UNC93B1
Unc-93 homolog B1 (C. elegans), also known as UNC93B1, is a protein which in humans is encoded by the UNC93B1 gene.[5][6]
| UNC93B1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | UNC93B1, IIAE1, UNC93, UNC93B, Unc-93B1, unc-93 homolog B1 (C. elegans), unc-93 homolog B1, TLR signaling regulator | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 608204 MGI: 1859307 HomoloGene: 41325 GeneCards: UNC93B1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Function
This gene encodes a protein with similarity to the Caenorhabditis elegans unc93 protein. The Unc93 protein is involved in the regulation or coordination of muscle contraction in the worm.[5]
Molecular biology
The gene is located on long arm of chromosome 11 (11q13) on the minus (Crick) strand[6] and was first identified in 2002.[6] This protein is an intrinsic membrane protein that spans the membrane twelve times. It is found in the endoplasmic reticulum and is highly conserved.
Clinical importance
Unc93B1 protein appears to be involved in the innate immune response. Defects in the protein predispose to hypersensitity to infections with herpes simplex virus and mouse cytomegalovirus.[7] The mechanism is unclear but Unc93B1 is known to interact with the toll-like receptors TLR3, TLR7 and TLR9 and it appears to be involved in the trafficking of these receptors within the cell.[8][9] Mutations in this gene lead to selective impairment of dsRNA-induced interferon alpha/beta and interferon 1 lambda production.
The intracellular toll-like receptors have been shown to interact with UNC93B in splenocytes and bone marrow-derived dendritic cells. TLR3 and TLR9 bind to UNC93B via their transmembrane domains. Introduction of the point mutation H412R (histidine to arginine at amino acid 412: a single base transition - adenosine to guanine at base 1235) in UNC93B abolishes this interaction.
References
- GRCh38: Ensembl release 89: ENSG00000110057 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000036908 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: UNC93B1 unc-93 homolog B1 (C. elegans)".
- Kashuba VI, Protopopov AI, Kvasha SM, Gizatullin RZ, Wahlestedt C, Kisselev LL, Klein G, Zabarovsky ER (January 2002). "hUNC93B1: a novel human gene representing a new gene family and encoding an unc-93-like protein". Gene. 283 (1–2): 209–17. doi:10.1016/S0378-1119(01)00856-3. PMID 11867227.
- Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, Yang K, Alcais A, Picard C, Mahfoufi N, Nicolas N, Lorenzo L, Plancoulaine S, Sénéchal B, Geissmann F, Tabeta K, Hoebe K, Du X, Miller RL, Héron B, Mignot C, de Villemeur TB, Lebon P, Dulac O, Rozenberg F, Beutler B, Tardieu M, Abel L, Casanova JL (October 2006). "Herpes simplex virus encephalitis in human UNC-93B deficiency". Science. 314 (5797): 308–12. Bibcode:2006Sci...314..308C. doi:10.1126/science.1128346. PMID 16973841. S2CID 12501759.
- Tabeta K, Hoebe K, Janssen EM, Du X, Georgel P, Crozat K, Mudd S, Mann N, Sovath S, Goode J, Shamel L, Herskovits AA, Portnoy DA, Cooke M, Tarantino LM, Wiltshire T, Steinberg BE, Grinstein S, Beutler B (February 2006). "The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9". Nat. Immunol. 7 (2): 156–64. doi:10.1038/ni1297. PMID 16415873. S2CID 33401155.
- Kim YM, Brinkmann MM, Paquet ME, Ploegh HL (March 2008). "UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes". Nature. 452 (7184): 234–8. Bibcode:2008Natur.452..234K. doi:10.1038/nature06726. PMID 18305481. S2CID 4397023.
Further reading
- Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Yu W, Andersson B, Worley KC, et al. (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
- Sanger Centre, The; Washington University Genome Sequencing Cente, The (1999). "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. doi:10.1101/gr.8.11.1097. PMID 9847074.
- Kashuba VI, Protopopov AI, Kvasha SM, et al. (2002). "hUNC93B1: a novel human gene representing a new gene family and encoding an unc-93-like protein". Gene. 283 (1–2): 209–17. doi:10.1016/S0378-1119(01)00856-3. PMID 11867227.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Arnlöv J, Sundström J, Lind L, et al. (2006). "hUNC-93B1, a novel gene mainly expressed in the heart, is related to left ventricular diastolic function, heart failure morbidity and mortality in elderly men". Eur. J. Heart Fail. 7 (6): 958–65. doi:10.1016/j.ejheart.2004.06.009. PMID 16111919. S2CID 22339419.
- Taylor TD, Noguchi H, Totoki Y, et al. (2006). "Human chromosome 11 DNA sequence and analysis including novel gene identification". Nature. 440 (7083): 497–500. Bibcode:2006Natur.440..497T. doi:10.1038/nature04632. PMID 16554811.
- Casrouge A, Zhang SY, Eidenschenk C, et al. (2006). "Herpes simplex virus encephalitis in human UNC-93B deficiency". Science. 314 (5797): 308–12. Bibcode:2006Sci...314..308C. doi:10.1126/science.1128346. PMID 16973841. S2CID 12501759.