1UGK


Conserved Protein Domain Family
C2A_Synaptotagmin-4-11

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cd08388: C2A_Synaptotagmin-4-11 
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C2A domain first repeat present in Synaptotagmins 4 and 11
Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. 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: 176034
View PSSM: cd08388
Aligned: 10 rows
Threshold Bit Score: 201.81
Threshold Setting Gi: 7508345
Created: 21-Oct-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:
1UGK_A         7 GLGTLFFSLEYNFErKAFVVNIKEARGLPAm-------DEq-------sMTSDPYIKMTILPEkKHKVKTRVLRKtLDPA 72  human
7508345      120 ERGNISFTLSYDSHtLTLLVSIINCRNLCEmvv---srDGq--------CLLDPYVKLQLLPErEHRVKTRIVRStTSPV 188 Caenorhabditis ...
AAL49242     179 KLGTIYFKLRYLAErNALMVSITRCRGLPCkggssgtgDIptgmngrtqAATDPYVKLQLLPDkQHKVKTRVVRNtRNPV 258 fruit fly
AAH74396     152 KLGTLFFSLEYNFEkKAFVVNIKEARSLPAm-------DEq-------sMTSDPYIKMTILPEkKHKVKTRVLRKtLDPA 217 African clawed ...
NP_001041726 153 KLGTLFFSLEYNFEkKAFVVNIKEARGLPAm-------DEq-------sMTSDPYIKMTILPEkKHKVKTRVLRKtLDPA 218 zebra finch
XP_001896778 163 DRGFINFTLHYTIEnSTLQVNIICCRDLPElvv---asGGq--------CLLEPYVKLQLLPEkEHHVKTRLVRAsRNPQ 231 agent of lympha...
EEC11410     120 QLGQLHFRLRYNSEkHALLVTIVRCADLPAr-------DPn-------tGSSDPYVKLQLLPEkQHKVKTRVLRRtLSPV 185 black-legged tick
XP_393448    169 NLGQLMFKLRYVSEqNALGVTVVNCKGLPA--------REq-------nATSDPYVKLKLLPDkQHQAKTRVLRNtRDPV 233 honey bee
XP_002609763   9 TLGTLNFSVGYDMHkSAFRVTIHKANDLPIr-------DPq-------sGSADPYIKLCLLPDkKHKVKTRVLRRtRNPV 74  Florida lancelet
NP_001165866 178 KMGVLFFKLRYKKDkKVLLVNINKCMDLTP--------KEkn------sGTSDPYVKLQLLPDkEHKVKTRVLRKtRNPV 243 pea aphid
1UGK_A        73 FDETFTFYGipytQIQELALHFTILSFDRFsrDDIIGEVLIPLSGIels----------------------------egK 124 human
7508345      189 YEEQFAMYGvtheQVNFATLHFQVVAFDRYsrDTVVGECVYRLADA---------------------------------E 235 Caenorhabditis ...
AAL49242     259 YDEDFTFYGlnmnDLQNMSLHFVILSFDRYsrDDVIGEVVCPLTSIeigd-------------------------iskeA 313 fruit fly
AAH74396     218 FDETFTFYGipysQVQDLVLHFIILSFDRFsrDDVIGEVCFPLSGIdls----------------------------dgR 269 African clawed ...
NP_001041726 219 FDETFTFYGipysQIQDLTLHFMVLSFDRFsrDDVIGEVLIPLAGT---------------------------------E 265 zebra finch
XP_001896778 232 YDETFSMYGldalQLATTSIHFAVIAFDRYsrDTLLGEAVYSLKDAnll---------------------------nseI 284 agent of lympha...
EEC11410     186 YDEDFTFYGinpnQLQATTLHFVVLSFDRYsrDDVIGEVVCSMAGLdteh--------------------------ldkT 239 black-legged tick
XP_393448    234 YDEDFTFFGiskdQLQKISLHFIVLSFDRYsrDDIIGELTCALSSVpgleeadnqaislcrkicprslkiqsqgrgellV 313 honey bee
XP_002609763  75 FEETFTFFGlergQLPGISLHFSVLSFDRFsrDHLIGEVTMSLAKVdmt----------------------------egE 126 Florida lancelet
NP_001165866 244 YDEDFTFFGiqtnKLQSMTLHFAILSFDRYsrDSLIGEVFFTLNEKdvlesiekeqisiqk---diilrsvksqianrgE 320 pea aphid
1UGK_A       125 MLMNREIIS 133 human
7508345      236 LQVHNEMRV 244 Caenorhabditis elegans
AAL49242     314 LSISKEIQP 322 fruit fly
AAH74396     270 VLMNREINK 278 African clawed frog
NP_001041726 266 LSEGRLLMD 274 zebra finch
XP_001896778 285 ITVELKLEG 293 agent of lymphatic filariasis
EEC11410     240 LALSREIAP 248 black-legged tick
XP_393448    314 SLCWQPINS 322 honey bee
XP_002609763 127 VTMTGEIVG 135 Florida lancelet
NP_001165866 321 LLVSLCWQP 329 pea aphid
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