Conserved Protein Domain Family
C2A_Synaptotagmin-14_16

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cd08389: C2A_Synaptotagmin-14_16 
C2A domain first repeat present in Synaptotagmins 14 and 16
Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. 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 and this is indeed the case here. 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: 176035
View PSSM: cd08389
Aligned: 18 rows
Threshold Bit Score: 163.181
Threshold Setting Gi: 198415724
Created: 15-Sep-2009
Updated: 2-Oct-2020
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:
XP_002203939  69 KCGVLEVAFAYDAPnRKMTVSIVQARDVPSkd-rgGTGGYQVHMVLLPTkKQRCKTKVRQG-NNPVFKESFRFSRvnqdE 146 Florida lancelet
XP_396416    175 EVGSLEVAFLYDAPmREMTVHVLQGRNYPE-----GIGGSQVRLVLLPSkKQRRKTRVRQG-TSPQYMESFLLPRvnpeD 248 honey bee
XP_001177199 127 SIGDLELAFQYNGEaRRMNVTIIKCHNLPTkd-egGASSFRLRLLLLPSkRQRAKTHIRES-KEPLFKELFRFSRifphE 204 purple urchin
Q8NB59       260 KYGTLDVTFDYDSQeQKLLVTVTAVTDIPTyn-rtGGNSWQVHLVLLPIkKQRAKTSIQRG-PCPVFTETFKFNHveseM 337 human
XP_426122    304 KYGTLDVTFDYDSQeQKLLVTVTAVTDIPTys-rtGGSSWQVHLVLLPIkKQRAKTSIQRG-PCPVFTETFKFNHveseM 381 chicken
NP_649453    290 GPIELELSLLYDAPmRKMTVHVMQAKNLPPlg-sgQTTHTQVRMLMLPSkKQKLKTKIRSG-ENPQYMESFLLHRvnpeD 367 fruit fly
NP_001087543 250 KYGTLDVTFDYDSPeQKLLVTVTAATDLPThnrtgNCNSWQVHLVLLPAkKQRAKTAVQRG-PCPAFTESFKFNHieseM 328 African clawed ...
XP_001633287   8 TAGRIQISASYAPTaEKLSVTVVRAEDIPTkq-rgGASSVQVRIVILPTkKQRFKTKAKPA-TNPNFHETFTFTRitqnE 85  starlet sea ane...
EEC10443      30 RCGALELTFNYSPAsRKLTVGVLRAHDLPSrd-rgGANSVQVRLLLLPHkRQKFKTKIRQAsQDTRFDESFAFSRispeE 108 black-legged tick
XP_002161287 139 VAGKVLIQFTYMPAaNKVNLTVIRVQDMPEve-rgGSDMIAIHLCVLPIrKQRQRTKPIAV-SKGVFNETFSFIHmtkdK 216 green hydra
XP_002203939 147 LPDMGVRFRLYACERMk-kERLIGEKLVGFSNLkld-qreSMAVTLPLEP 194 Florida lancelet
XP_396416    249 VNAMGVRLRVYLWGGRmrrERLLGEARVSFDQInl---qlETTLWLTLQP 295 honey bee
XP_001177199 205 VVSTALRCRLYGCERMr-kEKLIGESIIKFSSLni---anKQIIKVRIDP 250 purple urchin
Q8NB59       338 IGNYAVRFRLYGVHRMk-kEKIVGEKIFYLTKLnl---qgKMSLPVILEP 383 human
XP_426122    382 IGNYAVRFRLYSVRRMk-kERIVGEKIFHLTKLnl---qgKMSVPVILEP 427 chicken
NP_649453    368 VNNMGLRVRLYGCERLr-kERLIGEAYVSFATVdl---elETNLWLPLEP 413 fruit fly
NP_001087543 329 IANYAVRFRLYLVRRLk-kERMVGEKVFYLTKLnl---qgKLSVPVVLDP 374 African clawed frog
XP_001633287  86 LRNLCLRVRLYGHERIg-kDKLLGESKIELTEFeld--geGTPLWRTLTP 132 starlet sea anemone
EEC10443     109 VNTMGLRVRLYGCERMr-rEHLVGETVVPFSFLgl---dqQTTLWLLTAS 154 black-legged tick
XP_002161287 217 IETCGIRLRVYGTQRFs--RRLIGEVKLPLAQLdlvsplsDEQVWKYLRP 264 green hydra
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