Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV.
Reactions of oestrogens and androgens at position C-17 are catalysed by 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs). Cloning of the cDNA of a novel human 17 beta-HSD IV and expression of its mRNA are described. A probe derived from the recently discovered porcine 17 beta-oestradiol dehydrogenase (17 beta-EDH) was used to isolate a 2.6 kb human cDNA encoding a continuous protein of 736 amino acids of high (84%) similarity to the porcine 17 beta-EDH. The calculated molecular mass of the human enzyme is 79,595 Da. Other sequence similarities shared by the two enzymes are: an N-terminal sequence which is similar to that of members of the short-chain alcohol dehydrogenase family; amino acids 343-607 which are similar to the C-terminal domains of a trifunctional Candida tropicalis enzyme and the FOX2 gene product of Saccharomyces cerevisiae; amino acids 596-736 which are similar to human sterol carrier protein 2. The previously cloned human 17 beta-HSD I, II and III are less than 25% identical with 17 beta-HSD IV. mRNA for HSD IV is a single species of 3.0 kb, present in many tissues with highest concentrations in liver, heart, prostate and testes. When over-expressed in mammalian cells, the human 17 beta-HSD IV enzyme displays a specific unidirectional oxidative 17 beta-HSD activity.
D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002175:Candida / Q000201:enzymology; D002460:Cell Line; D003001:Cloning, Molecular; D015342:DNA Probes / Q000737:chemistry; D018076:DNA, Complementary / Q000032:analysis / Q000737:chemistry; D004746:Enoyl-CoA Hydratase; D004960:Estradiol Dehydrogenases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006836:Hydro-Lyases; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes; D064029:Peroxisomal Multifunctional Protein-2; D012333:RNA, Messenger / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D018076:DNA, Complementary; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases; D000426:Alcohol Dehydrogenase; D004960:Estradiol Dehydrogenases; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D004746:Enoyl-CoA Hydratase