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Gene Review

UGT1A9  -  UDP glucuronosyltransferase 1 family,...

Homo sapiens

Synonyms: GNT1, HLUGP4, LUGP4, UDP-glucuronosyltransferase 1-9, UDP-glucuronosyltransferase 1-I, ...
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Disease relevance of UGT1A9


High impact information on UGT1A9


Chemical compound and disease context of UGT1A9


Biological context of UGT1A9


Anatomical context of UGT1A9

  • Membranes from the co-infected cells, or a mixture of membranes from separately infected cells, were subjected to detergent extraction and IMAC, and the resulting fractions were analyzed for the presence of each type of UGT1A9 using tag-specific antibodies [1].
  • In support of the involvement of UGT1A9, a strong coefficient of correlation was observed in the glucuronidation of SN-38 and a substrate, mainly glucuronidate, by UGT1A9 (flavopiridol) by human liver microsomes (coefficient of correlation, 0.905; p = 0.002) [13].
  • Treatment of human hepatocytes and macrophages and murine adipocytes with activators of PPAR alpha or PPAR gamma resulted in an enhanced UGT1A9 expression and activity [14].
  • UGT1A8 and 1A10 are expressed exclusively in the gastrointestinal tract, whereas UGT1A9 is expressed mainly in the liver and kidneys [15].
  • Microsomes expressing UGT1A9 produced N-hydroxy-PhIP-N3-glucuronide at the highest rate with an apparent Km and Vmax of 3.73 microM and 4.07 pmol/min/mg, respectively [16].

Associations of UGT1A9 with chemical compounds

  • Purified UGT1A9 glucuronidated scopoletin at a high rate, whereas its glucuronidation activity toward entacapone was low and largely dependent on phospholipid addition [1].
  • In the case of UGT1A9, however, glucuronidation of alpha-naphthol and scopoletin was resistant to such inhibition, whereas glucuronidation of entacapone and several other aglycones was sensitive [1].
  • When co-infected with His-tagged UGT1A9, however, part of the HA-tagged enzyme was bound to the column and was eluted by imidazole concentration gradient together with the His-tagged UGT1A9, suggesting the formation of stable dimers that contain one His-tagged and one HA-tagged UGT1A9 monomers [1].
  • Entacapone in particular was seen to be an exceptionally good substrate for UGT1A9 with an even higher reaction velocity value at 500 microM substrate concentration compared with that of the commonly used substrate, propofol (1.3 and 0.78 nmol min(-1) mg(-1), respectively) [17].
  • Nicotine and cotinine N-glucuronidations in pooled human liver microsomes were competitively inhibited by bilirubin as a substrate for UGT1A1 (K(i) = 3.9 and 3.3 micro M), imipramine as a substrate for UGT1A4 (K(i) = 6.1 and 2.7 micro M), and propofol as a substrate for UGT1A9 (K(i) = 6.0 and 12.0 micro M) [18].

Enzymatic interactions of UGT1A9


Regulatory relationships of UGT1A9

  • Vmax for 1A9 was fourfold higher than that measured for UGT2B7, 92 compared with 21 pmol min(-1) mg(-1), respectively, but UGT1A9 was expressed at approximately twofold higher level than the UGT2B7 in the recombinant cell lines [20].
  • Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism [21].

Other interactions of UGT1A9

  • In addition, both UGT1A9 and UGT1A7 preferentially formed BPD-7R-Gluc [22].
  • Significantly lower expression of UGT1A9 and UGT2B4 mRNA was identified in paediatric liver [23].
  • Evidence for at least two PAH-inducible UGTs (UGT1A6 and UGT1A9) is presented, which, however, are also constitutively expressed in a tissue- and cell-specific manner [24].
  • These results imply that concomitant chronic intake of therapeutic drugs and dietary components that are UGT2B7 and/or UGT1A9 substrates may interfere with estragole metabolism [25].
  • The inhibitory effects of propofol as a specific substrate for UGT1A9 (IC(50) = 167.1 microM) and emodin as a substrate for UGT1A8 and UGT1A10 (IC(50) = 287.6 microM) were not prominent [26].

