkVKKKTNNPQFDEAfyfdvtidsspekkqfempeedAEKL 79
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578824333 188 EmpgapspLRVELWDWDMVGKNDFLGMVE--FSPKTLQQKPPKGWFRLLPFPRAEEDSG------GNLGALRVKV 254
Cdd:cd04010   80 E-------LRVDLWHASMGGGDVFLGEVRipLRGLDLQAGSHQAWYFLQPREEKSTPPGtrsskdNSLGSLRLKI 147
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
9-85 2.34e-05

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 44.10  E-value: 2.34e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   9 VRVVEGRALPakdvSGSSDPYCLVKVDDEvVARTATVWRSLGPFWGEE--YTVHLPLD--FHQ-LAFYVLDEDTVGHDDI 83
Cdd:cd04011    8 VRVIEARQLV----GGNIDPVVKVEVGGQ-KKYTSVKKGTNCPFYNEYffFNFHESPDelFDKiIKISVYDSRSLRSDTL 82

                 ..
gi 578824333  84 IG 85
Cdd:cd04011   83 IG 84
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
138-223 2.38e-05

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 45.39  E-value: 2.38e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 138 HVLQARDLAPRDISGTSDPFARVFW-----GSQSLETSTIKKTRFPHWDEVL--------ELREMPgapspLRVELWDWD 204
Cdd:cd04020   32 WVKEAKNLPALKSGGTSDSFVKCYLlpdksKKSKQKTPVVKKSVNPVWNHTFvydgvspeDLSQAC-----LELTVWDHD 106
                         90
                 ....*....|....*....
gi 578824333 205 MVGKNDFLGMVEFSPKTLQ 223
Cdd:cd04020  107 KLSSNDFLGGVRLGLGTGK 125
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
135-217 2.80e-05

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 44.22  E-value: 2.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARVFW-GSQSLETSTIKKTRFPHWDEVLELREMPGapSPLRVELWDWDMVGKND--F 211
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRLPDPFAVITVdGGQTHSTDVAKKTLDPKWNEHFDLTVGPS--SIITIQVFDQKKFKKKDqgF 79

                 ....*.
gi 578824333 212 LGMVEF 217
Cdd:cd08382   80 LGCVRI 85
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
138-237 3.90e-05

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 43.86  E-value: 3.90e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 138 HVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELR-EMPGAPSPLRVELW---DWDMVGKNDFLG 213
Cdd:cd04022    5 EVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNvSDPSRLSNLVLEVYvynDRRSGRRRSFLG 84
                         90       100
                 ....*....|....*....|....
gi 578824333 214 MVEFSPKTLqqkPPKGWFRLLPFP 237
Cdd:cd04022   85 RVRISGTSF---VPPSEAVVQRYP 105
BTK smart00107
Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and ...
675-706 4.32e-05

Bruton's tyrosine kinase Cys-rich motif; Zinc-binding motif containing conserved cysteines and a histidine. Always found C-terminal to PH domains (but not all PH domains are followed by BTK motifs). The crystal structure shows this motif packs against the PH domain. The PH+Btk module pair has been called the Tec homology (TH) region.


Pssm-ID: 128417  Cd Length: 36  Bit Score: 41.21  E-value: 4.32e-05
                           10        20        30
                   ....*....|....*....|....*....|..
gi 578824333   675 NPNKLAACHPGAFRSARWTCCLQAERSAAGCS 706
Cdd:smart00107   1 NNNLLQKYHPSFWVDGKWLCCQQSEKNAPGCT 32
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
118-215 5.87e-05

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


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 43.73  E-value: 5.87e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 118 GEICLSVQMLEDGqGRcLRCHVLQARDLAPRDISGTSDPFARVFWGS-----QSLETSTIKKTRFPHWDEVLELREMPGA 192
Cdd:cd08410    1 GELLLSLNYLPSA-GR-LNVDIIRAKQLLQTDMSQGSDPFVKIQLVHglkliKTKKTSCMRGTIDPFYNESFSFKVPQEE 78
                         90       100
                 ....*....|....*....|....*
gi 578824333 193 PS--PLRVELWDWDMVGKNDFLGMV 215
Cdd:cd08410   79 LEnvSLVFTVYGHNVKSSNDFIGRI 103
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
5-90 5.91e-05

