2D8K


Conserved Protein Domain Family
C2A_Synaptotagmin-7

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cd08386: C2A_Synaptotagmin-7 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 176032
View PSSM: cd08386
Aligned: 12 rows
Threshold Bit Score: 224.902
Threshold Setting Gi: 71981445
Created: 15-Dec-2009
Updated: 2-Oct-2020
Structure
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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:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                        #     #                                         
2D8K_A        11 NLGRIQFSVGYNFQe-STLTVKIMKAQELPAKDfsGTSDPFVKIYLLPDkKHKLETKVKRKnLNPHWNETFLFEGfpyeK 89  human
CAG08772      33 KLGRIQFSIGYSFQn-TTLTVKVLRGQELPAKDfsGTSDPFVKIYLLPDkKHKLETKVKRKnLNPHWNETFLFEGfpyeK 111 Tetraodon nigro...
NP_001014686 147 NVGQIHFSLEYDFQn-TTLILKVLQGKELPAKDlsGTSDPYVRVTLLPDkKHRLETKIKRRtLNPRWNETFYFEGfpiqK 225 fruit fly
XP_001191249 134 ELGKIQFSLMYDFPd-QTLVLRIVKANHLPAKDfsGTSDPFVKIMLLPDkKVKMETKVKRKnLNPIWNESFHFEGypysK 212 purple urchin
NP_001072834 378 NLGRIQFSVGYNFQe-STLTVKILKAQELPAKDfsGTSDPFVKIYLLPDkKHKLETKVKRKnLNPHWNETFLFEGfpyeK 456 western clawed ...
XP_001635767   2 QLGKIFFSLTYYSSd-SVLTLKVLKAQGLPAKDfsGTSDPFVKIMLLPDkKHKLETRVKRKnLNPVWNEVFTFEGfphnK 80  starlet sea ane...
XP_002117784 106 DLGSIQFSLSYDYSk-MTLIVKIMRAFNLPAKDlgGTSDPFVKTMLLPDkKHKLTTKVKRKnLNPVWGETFAFEGfpanK 184 Trichoplax adha...
XP_002160708 163 DLGSIYFSISYDVYg-LVLKLTIQKAVNLPAKDisGSSDPYVKVLLLPDrKNKLETRVKRKkLNPIWNEVFTFEGfpyqK 241 green hydra
XP_002130498 167 YLGKLEFSTVYQFNe-STLLVKVLKAVDLPAMDlsGTSDPFVKCCLLPDrKRKLETKIRRKtLHPVWNETMSFEGlpyeK 245 Ciona intestinalis
XP_002195910 514 RKTEPHSSVSDLVNslTSEMLMVMKAQELLFKEftGTIDPFVKIYLLPDkKHKLETKVKRKnLNPHWNETFLFEGfpyeK 593 zebra finch
NP_493802    101 FRGRINFSVAFEKEc-STLHVHLMEAVDLPVKDftGSSDPYVRAFLLQDpGQSERSKVHRRnLNPTFNETLSFRGhsmkK 179 nematode
XP_002595832   1 NLGRIQFSMSYNFDt-MTLVLHIKRAVELPAKDfsGTSDPFVKICLLPDkKNKMETKVKRRnLNPHWNETFQFEGfpydK 79  Florida lancelet
Feature 1                   # #     #                           
2D8K_A        90 VVQRILYLQVLDYDRFsrNDPIGEVSIPLNKVdl-tqMQTFWKDLKP 135 human
CAG08772     112 VRERTLYLQVLDYDRFsrNDPIGEVSIPLNKVel-gqIKTFWKELKP 157 Tetraodon nigroviridis
NP_001014686 226 LQSRVLHLHVFDYDRFsrDDSIGEVFLPLCQVdf-agKQSFWKALKP 271 fruit fly
XP_001191249 213 IQERVLHLQVLDYDRFsrNDPIGEINLPLAEIdl-thEKLYWRSLTP 258 purple urchin
NP_001072834 457 VVQRVLYLQVLDYDRFsrNDPIGEVSIPLNKTdl-tqMQTFWKELKP 502 western clawed frog
XP_001635767  81 LMGKTLYMQVLDYDRFsrNDPIGEVEIPLENIdlgpvTLTFTKDLLP 127 starlet sea anemone
XP_002117784 185 LQSRILHLQVLDYDRFsrNDPIGEVNLDMGEIel-gdEVMFKRDLQP 230 Trichoplax adhaerens
XP_002160708 242 LLQRSVYLQVLDYDRFsrNDPIGEIEVALSDIelqsePVPFVKKLKP 288 green hydra
XP_002130498 246 IKQRVLHLQVLDYDRFsrNDPIGETYVPLHTInl-geEMIQYVNLAP 291 Ciona intestinalis
XP_002195910 594 VVQRVLYLQVLDYDRFsrNDPIGEVSIPLNKVdl-tqMQTFWKDLKP 639 zebra finch
NP_493802    180 LHDMTLVLQVMDYDRFssDDPIGEILLPLKHVkf-esSPVYWKHLQR 225 nematode
XP_002595832  80 LQHRVLYLQVFDYDRFsrNDPIGEVHLPLCEVdl-teSPTFWKDLRP 125 Florida lancelet

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