Molecular cloning, modeling, and localization of rat type 10 17β-hydroxysteroid dehydrogenase

Rat and mouse complementary DNAs of type 10 17 beta -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 27 250 Da. Compared with its human counterpart, rat 17 beta HSD type 10 shows 88% identity. Mouse 17 beta HSD type 10 is composed of 261 amino acid residues with a calculated molecular mass of 27 274 Da. There is 95%, identity between the two rodent enzymes. A stereostructure model of rat 17 beta HSD type 10 was constructed based on its amino acid sequence. Similar to human type 10 17 beta HSD, the rodent enzymes also displayed relatively higher 3 alpha HSD activity than 17 beta HSD activity. Intracellular localization of rat 17 beta HSD 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 17 beta HSD is not associated with the endoplasmic reticulum. The unique location distinguishes type 10 From other types of 17 beta -hydroxysteroid dehydrogenases. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.