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 43.49  E-value: 5.91e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   5 SSLNVRVVEGRALPAKDV-SGSSDPYclVKV----DDEVVARTATVWRSLGPFWGEEYTV----HLPLDFHQLAFYVLDE 75
Cdd:cd08388   16 KALLVNIIECRDLPAMDEqSGTSDPY--VKLqllpEKEHKVKTRVLRKTRNPVYDETFTFygipYNQLQDLSLHFAVLSF 93
                         90
                 ....*....|....*
gi 578824333  76 DTVGHDDIIGKISLS 90
Cdd:cd08388   94 DRYSRDDVIGEVVCP 108
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
135-256 6.27e-05

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


Pssm-ID: 175986 [Multi-domain]  Cd Length: 150  Bit Score: 43.81  E-value: 6.27e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARVFWGSQSLETSTIK-KTRFPHWDEVLelreMPGAPSP------LRVElwdwDMVG 207
Cdd:cd04019    2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPSQtRNGNPSWNEEL----MFVAAEPfedhliLSVE----DRVG 73
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 578824333 208 KN--DFLGMV-----EFSPKTLQQKPPKGWFRLLPFPRAEEDSGGNLGALRVKVRL 256
Cdd:cd04019   74 PNkdEPLGRAviplnDIERRVDDRPVPSRWFSLERPGGAMEQKKKRKFASRIHLRL 129
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
142-244 7.31e-05

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 46.68  E-value: 7.31e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  142 ARDLAPRDISGTSDPFARVFWGSQSL-ETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVGKNDFLGMVEFSPK 220
Cdd:COG5038  1049 GENLPSSDENGYSDPFVKLFLNEKSVyKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLS 1128
                          90       100
                  ....*....|....*....|....
gi 578824333  221 TLQQKPPKGWFRLLPFPRAEEDSG 244
Cdd:COG5038  1129 KLEPGGTTNSNIPLDGKTFIVLDG 1152
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
139-220 7.33e-05

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 43.19  E-value: 7.33e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 139 VLQARDLAPRDISGTSDPFARV--FWGSQSL---ETSTIKKTRFPHWDE--VLELREMPGAPSPLRVELWDWDMVGKNDF 211
Cdd:cd08404   21 VLKARHLPKMDVSGLADPYVKVnlYYGKKRIskkKTHVKKCTLNPVFNEsfVFDIPSEELEDISVEFLVLDSDRVTKNEV 100

                 ....*....
gi 578824333 212 LGMVEFSPK 220
Cdd:cd08404  101 IGRLVLGPK 109
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
2-107 8.29e-05

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


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 43.01  E-value: 8.29e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   2 AKSSSLNVRVVEGRALPAKDVSGSSDPYclVKV------DDEVVARTATVWRSLGPFWGE--EYTVHLPLDF--HQLAFY 71
Cdd:cd04031   13 KVTSQLIVTVLQARDLPPRDDGSLRNPY--VKVyllpdrSEKSKRRTKTVKKTLNPEWNQtfEYSNVRRETLkeRTLEVT 90
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 578824333  72 VLDEDTVGHDDIIGK--ISLSREAITADPRgidsWINL 107
Cdd:cd04031   91 VWDYDRDGENDFLGEvvIDLADALLDDEPH----WYPL 124
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
6-75 8.92e-05

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 42.68  E-value: 8.92e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578824333   6 SLNVRVVEGRALPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHL-PLDFhqLAFYVLDE 75
Cdd:cd08382    1 KVRLTVLCADGLAKRDLFRLPDPFAVITVDGGQTHSTDVAKKTLDPKWNEHFDLTVgPSSI--ITIQVFDQ 69
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
4-90 1.38e-04

