Pathways & interactions
Protein Unc-13, C2B domain (IPR037302)
Short name: Unc-13_C2B
Overlapping homologous superfamilies
- C2 domain (IPR000008)
- Protein Unc-13, C2B domain (IPR037302)
C. elegans Unc-13 is a phorbol ester/diacylglycerol-binding protein that plays a role in vesicle maturation during exocytosis [PMID: 10233166, PMID: 9697857]. Unc-13 disruption causes diverse defects in the nervous system [PMID: 2062851, PMID: 1445255]. Mammals contain three Unc-13 homologues: Unc-13 A, B and C (also known as Munc13-1/2/3) [PMID: 7559667]. Unc13 homologue C is cerebellum-specific and regulates cerebellar synaptic transmission [PMID: 11150314]. Homologues A and B are involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion [PMID: 12070347]. They are essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses [PMID: 10440375].
Unc-13 and its homologues contain both C1 and C2 domains. There are at least two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. The central C2 domain (C2B) is part of a C1-C2 tandem that functions in part to inhibit calcium-triggered neurotransmitter release. The C1 domain of Munc13 binds diacylglycerol (DAG) and beta phorbol esters (beta-PEs), while the neighbouring C2 domain (C2B) binds calcium and anionic phospholipids with a preference for both PI(4)P and PI(4,5)P2 [PMID: 28772122].
This entry represents the second C2 domain, C2B, and has a type-II topology.
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 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 [PMID: 9632630, PMID: 8976547, PMID: 8771209, PMID: 8662510, PMID: 7791877, PMID: 7697723, PMID: 1589771, PMID: 2333096].
- cd04027 (C2B_Munc13)