Comparative genomic and phylogenetic analysis of short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity

Olga V Belyaeva; Natalia Y Kedishvili

doi:10.1016/j.ygeno.2006.06.004

Comparative genomic and phylogenetic analysis of short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity

Genomics. 2006 Dec;88(6):820-830. doi: 10.1016/j.ygeno.2006.06.004. Epub 2006 Jul 24.

Authors

Olga V Belyaeva¹, Natalia Y Kedishvili²

Affiliations

¹ 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: [email protected].
² 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.

PMID: 16860536
DOI: 10.1016/j.ygeno.2006.06.004

Abstract

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.

Publication types

Comparative Study
Research Support, N.I.H., Extramural

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 2 / chemistry
11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics
11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
3-Hydroxysteroid Dehydrogenases / chemistry
3-Hydroxysteroid Dehydrogenases / genetics
3-Hydroxysteroid Dehydrogenases / metabolism
Alcohol Dehydrogenase / chemistry
Alcohol Dehydrogenase / genetics
Alcohol Dehydrogenase / metabolism
Alcohol Oxidoreductases / chemistry
Alcohol Oxidoreductases / genetics
Alcohol Oxidoreductases / metabolism
Amino Acid Sequence
Animals
Estradiol Dehydrogenases / chemistry
Estradiol Dehydrogenases / genetics
Estradiol Dehydrogenases / metabolism
Genomics*
Humans
Hydroxysteroids / metabolism*
Molecular Sequence Data
Oxidoreductases / chemistry
Oxidoreductases / genetics*
Oxidoreductases / metabolism
Phylogeny*
Substrate Specificity
Vitamin A / metabolism*

Substances

Hydroxysteroids
Vitamin A
Oxidoreductases
3-Hydroxysteroid Dehydrogenases
Alcohol Oxidoreductases
DHRS9 protein, human
Alcohol Dehydrogenase
retinol dehydrogenase
11-beta-Hydroxysteroid Dehydrogenase Type 2
HSD11B2 protein, human
Estradiol Dehydrogenases
HSD17B1 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding