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.[7]
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. doi:10.1096/fasebj.6.10.1634050. PMID 1634050. S2CID 24007614.
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. doi:10.1016/S0021-9258(17)35280-8. 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. doi:10.1124/mol.52.2.212. PMID 9271343. S2CID 37098463.
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. S2CID 32446541.
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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. 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. S2CID 23434477.
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. S2CID 11360859.
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ugt1a4, glucuronosyltransferase, enzyme, that, humans, encoded, gene, identifiersaliases, udpgt, udpgt, ugt1, ugt1, ugt1d, glucuronosyltransferase, family, member, ugt1, ugt1a, ugt1, gnt1, ugt1, ugt1a1external, idsomim, 606429, 3032634, homologene, 88621, gene. UDP glucuronosyltransferase 1 4 is an enzyme that in humans is encoded by the UGT1A4 gene 5 6 7 UGT1A4IdentifiersAliasesUGT1A4 HUG BR2 UDPGT UDPGT 1 4 UGT 1D UGT1 04 UGT1 4 UGT1D UGT1A4S UDP glucuronosyltransferase family 1 member A4 UGT1 01 UGT 1A UGT1A hUG BR1 UGT1 GNT1 UGT1 1 UGT1A1External IDsOMIM 606429 MGI 3032634 HomoloGene 88621 GeneCards UGT1A4Gene location Human Chr Chromosome 2 human 1 Band2q37 1Start233 718 736 bp 1 End233 773 300 bp 1 Gene location Mouse Chr Chromosome 1 mouse 2 Band1 1 DStart88 093 734 bp 2 End88 146 719 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inright lobe of liverduodenumgallbladderkidneyurinary bladderrenal cortexzone of skinskin of abdomenthymusbody of stomachTop expressed inhepatobiliary systemliverurinary bladderuterusmouthlipspleencolonkidneyduodenumMore reference expression dataBioGPSn aGene ontologyMolecular functiontransferase activity retinoic acid binding hexosyltransferase activity protein homodimerization activity glycosyltransferase activity protein heterodimerization activity enzyme binding glucuronosyltransferase activity UDP glycosyltransferase activityCellular componentintegral component of membrane endoplasmic reticulum membrane membrane intracellular membrane bounded organelle endoplasmic reticulumBiological processnegative regulation of cellular glucuronidation heme catabolic process cellular glucuronidation xenobiotic glucuronidation metabolism negative regulation of glucuronosyltransferase activity negative regulation of fatty acid metabolic process bilirubin conjugation flavonoid glucuronidationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez54657394433EnsemblENSG00000244474ENSMUSG00000089943UniProtP22310n aRefSeq mRNA NM 007120NM 201643RefSeq protein NP 009051n aLocation UCSC Chr 2 233 72 233 77 MbChr 1 88 09 88 15 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseThis 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 7 It is the main enzyme responsible for glucuronidation of the anticonvulsant lamotrigine 8 References edit a b c GRCh38 Ensembl release 89 ENSG00000244474 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000089943 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 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 doi 10 1016 S0021 9258 19 50724 4 PMID 1339448 a b Entrez Gene UGT1A4 UDP glucuronosyltransferase 1 family polypeptide A4 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 editTukey 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 doi 10 1096 fasebj 6 10 1634050 PMID 1634050 S2CID 24007614 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 doi 10 1016 S0021 9258 17 35280 8 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 doi 10 1124 mol 52 2 212 PMID 9271343 S2CID 37098463 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 S2CID 32446541 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 Bibcode 2002PNAS 9916899M 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 S2CID 23434477 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 S2CID 11360859 nbsp This protein related article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title UGT1A4 amp oldid 1170088926, wikipedia, wiki, book, books, library,
