Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:024963 (UGT2B8)
 8 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Characterization of a cloned human dihydrotestosterone/androstanediol UDP-glucuronosyltransferase and its comparison to other steroid isoforms. 839 10

To isolate cDNA clones encoding novel UGT2B enzymes, human prostate and LNCaP cell cDNA libraries were screened using a pool of steroid-specific UGT2B cDNA probes. In approximately 10(6) recombinants, we isolated 3 cDNA clones of 2.1 kilobases that encode a novel UGT2B enzyme. UGT2B17 is 95% identical with UGT2B15 and 91% identical with UGT2B8. Primary structure analysis of UGT2B17 based on the nucleotide sequence revealed a putative amino-terminal membrane insertion signal peptide, a carboxyl-terminal membrane-spanning region, and three potential asparagine-linked glycosylation sites. UGT2B17 cloned in the pBK-CMV expression vector was transfected into HK293 cells to obtain a stable clonal cell line expressing a high level of the active 53-kDa UGT2B17 enzyme. Of the over 60 endogenous and exogenous substances tested, 25 compounds revealed reactivity. The major substrates are eugenol > 4-methylumbelliferone > dihydrotestosterone > androstane-3alpha, 17beta-diol (3alpha-diol) > testosterone > androsterone (ADT). The apparent Km values obtained with tritiated steroids in intact cells were 0.4 microM for ADT, 0.7 microM for dihydrotestosterone, 1.0 microM for 3alpha-diol, and 3.4 microM for testosterone. Southern blot analysis of reverse transcription-polymerase chain reaction products revealed expression of UGT2B17 mRNA in various tissues including the liver, kidney, testis, uterus, placenta, mammary gland, adrenal gland, skin, and prostate. UGT2B17 is the first human uridine diphosphoglucuronosyltransferase enzyme expressed in extrahepatic tissues to have a specificity for ADT as well as testosterone, dihydrotestosterone, and 3alpha-diol.
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PMID:Isolation and characterization of a novel cDNA encoding a human UDP-glucuronosyltransferase active on C19 steroids. 879 64