UNC93B1

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. 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. doi:10.1038/nature06726. PMID 18305481. S2CID 4397023.

Further reading


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