UGT1A6

UDP glucuronosyltransferase 1 family, polypeptide A6
Identifiers
Symbols	UGT1A6 ; GNT1; HLUGP; HLUGP1; UDPGT; UDPGT 1-6; UGT1; UGT1A6S; UGT1F
External IDs	OMIM: 606431 MGI: 2137698 HomoloGene: 85959 ChEMBL: 1743316 GeneCards: UGT1A6 Gene
EC number	2.4.1.17
Gene ontology Molecular function • retinoic acid binding • glucuronosyltransferase activity • enzyme binding • protein homodimerization activity • protein heterodimerization activity Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • integral component of membrane • extracellular exosome Biological process • xenobiotic metabolic process • flavonoid biosynthetic process • drug metabolic process • cellular response to hormone stimulus • small molecule metabolic process • negative regulation of fatty acid metabolic process • cellular glucuronidation • flavonoid glucuronidation • xenobiotic glucuronidation • negative regulation of glucuronosyltransferase activity • negative regulation of cellular glucuronidation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	54578	94284
Ensembl	ENSG00000167165	ENSMUSG00000054545
UniProt	P19224	Q64435
RefSeq (mRNA)	NM_001072	NM_145079
RefSeq (protein)	NP_001063	NP_659545
Location (UCSC)	Chr 2: 233.69 – 233.77 Mb	Chr 1: 88.13 – 88.22 Mb
PubMed search

UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the UGT1A6 gene.^[1][2][3]

Function

UDP-glucuronosyltransferase 1-6 is 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. The enzyme encoded by this gene is active on phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants.^[3]

UDP-glucuronosyltransferase is also responsible for the inactivation of popular analgesic drugs, such as aspirin and acetaminophen, by glucuronidation. The loss of a functional UGT1A6 gene in certain hypercarnivores, and particularly cats, renders the animals extremely sensitive to the adverse effects of these analgesics.^[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): 255–269. 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. "Entrez Gene: UGT1A6 UDP glucuronosyltransferase 1 family, polypeptide A6".
4. Shrestha B, Reed JM, Starks PT, Kaufman GE, Goldstone JV, Roelke ME, O'Brien SJ, Koepfli K-P, Frank LG, Court MH, Zanger U (2011). Zanger, Ulrich, ed. "Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory". PLoS ONE 6 (3): e18046. doi:10.1371/journal.pone.0018046. PMC 3065456. PMID 21464924.

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): 143–161. doi:10.2174/1389200003339171. PMID 11465080.
• Bock KW, Köhle C (2006). "UDP-glucuronosyltransferase 1A6: structural, functional, and regulatory aspects". Meth. Enzymol. 400: 57–75. doi:10.1016/S0076-6879(05)00004-2. PMID 16399343.
• 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.
• Harding D, Jeremiah SJ, Povey S, Burchell B (1990). "Chromosomal mapping of a human phenol UDP-glucuronosyltransferase, GNT1". Ann. Hum. Genet. 54 (Pt 1): 17–21. doi:10.1111/j.1469-1809.1990.tb00356.x. PMID 2108603.
• Harding D, Fournel-Gigleux S, Jackson MR, Burchell B (1988). "Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells". Proc. Natl. Acad. Sci. U.S.A. 85 (22): 8381–8385. doi:10.1073/pnas.85.22.8381. PMC 282461. PMID 3141926.
• 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): 171–173. 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): 1239–1244. doi:10.1006/bbrc.1993.2610. PMID 8280139.
• Killard AJ, O'Kennedy R, Bogan DP (1997). "Analysis of the glucuronidation of 7-hydroxycoumarin by HPLC". Journal of pharmaceutical and biomedical analysis 14 (11): 1585–1590. doi:10.1016/0731-7085(96)01801-8. PMID 8877866.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Ciotti M, Marrone A, Potter C, Owens IS (1998). "Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications". Pharmacogenetics 7 (6): 485–495. doi:10.1097/00008571-199712000-00007. PMID 9429234.
• Münzel PA, Lehmköster T, Brück M, et al. (1998). "Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6". Arch. Biochem. Biophys. 350 (1): 72–78. doi:10.1006/abbi.1997.0485. PMID 9466822.
• Duffy CF, O'Kennedy R (1999). "Determination of 7-hydroxycoumarin and its glucuronide and sulphate conjugates in liver slice incubates by capillary zone electrophoresis". Journal of pharmaceutical and biomedical analysis 17 (8): 1279–1284. doi:10.1016/S0731-7085(98)00015-6. PMID 9800648.
• Gong QH, Cho JW, Huang T, et al. (2001). "Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus". Pharmacogenetics 11 (4): 357–368. doi:10.1097/00008571-200106000-00011. PMID 11434514.