Molecular cloning, modeling, and localization of rat type 10 17beta-hydroxysteroid dehydrogenase.
Rat and mouse complementary DNAs of type 10 17beta-hydroxysteroid dehydrogenase were cloned and sequenced. The mouse cDNA clone's sequence corrected the previously published nucleotide and amino acid sequence of mouse endoplasmic reticulum-associated beta-amyloid-binding protein. A subunit of the rat enzyme consists of 261 amino acid residues with a calculated molecular mass of 27250 Da. Compared with its human counterpart, rat 17betaHSD type 10 shows 88% identity. Mouse 17betaHSD type 10 is composed of 261 amino acid residues with a calculated molecular mass of 27274 Da. There is 95% identity between the two rodent enzymes. A stereostructure model of rat 17betaHSD type 10 was constructed based on its amino acid sequence. Similar to human type 10 17betaHSD, the rodent enzymes also displayed relatively higher 3alphaHSD activity than 17betaHSD activity. Intracellular localization of rat 17betaHSD type 10 has been determined by subcellular fractionation and confocal microscopy studies. The results unequivocally establish that this is a nuclear gene-encoded mitochondrial enzyme, and that this 17betaHSD is not associated with the endoplasmic reticulum. The unique location distinguishes type 10 from other types of 17beta-hydroxysteroid dehydrogenases.
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Department of Pharmacology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Merz
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Chu
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Lin
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Yang
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Mehta
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Schulz
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Yang
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D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics*; D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005456:Fluorescent Dyes; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics*; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051381:Rats; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014162:Transfection
D018076:DNA, Complementary; D005456:Fluorescent Dyes; D007527:Isoenzymes; D015067:17-Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human