Conserved Protein Domain Family
C2A_Synaptotagmin-like

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cd04024: C2A_Synaptotagmin-like 
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.
Statistics
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PSSM-Id: 175990
View PSSM: cd04024
Aligned: 11 rows
Threshold Bit Score: 157.971
Threshold Setting Gi: 91083275
Created: 3-Jan-2005
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
putative Ca2+
Feature 1:putative Ca2+ binding pocket [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                         #         #                                               # #   
CAG80553       22 VFLRVHLIQARGIAPRDre--knTKCEPYAVLSCGdfRFTTHTIHNSVDPDWNCWIDIPVrs--gDESLDLVVWDRIRF- 96   Yarrowia lipo...
NP_733010     315 GILRIHVVEAKDLMKKDisvlgkGKSDPYAIINVGaqEFKTQIIDNNVNPKWDYWCEATVfi-emGQFVEIQLKDSDDSk 393  fruit fly
XP_974354     294 GVLRVHVFEAKDLMAKDi----tGKSDPYVILYVGaqERKSNTVNQCLNPKWDYWCEFVIid-pkAQHLGFKLYDRDNVn 368  red flour beetle
XP_974330     290 GILRVHVVEAKNLVNRDl----iGKSDPYVVLSCGsiRVETPVVENCLNPKWDFWTNFEIe---pNSELKIEVWDKDEGs 362  red flour beetle
XP_001943644  313 GVLRVHIFQAKNLVAKDmslirkGKSDPYVIVTLGaqQYKTHTINNELNPKWDYWCEFASfs-prGQVLKLKLYDEDEMv 391  pea aphid
XP_367112      47 LVLNIVILRGRNLAAKDr----sGTSDPYLVLNCGdsKHVTATVSKSLNPEWNEQCEFPIng-aqHLLLDVCAWDKDRF- 120  Magnaporthe g...
EEC12286      317 GVLRLEVVAAKDLVKADigmlglGKSDPYAIITVGaqEFRTQVIPSTVNPKWNFYCEVSHfs-hiCPILKCFLKLFIYLf 395  black-legged ...
EAA62952       40 LVLKVSVLRGRNLAAKDr----gGTSDPYLIVTLGeaRQSTPTIFKTLNPEWNVTFEMPVv---gVPLLECICWDHDRF- 111  Aspergillus n...
XP_961616      42 LVLDVKIIQARNLAAKDr----gGTSDPYLVLTLGdaKYTTSTIPKTLDPIWNEHYQFPIns-aqSLSLTGICWDKDRF- 115  Neurospora cr...
XP_001843295  354 GVLRIHVVEAKDLMKKDigvlgkGKSDPYTIVSVGaqQFRTQTIDNTVNPKWDYWCEWLTleqakHGLIHLRLTWFTLSa 433  southern hous...
XP_390183      57 LALRVWIIRGKDLAAKDrsg-tsDPPPQYIIVSTGesRIVTNDVPKTLNPEWNVSEEIPLts-vqNLLLSVICWDKDRF- 133  Gibberella ze...
Feature 1             #                                                               
CAG80553       97 --NKDYLGEVAIPLKDMfhkgvtEIETPVQWFPLhstrsk-------------aagyvsGDVSLQFSL 149  Yarrowia lipolytica CLIB99
NP_733010     394 --KDENLGRASIDIASVi-----KKGVVDSWLTLeda--------------------khGLLHVRLQW 434  fruit fly
XP_974354     369 --EDDFLGSGEVDIASV------LKGQTDQWITLdsa--------------------khGAIHLRFTW 408  red flour beetle
XP_974330     363 --KDDSLGQYCFSAKINvaq-vaKIGQSDMPIALqgv--------------------tkGRIYIRLTW 407  red flour beetle
XP_001943644  392 gkKHSNLGRASIQIGNVa-----KTGYFDKWINLedt--------------------khGMIHVRMLW 434  pea aphid
XP_367112     121 --GKDYMGEFDLALEEIfl--deKTEQPPKWYPLkskrpgk------------ktsvvsGEVLLQFTI 172  Magnaporthe grisea 70-15
EEC12286      396 keGENPLGGRCDSFCASa----pPSRVSVSWLTLddt--------------------ksGKIRLRTFW 439  black-legged tick
EAA62952      112 --GKDYLGEFDIALEDIft--dgEIQQQPKWYTLksnrkpgk----------rkdnnvsGEILLQFSL 165  Aspergillus nidulans FGSC A4
XP_961616     116 --GKDYLGEFELALDEAfae-dgITDLGPGWIPLkskrtgk------------kssvvsGEVELQLTI 168  Neurospora crassa OR74A
XP_001843295  434 --EKNDLKAALEETQLLr-----VTSMSTALLTVfidsaknlpqarqqsqpdpymilsvGKKTEQTSV 494  southern house mosquito
XP_390183     134 --GKDYMGEFDLALEEIfn--ngKVEQQPTWYRLkskrpgk------------ktsvvsGEVQLQFSL 185  Gibberella zeae PH-1

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