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Eur J Biochem. 1987 Nov 2;168(3):515-21.

Mouse UDP glucuronosyltransferase. cDNA and complete amino acid sequence and regulation.

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1
Laboratory of Developmental Pharmacology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.

Abstract

A cDNA clone (UDPGTm-1) encoding a mouse UDP glucuronosyltransferase (transferase) was isolated from pBR322 and lambda gt11 libraries by hybridization to a rat transferase clone. This cDNA is 1860 bp long and 65-87% similar at both the nucleotide and the deduced amino acid sequence levels to three different rat transferase clones [Mackenzie, P.I. et al. (1984) J. Biol. Chem. 259, 12153-12160; Mackenzie, P.I. (1986) J. Biol. Chem. 261, 6119-6125]. UDPGTm-1, like the rat transferase clones already described, contains an open reading frame of 1590 bp encoding 530 amino acids (unmodified Mr = 60,856), an N-terminus membrane-insertion signal sequence, a carboxy-terminus hydrophobic putative membrane-spanning region, and potential asparagine-linked glycosylation sites (residues 316 and 483). The cDNA contains two poly(A) addition consensus sequences at positions 1695-1837. UDPGTm-1 is complementary to a 2200-base mRNA and also cross-hybridizes to a 2000-base mRNA species due to sequence homology in the 5' region of the clone. Both the 2200-base and the 2000-base mRNA are induced approximately 2.5-fold by the hypolipidemic agent clofibrate, and also by phenobarbital and benzo[a]pyrene. A new and more potent hypolipidemic agent, perfluorooctanoic acid, is also shown to induce both mRNA species. Each of these compounds induces bilirubin transferase activity in a manner parallel to the effects on mRNA, i.e. perfluorooctanoic acid being the most effective, followed by phenobarbital, benzo[a]pyrene, and clofibrate. Southern blot hybridization of UDPGTm-1 to mouse genomic DNA showed sequence homology to a total DNA size of 40-50 kb. These data indicate that UDPGTm-1 is a member of a new subfamily of transferases in mouse with patterns of regulation of their mRNAs similar to that seen for bilirubin transferase activity.

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