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 42.26  E-value: 1.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   4 SSSLNVRVVEGRaLPAKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHL-PldFHQLAFYVLDEDTVGHDD 82
Cdd:cd04021    1 KSQLQITVESAK-LKSNSKSFKPDPYVEVTVDGQPPKKTEVSKKTSNPKWNEHFTVLVtP--QSTLEFKVWSHHTLKADV 77

                 ....*...
gi 578824333  83 IIGKISLS 90
Cdd:cd04021   78 LLGEASLD 85
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
19-125 2.04e-04

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 41.43  E-value: 2.04e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  19 AKDVSGSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPlDFH--QLAFYVLDeDTVGHDDIIGKISLS-REAIT 95
Cdd:cd04052    6 SESKTGLLSPYAELYLNGKLVYTTRVKKKTNNPSWNASTEFLVT-DRRksRVTVVVKD-DRDRHDPVLGSVSISlNDLID 83
                         90       100       110
                 ....*....|....*....|....*....|
gi 578824333  96 ADPRGiDSWINLSRVDpdaevQGEICLSVQ 125
Cdd:cd04052   84 ATSVG-QQWFPLSGNG-----QGRIRISAL 107
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
118-185 2.20e-04

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 41.87  E-value: 2.20e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 578824333 118 GEICLSVQMleDGQGRCLRCHVLQARDLAPRDISGTSDPFARVF------WGSQSlETSTIKKTRFPHWDEVLE 185
Cdd:cd04030    3 GRIQLTIRY--SSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYllpdksKSTRR-KTSVKKDNLNPVFDETFE 73
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
139-244 2.52e-04

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 41.48  E-value: 2.52e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 139 VLQARDLAPRDISGTSDPFARVFWGSQS---LETSTIKKTRFPHWDEVLELREMPGAPSPLRVELWDWDMVgKNDFLGMV 215
Cdd:cd04036    6 VLRATNITKGDLLSTPDCYVELWLPTASdekKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDDHLGTV 84
                         90       100
                 ....*....|....*....|....*....
gi 578824333 216 EFSPKTLqqkpPKGWFRLLPFPRAEEDSG 244
Cdd:cd04036   85 LFDVSKL----KLGEKVRVTFSLNPQGKE 109
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
152-213 3.21e-04

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 41.09  E-value: 3.21e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 578824333 152 GTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLE--LREMPGAPSPLRVELWDWDMVGKNDFLG 213
Cdd:cd08373   13 GKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEwpLAGSPDPDESLEIVVKDYEKVGRNRLIG 76
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
7-87 3.30e-04

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


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 41.41  E-value: 3.30e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKVDDEV----VARTATVWRSLGPFWGEEYTVHLP---LDFHQLAFYVLDEDTVG 79
Cdd:cd08410   16 LNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLklikTKKTSCMRGTIDPFYNESFSFKVPqeeLENVSLVFTVYGHNVKS 95

                 ....*...
gi 578824333  80 HDDIIGKI 87
Cdd:cd08410   96 SNDFIGRI 103
PLN03008 PLN03008
Phospholipase D delta
25-165 3.63e-04

Phospholipase D delta


Pssm-ID: 178585 [Multi-domain]  Cd Length: 868  Bit Score: 44.31  E-value: 3.63e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  25 SSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDTVGHdDIIGKISLSREAITADPRgIDSW 104
Cdd:PLN03008  76 TSDPYVTVVVPQATLARTRVLKNSQEPLWDEKFNISIAHPFAYLEFQVKDDDVFGA-QIIGTAKIPVRDIASGER-ISGW 153
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 578824333 105 ---INLSRVDPDAEVQgeICLSVQMLEDGQGRCLRCHVlqARDLAPRDISGTSDPFARvfwGSQ 165
Cdd:PLN03008 154 fpvLGASGKPPKAETA--IFIDMKFTPFDQIHSYRCGI--AGDPERRGVRRTYFPVRK---GSQ 210
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
134-226 4.21e-04

