UGT1A4

UGT1A4
Identifiers
Aliases	UGT1A4 , 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, UGT1A1
External IDs	OMIM: 606429 MGI: 3032634 HomoloGene: 88621 GeneCards: UGT1A4
Gene location (Human) Chr. Chromosome 2 (human) [1] Band 2q37.1 Start 233,718,736 bp [1] End 233,773,300 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1|1 D Start 88,093,734 bp [2] End 88,146,719 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver duodenum gallbladder kidney urinary bladder renal cortex zone of skin skin of abdomen thymus body of stomach Top expressed in hepatobiliary system liver urinary bladder uterus mouth lip spleen colon kidney duodenum More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity retinoic acid binding hexosyltransferase activity protein homodimerization activity glycosyltransferase activity protein heterodimerization activity enzyme binding glucuronosyltransferase activity UDP-glycosyltransferase activity Cellular component integral component of membrane endoplasmic reticulum membrane membrane intracellular membrane-bounded organelle endoplasmic reticulum Biological process negative 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 glucuronidation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54657 394433 Ensembl ENSG00000244474 ENSMUSG00000089943 UniProt P22310 n/a RefSeq (mRNA) NM_007120 NM_201643 RefSeq (protein) NP_009051 n/a Location (UCSC) Chr 2: 233.72 – 233.77 Mb Chr 1: 88.09 – 88.15 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the UGT1A4 gene. ^{[5] [6] [7]}

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]

It is the main enzyme responsible for glucuronidation of the anticonvulsant lamotrigine. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000244474 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000089943 - Ensembl, 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, 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.
6. 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.
7. "Entrez Gene: UGT1A4 UDP glucuronosyltransferase 1 family, polypeptide A4".
8. 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. 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.