Rat liver UDP-glucuronosyltransferase. cDNA sequence and expression of a form glucuronidating 3-hydroxyandrogens

J Biol Chem. 1986 Oct 25;261(30):14112-7.

Abstract

A cDNA clone, pUDPGTr-4, encoding a form of rat UDP-glucuronosyltransferase has been isolated from a SV40 expression library. Sequence analysis revealed that the cDNA is 1970 base pairs in length and encodes a protein of 530 amino acids, which has amino- and carboxyl-terminal sequences characteristic of signal peptide and transmembrane segments, respectively. There is one potential asparagine-linked glycosylation site. Transfection of UDPGTr-4 cDNA into COS cells resulted in the glucuronidation of etiocholanolone, androsterone, and lithocholic acid in a transient expression assay. Several other common substrates of UDP-glucuronosyltransferase were not conjugated by the UDPGTr-4 enzyme. UDPGTr-4 cDNA is identical in sequence over a common 1.7 kilobase-region of overlap to UDPGTr-1, a cDNA previously isolated in this laboratory (Mackenzie, P. I., Gonzalez, F. J., and Owens, I. S. (1984) J. Biol. Chem. 259, 12153-12160). UDPGTr-4 cDNA, however, contains a shorter 3'-untranslated region. Northern analysis showed that the poly(A) RNA counterparts of UDPGTr-4 and UDPGTr-1 cDNAs are approximately 2.3 and 3.0 kilobases in length, respectively. The steady-state level of UDPGTr-4 poly(A) RNA in the liver is 20-fold higher than that of UDPGTr-1 poly(A) RNA. These data indicate that the UDPGTr-4 enzyme is a 3-hydroxyandrogen UDP-glucuronosyltransferase which is encoded by two distinct species of mRNA transcribed from the same gene.

MeSH terms

  • Amino Acid Sequence
  • Androgens / metabolism*
  • Androsterone / metabolism
  • Animals
  • Base Sequence
  • Cell Line
  • DNA / analysis*
  • Etiocholanolone / metabolism
  • Glucuronates / metabolism*
  • Glucuronosyltransferase / genetics*
  • Glycosylation
  • Lithocholic Acid / metabolism
  • Liver / enzymology*
  • Poly A / metabolism
  • RNA / metabolism
  • RNA, Messenger
  • Simian virus 40
  • Transfection

Substances

  • Androgens
  • Glucuronates
  • RNA, Messenger
  • Poly A
  • Lithocholic Acid
  • RNA
  • DNA
  • Etiocholanolone
  • Androsterone
  • Glucuronosyltransferase

Associated data

  • GENBANK/J02589