UGT1A6

UGT1A6
Identifiers
Aliases	UGT1A6 , GNT1, HLUGP, HLUGP1, UDPGT, UDPGT 1-6, UGT1, UGT1A6S, UGT1F, UDP glucuronosyltransferase family 1 member A6, UGT1.5, hUG-BR1, UGT1.3, UGT-1C, UGT1A, UGT1E, UGT-1A, UGT-1E, UGT1A3, UGT1A1, UGT1A5, UGT1-01, UGT1C, UGT1-05, UGT1-03, UGT1.1, UGT1.6, UGT1-06, UGT-1F
External IDs	OMIM: 606431 MGI: 3580629 HomoloGene: 85959 GeneCards: UGT1A6
Gene location (Human) Chr. Chromosome 2 (human) [1] Band 2q37.1 Start 233,691,607 bp [1] End 233,773,300 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1|1 D Start 88,030,974 bp [2] End 88,146,725 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in liver right lobe of liver kidney urinary bladder skin of abdomen duodenum renal cortex islet of Langerhans body of stomach fundus Top expressed in urinary bladder white adipose tissue exocrine gland hepatobiliary system liver kidney tubule proximal tubule lateral recess renal medulla loop of Henle 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 cellular glucuronidation xenobiotic glucuronidation metabolism negative regulation of glucuronosyltransferase activity negative regulation of fatty acid metabolic process xenobiotic metabolic process flavonoid glucuronidation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54578 394435 Ensembl ENSG00000167165 ENSMUSG00000090145 UniProt P19224 K9J7B2 RefSeq (mRNA) NM_205862 NM_001072 NM_201410 RefSeq (protein) NP_001063 NP_995584 NP_958812 Location (UCSC) Chr 2: 233.69 – 233.77 Mb Chr 1: 88.03 – 88.15 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the UGT1A6 gene. ^{[5] [6] [7]}

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. ^[7]

This enzyme 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. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000167165 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000090145 - 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, 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 (August 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 (February 1992). "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. doi: 10.1016/S0021-9258(19)50724-4 . PMID   1339448.
7. "Entrez Gene: UGT1A6 UDP glucuronosyltransferase 1 family, polypeptide A6".
8. Shrestha B, Reed JM, Starks PT, Kaufman GE, Goldstone JV, Roelke ME, O'Brien SJ, Koepfli KP, Frank LG, Court MH (2011). Zanger U (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. Bibcode:2011PLoSO...618046S. doi: 10.1371/journal.pone.0018046 . PMC   3065456 . PMID   21464924.

Further reading

• Tukey RH, Strassburg CP (2000). "Human UDP-glucuronosyltransferases: metabolism, expression, and disease". Annual Review of Pharmacology and Toxicology. 40: 581–616. doi:10.1146/annurev.pharmtox.40.1.581. PMID   10836148.
• King CD, Rios GR, Green MD, Tephly TR (September 2000). "UDP-glucuronosyltransferases". Current Drug Metabolism. 1 (2): 143–61. doi:10.2174/1389200003339171. PMID   11465080.
• Bock KW, Köhle C (2006). "UDP-Glucuronosyltransferase 1A6: Structural, Functional, and Regulatory Aspects". Phase II Conjugation Enzymes and Transport Systems. Methods in Enzymology. Vol. 400. pp. 57–75. doi:10.1016/S0076-6879(05)00004-2. ISBN   9780121828059. PMID   16399343.
• Bosma PJ, Chowdhury JR, Huang TJ, Lahiri P, Elferink RP, Van Es HH, Lederstein M, Whitington PF, Jansen PL, Chowdhury NR (July 1992). "Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I". FASEB Journal. 6 (10): 2859–63. doi: 10.1096/fasebj.6.10.1634050 . PMID   1634050. S2CID   24007614.
• Ritter JK, Crawford JM, Owens IS (January 1991). "Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells". The Journal of Biological Chemistry. 266 (2): 1043–7. doi: 10.1016/S0021-9258(17)35280-8 . PMID   1898728.
• Harding D, Jeremiah SJ, Povey S, Burchell B (January 1990). "Chromosomal mapping of a human phenol UDP-glucuronosyltransferase, GNT1". Annals of Human Genetics. 54 (Pt 1): 17–21. doi:10.1111/j.1469-1809.1990.tb00356.x. PMID   2108603. S2CID   35661967.
• Harding D, Fournel-Gigleux S, Jackson MR, Burchell B (November 1988). "Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells". Proceedings of the National Academy of Sciences of the United States of America. 85 (22): 8381–5. Bibcode:1988PNAS...85.8381H. doi: 10.1073/pnas.85.22.8381 . PMC   282461 . PMID   3141926.
• Moghrabi N, Clarke DJ, Boxer M, Burchell B (October 1993). "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, Hanada N, Nakagawa T, Sasaoka Y, Yazawa T, Sato H, Koiwai O (December 1993). "Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II". Biochemical and Biophysical Research Communications. 197 (3): 1239–44. doi:10.1006/bbrc.1993.2610. PMID   8280139.
• Killard AJ, O'Kennedy R, Bogan DP (August 1996). "Analysis of the glucuronidation of 7-hydroxycoumarin by HPLC". Journal of Pharmaceutical and Biomedical Analysis. 14 (11): 1585–90. doi:10.1016/0731-7085(96)01801-8. PMID   8877866.
• Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Ciotti M, Marrone A, Potter C, Owens IS (December 1997). "Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications". Pharmacogenetics. 7 (6): 485–95. doi:10.1097/00008571-199712000-00007. PMID   9429234.
• Münzel PA, Lehmköster T, Brück M, Ritter JK, Bock KW (February 1998). "Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6". Archives of Biochemistry and Biophysics. 350 (1): 72–8. doi:10.1006/abbi.1997.0485. PMID   9466822.
• Duffy CF, O'Kennedy R (September 1998). "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): 1279–84. doi:10.1016/S0731-7085(98)00015-6. PMID   9800648.
• Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC (June 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.