Analytical, diagnostic and therapeutic context of UGT1A9


  1. Expression and characterization of recombinant human UDP-glucuronosyltransferases (UGTs). UGT1A9 is more resistant to detergent inhibition than other UGTs and was purified as an active dimeric enzyme. Kurkela, M., García-Horsman, J.A., Luukkanen, L., Mörsky, S., Taskinen, J., Baumann, M., Kostiainen, R., Hirvonen, J., Finel, M. J. Biol. Chem. (2003) [Pubmed]
  2. Regulation and function of family 1 and family 2 UDP-glucuronosyltransferase genes (UGT1A, UGT2B) in human oesophagus. Strassburg, C.P., Strassburg, A., Nguyen, N., Li, Q., Manns, M.P., Tukey, R.H. Biochem. J. (1999) [Pubmed]
  3. UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Carlini, L.E., Meropol, N.J., Bever, J., Andria, M.L., Hill, T., Gold, P., Rogatko, A., Wang, H., Blanchard, R.L. Clin. Cancer Res. (2005) [Pubmed]
  4. Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. Han, J.Y., Lim, H.S., Shin, E.S., Yoo, Y.K., Park, Y.H., Lee, J.E., Jang, I.J., Lee, D.H., Lee, J.S. J. Clin. Oncol. (2006) [Pubmed]
  5. Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis. Strassburg, C.P., Obermayer-Straub, P., Alex, B., Durazzo, M., Rizzetto, M., Tukey, R.H., Manns, M.P. Gastroenterology (1996) [Pubmed]
  6. Genetic link of hepatocellular carcinoma with polymorphisms of the UDP-glucuronosyltransferase UGT1A7 gene. Vogel, A., Kneip, S., Barut, A., Ehmer, U., Tukey, R.H., Manns, M.P., Strassburg, C.P. Gastroenterology (2001) [Pubmed]
  7. Characterization of common UGT1A8, UGT1A9, and UGT2B7 variants with different capacities to inactivate mutagenic 4-hydroxylated metabolites of estradiol and estrone. Thibaudeau, J., Lépine, J., Tojcic, J., Duguay, Y., Pelletier, G., Plante, M., Brisson, J., Têtu, B., Jacob, S., Perusse, L., Bélanger, A., Guillemette, C. Cancer Res. (2006) [Pubmed]
  8. Glucuronidation as a mechanism of intrinsic drug resistance in human colon cancer: reversal of resistance by food additives. Cummings, J., Ethell, B.T., Jardine, L., Boyd, G., Macpherson, J.S., Burchell, B., Smyth, J.F., Jodrell, D.I. Cancer Res. (2003) [Pubmed]
  9. Characterization of autoantibodies against uridine-diphosphate glucuronosyltransferase in patients with inflammatory liver diseases. Bachrich, T., Thalhammer, T., Jäger, W., Haslmayer, P., Alihodzic, B., Bakos, S., Hitchman, E., Senderowicz, A.M., Penner, E. Hepatology (2001) [Pubmed]
  10. The contribution of UDP-glucuronosyltransferase 1A9 on CYP1A2-mediated genotoxicity by aromatic and heterocyclic amines. Yueh, M.F., Nguyen, N., Famourzadeh, M., Strassburg, C.P., Oda, Y., Guengerich, F.P., Tukey, R.H. Carcinogenesis (2001) [Pubmed]
  11. Functional characterization of human UDP-glucuronosyltransferase 1A9 variant, D256N, found in Japanese cancer patients. Jinno, H., Saeki, M., Saito, Y., Tanaka-Kagawa, T., Hanioka, N., Sai, K., Kaniwa, N., Ando, M., Shirao, K., Minami, H., Ohtsu, A., Yoshida, T., Saijo, N., Ozawa, S., Sawada, J. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  12. Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus. Gong, Q.H., Cho, J.W., Huang, T., Potter, C., Gholami, N., Basu, N.K., Kubota, S., Carvalho, S., Pennington, M.W., Owens, I.S., Popescu, N.C. Pharmacogenetics (2001) [Pubmed]
  13. Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Gagné, J.F., Montminy, V., Belanger, P., Journault, K., Gaucher, G., Guillemette, C. Mol. Pharmacol. (2002) [Pubmed]
  14. The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. Barbier, O., Villeneuve, L., Bocher, V., Fontaine, C., Torra, I.P., Duhem, C., Kosykh, V., Fruchart, J.C., Guillemette, C., Staels, B. J. Biol. Chem. (2003) [Pubmed]
