Conserved Protein Domain Family
C2B_Synaptotagmin-15

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cd08409: C2B_Synaptotagmin-15 
C2 domain second repeat present in Synaptotagmin 15
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. 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: 176054
View PSSM: cd08409
Aligned: 9 rows
Threshold Bit Score: 213.736
Threshold Setting Gi: 198430101
Created: 21-Sep-2009
Updated: 17-Jan-2013
Structure
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Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37999765  279 FGDLQFCLSYNDYlSRLTVVVLRAKGLRlqddrgIVSVFVKVSLMNhnkFVKCKKTSAVLG--SINPVYNETFSFKADat 356
gi 118092421 175 YGDIQFSLSYNDYlGRLTVVVLRARGLKfqdesrDVSVYVKVSLMNhnkLVRSKKTAAVLG--SPNPEYNESFSFKANqt 252
gi 125831745 277 NGDIQVSLNYNQSlHRLTVVVLRARGLQcc---sEAAVCAKVCLKIh-tQVVRNKWTTVAK--GNSPSFNEKLTFRLLpm 350
gi 47204884  174 LGDVQISLCYSPAlQRLSVVVLRARGLQpl---tDAGVCVQVSLQIhtqVVKIKRSCEVTG--GRDPCFSHRMTFKLRsr 248
gi 115947235 396 TGDIHFSLNYNNTnERLTVVMAEGKGFKmldgfqHVDSYVKVSLMNigkVVKAKKTEIIKK--NPSPTFNESFHFKLPpd 473
gi 156402895 165 LGDIHISLSYYPTlDRLTIIILRAANLRtig-hkGTDPFVKIAFSIgnkVMKTKKTAVHQD--TVNPMFNDAFNYTVTed 241
gi 198430101 310 LGELKILLTYLPRmNRLNVVVQEARNLRkmd-ldATGIYVKVSLTQghnVIKSKRTSTQDG--AADPQYNESFSFKVTsk 386
gi 241834368   8 IGEIQISLTCNPFtNRIKAAALQVRRFSrle-enSTSVYVKLSLNHgrkSVKEKATEVREWrsADEVSFTDVFSFGVAgr 86
gi 156360750 140 RGEISLSLTYNPGtSRLVVGVRQARNILqfeghaHKEYFVKISRIHlnrKVKTKRTPSTDG--DASPIFKHDMSFNIPte 217
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 37999765  357 eldtaSLSLTVVQNMe-------------------GDKSQQLGRVVVGPYMYTRGrELEHWDEMLSKpkELVKRWHALC 416
gi 118092421 253 eldtaSLSLSVLQNT--------------------EQKSHVLGRVVVGPFMYSRGkELEHWNEMISKpkELVKQWHALC 311
gi 125831745 351 qldtaCLSLQIQQPS--------------------TEKPVLLAIVVIGPFMYARGrELEHWNDMVSKpqELVRQWHPLG 409
gi 47204884  249 hldeaCLRFELLQPGgv-----------------hSEPEAILGVLVLGPFMYARGpQLQHWMDMLSTpqDTIKRWHGLG 310
gi 115947235 474 gldmySISVAVMQHAp------------------gVKGDKQIGRVVVGPFMYARGkELEHWNDMVSHpkEPISQWHSLT 534
gi 156402895 242 dlgtsSLLVSVWHSGg------------------gVREDKLIGRVLLGGMMYARGkECEHWTEMMTNprKMIKYWHPLG 302
gi 198430101 387 dmeqtCLLLNVITTGgrgtlhkmtstlkntvtrgrYGAELKYGRVSVGSFMYCRGeQLLHWQEMMAQpsKSIARWHTLS 465
gi 241834368  87 yfdscSLCFTVMVSPd-------------------GSDYSRLGKTVLGPFMYARGeELRHWQDMLTNprSAVVRWHALE 146
gi 156360750 218 qlsdsCLVLSLMNHGv-------------------VRGSTTIGRVVLGPYVFGSGnERSHWGRMIRSplNTIEQWHSLY 277
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