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 41.00  E-value: 4.21e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 134 CLRCHVLQARDLAPRD-ISGTSDPFArVFWGSQSLE---TSTIKKTRFPHWDEVL-----ELREmpgapsPLRVELWDWD 204
Cdd:cd04044    3 VLAVTIKSARGLKGSDiIGGTVDPYV-TFSISNRRElarTKVKKDTSNPVWNETKyilvnSLTE------PLNLTVYDFN 75
                         90       100
                 ....*....|....*....|..
gi 578824333 205 MVGKNDFLGMVEFSPKTLQQKP 226
Cdd:cd04044   76 DKRKDKLIGTAEFDLSSLLQNP 97
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
7-93 6.77e-04

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175998 [Multi-domain]  Cd Length: 127  Bit Score: 40.32  E-value: 6.77e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAkDVSGSSDPYCLVKVDDEVVaRTATVWRSLGPFWGEEY---TVHLPLdFHQLAFYVLDEDTVGHDDI 83
Cdd:cd04032   30 LTVTVLRATGLWG-DYFTSTDGYVKVFFGGQEK-RTEVIWNNNNPRWNATFdfgSVELSP-GGKLRFEVWDRDNGWDDDL 106
                         90
                 ....*....|
gi 578824333  84 IGKISLSREA 93
Cdd:cd04032  107 LGTCSVVPEA 116
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
135-215 8.04e-04

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 39.94  E-value: 8.04e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 135 LRCHVLQARDLAPRDISGTSDPFARVFW---GSQSLETSTIKKTRFPHWDEVL-------ELREmpgapSPLRVELWDWD 204
Cdd:cd08385   18 LTVGIIQAADLPAMDMGGTSDPYVKVYLlpdKKKKFETKVHRKTLNPVFNETFtfkvpysELGN-----KTLVFSVYDFD 92
                         90
                 ....*....|.
gi 578824333 205 MVGKNDFLGMV 215
Cdd:cd08385   93 RFSKHDLIGEV 103
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
24-108 1.00e-03

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 40.37  E-value: 1.00e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  24 GSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEYTVHLPLDFHQLAFYVLDEDTVGhDDIIGKISLSREAItADPRGIDS 103
Cdd:cd04015   56 ITSDPYATVDLAGARVARTRVIENSENPVWNESFHIYCAHYASHVEFTVKDNDVVG-AQLIGRAYIPVEDL-LSGEPVEG 133

                 ....*
gi 578824333 104 WINLS 108
Cdd:cd04015  134 WLPIL 138
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
139-222 1.04e-03

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 39.86  E-value: 1.04e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 139 VLQARDLAPRDISGTSDPFARVFWGSQSLETSTIKKTRFPHWDEVLELrEMPGAPSPLRVELWDWDMVGK---------- 208
Cdd:cd04027    7 VVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHF-ECHNSSDRIKVRVWDEDDDIKsrlkqkftre 85
                         90
                 ....*....|....*
gi 578824333 209 -NDFLGMVEFSPKTL 222
Cdd:cd04027   86 sDDFLGQTIIEVRTL 100
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
5-57 1.08e-03

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176045 [Multi-domain]  Cd Length: 126  Bit Score: 39.66  E-value: 1.08e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 578824333   5 SSLNVRVVEGRALPAKDVsgsSDPYCLVKVDDEVVARTaTVWRSLGPFWGEEY 57
Cdd:cd08400    4 RSLQLNVLEAHKLPVKHV---PHPYCVISLNEVKVART-KVREGPNPVWSEEF 52
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
19-90 1.37e-03

