Regular Article
Isolation and Characterization of the Human UGT2B7 Gene

https://doi.org/10.1006/bbrc.2000.2795Get rights and content

Abstract

Glucuronidation is a major pathway involved in the metabolism of drugs and numerous endogenous compounds, such as bile acids and steroid hormones. The enzymes responsible for this conjugation reaction are UDP-glucuronosyltransferases (UGT). Among the UGT2B subfamily, UGT2B7 , a UGT enzyme present in the liver and several steroid target tissues, is an important member since it conjugates a large variety of compounds including estrogens, androgens, morphine, AZT, and retinoic acid. Although this enzyme is well characterized, the gene encoding the UGT2B7 protein and its promoter region remain unknown. In this article, we report the genomic organization and the promoter region of the human UGT2B7 gene. To isolate this gene, a P-1 artificial chromosome (PAC) library was screened with a full length UGT2B7 probe and a clone of approximately 100 kb in length was isolated. In addition to the UGT2B7 gene, this PAC contains two other UGT2B genes previously characterized, namely UGT2B26P and UGT2B27P. The UGT2B7 gene is composed of six exons spanning approximately 16 kb, with introns ranging from 0.7 to 4.2 kb. The 5′-flanking region of the human UGT2B7 gene contains several potential cis-acting elements such as Oct-1, Pbx-1, and C/EBP. Only one TATA-box at nucleotide −106 was found within the first 500 nucleotides relative to the adenine base of the initiator ATG codon. Characterization of the UGT2B7 gene provides insight into the organization and regulation of this important metabolic gene.

References (37)

  • C.D. King et al.

    Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate

    Arch. Bio. Biophy.

    (1999)
  • G.J. Dutton

    Glucuronidation of Drugs and Other Compounds

    (1980)
  • P.I. Mackenzie et al.

    The UDP glycosyltransferase gene superfamily: Recommended nomenclature update based on evolutionary divergence

    Pharmacogenetics

    (1997)
  • M.R. Jackson et al.

    Cloning of a human liver microsomal UDP-glucuronosyltransferase cDNA

    Biochem. J.

    (1987)
  • E. Lévesque et al.

    Characterization and substrate specificity of UGT2B4(E458): A UDP-glucuronosyltransferase encoded by a polymorphic gene

    Pharmacogenetics

    (1999)
  • C. Jin et al.

    Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs

    J. Pharmacol. Exp. Ther.

    (1993)
  • F. Chen et al.

    Characterization of a cloned human dihydrotestosterone/androstanediol UDP-Glucuronosyltransferase and its comparison to other steroid isoforms

    Biochemistry

    (1993)
  • É. Lévesque et al.

    Isolation and characterization of UGT2B15(Y85): A UDP- glucuronosyltransferase encoded by a polymorphic gene

    Pharmacogenetics

    (1997)

    • Cited by (0)

    1

    These authors contributed equally.

    2

    To whom correspondence should be addressed at Laboratory of Molecular Endocrinology, CHUL Research Center, 2705 Laurier Blvd., Québec, G1V 4G2, Canada. Fax: (418) 654-2761. E-mail: [email protected].

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