title: 11Beta-hydroxysteroid dehydrogenase-type 2 evolved from an ancestral 17beta-hydroxysteroid dehydrogenase-type 2.
abstract: 11Beta-hydroxysteroid dehydrogenase-type 2 (11beta-HSD2) regulates the local concentration of cortisol that can activate the glucocorticoid receptor and mineralocorticoid receptor, as well as the concentration of 11-keto-testosterone, the active androgen in fish. Similarly, 17beta-HSD2 regulates the levels of testosterone and estradiol that activate the androgen receptor and estrogen receptor, respectively. Interestingly, although human 11beta-HSD2 and 17beta-HSD2 act at different positions on different steroids, these enzymes are paralogs. Despite the physiological importance of 11beta-HSD2 and 17beta-HSD2, details of their origins and divergence from a common ancestor are not known. An opportunity to understand their evolution is presented by the recent sequencing of genomes from sea urchin, a basal deuterostome, and amphioxus, a basal chordate, and the availability of substantial sequence for acorn worm and elephant shark, which together provide a more complete dataset for analysis of the origins of 11beta-HSD2 and 17beta-HSD2. BLAST searches find an ancestral sequence of 17beta-HSD2 in sea urchin, acorn worm and amphioxus, while an ancestral sequence of 11beta-HSD2 first appears in sharks. Sequence analyses indicate that 17beta-HSD2 in sea urchin may have a non-enzymatic activity. Evolutionary analyses indicate that if acorn worm 17beta-HSD2 is catalytically active, then it metabolizes novel substrate(s).
authors.affiliation: Department of Medicine, 0693, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, United States. mbaker@ucsd.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Baker
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000145:classification* / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D012617:Sea Urchins / Q000201:enzymology / Q000235:genetics; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2