UNC93B1

UNC93B1
Identifiers
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
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q13.2 Start 67,991,100 bp [1] End 68,004,982 bp [1]
Gene location (Mouse) Chr. Chromosome 19 (mouse) [2] Band 19|19 A Start 3,985,186 bp [2] End 3,999,340 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte spleen bone marrow cells appendix right lung right uterine tube upper lobe of left lung minor salivary gland gallbladder stromal cell of endometrium Top expressed in spleen calvaria ankle joint ankle submandibular gland subcutaneous adipose tissue lip duodenum thymus white adipose tissue More reference expression data BioGPS n/a
Gene ontology Molecular function Toll-like receptor binding Cellular component integral component of membrane early phagosome Golgi membrane endosome lysosome phagocytic vesicle endoplasmic reticulum membrane endoplasmic reticulum membrane cytoplasmic vesicle Biological process toll-like receptor 9 signaling pathway intracellular protein transport toll-like receptor 3 signaling pathway adaptive immune response defense response to virus toll-like receptor 7 signaling pathway toll-like receptor signaling pathway immune system process innate immune response Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 81622 54445 Ensembl ENSG00000110057 ENSMUSG00000036908 UniProt Q9H1C4 Q8VCW4 RefSeq (mRNA) NM_030930 NM_001161428 NM_019449 RefSeq (protein) NP_112192 NP_001154900 NP_062322 Location (UCSC) Chr 11: 67.99 – 68 Mb Chr 19: 3.99 – 4 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Unc-93 homolog B1 ( C. elegans ), also known as UNC93B1, is a protein which in humans is encoded by the UNC93B1 gene. ^{[5] [6]}

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

1. GRCh38: Ensembl release 89: ENSG00000110057 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036908 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: UNC93B1 unc-93 homolog B1 (C. elegans)".
6. 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.
7. 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.
8. 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.
9. 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.