2CJT,2CJS


Conserved Protein Domain Family
C2A_Munc13

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cd08394: C2A_Munc13 
Click on image for an interactive view with Cn3D
C2 domain first repeat in Munc13 (mammalian uncoordinated) 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 first C2 repeat, C2A, and has a type-II topology.
Statistics
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PSSM-Id: 176040
View PSSM: cd08394
Aligned: 9 rows
Threshold Bit Score: 201.909
Threshold Setting Gi: 221090556
Created: 12-Oct-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
homodimer
Conserved site includes 13 residues -Click on image for an interactive view with Cn3D
Feature 1:homodimer interface [polypeptide binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                # # #   ####                            # #     ####     
2CJT_A          4 MSLLCVGVKKAKFD-GAQEKFNTYVTLKVQNVKSTTIAVRGSQPSWEQDFMFEINrldlGLTVEVWNKGliWDTMVGTVW 82   Norway rat
2CJS_A         13 LSLLCVGVKKAKFD-GAQEKFNTYVTLKVQNVESTTIAVRGSQPSWEQDFMFEINrldlGLTVEVWNKGliWDTMVGTVW 91   Norway rat
NP_001021873   18 MRLLCITIKKARLQ-GAVDEFNSYVTVKLQTVKSTTVAVRGNLPCWEQEFIFETNrpddGMVLELWAKGvlWDKLIGVHY 96   nematode
CAJ83554        1 MSLLCVRVKKAKLQ-GPPDKFNTYVTLKVQNVKSTTVAVRGDQPCWEQDFMFEISrldlGLVVEMWNKGliWDTMVGTVW 79   western clawe...
NP_001038630    7 HTRLSVTVKKAKLD-GPQEKFNTYVSLKVQNVKSTTIAVRGSQPCWEQDFMFEINrldlGLTVEVWNKGliWDTMVGTLW 85   zebrafish
XP_002124363    1 MSLLCVKVKQGKLD-GAPDKFNTYVSLKVQNVKSTTICVKGCDPLWEQDYMFEISrvdlGLSIEIWNKGvlWDTLLGTAW 79   Ciona intesti...
XP_002190463   31 FPPFVPAVKKAKYD-GPQEKFNTYVTLKVQNVKSTTIAVRGNLPSWEQDFMFEINrldlGLTVEVWNKGliWDTMVGTVW 109  zebra finch
XP_002580147   38 CGRSFTEIIEARLE-SSDSSLNTYISVKLRQAHSSTQTVKGTAPKWNEEFIFETErmdgGLLIELHSKGllKDKLLGVVW 116  Schistosoma m...
XP_002169960   21 AVKFNVLVKKAKAVfKDPGKVKTFLILQIDKTIIKTPVVVGSYPTWHQVFTFKVCgpnkHLVIKFMKDGliFQDLCGFVI 100  green hydra
Feature 1                                                         
2CJT_A         83 IPlrTIRQSNEEgpGEWLTLdSQAIMADSEICGTKDptfHRILLDAHF 130  Norway rat
2CJS_A         92 IPlrTIRQSNEEgpGEWLTLdSQAIMADSEICGTKDptfHRILLDAHF 139  Norway rat
NP_001021873   97 MPlsEIRYSNAAgsGQWLQMdHELETRNGQTVGTRGptgHNLLTDVRF 144  nematode
CAJ83554       80 IPlqTVRQSEEEgpGEWAALeSEVLMKNDEICGTQNptlHRILLDTRF 127  western clawed frog
NP_001038630   86 IPlsSIRQSNEEgpGQWLTLdAQVIMAENEICGTKDptfHRVLLDTRF 133  zebrafish
XP_002124363   80 LPlsHVPHCNEEgdGAWYQLyTNVNSDKGVVPDVKNatnHKVLCDVRF 127  Ciona intestinalis
XP_002190463  110 IPlrTIRQSNEEgpGEWLTLdSQVIMTDNEISGTKDptfHRILLDTRF 157  zebra finch
XP_002580147  117 LPlnKILHSNKDgpGMWLNFdSEAVTENGQIVATKTatkHSCLATVRF 164  Schistosoma mansoni
XP_002169960  101 IPlvDVHFSDKEgpGTWIPLyIEQNNKNIQTDYKLLi-dMRYALPQGL 147  green hydra

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