UGT1A4

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the UGT1A4 gene.[1][2][3]

This gene encodes 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. This enzyme has some glucuronidase activity towards bilirubin, although it is more active on amines, steroids, and sapogenins.[3] It is the main enzyme responsible for glucuronidation of the anticonvulsant lamotrigine.[4]

References

  1. ↑ Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Belanger 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 (Oct 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 (Mar 1992). "A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini". J Biol Chem. 267 (5): 3257–61. PMID 1339448.
  3. ↑ 3.0 3.1 "Entrez Gene: UGT1A4 UDP glucuronosyltransferase 1 family, polypeptide A4".
  4. ↑ Sandson NB, Armstrong SC, Cozza KL (2005). "An overview of psychotropic drug-drug interactions". Psychosomatics. 46 (5): 464–94. doi:10.1176/appi.psy.46.5.464. PMID 16145193.

Further reading

  • Tukey RH, Strassburg CP (2000). "Human UDP-glucuronosyltransferases: metabolism, expression, and disease". Annu. Rev. Pharmacol. Toxicol. 40: 581–616. doi:10.1146/annurev.pharmtox.40.1.581. PMID 10836148.
  • King CD, Rios GR, Green MD, Tephly TR (2001). "UDP-glucuronosyltransferases". Curr. Drug Metab. 1 (2): 143–61. doi:10.2174/1389200003339171. PMID 11465080.
  • Bosma PJ, Chowdhury JR, Huang TJ, et al. (1992). "Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I.". FASEB J. 6 (10): 2859–63. PMID 1634050.
  • Ritter JK, Crawford JM, Owens IS (1991). "Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells". J. Biol. Chem. 266 (2): 1043–7. PMID 1898728.
  • Moghrabi N, Clarke DJ, Boxer M, Burchell B (1994). "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, et al. (1994). "Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II". Biochem. Biophys. Res. Commun. 197 (3): 1239–44. doi:10.1006/bbrc.1993.2610. PMID 8280139.
  • van Es HH, Bout A, Liu J, et al. (1993). "Assignment of the human UDP glucuronosyltransferase gene (UGT1A1) to chromosome region 2q37". Cytogenet. Cell Genet. 63 (2): 114–6. doi:10.1159/000133513. PMID 8467709.
  • Strassburg CP, Oldhafer K, Manns MP, Tukey RH (1997). "Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue". Mol. Pharmacol. 52 (2): 212–20. PMID 9271343.
  • Strassburg CP, Manns MP, Tukey RH (1998). "Expression of the UDP-glucuronosyltransferase 1A locus in human colon. Identification and characterization of the novel extrahepatic UGT1A8". J. Biol. Chem. 273 (15): 8719–26. doi:10.1074/jbc.273.15.8719. PMID 9535849.
  • Hiller A, Nguyen N, Strassburg CP, et al. (1999). "Retigabine N-glucuronidation and its potential role in enterohepatic circulation". Drug Metab. Dispos. 27 (5): 605–12. PMID 10220490.
  • Gong QH, Cho JW, Huang T, et al. (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.
  • Nakajima M, Tanaka E, Kwon JT, Yokoi T (2003). "Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes". Drug Metab. Dispos. 30 (12): 1484–90. doi:10.1124/dmd.30.12.1484. PMID 12433823.
  • 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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Zhang JY, Zhan J, Cook CS, et al. (2003). "Involvement of human UGT2B7 and 2B15 in rofecoxib metabolism". Drug Metab. Dispos. 31 (5): 652–8. doi:10.1124/dmd.31.5.652. PMID 12695355.
  • Kuehl GE, Murphy SE (2004). "N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases". Drug Metab. Dispos. 31 (11): 1361–8. doi:10.1124/dmd.31.11.1361. PMID 14570768.



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