Conserved Protein Domain Family
C2_Munc13_fungal

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cd04043: C2_Munc13_fungal 
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group
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 second C2 repeat, C2B, and has a type-II topology.
Statistics
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PSSM-Id: 176008
View PSSM: cd04043
Aligned: 18 rows
Threshold Bit Score: 162.432
Threshold Setting Gi: 50254398
Created: 11-Jan-2005
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:
6324870       856 QVYTLRIIGAENIKGFSk--tGLSNTYVSMRNitlqreIGTTKIVArsiTPKWDEEFVFEspfg-ksnDIMFTIWHHPhs 932  baker's yeast
NP_594926     806 YLYTIKVVRGEGLHPDGa--gKIRTSYIVLTDnkg-rrIGKTRPIHs-mNPRWDDTFEVKtkd---alMITANLWSKGkf 878  fission yeast
NP_982931     859 QLYTIRIVKAENILSFNs--dGSSNSAVTLVDtsvqreIAKTKVVRktvNPMWDELFELVvpag-earMISATVWHHSak 935  Ashbya gossyp...
EAL00073      828 HVFSIRIVRGENLRASKdamwGKINPYVAAVDlngkrlLTRTRTIDhnpDPEWDEEFEITippeqsslDISVVVWDDRfg 907  Candida albic...
CAG89134      869 HIFSLRIIKAENLKSATs--sSSVHPYITMIDtkvrktIGKTRTISnncNPEWDEEFELTipan-sslTISTTVWDERfg 945  Debaryomyces ...
EAL17151      868 HLFTVMILRGEGLLGKGl--vKAADGFVVVLDkqsgerCIKTKTVLgteDPKWDQSFEVSvga---vkILELQVYDRQlv 942  Cryptococcus ...
XP_002173780  800 AYYTITVLRGEGLPTDSs--gRVRNVYVVLTDsgg-hrVGKTKSLCt-lNPRWNKSFEMKskg---pvWINATVWERGrl 872  Schizosacchar...
XP_001526545  863 HVFTIRIVKGENLLLSKdtgfGKLNPYVSLVDvgkkvaIARTRAIKrtsDPDWDEEFEIStpvn-ttlELSAIVWSDSfg 941  Lodderomyces ...
XP_001644273  847 LIYSLRVVAAENLKPLKm--nEIPDVFVSIVNtdeskeISKTNIISktyNPVWDEEFELEeikg-ntcLLSFNIWQNYss 923  Vanderwaltozy...
CAY67450      807 HFFTIKVVQAEGIKSPVg--kDAPDANVWLSNnntkkvFARTRTIPssdRPEWDEEFEVVlfpg-asvSILATLWDKSfk 883  Pichia pastor...
6324870       933 rlk-nlaedDLCGKANMKFTPRKLkddgFPIDFSLTLNPQGTLYCQISLESEKID 986  baker's yeast
NP_594926     879 n------dhEIFGRSSFTLSPKIYgd-yLPREEWFDLNPHGELLLRIEMEGEREH 926  fission yeast
NP_982931     936 inp--vssyKVCGKCSLLLDPTVYrsdgYPQETNLDLDTQGRLILQVSLESERFD 988  Ashbya gossypii ATCC 10895
EAL00073      908 -------qhQLCGKAFLELNPRRFstsgIPEEITLDLDFQGKVVLEVAVESEILD 955  Candida albicans SC5314
CAG89134      946 -------thSICGRALLQLDPRRFkhdgIPQEVYLDLDSQGRVLIEIAVESERVD 993  Debaryomyces hansenii
EAL17151      943 g------khDLIGTSTFKLDPRLFad-ySTRDIVLPLNPRGTVHIRISMEGGEKH 990  Cryptococcus neoformans var. neoforman...
XP_002173780  873 r------nhEVIGRASFCLDPKVYgd-yVPREMWYNLNTKGELLIRTEMEGEKEH 920  Schizosaccharomyces japonicus yFS275
XP_001526545  942 -------qhQMCGKSLFELDPKKFkhngFPEEITLNLDLLGRLVLEVSVETETMD 989  Lodderomyces elongisporus NRRL YB-4239
XP_001644273  924 qklrrsekyELCGKATLLLDSKKFkddgLPSDIILDLDTQGKLFLQVSLENEQLD 978  Vanderwaltozyma polyspora DSM 70294
CAY67450      884 rf----ssdAVIGRTLFHLSPKEFnnngIPRDLILNLDTEGTLVLQVSLESERED 934  Pichia pastoris GS115
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