  15. Cloning and characterization of the human UDP-glucuronosyltransferase 1A8, 1A9, and 1A10 gene promoters: differential regulation through an interior-like region. Gregory, P.A., Gardner-Stephen, D.A., Lewinsky, R.H., Duncliffe, K.N., Mackenzie, P.I. J. Biol. Chem. (2003) [Pubmed]
  16. N-glucuronidation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N_hydroxy-PhIP by specific human UDP-glucuronosyltransferases. Malfatti, M.A., Felton, J.S. Carcinogenesis (2001) [Pubmed]
  17. The specificity of glucuronidation of entacapone and tolcapone by recombinant human UDP-glucuronosyltransferases. Lautala, P., Ethell, B.T., Taskinen, J., Burchell, B. Drug Metab. Dispos. (2000) [Pubmed]
  18. Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes. Nakajima, M., Tanaka, E., Kwon, J.T., Yokoi, T. Drug Metab. Dispos. (2002) [Pubmed]
  19. The effect of valproic acid on drug and steroid glucuronidation by expressed human UDP-glucuronosyltransferases. Ethell, B.T., Anderson, G.D., Burchell, B. Biochem. Pharmacol. (2003) [Pubmed]
  20. Almokalant glucuronidation in human liver and kidney microsomes: evidence for the involvement of UGT1A9 and 2B7. Gaiser, B.K., Lockley, D.J., Staines, A.G., Baarnhielm, C., Burchell, B. Xenobiotica (2003) [Pubmed]
  21. Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism. Martignoni, E., Cosentino, M., Ferrari, M., Porta, G., Mattarucchi, E., Marino, F., Lecchini, S., Nappi, G. Neurology (2005) [Pubmed]
  22. Characterization of benzo(a)pyrene-trans-7,8-dihydrodiol glucuronidation by human tissue microsomes and overexpressed UDP-glucuronosyltransferase enzymes. Fang, J.L., Beland, F.A., Doerge, D.R., Wiener, D., Guillemette, C., Marques, M.M., Lazarus, P. Cancer Res. (2002) [Pubmed]
  23. Developmental aspects of human hepatic drug glucuronidation in young children and adults. Strassburg, C.P., Strassburg, A., Kneip, S., Barut, A., Tukey, R.H., Rodeck, B., Manns, M.P. Gut (2002) [Pubmed]
  24. Functions and transcriptional regulation of PAH-inducible human UDP-glucuronosyltransferases. Bock, K.W., Gschaidmeier, H., Heel, H., Lehmköster, T., Münzel, P.A., Bock-Hennig, B.S. Drug Metab. Rev. (1999) [Pubmed]
  25. Glucuronidation of 1'-hydroxyestragole (1'-HE) by human UDP-glucuronosyltransferases UGT2B7 and UGT1A9. Iyer, L.V., Ho, M.N., Shinn, W.M., Bradford, W.W., Tanga, M.J., Nath, S.S., Green, C.E. Toxicol. Sci. (2003) [Pubmed]
  26. Involvement of multiple UDP-glucuronosyltransferase 1A isoforms in glucuronidation of 5-(4'-hydroxyphenyl)-5-phenylhydantoin in human liver microsomes. Nakajima, M., Sakata, N., Ohashi, N., Kume, T., Yokoi, T. Drug Metab. Dispos. (2002) [Pubmed]
  27. Hepatic expression of the UGT1A9 gene is governed by hepatocyte nuclear factor 4alpha. Barbier, O., Girard, H., Inoue, Y., Duez, H., Villeneuve, L., Kamiya, A., Fruchart, J.C., Guillemette, C., Gonzalez, F.J., Staels, B. Mol. Pharmacol. (2005) [Pubmed]
  28. The impact of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) gene promoter region single-nucleotide polymorphisms T-275A and C-2152T on early mycophenolic acid dose-interval exposure in de novo renal allograft recipients. Kuypers, D.R., Naesens, M., Vermeire, S., Vanrenterghem, Y. Clin. Pharmacol. Ther. (2005) [Pubmed]
  29. The monkey and human uridine diphosphate-glucuronosyltransferase UGT1A9, expressed in steroid target tissues, are estrogen-conjugating enzymes. Albert, C., Vallée, M., Beaudry, G., Bélanger, A., Hum, D.W. Endocrinology (1999) [Pubmed]
  30. The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver. Girard, H., Villeneuve, L., Court, M.H., Fortier, L.C., Caron, P., Hao, Q., von Moltke, L.L., Greenblatt, D.J., Guillemette, C. Drug Metab. Dispos. (2006) [Pubmed]
  31. Cloning of UGT1A9 cDNA from liver tissues and its expression in CHL cells. Li, X., Yu, Y.N., Zhu, G.J., Qian, Y.L. World J. Gastroenterol. (2001) [Pubmed]
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