Conserved Protein Domain Family
C2A_Synaptotagmin-8

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cd08387: C2A_Synaptotagmin-8 
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.
Statistics
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PSSM-Id: 176033
View PSSM: cd08387
Aligned: 7 rows
Threshold Bit Score: 210.723
Threshold Setting Gi: 156547611
Created: 6-Jan-2010
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
putative Ca2+
Feature 1:putative Ca2+ binding site [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                       #     #                                          
XP_001658196 231 SRGAIHLTLNYDPSAGILNVKLIEAQDLQPRDFSGTADPYAKIRLlpdrnnMWQTRIHKktlNPVFDEDFVFEvrpat-i 309 yellow fever mo...
XP_790149    153 TLGIMNFSLKYNSEMGLLTVRLIQARNLQPRDFSGTADPYCKVCViphaskTLQSKVHRktvLPEFRESFVFEipeie-i 231 purple urchin
XP_001603471 190 TRGELQMSITYDAPDGILNVKLVEARDLRARDLSETADPYAKIRLlpdrstVKQTRIHKktlNPEFDEDFVFQvapncql 269 jewel wasp
XP_002128383 145 RPPQVFFSIEFDKNFNILKIFVNQARYLKPRTYTSMCDPYCTVNLlpg-htEKQSQVMRrtmDPLFQEHFSFGvpiqe-l 222 Ciona intestinalis
NP_609853    208 VRGNLHVSLGYDPVGGLLNVRLLEAQNLQPRQFSGTADPYAKVRLlpdkknFWQTRIHKrtlNPVFDEQFVFEvtagv-i 286 fruit fly
XP_002126514 344 DTPMIHFDVSYNGDLEVLNVKLIQARNLATQDFSGTSDPYCTVALvpg-fnPRRSKVHKktsNPEFGESFVFSvssdn-l 421 Ciona intestinalis
XP_002609348  10 YAGELHFALHYNKDMGILTIRLIQARDLQPREFSGTADPYFKISVlpdeprTLQSKIHRktlDPEFEEKFAFEipptd-l 88  Florida lancelet
Feature 1                  # #     #                            
XP_001658196 310 grrTLEVLLFDFDaYSRHVIIGGSQLALAHVDlsd--rlDIWRPLGP 354 yellow fever mosquito
XP_790149    232 hrqTVRVYLYDYDqFSRDECIGVVELPLAHVDlte--klEVWKGIRA 276 purple urchin
XP_001603471 270 aerTLEVLLYDFDaSSKHRGLGYVQIPLSTVTdlglepkTLTKSVMR 316 jewel wasp
XP_002128383 223 pkkKLQIKFFNYDqFSRDEFTGIVEQKLDEINlda--kvDLWRKIQN 267 Ciona intestinalis
NP_609853    287 dkrTVEILLYDFDaYSRHVCIGGSKLHLANLDlse--qlKLWTPLSS 331 fruit fly
XP_002126514 422 edkVLQVKTYDFDqFSRDECTGVMELNLKEIDfvmtpniDLWRKMKF 468 Ciona intestinalis
XP_002609348  89 pnrTIRFLLFDYDqFSRDECVGQVLLPLENVDlse--rvELWKMIES 133 Florida lancelet

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