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DeutschUGT1A9
UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the UGT1A9 gene.[5][6][7][8]
Function
[edit]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. The enzyme encoded by this gene is active on phenols.[8]
Interactive pathway map
[edit]Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Irinotecan Pathway edit
- ^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP229".
Inhibitors
[edit]BI-3231, an inhibitor of HSD17B13, was also found to inhibit UGT1A9.[9]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000241119 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000090165 – 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.
- ^ Wooster R, Sutherland L, Ebner T, Clarke D, Da Cruz e Silva O, Burchell B (September 1991). "Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family". The Biochemical Journal. 278 (Pt 2): 465–469. doi:10.1042/bj2780465. PMC 1151367. PMID 1910331.
- ^ Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Bélanger A, et al. (August 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.
- ^ Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, et al. (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): 3257–3261. doi:10.1016/S0021-9258(19)50724-4. PMID 1339448.
- ^ a b "Entrez Gene: UGT1A9 UDP glucuronosyltransferase 1 family, polypeptide A9".
- ^ Thamm S, Willwacher MK, Aspnes GE, Bretschneider T, Brown NF, Buschbom-Helmke S, et al. (February 2023). "Discovery of a Novel Potent and Selective HSD17B13 Inhibitor, BI-3231, a Well-Characterized Chemical Probe Available for Open Science". Journal of Medicinal Chemistry. 66 (4): 2832–2850. doi:10.1021/acs.jmedchem.2c01884. PMC 9969402. PMID 36727857.
Further reading
[edit]- Innocenti F, Kroetz DL, Schuetz E, Dolan ME, Ramírez J, Relling M, et al. (June 2009). "Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics". Journal of Clinical Oncology. 27 (16): 2604–2614. doi:10.1200/JCO.2008.20.6300. PMC 2690389. PMID 19349540.
- Holmes MV, Shah T, Vickery C, Smeeth L, Hingorani AD, Casas JP (December 2009). Luo Y (ed.). "Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies". PLOS ONE. 4 (12): e7960. Bibcode:2009PLoSO...4.7960H. doi:10.1371/journal.pone.0007960. PMC 2778625. PMID 19956635.
- Prausa SE, Fukuda T, Maseck D, Curtsinger KL, Liu C, Zhang K, et al. (May 2009). "UGT genotype may contribute to adverse events following medication with mycophenolate mofetil in pediatric kidney transplant recipients". Clinical Pharmacology and Therapeutics. 85 (5): 495–500. doi:10.1038/clpt.2009.3. PMID 19225446. S2CID 33309241.
- Ross CJ, Katzov-Eckert H, Dubé MP, Brooks B, Rassekh SR, Barhdadi A, et al. (December 2009). "Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy". Nature Genetics. 41 (12): 1345–1349. doi:10.1038/ng.478. PMID 19898482. S2CID 21293339.
- Korprasertthaworn P, Udomuksorn W, Yoovathaworn K (2009). "Three novel single nucleotide polymorphisms of UGT1A9 in a Thai population". Drug Metabolism and Pharmacokinetics. 24 (5): 482–485. doi:10.2133/dmpk.24.482. PMID 19881262.
- Nakajima M, Koga T, Sakai H, Yamanaka H, Fujiwara R, Yokoi T (April 2010). "N-Glycosylation plays a role in protein folding of human UGT1A9". Biochemical Pharmacology. 79 (8): 1165–1172. doi:10.1016/j.bcp.2009.11.020. hdl:2297/23493. PMID 19951703. S2CID 11013645.
- van Schaik RH, van Agteren M, de Fijter JW, Hartmann A, Schmidt J, Budde K, et al. (September 2009). "UGT1A9 -275T>A/-2152C>T polymorphisms correlate with low MPA exposure and acute rejection in MMF/tacrolimus-treated kidney transplant patients". Clinical Pharmacology and Therapeutics. 86 (3): 319–327. doi:10.1038/clpt.2009.83. PMID 19494809. S2CID 21082902.
- Sanna S, Busonero F, Maschio A, McArdle PF, Usala G, Dei M, et al. (July 2009). "Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia". Human Molecular Genetics. 18 (14): 2711–2718. doi:10.1093/hmg/ddp203. PMC 2701337. PMID 19419973.
- King CD, Rios GR, Green MD, Tephly TR (September 2000). "UDP-glucuronosyltransferases". Current Drug Metabolism. 1 (2): 143–161. doi:10.2174/1389200003339171. PMID 11465080.
- Sánchez-Fructuoso AI, Maestro ML, Calvo N, Viudarreta M, Pérez-Flores I, Veganzone S, et al. (2009). "The prevalence of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) gene promoter region single-nucleotide polymorphisms T-275A and C-2152T and its influence on mycophenolic acid pharmacokinetics in stable renal transplant patients". Transplantation Proceedings. 41 (6): 2313–2316. doi:10.1016/j.transproceed.2009.06.038. PMID 19715905.
- Chu XY, Liang Y, Cai X, Cuevas-Licea K, Rippley RK, Kassahun K, et al. (February 2009). "Metabolism and renal elimination of gaboxadol in humans: role of UDP-glucuronosyltransferases and transporters". Pharmaceutical Research. 26 (2): 459–468. doi:10.1007/s11095-008-9799-5. PMID 19082692. S2CID 24490597.
- Bock KW, Gschaidmeier H, Heel H, Lehmköster T, Münzel PA, Bock-Hennig BS (May 1999). "Functions and transcriptional regulation of PAH-inducible human UDP-glucuronosyltransferases". Drug Metabolism Reviews. 31 (2): 411–422. doi:10.1081/DMR-100101927. PMID 10335444.
- Saito Y, Sai K, Maekawa K, Kaniwa N, Shirao K, Hamaguchi T, et al. (February 2009). "Close association of UGT1A9 IVS1+399C>T with UGT1A1*28, *6, or *60 haplotype and its apparent influence on 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronidation in Japanese". Drug Metabolism and Disposition. 37 (2): 272–276. doi:10.1124/dmd.108.024208. PMID 18981166. S2CID 2886803.
- 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.
- Ménard V, Girard H, Harvey M, Pérusse L, Guillemette C (April 2009). "Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian population". Human Mutation. 30 (4): 677–687. doi:10.1002/humu.20946. PMID 19204906. S2CID 6235077.
- Cecchin E, Innocenti F, D'Andrea M, Corona G, De Mattia E, Biason P, et al. (May 2009). "Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan". Journal of Clinical Oncology. 27 (15): 2457–2465. doi:10.1200/JCO.2008.19.0314. PMID 19364970.
- Fujiwara R, Nakajima M, Yamamoto T, Nagao H, Yokoi T (2009). "In silico and in vitro approaches to elucidate the thermal stability of human UDP-glucuronosyltransferase (UGT) 1A9". Drug Metabolism and Pharmacokinetics. 24 (3): 235–244. doi:10.2133/dmpk.24.235. PMID 19571435.
- Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR (October 2000). "Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype". Human Mutation. 16 (4): 297–306. doi:10.1002/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z. PMID 11013440. S2CID 24275067.
- Johnson AD, Kavousi M, Smith AV, Chen MH, Dehghan A, Aspelund T, et al. (July 2009). "Genome-wide association meta-analysis for total serum bilirubin levels". Human Molecular Genetics. 18 (14): 2700–2710. doi:10.1093/hmg/ddp202. PMC 2701336. PMID 19414484.
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