UGT1A3 explained

UDP-glucuronosyltransferase 1-3 is an enzyme that in humans is encoded by the UGT1A3 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. Substrates of this enzyme include estrone, 2-hydroxyestrone, and metabolites of benzo(a)pyrene.^{[4] [5] [6]}

References

Further reading

• Tukey RH, Strassburg CP . Human UDP-glucuronosyltransferases: metabolism, expression, and disease . Annual Review of Pharmacology and Toxicology . 40 . 581–616 . 2000 . 10836148 . 10.1146/annurev.pharmtox.40.1.581 .
• Tukey RH, Strassburg CP . Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract . Molecular Pharmacology . 59 . 3 . 405–14 . March 2001 . 11179432 . 10.1124/mol.59.3.405. 21500183 .
• King CD, Rios GR, Green MD, Tephly TR . UDP-glucuronosyltransferases . Current Drug Metabolism . 1 . 2 . 143–61 . September 2000 . 11465080 . 10.2174/1389200003339171 .
• Moghrabi N, Sutherland L, Wooster R, Povey S, Boxer M, Burchell B . Chromosomal assignment of human phenol and bilirubin UDP-glucuronosyltransferase genes (UGT1A-subfamily) . Annals of Human Genetics . 56 . 2 . 81–91 . May 1992 . 1503396 . 10.1111/j.1469-1809.1992.tb01134.x . 40140345 .
• Mojarrabi B, Butler R, Mackenzie PI . cDNA cloning and characterization of the human UDP glucuronosyltransferase, UGT1A3 . Biochemical and Biophysical Research Communications . 225 . 3 . 785–90 . August 1996 . 8780690 . 10.1006/bbrc.1996.1251 .
• Strassburg CP, Manns MP, Tukey RH . Differential down-regulation of the UDP-glucuronosyltransferase 1A locus is an early event in human liver and biliary cancer . Cancer Research . 57 . 14 . 2979–85 . July 1997 . 9230212 .
• Strassburg CP, Oldhafer K, Manns MP, Tukey RH . Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue . Molecular Pharmacology . 52 . 2 . 212–20 . August 1997 . 9271343 . 10.1124/mol.52.2.212. 37098463 .
• Strassburg CP, Manns MP, Tukey RH . Expression of the UDP-glucuronosyltransferase 1A locus in human colon. Identification and characterization of the novel extrahepatic UGT1A8 . The Journal of Biological Chemistry . 273 . 15 . 8719–26 . April 1998 . 9535849 . 10.1074/jbc.273.15.8719 . free .
• Green MD, King CD, Mojarrabi B, Mackenzie PI, Tephly TR . Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3 . Drug Metabolism and Disposition . 26 . 6 . 507–12 . June 1998 . 9616184 .
• Strassburg CP, Kneip S, Topp J, Obermayer-Straub P, Barut A, Tukey RH, Manns MP . Polymorphic gene regulation and interindividual variation of UDP-glucuronosyltransferase activity in human small intestine . The Journal of Biological Chemistry . 275 . 46 . 36164–71 . November 2000 . 10748067 . 10.1074/jbc.M002180200 . free .
• Barbier O, Albert C, Martineau I, Vallée M, High K, Labrie F, Hum DW, Labrie C, Bélanger A . Glucuronidation of the nonsteroidal antiestrogen EM-652 (SCH 57068), by human and monkey steroid conjugating UDP-glucuronosyltransferase enzymes . Molecular Pharmacology . 59 . 3 . 636–45 . March 2001 . 11179460 . 10.1124/mol.59.3.636. 38640331 .
• Turgeon D, Chouinard S, Belanger P, Picard S, Labbe JF, Borgeat P, Belanger A . Glucuronidation of arachidonic and linoleic acid metabolites by human UDP-glucuronosyltransferases . Journal of Lipid Research . 44 . 6 . 1182–91 . June 2003 . 12639971 . 10.1194/jlr.M300010-JLR200 . free .
• Zhang JY, Zhan J, Cook CS, Ings RM, Breau AP . Involvement of human UGT2B7 and 2B15 in rofecoxib metabolism . Drug Metabolism and Disposition . 31 . 5 . 652–8 . May 2003 . 12695355 . 10.1124/dmd.31.5.652 . 23434477 .

Notes and References

1. Web site: Gene: UGT1A3 (ENSG00000243135) - Summary - Homo sapiens - Ensembl genome browser 89. may2017.archive.ensembl.org. 2019-05-18.
2. Web site: Gene: Ugt1a2 (ENSMUSG00000090171) - Summary - Mus musculus - Ensembl genome browser 89. may2017.archive.ensembl.org. 2019-05-18.
3. 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 . 6 . The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence . Pharmacogenetics . 7 . 4 . 255–69 . August 1997 . 9295054 . 10.1097/00008571-199708000-00001 .
4. Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS . 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 . February 1992 . 10.1016/S0021-9258(19)50724-4 . 1339448 . free .
5. Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC . Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus . Pharmacogenetics . 11 . 4 . 357–68 . June 2001 . 11434514 . 10.1097/00008571-200106000-00011 .
6. Web site: UGT1A3 UDP glucuronosyltransferase family 1 member A3 [Homo sapiens (human)] - Gene - NCBI]. www.ncbi.nlm.nih.gov. 2019-05-18.