UGT1A6

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the UGT1A6 gene.[1][2][3]

Function

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.[3]

UDP-glucuronosyltransferase 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.[4]

References

  1. ↑ 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.
  2. ↑ 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. PMID 1339448.
  3. ↑ 3.0 3.1 "Entrez Gene: UGT1A6 UDP glucuronosyltransferase 1 family, polypeptide A6".
  4. ↑ 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. doi:10.1371/journal.pone.0018046. PMC 3065456. PMID 21464924.

Further reading

  • Tukey RH, Strassburg CP (2000). "Human UDP-glucuronosyltransferases: metabolism, expression, and disease". Annual Review of Pharmacology and Toxicology. 40: 581–616. doi:10.1146/annurev.pharmtox.40.1.581. PMID 10836148.
  • King CD, Rios GR, Green MD, Tephly TR (September 2000). "UDP-glucuronosyltransferases". Current Drug Metabolism. 1 (2): 143–61. doi:10.2174/1389200003339171. PMID 11465080.
  • Bock KW, Köhle C (2006). "UDP-glucuronosyltransferase 1A6: structural, functional, and regulatory aspects". Methods in Enzymology. 400: 57–75. doi:10.1016/S0076-6879(05)00004-2. PMID 16399343.
  • Bosma PJ, Chowdhury JR, Huang TJ, Lahiri P, Elferink RP, Van Es HH, Lederstein M, Whitington PF, Jansen PL, Chowdhury NR (July 1992). "Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I". FASEB Journal. 6 (10): 2859–63. PMID 1634050.
  • Ritter JK, Crawford JM, Owens IS (January 1991). "Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells". The Journal of Biological Chemistry. 266 (2): 1043–7. PMID 1898728.
  • Harding D, Jeremiah SJ, Povey S, Burchell B (January 1990). "Chromosomal mapping of a human phenol UDP-glucuronosyltransferase, GNT1". Annals of Human Genetics. 54 (Pt 1): 17–21. doi:10.1111/j.1469-1809.1990.tb00356.x. PMID 2108603.
  • Harding D, Fournel-Gigleux S, Jackson MR, Burchell B (November 1988). "Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells". Proceedings of the National Academy of Sciences of the United States of America. 85 (22): 8381–5. doi:10.1073/pnas.85.22.8381. PMC 282461. PMID 3141926.
  • Moghrabi N, Clarke DJ, Boxer M, Burchell B (October 1993). "Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2". Genomics. 18 (1): 171–3. doi:10.1006/geno.1993.1451. PMID 8276413.
  • Aono S, Yamada Y, Keino H, Hanada N, Nakagawa T, Sasaoka Y, Yazawa T, Sato H, Koiwai O (December 1993). "Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II". Biochemical and Biophysical Research Communications. 197 (3): 1239–44. doi:10.1006/bbrc.1993.2610. PMID 8280139.
  • Killard AJ, O'Kennedy R, Bogan DP (August 1996). "Analysis of the glucuronidation of 7-hydroxycoumarin by HPLC". Journal of Pharmaceutical and Biomedical Analysis. 14 (11): 1585–90. doi:10.1016/0731-7085(96)01801-8. PMID 8877866.
  • Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
  • Ciotti M, Marrone A, Potter C, Owens IS (December 1997). "Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications". Pharmacogenetics. 7 (6): 485–95. doi:10.1097/00008571-199712000-00007. PMID 9429234.
  • Münzel PA, Lehmköster T, Brück M, Ritter JK, Bock KW (February 1998). "Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6". Archives of Biochemistry and Biophysics. 350 (1): 72–8. doi:10.1006/abbi.1997.0485. PMID 9466822.
  • Duffy CF, O'Kennedy R (September 1998). "Determination of 7-hydroxycoumarin and its glucuronide and sulphate conjugates in liver slice incubates by capillary zone electrophoresis". Journal of Pharmaceutical and Biomedical Analysis. 17 (8): 1279–84. doi:10.1016/S0731-7085(98)00015-6. PMID 9800648.
  • Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC (June 2001). "Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus". Pharmacogenetics. 11 (4): 357–68. doi:10.1097/00008571-200106000-00011. PMID 11434514.


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