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Gene Review

UGT2B17  -  UDP glucuronosyltransferase 2 family,...

Homo sapiens

Synonyms: BMND12, C19-steroid-specific UDP-glucuronosyltransferase, C19-steroid-specific UDPGT, UDP-glucuronosyltransferase 2B17, UDPGT 2B17, ...
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Disease relevance of UGT2B17


High impact information on UGT2B17

  • In contrast to previously defined human minor H antigens, UGT2B17 is immunogenic because of differential expression of the protein in donor and recipient cells as a consequence of a homozygous gene deletion in the donor [5].
  • Here, we have used cDNA expression cloning to identify a novel human minor H antigen encoded by UGT2B17, an autosomal gene in the multigene UDP-glycosyltransferase 2 family that is selectively expressed in liver, intestine, and antigen-presenting cells [5].
  • These findings suggest considerable heterogeneity with regard to the expression of UDPGT isoenzymes among CN type I patients [3].
  • The steroid form of the UDPGT transcript was expressed in LNCaP cells and was enhanced in biochanin A-treated LNCaP cells [6].
  • Biochanin A significantly decreased the testosterone-stimulated release of PSA, presumably because biochanin A increased UDPGT and increased the intracellular glucuronidation of testosterone [6].

Chemical compound and disease context of UGT2B17

  • Crigler-Najjar syndrome type 1 (CN type 1) is an autosomal recessive disorder characterized by nonhemolytic jaundice resulting from mutations to the gene encoding bilirubin-UDP-glucuronosyltransferase (UDPGT) [7].

Biological context of UGT2B17


Anatomical context of UGT2B17


Associations of UGT2B17 with chemical compounds

  • UGT2B17 is the first human uridine diphosphoglucuronosyltransferase enzyme expressed in extrahepatic tissues to have a specificity for ADT as well as testosterone, dihydrotestosterone, and 3alpha-diol [8].
  • UGT2B15 and UGT2B17 are 95% identical in primary structure, and are expressed in steroid target tissues where they conjugate C19 steroids [9].
  • Cycloheximide treatment of stably transfected HK293 cells demonstrated that the UGT2B17 protein is more labile than the other enzymes; the protein levels decrease after 1 h of treatment, whereas other UGT2B proteins were stable for at least 12 h [15].
  • We found that UGT2B17 is expressed in basal cells where DHEA is converted into 3alpha-DIOL and ADT [13].
  • However, mutation of the serine residue at position 121 of UGT2B17 to a tyrosine, as found in UGT2B15, abolished the ability of UGT2B17 to conjugate androsterone at the 3alpha position, but still retained activity for dihydrotestosterone and 5alpha-androstane-3alpha, 17beta-diol, which have an OH-group at the 17beta position [10].

Regulatory relationships of UGT2B17

  • To determine if UGT2B17 is regulated by physiological effectors of the human prostate, DHT and epidermal growth factor (EGF) were demonstrated to specifically down-regulate the steady-state levels of UGT2B17 transcript and protein in LNCaP cells (Guillemette et al., 1997) [16].

Other interactions of UGT2B17

  • UGT2B17 is 95% identical with UGT2B15 and 91% identical with UGT2B8 [8].
  • 1. The other PAC clones isolated contain exons from the UGT2B4, UGT2B11 and UGT2B17 genes [9].
  • EGF treatment resulted in a decreased UGT2B17 expression, whereas UGT2B10 and -B11 mRNA remained at their basal levels [17].
  • Glucuronidation of gemcabene was catalyzed by recombinant UGT1A3, recombinant UGT2B7, and recombinant UGT2B17, as well as by human liver microsomes (HLM) [18].
  • The UGT2B17 Pbx site matches a consensus Pbx site known to bind members of the Pbx, Hox, Meis, and Prep1 families of homeodomain-containing proteins and has previously been shown to bind nuclear proteins in DNaseI footprint assays [19].

