3KWT,3KWU


Conserved Protein Domain Family
C2B_Munc13

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cd04027: C2B_Munc13 
Click on image for an interactive view with Cn3D
C2 domain second 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 second C2 repeat, C2B, and has a type-II topology.
Statistics
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PSSM-Id: 175993
View PSSM: cd04027
Aligned: 12 rows
Threshold Bit Score: 252.489
Threshold Setting Gi: 288965797
Created: 23-Dec-2004
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 site [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                         #     #                                             # #         
3KWT_A         17 AKISITVVCAQGLQAKDkTGSSDPYVTVQVGktKKRTKTIYGNLNPVWEENFHFECHNssDRIKVRVLDEDDDIKSRVKQ 96   Norway rat
NP_651949    1845 CKLTITVICAQGLIAKDkSGTSDPYVTVQVSkvKKRTRTMPQELNPVWNEKFHFECHNssDRIKVRVWDEDNDLKSKLRQ 1924 fruit fly
NP_001038630  733 AKISITVLCAQGLQAKDkTGSSDPYVTVQVGktKKRTKTIYGNLNPVWDESFNFECHNssDRIKVRVWDEDDDIKSRVKQ 812  zebrafish
EEC20186       84 AKIAITVICAQGLIAKDkSGTSDPYVTVQVGktKKRTRTMPRDLNPVWNEKFFFECHNssDRIKVRVWDEDNDLKSKLRQ 163  black-legged ...
XP_002124363  529 AKLSITVISAQGLQAKDkTGSSDPYVTVQVGktRKRTKTIYGDLNPLWNENFHFECHNstDRIKVRVWDEDDDIKSVLKQ 608  Ciona intesti...
XP_781920     854 AKLAITVVSAQGLIAKDkTGTSDPYVTVQVGkvKKRTRTVQQNLNPEWNEKFFFECHNssDRIKVRVWDEDDDLKSKLMQ 933  purple urchin
XP_001624150  167 AKISITVVSAQGLIAKDkTGTSDPYVTVQVGktKKRTSTIPHELNPEWNETFLFECHNssDRIKVRVWDEDDDIKSRVRQ 246  starlet sea a...
XP_002110349  144 AKIKTKVVCAQGLIAKDrTGLSDPYVTVQVGktKKRTETVQQNLNPEWNEEFVFDCNNasDRIKVRVWDEDDDFKSRIKS 223  Trichoplax ad...
XP_002580147 1889 AKIAITIKCAQGLIGKDkTGTSDPYVTVQVGkvKKRTKTVPQELNPVWNEKFYFECHNasDRIKIRVWDEDYDLKSKIRQ 1968 Schistosoma m...
NP_001021873 1157 AKITLTVLCAQGLIAKDkTGKSDPYVTAQVGktKRRTRTIHQELNPVWNEKFHFECHNstDRIKVRVWDEDNDLKSKLRQ 1236 nematode
XP_413798    1105 AKITITVLCAQGLQAKDkTGSSDPYVTVQVGktKRRTKTIFGNLNPVWDEKFYFECHNstDRIKVRVWDEDDDIKSRVKQ 1184 chicken
3KWU_A         17 AKISITVVCAQGLQAKDkTGSSDPYVTVQVGktKKRTKTIYGNLNPVWEENFHFECHNssDRIKVRVLDEDDDIKSRVKQ 96   Norway rat
Feature 1                #                                       
3KWT_A         97 RFKRESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSAVSGAIRLHI 143  Norway rat
NP_651949    1925 KLTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 1971 fruit fly
NP_001038630  813 KFKRESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSAVSGAIRMHI 859  zebrafish
EEC20186      164 KLTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 210  black-legged tick
XP_002124363  609 QFKRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 655  Ciona intestinalis
XP_781920     934 KLTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 980  purple urchin
XP_001624150  247 KLIREPDDFLGQTIIEVRTLSGEMDVWYNLEKRTDRSAVSGAIRLRI 293  starlet sea anemone
XP_002110349  224 TFSREADDFLGQAIIDVRTLNGQMDVWYNLEKRTEKSLVSGSIRLII 270  Trichoplax adhaerens
XP_002580147 1969 KFTRESDDFLGQTIVEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLFI 2015 Schistosoma mansoni
NP_001021873 1237 KLTRESDDFLGQTVIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 1283 nematode
XP_413798    1185 HFKKESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGALRLKI 1231 chicken
3KWU_A         97 RFKRESDDFLGQTIIEVRTLSGEMDVWYNLDKRTDKSAVSGAIRLHI 143  Norway rat

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