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; OMA:UGT1A4 - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	233,773,300 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	88,146,719 bp
RNA expression pattern
	Top expressed in
	right lobe of liver; ; duodenum; ; gallbladder; ; mucosa of transverse colon; ; human kidney; ; olfactory zone of nasal mucosa; ; urinary bladder; ; mucosa of esophagus; ; renal cortex; ; zone of skin;
	Top expressed in
	hepatobiliary system; ; liver; ; granulocyte; ; urinary bladder; ; uterus; ; mouth; ; lip; ; spleen; ; colon; ; human kidney;
	More reference expression data
	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
	54657
	394433
	ENSG00000244474
	ENSMUSG00000089943
	P22310
	n/a
	NM_007120
	NM_201643
	NP_009051
	n/a
	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

^ ^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.

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.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000244474 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid9295054-5] 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.

[pmid1339448-6] 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.

[entrez-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.

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References

Further reading