CDNA CLONING AND EXPRESSION OF 2 NEW MEMBERS OF THE HUMAN LIVER UDP-GLUCURONOSYLTRANSFERASE-2B SUBFAMILY

被引:111
作者
JIN, CJ [1 ]
MINERS, JO [1 ]
LILLYWHITE, KJ [1 ]
MACKENZIE, PI [1 ]
机构
[1] FLINDERS UNIV S AUSTRALIA,MED CTR,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA
关键词
D O I
10.1006/bbrc.1993.1847
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Two new UDP-glucuronosyltransferase cDNAs, designated UGT2B10 and UGT2B11, encoding 528 amino acid proteins were isolated from a human liver cDNA library. The deduced amino acid sequences of UGTs 2B10 and 2B11 share >76% sequence similarity with other known human liver UGT2B subfamily isoforms and <48% sequence similarity with UGT1 family proteins. COS-7 cells transfected with UGT 2B10 and 2B11 synthesized proteins with respective molecular masses of 49 kDa and 51 kDa. UGT2B11 expressed in COS-7 cells glucuronidated a number of polyhydroxylated estrogens (estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (4-methylumbelliferone, 1-naphthol, 4-nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). Despite the screening of more than forty potential substrates, glucuronidation activity was not observed for expressed UGT2B10. © 1993 Academic Press, Inc.
引用
收藏
页码:496 / 503
页数:8
相关论文
共 24 条
[1]   A UNIFIED METHOD FOR THE ASSAY OF URIDINE DIPHOSPHOGLUCURONYLTRANSFERASE ACTIVITIES TOWARD VARIOUS AGLYCONES USING URIDINE DIPHOSPHO[U-C-14]GLUCURONIC ACID [J].
BANSAL, SK ;
GESSNER, T .
ANALYTICAL BIOCHEMISTRY, 1980, 109 (02) :321-329
[2]   THE UDP GLUCURONOSYLTRANSFERASE GENE SUPERFAMILY - SUGGESTED NOMENCLATURE BASED ON EVOLUTIONARY DIVERGENCE [J].
BURCHELL, B ;
NEBERT, DW ;
NELSON, DR ;
BOCK, KW ;
IYANAGI, T ;
JANSEN, PLM ;
LANCET, D ;
MULDER, GJ ;
CHOWDHURY, JR ;
SIEST, G ;
TEPHLY, TR ;
MACKENZIE, PI .
DNA AND CELL BIOLOGY, 1991, 10 (07) :487-494
[3]   UDP-GLUCURONOSYLTRANSFERASES [J].
BURCHELL, B ;
COUGHTRIE, MWH .
PHARMACOLOGY & THERAPEUTICS, 1989, 43 (02) :261-289
[4]   CHARACTERIZATION AND PRIMARY SEQUENCE OF A HUMAN HEPATIC-MICROSOMAL ESTRIOL UDPGLUCURONOSYLTRANSFERASE [J].
COFFMAN, BL ;
TEPHLY, TR ;
IRSHAID, YM ;
GREEN, MD ;
SMITH, C ;
JACKSON, MR ;
WOOSTER, R ;
BURCHELL, B .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1990, 281 (01) :170-175
[5]   GLUCURONIDATION OF IMIPRAMINE IN RABBIT AND HUMAN LIVER-MICROSOMES - ASSAY CONDITIONS AND INTERACTION WITH OTHER TERTIARY AMINE DRUGS [J].
COUGHTRIE, MWH ;
SHARP, S .
BIOCHEMICAL PHARMACOLOGY, 1991, 42 (07) :1497-1501
[6]   EXPRESSION OF A HUMAN-LIVER CDNA-ENCODING A UDP-GLUCURONOSYLTRANSFERASE CATALYZING THE GLUCURONIDATION OF HYODEOXYCHOLIC ACID IN CELL-CULTURE [J].
FOURNELGIGLEUX, S ;
JACKSON, MR ;
WOOSTER, R ;
BURCHELL, B .
FEBS LETTERS, 1989, 243 (02) :119-122
[7]   CONVERSION OF A SECRETORY PROTEIN INTO A TRANSMEMBRANE PROTEIN RESULTS IN ITS TRANSPORT TO THE GOLGI-COMPLEX BUT NOT TO THE CELL-SURFACE [J].
GUAN, JL ;
ROSE, JK .
CELL, 1984, 37 (03) :779-787
[8]   CLONING AND SUBSTRATE-SPECIFICITY OF A HUMAN PHENOL UDP-GLUCURONOSYLTRANSFERASE EXPRESSED IN COS-7 CELLS [J].
HARDING, D ;
FOURNELGIGLEUX, S ;
JACKSON, MR ;
BURCHELL, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (22) :8381-8385
[9]  
IRSHAID YM, 1987, MOL PHARMACOL, V31, P27
[10]  
JIN CJ, 1993, J PHARMACOL EXP THER, V264, P475