The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

UNC13A  -  unc-13 homolog A (C. elegans)

Homo sapiens

Synonyms: KIAA1032, Munc13-1, Protein unc-13 homolog A
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

High impact information on UNC13A

  • Moreover, the levels of Munc13-1 and ubMunc13-2 levels are decreased in RIM1alpha-deficient brain, and Munc13-1 is not properly enriched at active zones of mossy fiber terminals of the mouse hippocampus if RIM1alpha is absent [1].
  • We identify a single point mutation in Munc13-1 and ubMunc13-2 (I121N) that, depending on the type of assay used, strongly perturbs or abolishes RIM1alpha binding in vitro and in cultured fibroblasts, and we demonstrate that RIM1alpha binding-deficient ubMunc13-2(I121) is not efficiently recruited to synapses [1].
  • Members of the Munc13 protein family consisting of Munc13-1, -2, -3, and -4 were found to be absolutely required for this priming process . In the present study, we identified the minimal Munc13-1 domain that is responsible for its priming activity [2].
  • Using Munc13-1 deletion constructs in an electrophysiological gain-of-function assay of chromaffin-granule secretion, we show that priming activity is mediated by the C-terminal residues 1100-1735 of Munc13-1, which contains both Munc13-homology domains and the C-terminal C2 domain [2].
  • Identification of the minimal protein domain required for priming activity of Munc13-1 [2].

Biological context of UNC13A

  • We show here that the active zone recruitment of Munc13 isoforms Munc13-1 and ubMunc13-2 is regulated by their binding to the Rab3A-interacting molecule RIM1alpha, a key determinant of long term potentiation of synaptic transmission at mossy fiber synapses in the hippocampus [1].
  • These results suggest that ELKS is involved in Ca(2+)-dependent exocytosis from PC12 cells at least partly via the RIM2-Munc13-1 pathway [3].
  • Indeed, Munc13-1 and ubMunc13-2 contain a conserved calmodulin (CaM) binding site and the Ca(2+)-dependent interaction of these Munc13 isoforms with CaM constitutes a molecular mechanism that transduces residual Ca(2+) signaling to the synaptic exocytotic machinery [4].
  • Thus, neurosecretion involves two key processes: the docking of vesicles at the transmitter release site, a process that involves the scaffold protein RIM (Rab3A interacting molecule) and its binding partner Munc-13, and the subsequent gating of vesicle fusion by activation of the Ca2+ channels [5].
  • In neurons, a Munc13-1 C(2)A-domain/RIM zinc-finger domain (ZF) heterodimer couples synaptic vesicle priming to presynaptic plasticity [6].

Anatomical context of UNC13A

  • Priming by Munc13-1 appears to require its interaction with Syntaxin 1 because point mutants that do not bind Syntaxin 1 do not prime chromaffin granules [2].
  • Due to their essential function in synaptic vesicle priming and in the modulation of synaptic strength, Munc13 proteins have emerged as key regulators of these adaptive mechanisms [4].

Associations of UNC13A with chemical compounds

  • The 51-mer chimaerin C1 peptides showed potent PDBu binding, while the Unc13 and Munc13-1 C1 peptides without sufficient positive charges hardly bound PDBu [7].
  • Pharmacological characterization showed that potentiation of exocytosis depended on the activation of PLC but not protein kinase C. Overexpression of wild-type Munc13-1 by adenoviral infection had no effect on histamine-induced potentiation per se, whereas DAG-insensitive Munc13-1(H567K) completely abolished it [8].

Physical interactions of UNC13A


Other interactions of UNC13A

  • The cytomatrix at the AZ (CAZ)-associated protein CAST and its family member ELKS form a large molecular complex at the AZ and regulate neurotransmitter release by binding other AZ proteins including Bassoon, Piccolo, Munc13-1, and RIM1 [9].
  • Furthermore, we affinity-purified a GTP-Rab27A-binding protein in platelets and identified it as Munc13-4, a homologue of Munc13-1 known as a priming factor for neurotransmitter release [10].
  • X-ray diffraction studies guided by nuclear magnetic resonance (NMR) experiments reveal the crystal structures of the Munc13-1 C(2)A-domain homodimer and the Munc13-1 C(2)A-domain/RIM ZF heterodimer at 1.44 A and 1.78 A resolution, respectively [6].

Analytical, diagnostic and therapeutic context of UNC13A

  • A PAL-based Ca(2+) titration assay revealed that all Munc13 isoforms can form a complex with CaM already at low Ca(2+) concentrations just above resting levels, underscoring the Ca(2+) sensor/effector function of this interaction in short-term synaptic plasticity phenomena [4].


  1. Binding to Rab3A-interacting molecule RIM regulates the presynaptic recruitment of Munc13-1 and ubMunc13-2. Andrews-Zwilling, Y.S., Kawabe, H., Reim, K., Varoqueaux, F., Brose, N. J. Biol. Chem. (2006) [Pubmed]
  2. Identification of the minimal protein domain required for priming activity of Munc13-1. Stevens, D.R., Wu, Z.X., Matti, U., Junge, H.J., Schirra, C., Becherer, U., Wojcik, S.M., Brose, N., Rettig, J. Curr. Biol. (2005) [Pubmed]
  3. ELKS, a protein structurally related to the active zone protein CAST, is involved in Ca2+-dependent exocytosis from PC12 cells. Inoue, E., Deguchi-Tawarada, M., Takao-Rikitsu, E., Inoue, M., Kitajima, I., Ohtsuka, T., Takai, Y. Genes Cells (2006) [Pubmed]
  4. Characterization of the Munc13-calmodulin interaction by photoaffinity labeling. Dimova, K., Kawabe, H., Betz, A., Brose, N., Jahn, O. Biochim. Biophys. Acta (2006) [Pubmed]
  5. N type Ca2+ channels and RIM scaffold protein covary at the presynaptic transmitter release face but are components of independent protein complexes. Khanna, R., Li, Q., Sun, L., Collins, T.J., Stanley, E.F. Neuroscience (2006) [Pubmed]
  6. Structural Basis for a Munc13-1 Homodimer to Munc13-1/RIM Heterodimer Switch. Lu, J., Machius, M., Dulubova, I., Dai, H., S??dhof, T.C., Tomchick, D.R., Rizo, J. PLoS Biol. (2006) [Pubmed]
  7. Tumor promoter binding of the protein kinase C C1 homology domain peptides of RasGRPs, chimaerins, and Unc13s. Irie, K., Masuda, A., Shindo, M., Nakagawa, Y., Ohigashi, H. Bioorg. Med. Chem. (2004) [Pubmed]
  8. Potentiation of exocytosis by phospholipase C-coupled G-protein-coupled receptors requires the priming protein Munc13-1. Bauer, C.S., Woolley, R.J., Teschemacher, A.G., Seward, E.P. J. Neurosci. (2007) [Pubmed]
  9. The active zone protein CAST directly associates with Ligand-of-Numb protein X. Higa, S., Tokoro, T., Inoue, E., Kitajima, I., Ohtsuka, T. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  10. Munc13-4 is a GTP-Rab27-binding protein regulating dense core granule secretion in platelets. Shirakawa, R., Higashi, T., Tabuchi, A., Yoshioka, A., Nishioka, H., Fukuda, M., Kita, T., Horiuchi, H. J. Biol. Chem. (2004) [Pubmed]
WikiGenes - Universities