1W16,1W15


Conserved Protein Domain Family
C2B_Synaptotagmin-4

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cd08404: C2B_Synaptotagmin-4 
Click on image for an interactive view with Cn3D
C2 domain second repeat present in Synaptotagmin 4
Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176049
View PSSM: cd08404
Aligned: 10 rows
Threshold Bit Score: 213.829
Threshold Setting Gi: 7508345
Created: 22-Sep-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 pocket [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                      #      #                                          
1W16_A        16 RGELLVSLCYQSTtNTLTVVVLKARHLPKSDvs-gLSDPYVKVNLYHa-kKRISKKKTHVKKCTPNAVFNELFVFDIPce 93  Norway rat
1W15_A        16 RGELLVSLCYQSTtNTLTVVVLKARHLPKSDvs-gLSDPYVKVNLYHa-kKRISKKKTHVKKCTPNAVFNELFVFDIPce 93  Norway rat
CAF89500     307 RGELLLSLCYQSTtNALTVVVLKARNLPKTDnn-gPTDPYVKVNMYQg-kKRVCKKKTHMKKCSPNPVFNELFVFDLPsd 384 spotted green p...
AAH74396     287 RGELLISLCYQSTtNTLTVVVLKARHLPKVDvs-gLSDPYVKVNLYHa-kKRISKKKTHVKKCTPNAVFNELFVFDIPce 364 African clawed ...
NP_001041726 288 RGELLVSLCYQSTtNTLTVVVLKARHLPKSDvs-gLSDPYVKVNLYHa-kKRISKKKTHVKKCTPNAVFNELFVFDIPce 365 zebra finch
EEC11410     258 RGELLVSLCHQPAaNRLTVVVLKARNLPKVDit-gLSDPYVKIYLLYn-qQRIAKKKTHIKKRTVNPVFNESFVFEVPyn 335 black-legged tick
AAL49242     332 RGELLISLCWQPAaGRLTVVLLKARNLPRMDvt-gLADPYVKIYLLYn-gQRIAKKKTHVKKRTLSPVFNESFAFDIPaa 409 fruit fly
NP_998625    312 RGELLVSLSYHPVtHRLNVVVLKAKHLPTMDitglSGNPYVKVNVFYg-rKRIAKKKTHVKKCTLNPVFNESFIYDVPae 390 zebrafish
XP_001896778 303 RGQVLLSLCYQPTtHRITVVLLKVKGLPKLDvs-gMADPYVKIYLLYk-eQRISKRKSHVKKCTLSPVYNESFVFEFPss 380 agent of lympha...
7508345      259 RGELLLSLTYQAAfNNLTVVVLKARGLGGRNda-gTADPFVKLYLRKesgERIVKKRTHVRRSTLNPVYNESFVFELPdd 337 Caenorhabditis ...
Feature 1                         # #       #                                       
1W16_A        94 sl-----eeiSVEFLVLDSER---GSRNEVIGRLVLGAta-egSGGGHWKEICDFpRRQIAKWHMLC 151 Norway rat
1W15_A        94 sl-----eeiSVEFLVLDSER---GSRNEVIGRLVLGAta-egSGGGHWKEICDFpRRQIAKWHMLC 151 Norway rat
CAF89500     385 eg----lrdtSVELLLMDSASgtaRCPSPVLGRLAESWkltsaHAGRKDKDGAGGgGRGRGERSSIH 447 spotted green pufferfish
AAH74396     365 gl-----ediSVEFLVMDSDR---GSKNEVIGRLSLGSsa-dgTGGEHWKEICEHpRRQIAKWHMLC 422 African clawed frog
NP_001041726 366 gl-----ddiSIEFLVLDSDR---GSRNEVIGRLTLGSsa-egTGGEHWKEICEYpRRQIAKWHMLC 423 zebra finch
EEC11410     336 eg----ldnlSLEFLVLDWDR---VTKNEVVGRLELGPrg-spAAQQHWLEVCNSpRRQIAEWHKLR 394 black-legged tick
AAL49242     410 egagaslegvSLELMLLDWDR---VTKNEVIGRLELGGpnsssTALNHWNEVCNSpRRQIAEWHKLN 473 fruit fly
NP_998625    391 lm-----pdiSVEFLVIDFDR---TTKNEVVGRLVLGGqspipSGVTHWREVCDNpRRQIAKWHNLI 449 zebrafish
XP_001896778 381 eeq--dldniKFEIVVMDWDR---LTKNEVMGKCFIGP-----NDKHWLQVRSNP-RRQIAEWHQLS 436 agent of lymphatic filariasis
7508345      338 rl-----ehsVIDLQVINHDR---VNRNDVIGRALLNM-----EDSHVVEVLENP-GRQVAQWHHLD 390 Caenorhabditis elegans

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