Conserved Protein Domain Family
C2C_Munc13

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cd08395: C2C_Munc13 
C2 domain third 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 third C2 repeat, C2C, and has a type-II topology.
Statistics
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PSSM-Id: 176041
View PSSM: cd08395
Aligned: 12 rows
Threshold Bit Score: 218.035
Threshold Setting Gi: 256084371
Created: 16-Jun-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:
Q9UPW8       1546 KVTVKVVAANDLKWQts-giFRPFIEVNIIGPQLSDKKRKFATKSKNNSWAPKYNESFQFTLSADAGPECyELQVCVKDY 1624 human
NP_726614    2720 KVNVKVVAANDLKWQipsgmFRPFVDINLIGPHLQEKKRKFATKSKSNNWSPKYNESFSFTIGNEEQLDFfELHICVKDY 2799 fruit fly
NP_001021873 1989 KVTVKILAANDLRWQts-saFKPFVEVHLVGPHLSDKKRKWSTKTKAGNWAPKFNETFHFFLGNEGEPEHyELMFQVKDY 2067 nematode
NP_001038630 1589 KVTVKVVAANDLRWQts-giFRPFVEVYIIGPHLSDKKRKYATKSKNNSWAPKYNETFTFTLSNEVGPECyELQVCVKDY 1667 zebrafish
XP_781920    1608 KVNVKVVACNGLKWNtt-smFRPFVEVYMIGPHLSDKRRKHSTKSKANNWAPKYNETFQFILGNEDEPISyELHFCVKDY 1686 purple urchin
XP_001622333  349 KVTVKVVAAKDLKWQsp-gmFRPFVEVNVVGPHLGNKTRKQATKSKRNTWSPAYNESFFFILGNEVDMINyELHIAVKDY 427  starlet sea a...
XP_002110349  987 KVTVKVVEATGLLWQst-nmFRPFVEINVIGPHLHDRKRRQSTRSKSNNWDPKFNEIFYFILSNEDDPYSfELHICVRDY 1065 Trichoplax ad...
XP_002124363 1367 KLTIKVVAASNLKWNtt-gmFRPFVDVNLVGPHLSNVRRRYSTKSRSNAWSPKYNESFSYSIGNVEKISAyELHLCVKDY 1445 Ciona intesti...
EEC20186      938 KITIELVAANDIKWPnt-smFRPFVEVNLIGPHLSDKRRKHATKSKNNNWSPKYNETFHFIIGNEEEPSSfELHVCVKDY 1016 black-legged ...
XP_002159369  933 KVTVKVVEAKNLLWQtk-gvFRPFIEVNILGPHLTDKTKRNSTRSKNNNWSPKFNEIMNFQLGNEDPLSCyELQISAKDY 1011 green hydra
XP_413798    1945 KVTVKVVAINNLNWQtt-amFRPFVEVCVLGPNLSDKKRKHGTKTKSNTWSPKYNETFQFILSNEDKPGAyELHLSVKDY 2023 chicken
XP_002578403  548 KVTITVIAANNLKWTts-gtFKPFIEVVLFGPLLSEKKHKFATKSKNNVWSPVFNETFTFFLSAGSDPESyELHMCAKDY 626  Schistosoma m...
Q9UPW8       1625 CFARedRTVGLAVLqlrela----qrgsaACWLPLgRRIHMDDTG 1665 human
NP_726614    2800 CFARddRLVGVAVIplkdis----ekgsvACWLPLmRRIEMDETG 2840 fruit fly
NP_001021873 2068 CFARddRVVGVGVLqlssvv---dqagscAMWVQLgTRLHIDETG 2109 nematode
NP_001038630 1668 CFARedRTVGMAVLqlkdva----prgsvACWLPLgKRIHMDETG 1708 zebrafish
XP_781920    1687 CFARedHLIGIGVLqlhtivecgscacvcTLGRKLhVNDTGGTIL 1731 purple urchin
XP_001622333  428 CFARmdAIVGMTVLhlrdiadigsiacnaLLGRALhMDATGWTIL 472  starlet sea anemone
XP_002110349 1066 CFTRqnQLVGMCVIqlreia----dvgsrSCWWPLsRAVYMDETG 1106 Trichoplax adhaerens
XP_002124363 1446 CFARddRVIGVAVMqlrnis----qqgscACWCSLgKNIHLNQTG 1486 Ciona intestinalis
EEC20186     1017 CFARddRLVGVAVMqlrdia----dqgscACWLPLgRRIHMDETG 1057 black-legged tick
XP_002159369 1012 CFGRknHLIGVTVLplrnic----nrgsfASWCALgRSLYMNDTG 1052 green hydra
XP_413798    2024 CFARedRVIGMTVIqlqnia----ekgscASWYPLlRNIFVDETG 2064 chicken
XP_002578403  627 CFGRtdRLIGLTVLqlr----------dlATTTELnASPTMNSRD 661  Schistosoma mansoni
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