Comparative genomic and phylogenetic analysis of short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity.
Human short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity (RODH-like enzymes) are thought to contribute to the oxidation of retinol for retinoic acid biosynthesis and to the metabolism of androgenic and neuroactive 3alpha-hydroxysteroids. Here, we investigated the phylogeny and orthology of these proteins to understand better their origins and physiological roles. Phylogenetic and genomic analysis showed that two proteins (11-cis-RDH and RDHL) are highly conserved, and their orthologs can be identified in the lower taxa, such as amphibians and fish. Two other proteins (RODH-4 and 3alpha-HSD) are significantly less conserved. Orthologs for 3alpha-HSD are present in all mammals analyzed, whereas orthologs for RODH-4 can be identified in some mammalian species but not in others due to species-specific gene duplications. Understanding the evolution and divergence of RODH-like enzymes in various vertebrate species should facilitate further investigation of their in vivo functions using animal models.
Belyaeva
Olga V
OV
Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, 720 20th Street South, 466 Kaul Genetics Building, Birmingham, AL 35294, USA. Electronic address: belyaeva@uab.edu.
Kedishvili
Natalia Y
NY
Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, 720 20th Street South, 466 Kaul Genetics Building, Birmingham, AL 35294, USA.
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004960:Estradiol Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D023281:Genomics; D006801:Humans; D006914:Hydroxysteroids / Q000378:metabolism*; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D013379:Substrate Specificity; D014801:Vitamin A / Q000378:metabolism*
D006914:Hydroxysteroids; D014801:Vitamin A; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; C432414:DHRS9 protein, human; D000426:Alcohol Dehydrogenase; C022520:retinol dehydrogenase; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human