Rat liver UDP-glucuronosyltransferase. cDNA sequence and expression of a form glucuronidating 3-hydroxyandrogens.
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.
D000595:Amino Acid Sequence; D000728:Androgens / Q000378:metabolism*; D000738:Androsterone / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000032:analysis*; D005043:Etiocholanolone / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006031:Glycosylation; D008095:Lithocholic Acid / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D011061:Poly A / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger; D013539:Simian virus 40; D014162:Transfection
D000728:Androgens; D005965:Glucuronates; D012333:RNA, Messenger; D011061:Poly A; D008095:Lithocholic Acid; D012313:RNA; D004247:DNA; D005043:Etiocholanolone; D000738:Androsterone; D014453:Glucuronosyltransferase