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 39.11  E-value: 1.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  19 AKDVS-----GSSDPYCLVKVDDEVVARTATVWRSLGPFWGEEY--TVHLPldfHQ-LAFYVLDEDTVGHDDIIGKISLS 90
Cdd:cd04045   10 ANDLKnlegvGKIDPYVRVLVNGIVKGRTVTISNTLNPVWDEVLyvPVTSP---NQkITLEVMDYEKVGKDRSLGSVEIN 86
PH_MELT_VEPH1 cd01264
Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone ...
589-673 1.77e-03

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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: 269965  Cd Length: 105  Bit Score: 38.59  E-value: 1.77e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 589 FKKRYVWLSGETLSFSKSPEWQMCHSIPVSHIRAVERVDEGAFQLPHVMQVVTQDgtgalhTTY-LQCKNVNELNQWLSA 667
Cdd:cd01264   21 WRTRYFTLSGAQLSYRGGKSKPDAPPIELSKIRSVKVVRKKDRSIPKAFEIFTDD------KTYvLKAKDEKNAEEWLQC 94

                 ....*.
gi 578824333 668 LRKASA 673
Cdd:cd01264   95 LSIAVA 100
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
117-233 1.91e-03

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 38.81  E-value: 1.91e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 117 QGEICLSVQMlEDGQgrcLRCHVLQARDLAPRDisGTS-DPFARVF----WGSQS-LETSTIKKTRFPHWDEVLELREMP 190
Cdd:cd08381    1 GGQVKLSISY-KNGT---LFVMVMHAKNLPLLD--GSDpDPYVKTYllpdPQKTTkRKTKVVRKTRNPTFNEMLVYDGLP 74
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 578824333 191 GA---PSPLRVELWDWDMVGKNDFLGMVEFSPKTLQ-QKPPKGWFRL 233
Cdd:cd08381   75 VEdlqQRVLQVSVWSHDSLVENEFLGGVCIPLKKLDlSQETEKWYPL 121
C2D_MCTP_PRT_plant cd08379
C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
14-58 2.08e-03

C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 176025 [Multi-domain]  Cd Length: 126  Bit Score: 38.93  E-value: 2.08e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 578824333  14 GRALPAKDVSGSSDPYCLVKVDDEVVaRTATVWRSLGPFWGEEYT 58
Cdd:cd08379   12 LDVLRAKDGRGSTDAYCVAKYGPKWV-RTRTVEDSSNPRWNEQYT 55
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
138-230 2.21e-03

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


Pssm-ID: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 38.39  E-value: 2.21e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 138 HVLQARDLAP-RDISGTS---DPFARVFWGSQSLETSTIKKTRFPHWDEVLELREMPGAPS-PLRVELWDWDMVGKNDFL 212
Cdd:cd04039    6 EIKSITDLPPlKNMTRTGfdmDPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVYPHEKNfDIQFKVLDKDKFSFNDYV 85
                         90       100
                 ....*....|....*....|...
gi 578824333 213 GMVEFSPKTL-----QQKPPKGW 230
Cdd:cd04039   86 ATGSLSVQELlnaapQPDPETGL 108
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
570-668 2.68e-03

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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: 269975  Cd Length: 106  Bit Score: 37.98  E-value: 2.68e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 570 EGYLLkRK---EEPAGLATRFAFKKRYVWLSGETLSF---SKSPEWQMCHSI--PVSHIRAVERVDEGAFQLPHVMQVVT 641
Cdd:cd10571    2 EGFLE-RKhewESGGKKASNRSWKNVYTVLRGQELSFykdQKAAKSGITYAAepPLNLYNAVCEVASDYTKKKHVFRLKL 80
                         90       100
                 ....*....|....*....|....*..
gi 578824333 642 QDGTGALhttyLQCKNVNELNQWLSAL 668
Cdd:cd10571   81 SDGAEFL----FQAKDEEEMNQWVKKI 103
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
118-217 3.81e-03

