Structure and tissue-specific expression of the aldo-keto reductase superfamily.

We previously identified multiple proteins structurally related to 3 alpha-hydroxysteroid dehydrogenase in rat liver, lung, kidney, and testis ((1991) Arch. Biochem. Biophys. 291, 258-262). We further used these monoclonal antibodies to screen several lambda gt11 cDNA libraries derived from male rat liver, lung, and kidney. Five additional unique cDNA clones were isolated and sequenced; the proteins encoded by these cDNAs were found to exhibit 37-62% amino acid sequence homology to rat liver 3 alpha-hydroxysteroid dehydrogenase. Because these encoded proteins belong to the aldo-keto reductase superfamily, we named these proteins RAKa to RAKf. RAK represents rat aldo-keto reductase, and RAKa is the previously described rat liver 3 alpha-HSD. Northern blot analysis and reverse transcription-polymerase chain reactions were performed to examine their expression in various tissues. Only RAKe, which resembles human aldehyde reductase, was ubiquitously expressed in liver, kidney, lung, and other tissues, while the remaining mRNAs were found to have a more tissue- and sex-specific distribution. Genomic blot analysis showed complex, yet distinctive, restriction band patterns when different cDNAs were used as probes, suggesting that these cDNA clones are products of different genes and more related gene(s) may exist.