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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
40
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pubmed:dateCreated |
1993-11-24
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pubmed:abstractText |
A human cDNA, UDPGTh-3, encoding a dihydrotestosterone/5 alpha-androstane-3 alpha,17 beta-diol UDP- glucuronosyltransferase (transferase) has been isolated and characterized. The nucleotide sequence of UDPGTh-3 encodes a 530 amino acid protein with a typical membrane insertion-signal peptide, a membrane-anchoring domain, and three potential asparagine-linked glycosylation sites. Alignment shows that this encoded isozyme is 96% identical to an apparent estriol-metabolizing isoform, HLUG4 [Coffman, B. L., et al., (1990) Arch. Biochem. Biophys. 281, 170-175]. The udpgth-3 isozyme is 78% identical to two other steroid isoforms, HLUG25 (udpgth-1) [Jackson, M. R., et al. (1987) Biochem. J. 242, 581-588; Ritter, J. K., et. al. (1992) Biochemistry 31, 3409-3414] and udpgth-2 [Ritter, J. K., et al. (1990) J. Biol. Chem. 265, 7900-7906]. udpgth-2 and udpgth-1 metabolized parallel substrates (stereospecific estriols, 3,4-catechol estrogens, and the bile salt hyodeoxycholate), except that udpgth-2 was 100-fold more effective than udpgth-1. The mRNA encoding udpgth-3 is 2.4 kb in size and is present in liver, prostate, and testis; the mRNA encoding udpgth-2 is located in liver and kidney, whereas that for udpgth-1 is liver-specific. Each of the liver mRNA species encoding udpgth-3, udpgth-2, or udpgth-1 was induced 2.5-3-fold by phenobarbital treatment of the Erythrocebus patas monkey. In 16 human liver mRNA samples, the message encoding udpgth-3 was generally uniformly expressed and that for udpgth-1 exhibited wide variations in its level, whereas that for udpgth-2 was barely detectable in nine samples and not detectable in the others. Three samples contained no message for either isoform. Substrate turnover by udpgth-3 is ranked as follows: phenolphthalein > 5 alpha-androstane-3 alpha,17 beta-diol > 5 alpha- dihydrotestosterone = 4-hydroxybiphenyl > phenolsulfonphthalein (phenol red) > phenolphthalin. Genes encoding udpgth-3, udpgth-2, and udpgth-1 mapped to human chromosome 4 with genomic DNA from human/mouse and human/hamster somatic cell hybrids; the genes encoding udpgth-1 and udpgth-2 mapped specifically to band 4q28. udpgth-3 exhibited similar Km values both for 5 alpha-dihydrotestosterone (10 microM) and for its metabolite, 5 alpha-androstane-3 alpha,-17 beta-diol (12.5 microM).(ABSTRACT TRUNCATED AT 400 WORDS)
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Glucuronosyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
32
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pubmed:geneSymbol |
UDPGTh-3,
udpgth-1,
udpgth-2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10648-57
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8399210-Amino Acid Sequence,
pubmed-meshheading:8399210-Animals,
pubmed-meshheading:8399210-Blotting, Northern,
pubmed-meshheading:8399210-Chromosome Mapping,
pubmed-meshheading:8399210-Chromosomes, Human, Pair 4,
pubmed-meshheading:8399210-Cloning, Molecular,
pubmed-meshheading:8399210-DNA, Complementary,
pubmed-meshheading:8399210-Erythrocebus patas,
pubmed-meshheading:8399210-Glucuronosyltransferase,
pubmed-meshheading:8399210-Humans,
pubmed-meshheading:8399210-Isoenzymes,
pubmed-meshheading:8399210-Kinetics,
pubmed-meshheading:8399210-Liver,
pubmed-meshheading:8399210-Male,
pubmed-meshheading:8399210-Molecular Sequence Data,
pubmed-meshheading:8399210-Organ Specificity,
pubmed-meshheading:8399210-Prostate,
pubmed-meshheading:8399210-RNA, Messenger,
pubmed-meshheading:8399210-Recombinant Proteins,
pubmed-meshheading:8399210-Sequence Homology, Amino Acid,
pubmed-meshheading:8399210-Substrate Specificity,
pubmed-meshheading:8399210-Testis
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pubmed:year |
1993
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pubmed:articleTitle |
Characterization of a cloned human dihydrotestosterone/androstanediol UDP-glucuronosyltransferase and its comparison to other steroid isoforms.
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pubmed:affiliation |
Section on Genetic Disorders of Drug Metabolism, National Institute of Child Health and Human Development.
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pubmed:publicationType |
Journal Article,
Comparative Study
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