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UGT1A6

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UGT1A6
Identifiers
AliasesUGT1A6, GNT1, HLUGP, HLUGP1, UDPGT, UDPGT 1-6, UGT1, UGT1A6S, UGT1F, UDP glucuronosyltransferase family 1 member A6, UGT1.5, hUG-BR1, UGT1.3, UGT-1C, UGT1A, UGT1E, UGT-1A, UGT-1E, UGT1A3, UGT1A1, UGT1A5, UGT1-01, UGT1C, UGT1-05, UGT1-03, UGT1.1, UGT1.6, UGT1-06, UGT-1F
External IDsOMIM: 606431; MGI: 3580629; HomoloGene: 85959; GeneCards: UGT1A6; OMA:UGT1A6 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_205862
NM_001072

NM_201410

RefSeq (protein)

NP_001063
NP_995584

NP_958812

Location (UCSC)Chr 2: 233.69 – 233.77 MbChr 1: 88.03 – 88.15 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the UGT1A6 gene.[5][6][7]

Function

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UDP-glucuronosyltransferase 1-6 is a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites.

This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants.[7]

This enzyme is also responsible for the inactivation of popular analgesic drugs, such as aspirin and acetaminophen, by glucuronidation. The loss of a functional UGT1A6 gene in certain hypercarnivores, and particularly cats, renders the animals extremely sensitive to the adverse effects of these analgesics.[8]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000167165Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000090145Ensembl, 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. ^ Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Bélanger A, Fournel-Gigleux S, Green M, Hum DW, Iyanagi T, Lancet D, Louisot P, Magdalou J, Chowdhury JR, Ritter JK, Schachter H, Tephly TR, Tipton KF, Nebert DW (August 1997). "The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence". Pharmacogenetics. 7 (4): 255–69. doi:10.1097/00008571-199708000-00001. PMID 9295054.
  6. ^ Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS (February 1992). "A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini". The Journal of Biological Chemistry. 267 (5): 3257–61. doi:10.1016/S0021-9258(19)50724-4. PMID 1339448.
  7. ^ a b "Entrez Gene: UGT1A6 UDP glucuronosyltransferase 1 family, polypeptide A6".
  8. ^ Shrestha B, Reed JM, Starks PT, Kaufman GE, Goldstone JV, Roelke ME, O'Brien SJ, Koepfli KP, Frank LG, Court MH (2011). Zanger U (ed.). "Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: phylogenetic timing and the role of hypercarnivory". PLOS ONE. 6 (3): e18046. Bibcode:2011PLoSO...618046S. doi:10.1371/journal.pone.0018046. PMC 3065456. PMID 21464924.

Further reading

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