Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity.
17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) is an enzyme crucial to the regulation of intracellular levels of biologically active steroid hormones in a variety of tissues. Here, we report the isolation, structure, and characterization of a cDNA encoding the human 17 beta-HSD type 2. A 1.4-kilobase cDNA was identified, and DNA sequence analysis indicated that 17 beta-HSD type 2 was a protein of 387 amino acids with a predicted molecular weight of 42,782. The protein contained an amino-terminal type II signal-anchor motif and a carboxyl-terminal endoplasmic reticulum retention motif, which suggested that 17 beta-HSD type 2 was associated with the membranes of the endoplasmic reticulum. 17 beta-HSD type 2 was capable of catalyzing the interconversion of testosterone and androstenedione as well as estradiol and estrone. The enzyme also demonstrated 20 alpha-HSD activity toward 20 alpha-dihydroprogesterone. The amount of 17 beta-HSD type 2 mRNA in placenta was found to be high. The data suggest that the 17 beta-HSD type 2 cDNA encodes the microsomal 17 beta-HSD of human placenta, described by several laboratories.
Wu
L
L
Departments of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065.
Einstein
M
M
Geissler
W M
WM
Chan
H K
HK
Elliston
K O
KO
Andersson
S
S
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D015089:20-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D015723:Gene Library; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010920:Placenta / Q000201:enzymology; D011061:Poly A / Q000378:metabolism; D011247:Pregnancy; D011467:Prostate / Q000201:enzymology*; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014162:Transfection
D007527:Isoenzymes; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011061:Poly A; D015067:17-Hydroxysteroid Dehydrogenases; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase