UNC13B

Unc-13 homolog B (C. elegans)
Identifiers
Symbols	UNC13B ; MUNC13; UNC13; Unc13h2
External IDs	OMIM: 605836 MGI: 1342278 HomoloGene: 31376 GeneCards: UNC13B Gene
Gene ontology Molecular function • signal transducer activity • receptor activity • protein binding • diacylglycerol binding • metal ion binding Cellular component • cytoplasm • Golgi apparatus • cytosol • plasma membrane • cell junction • neuromuscular junction • terminal bouton • presynaptic active zone Biological process • apoptotic process • signal transduction • synaptic transmission • neurotransmitter secretion • neuromuscular junction development • excretion • positive regulation of synaptic vesicle priming • glutamate secretion • synaptic vesicle docking • synaptic vesicle priming • synaptic transmission, glutamatergic • intracellular signal transduction • regulation of short-term neuronal synaptic plasticity • innervation • positive regulation of inhibitory postsynaptic potential Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10497	22249
Ensembl	ENSG00000198722	ENSMUSG00000028456
UniProt	O14795	Q9Z1N9
RefSeq (mRNA)	NM_006377	NM_001081413
RefSeq (protein)	NP_006368	NP_001074882
Location (UCSC)	Chr 9: 35.16 – 35.41 Mb	Chr 4: 43.06 – 43.26 Mb
PubMed search

Protein unc-13 homolog B is a protein that in humans is encoded by the UNC13B gene.^[1][2]

Function

This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis.^[2]

Interactions

UNC13B has been shown to interact with:

• DOC2A,^[3][4]
• RIMS1,^[5][6]
• SPTBN2,^[7]
• STX1A,^[8] and
• STX1B.^[8]

References

1. Song Y, Ailenberg M, Silverman M (August 1998). "Cloning of a novel gene in the human kidney homologous to rat munc13s: its potential role in diabetic nephropathy". Kidney Int 53 (6): 1689–95. doi:10.1046/j.1523-1755.1998.00942.x. PMID 9607201.
2. "Entrez Gene: UNC13B unc-13 homolog B (C. elegans)".
3. Orita S, Naito A, Sakaguchi G, Maeda M, Igarashi H, Sasaki T, Takai Y (June 1997). "Physical and functional interactions of Doc2 and Munc13 in Ca2+-dependent exocytotic machinery". J. Biol. Chem. 272 (26): 16081–4. doi:10.1074/jbc.272.26.16081. PMID 9195900.
4. Mochida S, Orita S, Sakaguchi G, Sasaki T, Takai Y (September 1998). "Role of the Doc2 alpha-Munc13-1 interaction in the neurotransmitter release process". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11418–22. doi:10.1073/pnas.95.19.11418. PMC 21657. PMID 9736751.
5. Betz A, Thakur P, Junge HJ, Ashery U, Rhee JS, Scheuss V, Rosenmund C, Rettig J, Brose N (April 2001). "Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming". Neuron 30 (1): 183–96. doi:10.1016/s0896-6273(01)00272-0. PMID 11343654.
6. Ohtsuka T, Takao-Rikitsu E, Inoue E, Inoue M, Takeuchi M, Matsubara K, Deguchi-Tawarada M, Satoh K, Morimoto K, Nakanishi H, Takai Y (August 2002). "Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1". J. Cell Biol. 158 (3): 577–90. doi:10.1083/jcb.200202083. PMC 2173811. PMID 12163476.
7. Sakaguchi G, Orita S, Naito A, Maeda M, Igarashi H, Sasaki T, Takai Y (July 1998). "A novel brain-specific isoform of beta spectrin: isolation and its interaction with Munc13". Biochem. Biophys. Res. Commun. 248 (3): 846–51. doi:10.1006/bbrc.1998.9067. PMID 9704016.
8. Betz A, Okamoto M, Benseler F, Brose N (January 1997). "Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin". J. Biol. Chem. 272 (4): 2520–6. doi:10.1074/jbc.272.4.2520. PMID 8999968.

Further reading

• Betz A, Okamoto M, Benseler F, Brose N (1997). "Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin". J. Biol. Chem. 272 (4): 2520–6. doi:10.1074/jbc.272.4.2520. PMID 8999968.
• Orita S, Naito A, Sakaguchi G, Maeda M, Igarashi H, Sasaki T, Takai Y (1997). "Physical and functional interactions of Doc2 and Munc13 in Ca2+-dependent exocytotic machinery". J. Biol. Chem. 272 (26): 16081–4. doi:10.1074/jbc.272.26.16081. PMID 9195900.
• Sakaguchi G, Orita S, Naito A, Maeda M, Igarashi H, Sasaki T, Takai Y (1998). "A novel brain-specific isoform of beta spectrin: isolation and its interaction with Munc13". Biochem. Biophys. Res. Commun. 248 (3): 846–51. doi:10.1006/bbrc.1998.9067. PMID 9704016.
• Mochida S, Orita S, Sakaguchi G, Sasaki T, Takai Y (1998). "Role of the Doc2α–Munc13–1 interaction in the neurotransmitter release process". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11418–22. doi:10.1073/pnas.95.19.11418. PMC 21657. PMID 9736751.
• Song Y, Ailenberg M, Silverman M (1999). "Human munc13 Is a Diacylglycerol Receptor that Induces Apoptosis and May Contribute to Renal Cell Injury in Hyperglycemia". Mol. Biol. Cell 10 (5): 1609–19. doi:10.1091/mbc.10.5.1609. PMC 30485. PMID 10233166.
• Duncan RR, Betz A, Shipston MJ, Brose N, Chow RH (1999). "Transient, phorbol ester-induced DOC2-Munc13 interactions in vivo". J. Biol. Chem. 274 (39): 27347–50. doi:10.1074/jbc.274.39.27347. PMID 10488064.
• Betz A, Thakur P, Junge HJ, Ashery U, Rhee JS, Scheuss V, Rosenmund C, Rettig J, Brose N (2001). "Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming". Neuron 30 (1): 183–96. doi:10.1016/S0896-6273(01)00272-0. PMID 11343654.
• Schoch S, Castillo PE, Jo T, Mukherjee K, Geppert M, Wang Y, Schmitz F, Malenka RC, Südhof TC (2002). "RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone". Nature 415 (6869): 321–6. doi:10.1038/415321a. PMID 11797009.
• Ohtsuka T, Takao-Rikitsu E, Inoue E, Inoue M, Takeuchi M, Matsubara K, Deguchi-Tawarada M, Satoh K, Morimoto K, Nakanishi H, Takai Y (2002). "Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1". J. Cell Biol. 158 (3): 577–90. doi:10.1083/jcb.200202083. PMC 2173811. PMID 12163476.
• Sheu L, Pasyk EA, Ji J, Huang X, Gao X, Varoqueaux F, Brose N, Gaisano HY (2003). "Regulation of insulin exocytosis by Munc13-1". J. Biol. Chem. 278 (30): 27556–63. doi:10.1074/jbc.M303203200. PMID 12871971.
• Cheviet S, Coppola T, Haynes LP, Burgoyne RD, Regazzi R (2004). "The Rab-binding protein Noc2 is associated with insulin-containing secretory granules and is essential for pancreatic beta-cell exocytosis". Mol. Endocrinol. 18 (1): 117–26. doi:10.1210/me.2003-0300. PMID 14593078.
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S (2004). "Sequence Comparison of Human and Mouse Genes Reveals a Homologous Block Structure in the Promoter Regions". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
• Yamamoto K, Ishii E, Sako M, Ohga S, Furuno K, Suzuki N, Ueda I, Imayoshi M, Yamamoto S, Morimoto A, Takada H, Hara T, Imashuku S, Sasazuki T, Yasukawa M (2005). "Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes". J. Med. Genet. 41 (10): 763–7. doi:10.1136/jmg.2004.021121. PMC 1735600. PMID 15466010.
• Speight P, Silverman M (2005). "Diacylglycerol-activated Hmunc13 serves as an effector of the GTPase Rab34". Traffic 6 (10): 858–65. doi:10.1111/j.1600-0854.2005.00321.x. PMID 16138900.