Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
40
pubmed:dateCreated
1993-11-24
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)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
32
pubmed:geneSymbol
UDPGTh-3, udpgth-1, udpgth-2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10648-57
pubmed:dateRevised
2006-11-15
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
pubmed:year
1993
pubmed:articleTitle
Characterization of a cloned human dihydrotestosterone/androstanediol UDP-glucuronosyltransferase and its comparison to other steroid isoforms.
pubmed:affiliation
Section on Genetic Disorders of Drug Metabolism, National Institute of Child Health and Human Development.
pubmed:publicationType
Journal Article, Comparative Study