Conserved Protein Domain Family
C2B_Synaptotagmin-7

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cd08405: C2B_Synaptotagmin-7 
C2 domain second 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 second C2 repeat, C2B, and has a type-I topology.
Statistics
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PSSM-Id: 176050
View PSSM: cd08405
Aligned: 10 rows
Threshold Bit Score: 245.405
Threshold Setting Gi: 193606091
Created: 21-Sep-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Ca2+ binding
Feature 1:Ca2+ binding pocket [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                      #     #                                           
NP_001072834 510 RGELLLSLCYNPStNAIIVNIIKARNLKAMDIGGTSDPYVKVWLMYkdkRVEKKKTVVMKRCLNPIFNESFIFDIPtekl 589 western clawed ...
XP_002117784 237 LGDLLLSLCYHPTtGDLTIVVMRCRNLKIMDISGSTDPYVKLSLMYgdkRLEKKKTTVKRRSLNPVFNESFMFNIPferl 316 Trichoplax adha...
2724126      282 RGELLLSLCYNPSaNSIIVNIIKARNLKAMDIGGTSDPYVKVWLMYkdkRVEKKKTVTMKRNLNPNFNESFAFDIPtekl 361 human
CAG08772     173 RGDLLVSLCYNPTaNTITVNIIKARNLKAMDIGGTSDPYVKVWLMHkdkRVEKKKTVTMKRCLNPVFNESFPFDVPahvl 252 Tetraodon nigro...
XP_002195910 647 RGELLLSLCYNPSaNSIVVNIIKARNLKAMDIGGTSDPYVKVWLMYkdkRVEKKKTVVMKRCLNPVFNESFAFDIPterl 726 zebra finch
XP_001191249 266 LGSLLISLCYAPTaGRITITVLKCQNLAAKDITGKSDPYVKIWHMHkdkRVEKKKTVIKYHTLNPVYNESFVFNIPldri 345 purple urchin
XP_001635767 135 LGDLLVSLMYQPTnNRIIVVVMKANKLKAMDLTGSSDPYVKMYIMHkdrRLDKKKTTIKRRTRDPVWNESFIFDVPldki 214 starlet sea ane...
XP_002130498 298 RGELLLSLCYQPLeGILDVEIIKGRNMKPMDLNGTSDPYVKIWLIYrgkRIEKKKTEIHKNNLNPEFHEEFTFNAPmdrl 377 Ciona intestinalis
NP_001014686 277 CGELLSSLCYHPSnSILTLTLIKARNLKAKDINGKSDPYVKVWLQFgdkRVEKRKTPIFTCTLNPVFNESFSFNVPweki 356 fruit fly
XP_001948182  21 CGHLLTSLSYNPMtNNLTLGIIEARNLKAMDINGKSDPYVKVWLHVgdkKVEKRKSMVFKCNLNPMFDEKFEYQLPveql 100 pea aphid
Feature 1                  # #                                                
NP_001072834 590 retTIIITVMDKDKLSRNDVIGKIYLSWksg-----pgEVKHWKDMISHprTAVAQWHQLK 645 western clawed frog
XP_002117784 317 rdiSLIIHVMDYDKLSANDCLGHISLGTrat-----gyELKHWKEMLASprRPVAKWHMIH 372 Trichoplax adhaerens
2724126      362 retTIIITVMDKDKLSRNDVIGKIYLSWksg-----pgEVXHWKDMIARprQPVAQWHQLK 417 human
CAG08772     253 retTIIITVMDKDRLSRNDVIGKANLPImeerawggeaLEGHARSAAHQr-RPVARSQGLI 312 Tetraodon nigroviridis
XP_002195910 727 retTIVITVMDKDRLSRNDVIGKIYLSWksg-----pgEVKHWKDMIARprQAVAQWHQLK 782 zebra finch
XP_001191249 346 rdtTFVVSVLDKDRLSKNDMIGGILLGArts-----paEMSHWNEMMSKprTNIAKWHVLK 401 purple urchin
XP_001635767 215 rdlTFVFNVMDYDRITQNELIGQVILGYrtt-----gsSLRHWTEMMNNprKPVAQWHRLQ 270 starlet sea anemone
XP_002130498 378 remQLEITVMDHDTIGRNDTIGKIYLGHksa-----glEKQHWKDMLTNarKPSLQWHVLK 433 Ciona intestinalis
NP_001014686 357 recSLDVMVMDFDNIGRNELIGRILLAGkngs---gasETKHWQDMISKprQTVVQWHRLK 414 fruit fly
XP_001948182 101 reaALEVMVMDFDNIGRNELIGKITISSnkna--tgqlEAQHWKDMLSKpkQSVEYWHRLK 159 pea aphid

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