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 38.01  E-value: 3.81e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 118 GEICLSVQM-LEDGQgrcLRCHVLQARDLAPRDI-SGTSDPFARVFW---GSQSLETSTIKKTRFPHWDE-------VLE 185
Cdd:cd08390    1 GRLWFSVQYdLEEEQ---LTVSLIKARNLPPRTKdVAHCDPFVKVCLlpdERRSLQSKVKRKTQNPNFDEtfvfqvsFKE 77
                         90       100       110
                 ....*....|....*....|....*....|..
gi 578824333 186 LREmpgapSPLRVELWDWDMVGKNDFLGMVEF 217
Cdd:cd08390   78 LQR-----RTLRLSVYDVDRFSRHCIIGHVLF 104
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
7-87 4.27e-03

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 38.01  E-value: 4.27e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333   7 LNVRVVEGRALPAKDVSGSSDPYCLVKV---DDEvVARTATVWRSLGPFWGEeyTVHLPLDFHQ---LAFYVLDEDTVgH 80
Cdd:cd04036    2 LTVRVLRATNITKGDLLSTPDCYVELWLptaSDE-KKRTKTIKNSINPVWNE--TFEFRIQSQVknvLELTVMDEDYV-M 77

                 ....*..
gi 578824333  81 DDIIGKI 87
Cdd:cd04036   78 DDHLGTV 84
PH_Osh3p_yeast cd13289
Yeast oxysterol binding protein homolog 3 Pleckstrin homology (PH) domain; Yeast Osh3p is ...
570-671 4.53e-03

Yeast oxysterol binding protein homolog 3 Pleckstrin homology (PH) domain; Yeast Osh3p is proposed to function in sterol transport and regulation of nuclear fusion during mating and of pseudohyphal growth as well as sphingolipid metabolism. Osh3 contains a N-GOLD (Golgi dynamics) domain, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. GOLD domains are thought to mediate protein-protein interactions, but their role in ORPs are unknown. 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: 241443  Cd Length: 90  Bit Score: 36.85  E-value: 4.53e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 570 EGYLLKRKEEPAGlatrfAFKKRYVWLSGE--TLSFSKSPEWQMCHSIPVSH--IRAVER-----VDEGafqlphvmqvv 640
Cdd:cd13289    3 EGWLLKKRRKKMQ-----GFARRYFVLNFKygTLSYYFNPNSPVRGQIPLRLasISASPRrrtihIDSG----------- 66
                         90       100       110
                 ....*....|....*....|....*....|.
gi 578824333 641 tqdgtgaLHTTYLQCKNVNELNQWLSALRKA 671
Cdd:cd13289   67 -------SEVWHLKALNDEDFQAWMKALRKF 90
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
12-90 4.69e-03

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 37.55  E-value: 4.69e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333  12 VEGRALPAKDVSGSSDPYcLV--KVDDE----VVARTATVWRSLGPFWGEeytVHLPLD-------FHQLAFYVLDEDTV 78
Cdd:cd04047    7 FSGKKLDKKDFFGKSDPF-LEisRQSEDgtwvLVYRTEVIKNTLNPVWKP---FTIPLQklcngdyDRPIKIEVYDYDSS 82
                         90
                 ....*....|..
gi 578824333  79 GHDDIIGKISLS 90
Cdd:cd04047   83 GKHDLIGEFETT 94
PH_Bem3 cd13277
Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...
568-668 7.23e-03

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. 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: 270096  Cd Length: 111  Bit Score: 36.88  E-value: 7.23e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578824333 568 VREGYLLKRKEEPAGLATRfaFKKRYVWLSGETLSFSKSPEWQMCHSIPVSH--IRAVERVDEGAFQLPHVMQVVTQDGT 645
Cdd:cd13277    4 VKEGYLLKRRKKTLGSTGG--WKLRYGVLDGNILELYESRGGQLLESIKLRNaqIERQPNLPDDKYGTRHGFLINEHKKS 81
                         90       100
                 ....*....|....*....|....*
gi 578824333 646 GALHTT--YLQCKNVNELNQWLSAL 668
Cdd:cd13277   82 GLSSTTkyYLCAETDKERDEWVSAL 106
 
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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