Conserved Protein Domain Family
C2B_Munc13-like

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cd04009: C2B_Munc13-like 
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins
C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. 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 third C2 repeat, C2C, and has a type-II topology.
Statistics
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PSSM-Id: 175976
View PSSM: cd04009
Aligned: 22 rows
Threshold Bit Score: 161.637
Threshold Setting Gi: 118783235
Created: 27-Dec-2004
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Ca2+ binding
Feature 1:Ca2+ binding site [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                        #      #                                         
Q70J99        910 ELGAVTVKASYRAseQKLRVELLSASSLLPLDSn-GSSDPFVQLTLEPRhefpeLAARETQKHKKdLHPLFDETFEFLVp 988  human
XP_001186162  481 PLGTLTIKCNYKQsqQKLRVRVMNATQIRPMDDn-GLSDPYVIVYLQPHhvfpqTHFQKTQVIKKtLHPLFDETFEFNVp 559  purple urchin
XP_002116507  917 FYGSLTFKVFYSStaQSLFVNVINAKNLPVLDSn-GKADPYVTVELCPShi-fkCAEKSTKIVKKtLDPYFGETFTFNIs 994  Trichoplax ad...
EEZ97425      953 KYGVLSVKAKFENn-NNLKVTVMNARNLLAMDSn-GYSDSFVRIHLLPEhkfsgIPKPKTQTHYKtLFPLYDENFTVELp 1030 red flour beetle
XP_001946516  962 NEGVLTVKLIFIN--NVLKIDILNANGIKAMDSn-GFSDPFIKVRLLPRdkfihASKPTTSVQKKtLYPLFDECFRIPLt 1038 pea aphid
XP_002425918  908 NLGYVTVRGQFVD--NLLKIEIMNARNLHPKDSn-GSCDPYVKINLIPEekfssVTKPRTKTHKKtTFPLFDEVFSMQLt 984  human body louse
XP_001649616  974 IFGMLTVQCFFKN--NVLELEIMNARNLRPMDSn-GTCDSFVRVHFIPEerfvgVTKPRTNTQSKtLFPLYDEKFVVTFn 1050 yellow fever ...
XP_001608178 1052 PYGLLTVKAYFFGd-RLLNIQILNARNLKANDNs-GKCDSYVKIRLFPEnafigMKTYKTGVQKEtQFPLYEESFSIPLt 1129 jewel wasp
ACD81812      208 PYGQLTITAQLTD--TGLLLNILNARNLLPMDSn-GSVDSFVKASFMPTsrfndVPTVKTNVHNKsCFPLYDQEFRINLs 284  fruit fly
XP_001649615  857 DRGVLTVRCCLRN--DSLEIQIISADGIKLPLDykGNCDSYVKINLAPGyrysdVQMPKTRTKSKnHSPTYNEKFTMKLs 934  yellow fever ...
Feature 1                          # #      #                                   
Q70J99        989 ae-pcRKAGACLLLTVLDYDTLg-aDDLEGEAFLPLREVpg---------lsGSEEPGEVPQ 1039 human
XP_001186162  560 hd-qvLSYGATVHFVLMDYDFLt--NDFLSDTSCSNVRHnqv-------lsySATVHFVIMD 611  purple urchin
XP_002116507  995 dklcsSTNGAVVLFTVMDYNILr-kNDYAGECAVSLNNVpgls-----wdenVPGMGADLPE 1050 Trichoplax adhaerens
EEZ97425     1031 td-ykSVEDGLLLFSVKDKDMLgynNQYIGEAFLHFKDId-----------sSNTPMDDLPQ 1080 red flour beetle
XP_001946516 1039 pq-qrAEENGLVMFIVKDQDFMgvtNEFVSETFVHFKDIps---------tqLENDLGSVPQ 1090 pea aphid
XP_002425918  985 sd-qkNIENSLIHFIIKDQDFLg--NEFLGEAYMDLKNIpt---------tdSSVSIHSLSQ 1034 human body louse
XP_001649616 1051 pe-qrVVKDAIILFSVKDKDLFgmsNQYLAECYLSFNDIa-----------dISGESGKIEQ 1100 yellow fever mosquito
XP_001608178 1130 pe-qrKIENAIVMFEVKDKDFLr--TKFVAECFLPFSEIpe---------tdSHQGFGSLDQ 1179 jewel wasp
ACD81812      285 dh-qrSEKNSLIVFSIKDKDLFgmsSQYIAESYISFADLe-----------aTPPGEQIMMN 334  fruit fly
XP_001649615  935 qe-qrEVPDALIVFNLKVSEMLglsQRYVGECFVRMDSIpileserdiksieVQQLFLTLPE 995  yellow fever mosquito

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