2R83,1BYN,1DQV,3F04,3F00,1RSY,3HN8


Conserved Protein Domain Family
C2A_Synaptotagmin-1-5-6-9-10

?
cd08385: C2A_Synaptotagmin-1-5-6-9-10 
Click on image for an interactive view with Cn3D
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.
Statistics
?
PSSM-Id: 176031
Aligned: 30 rows
Threshold Bit Score: 220.985
Created: 15-Sep-2009
Updated: 2-Oct-2020
Structure
?
Program:
Drawing:
Aligned Rows:
 
Ca2+ binding
Conserved site includes 5 residues -Click on image for an interactive view with Cn3D
Feature 1:Ca2+ binding site [ion binding site]
Evidence:
  • Structure:1BYN; Rat C2 domain Synaptotagmin C2 domain binds 3 Ca2+
  • Citation:PMID 9819203
  • Structure:1DQV_A; Rat Synaptotagmin C2 domain binds 3 Mg2+
  • Citation:PMID 9665851

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1                                        #     #                                          
2R83_A          4 KLGKLQYSLDYDFQnNQLLVGIIQAAELPALDmgGTSDPYVKVFLLPDkKKKFETKVHRKtLNPVFNEQFTFKVpy-sEL 82   human
1BYN_A          2 KLGKLQYSLDYDFQnNQLLVGIIQAAELPALDmgGTSDPYVKVFLLPDkKKKFETKVHRKtLNPVFNEQFTFKVpy-sEL 80   Norway rat
1DQV_A          5 PCGRISFALRYLYGsDQLVVRILQALDLPAKDsnGFSDPYVKIYLLPDrKKKFQTKVHRKtLNPIFNETFQFSVpl-aEL 83   black rat
CAI20910      319 TCGKLSFALSYDYEeQALVVRILKALDLPAKDftGTSDPYVKIYLLPErKKKFQTRVHRKtLNPTFDEDFRFPVey-sEL 397  zebrafish
XP_698786     106 QRGKLQYSLEFNASrSELTVGIKEAAALKAMDsgGTSDPYVKVYILPNkSKTFETKVFRKtLNPVFNENFKYQIpq-kEL 184  zebrafish
AAI21382      247 SCGRISFILRYAYNsEQLVVKILKALELPAKDanGFSDPYVKMYLLPDrKKKFQTKVHRKtLNPIFNETFHFNVpf-nEL 325  western clawe...
XP_001187868 1128 NCGRLVFSLFYDYAtETLNVHIERAVGLPAKDfsGTSDPYVKIYLCPDrKRKYQTKVHRKnCDPVFDERFAFQIpy-nEL 1206 purple urchin
XP_416361     230 TCGKLNFTLRYDYEnELLAVTIVKALDLPAKDftGTSDPYVKIYLLPDrKKKFQTRVHRKtLNPVFDETFQFPVay-dQL 308  chicken
XP_001623846   83 KIGRINFTLDYSFTdNTLTVGIIRAEDIPAKDfsGSSDPYVKIMLLPDkKKKYETKVHRKtLNPVFNEQFVFKNipysEI 162  starlet sea a...
EEB19763      143 YCGKLHLALRYDSEiEGLVVKVLEARDLPIKDvtGSSDPYVKVYLLPDrKKKFQTKVHRKnLNPVFNETFIFSVsy-dDL 221  human body louse
Feature 1                   # #     #                            
2R83_A         83 AGKTLVMAVYDFDRFskHDIIGEFKVPMNTVdf--ghVTEEWRDLQS 127  human
1BYN_A         81 GGKTLVMAVYDFDRFskHDIIGEFKVPMNTVdf--ghVTEEWRDLQS 125  Norway rat
1DQV_A         84 AQRKLHFSVYDFDRFsrHDLIGQVVLDNLLElaeqppDRPLWRDILE 130  black rat
CAI20910      398 CNRKLHFSVYDFDRFtsHDMIGEVVVDNLFElsdlsrEAVVWKDILA 444  zebrafish
XP_698786     185 TESTLVMQVYDFNRFskHDIIGEIRLNLSTVdw--nhVIEEWRDLSE 229  zebrafish
AAI21382      326 QNRKLHFSIYDFDRFsrHDLIGQVVLDNLLEfsnatdETPIWRDILE 372  western clawed frog
XP_001187868 1207 ESKTLKFTVYDFDRFsrHDLIGEVNITSLLTdrdlskETQYVEDIMK 1253 purple urchin
XP_416361     309 SNRKLHFSVYDFDRFsrHDMIGEVILDNLFEvsdlsrEANVWKDIHC 355  chicken
XP_001623846  163 TNRILLMELFDFDRFsrHDLIGEARLPLIDVdl--asNINEWRVLTP 207  starlet sea anemone
EEB19763      222 QKRYLQFSVYDFDRFsrHDLIGQVVLKGLLD------ASDLHQEIEY 262  human body louse

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap