2ENP


Conserved Protein Domain Family
C2A_Synaptotagmin-15-17

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cd08390: C2A_Synaptotagmin-15-17 
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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.
Statistics
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PSSM-Id: 176036
View PSSM: cd08390
Aligned: 20 rows
Threshold Bit Score: 157.033
Threshold Setting Gi: 156390630
Created: 14-Sep-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
2ENP_A        13 GMLHFSTQYDLLhNHLTVRVIEARDLPPpishdg----srqdmAHSNPYVKICLLPDqKNSKQTGVKRKtQKPVFEERYT 88  human
XP_787981    199 GKIHYALKYEVNeGRLNVRIIKARDLPPpmfyds----skqdlSHSNPYVKVCLLPDqKDARQTSVKRKtQNPNFEESFC 274 purple urchin
XP_001922508 335 GMLHFSTQYDLInAHLIVRVIEARDLPPpvtcdg----arqdmAHSNPYVKMSLLPDnKNSRQTGVKRKtQNPVFEERFT 410 zebrafish
XP_001635373   3 GQVHFTVQYDIRrTVLTVRLIKAINLSPldg---------ewsKPCNPFAIVQLQPDyQHQLQSYVQRKtTNPNFDETFE 73  starlet sea ane...
NP_001096478 186 GMLHFSTQYDLLhNYLNVRVIEARDLPPpisydg----srqdmAHSNPYVKICLLPDqKNSKQTGVKRKtQNPVFEERYT 261 western clawed ...
XP_414910    448 GMLHFSTQYDLLhNYLIVRVIEAKDLPPpisydg----srqdmAHSNPYVKICLLPDqKNSKQTGVKRKtQNPVFEERYT 523 chicken
XP_002157004 133 GRIYFNLEYLAQsEKLVVTVDRIRNLLGrnas-------asqsTTCDPFIRLYLLPDeKRYLQSKMKRKtRHPVFKETFI 205 green hydra
XP_001625188   2 GTLLFEARYQKYeEQLTIHLIGAKRLPVrhhvidvgdcphydvMPCDPKVLVCLLPDeKPVLESYVKQStWDPNFDETFV 81  starlet sea ane...
XP_002607084 246 GQLYFNFHYNLIhSVFIVTVREARNLPFpmigde----trqdfAHSNPYVKVCLLPDqKSAKQTSVKPKtQNPEFNETFK 321 Florida lancelet
XP_002596512 158 GQLDFAVQHKVEeKQLEVYLIKAERLTPrt-----------skELRDPYVIVKLLPDiGRRKQSKIILDdLHPDFDEMFT 226 Florida lancelet
2ENP_A        89 FEIpflEAQRRTLLLTVVDFDKFs-rHCVIGKVSVPLCEVdlvkGGHWWKALIP 141 human
XP_787981    275 FNIphqEAQRRMLLLSVQDFDKFs-rHCVIGQHTVPLAGLnlvkGGHYWKPLQP 327 purple urchin
XP_001922508 411 FDLpflEAQRRTLLLSVVDFDKFs-rHCVIGKVALPLSEVdlvkGGHWWKALVP 463 zebrafish
XP_001635373  74 FEVlvqELQRLSLCITLHSFDTFa-sHDIIGQALLPLADLdlnkENIYITDLRP 126 starlet sea anemone
NP_001096478 262 FEIqflEAQRRTLLLTIVDFDKFs-rHCVIGKVAMPLNEVdlvkGGHWWKAIIP 314 western clawed frog
XP_414910    524 FEIpflEAQRRTLLLTVVDFDKFs-rHCVIGKVSMPLGDVdlvkGGHWWKALVP 576 chicken
XP_002157004 206 YTMsysLLIERTLRITVFDVDRFm-rQNIIGHALYPLSDLdvtmVTEVSRDVEK 258 green hydra
XP_001625188  82 FKLntnEVKEKTLRFSVYDCTRLh-kLCPIGHTLFSLKGQdldgTMAVERAIKP 134 starlet sea anemone
XP_002607084 322 FEIpflEVQRRMLLLSLQDYDKFs-rHCVIGQVILPLENYdllkVSNVWKPLQP 374 Florida lancelet
XP_002596512 227 FDIdgeDIRTLTLKFHVMDAGGKrkrRQEIGHVTFPLAGNdwsvQQEFWMNIVK 280 Florida lancelet
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