Analytical, diagnostic and therapeutic context of UGT2B17


  1. Effect of interleukins on UGT2B15 and UGT2B17 steroid uridine diphosphate-glucuronosyltransferase expression and activity in the LNCaP cell line. Lévesque, E., Beaulieu, M., Guillemette, C., Hum, D.W., Bélanger, A. Endocrinology (1998) [Pubmed]
  2. A UGT2B17-positive donor is a risk factor for higher transplant-related mortality and lower survival after bone marrow transplantation. Terakura, S., Murata, M., Nishida, T., Emi, N., Akatsuka, Y., Riddell, S.R., Morishima, Y., Kodera, Y., Naoe, T. Br. J. Haematol. (2005) [Pubmed]
  3. Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four patients with the Crigler-Najjar syndrome type I. van Es, H.H., Goldhoorn, B.G., Paul-Abrahamse, M., Elferink, R.P., Jansen, P.L. J. Clin. Invest. (1990) [Pubmed]
  4. Mechanism of thiazopyr-induced effects on thyroid hormone homeostasis in male Sprague-Dawley rats. Hotz, K.J., Wilson, A.G., Thake, D.C., Roloff, M.V., Capen, C.C., Kronenberg, J.M., Brewster, D.W. Toxicol. Appl. Pharmacol. (1997) [Pubmed]
  5. A human minor histocompatibility antigen resulting from differential expression due to a gene deletion. Murata, M., Warren, E.H., Riddell, S.R. J. Exp. Med. (2003) [Pubmed]
  6. Increased UDP-glucuronosyltransferase activity and decreased prostate specific antigen production by biochanin A in prostate cancer cells. Sun, X.Y., Plouzek, C.A., Henry, J.P., Wang, T.T., Phang, J.M. Cancer Res. (1998) [Pubmed]
  7. Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of Crigler-Najjar syndrome type 1. Li, Q., Murphree, S.S., Willer, S.S., Bolli, R., French, B.A. Hum. Gene Ther. (1998) [Pubmed]
  8. Isolation and characterization of a novel cDNA encoding a human UDP-glucuronosyltransferase active on C19 steroids. Beaulieu, M., Lévesque, E., Hum, D.W., Bélanger, A. J. Biol. Chem. (1996) [Pubmed]
  9. Isolation and characterization of the human UGT2B15 gene, localized within a cluster of UGT2B genes and pseudogenes on chromosome 4. Turgeon, D., Carrier, J.S., Lévesque, E., Beatty, B.G., Bélanger, A., Hum, D.W. J. Mol. Biol. (2000) [Pubmed]
  10. Alteration of human UDP-glucuronosyltransferase UGT2B17 regio-specificity by a single amino acid substitution. Dubois, S.G., Beaulieu, M., Lévesque, E., Hum, D.W., Bélanger, A. J. Mol. Biol. (1999) [Pubmed]
  11. Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. Jakobsson, J., Ekström, L., Inotsume, N., Garle, M., Lorentzon, M., Ohlsson, C., Roh, H.K., Carlström, K., Rane, A. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  12. UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term. Collier, A.C., Ganley, N.A., Tingle, M.D., Blumenstein, M., Marvin, K.W., Paxton, J.W., Mitchell, M.D., Keelan, J.A. Biochem. Pharmacol. (2002) [Pubmed]
  13. Cellular specific expression of the androgen-conjugating enzymes UGT2B15 and UGT2B17 in the human prostate epithelium. Chouinard, S., Pelletier, G., Bélanger, A., Barbier, O. Endocr. Res. (2004) [Pubmed]
  14. Tissue specific differences in the regulation of the UDP glucuronosyltransferase 2B17 gene promoter. Gregory, P.A., Hansen, A.J., Mackenzie, P.I. Pharmacogenetics (2000) [Pubmed]
  15. Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members. Turgeon, D., Carrier, J.S., Lévesque, E., Hum, D.W., Bélanger, A. Endocrinology (2001) [Pubmed]
  16. Chromosomal localization, structure, and regulation of the UGT2B17 gene, encoding a C19 steroid metabolizing enzyme. Beaulieu, M., Lévesque, E., Tchernof, A., Beatty, B.G., Bélanger, A., Hum, D.W. DNA Cell Biol. (1997) [Pubmed]
  17. Isoform-Specific Regulation of Uridine Diphosphate-Glucuronosyltransferase 2B Enzymes in the Human Prostate: Differential Consequences for Androgen and Bioactive Lipid Inactivation. Chouinard, S., Pelletier, G., B??langer, A., Barbier, O. Endocrinology (2006) [Pubmed]
  18. Udp-glucuronosyltransferase 2b7 is the major enzyme responsible for gemcabene glucuronidation in human liver microsomes. Bauman, J.N., Goosen, T.C., Tugnait, M., Peterkin, V., Hurst, S.I., Menning, L.C., Milad, M., Court, M.H., Williams, J.A. Drug Metab. Dispos. (2005) [Pubmed]
  19. The homeodomain Pbx2-Prep1 complex modulates hepatocyte nuclear factor 1alpha-mediated activation of the UDP-glucuronosyltransferase 2B17 gene. Gregory, P.A., Mackenzie, P.I. Mol. Pharmacol. (2002) [Pubmed]
  20. Isolation and characterization of a simian UDP-glucuronosyltransferase UGT2B18 active on 3-hydroxyandrogens. Beaulieu, M., Lévesque, E., Barbier, O., Turgeon, D., Bélanger, G., Hum, D.W., Bélanger, A. J. Mol. Biol. (1998) [Pubmed]
  21. Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate cancer in African American and Caucasian men. Park, J., Chen, L., Ratnashinge, L., Sellers, T.A., Tanner, J.P., Lee, J.H., Dossett, N., Lang, N., Kadlubar, F.F., Ambrosone, C.B., Zachariah, B., Heysek, R.V., Patterson, S., Pow-Sang, J. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  22. Evidence that tacrolimus augments the bioavailability of mycophenolate mofetil through the inhibition of mycophenolic acid glucuronidation. Zucker, K., Tsaroucha, A., Olson, L., Esquenazi, V., Tzakis, A., Miller, J. Therapeutic drug monitoring. (1999) [Pubmed]
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