cDNA cloning and characterization of the human UDP glucuronosyltransferase, UGT1A3.
The cDNA encoding the UDP glucuronosyltransferase, UGT1A3, has been cloned and expressed in cell culture. The deduced amino acid sequence of the cDNA is 90% similar in sequence to that of a previously characterized form, UGT1A4 and to that of a third form, UGT1A5 whose function in unknown. UGT1A3, when expressed in COS cells has a relative molecular mass of 55 kDa and is active in the glucuronidation of estrone and 2-hydroxyestrone. Activity towards other polyhydroxylated estrogens including 4-hydroxyestrogen and estriol and its metabolites was not detected. UGT1A3 was also inactive towards androgens and their metabolites. The enzyme preferentially glucuronidated the N-hydroxy metabolite of 2-acetylaminofluorence and was more active towards the 6- and 12-hydroxylated metabolites of benzo[alpha]pyrene. RNA encoding UGT1A3 was detected in human liver and colon tissue.
Mojarrabi
B
B
Department of Clinical Pharmacology, Flinders Medical Centre, Bedford Park, Australia.
Butler
R
R
Mackenzie
P I
PI
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003106:Colon / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics* / Q000302:isolation & purification; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D014453:Glucuronosyltransferase