PUBLICATION
Functional genome analysis indicates loss of 17beta-hydroxysteroid dehydrogenase type 2 enzyme in the zebrafish
- Authors
- Mindnich, R., Hrabe de Angelis, M., and Adamski, J.
- ID
- ZDB-PUB-061108-21
- Date
- 2007
- Source
- The Journal of steroid biochemistry and molecular biology 103(1): 35-43 (Journal)
- Registered Authors
- Hrabe de Angelis, Martin
- Keywords
- Hydroxysteroid dehydrogenase, Zebrafish, Hsd17b2, Hsd11b2, Steroid, Evolution, Comparative endocrinology
- MeSH Terms
-
- 17-Hydroxysteroid Dehydrogenases/genetics*
- 17-Hydroxysteroid Dehydrogenases/metabolism
- Amino Acid Sequence
- Animals
- Databases, Protein
- Genome*
- Isoenzymes/classification
- Isoenzymes/genetics
- Molecular Sequence Data
- Phylogeny
- Sequence Homology, Amino Acid
- Substrate Specificity
- Tissue Distribution
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 17085046 Full text @ Steroid Biochem. Mol. Biol.
Citation
Mindnich, R., Hrabe de Angelis, M., and Adamski, J. (2007) Functional genome analysis indicates loss of 17beta-hydroxysteroid dehydrogenase type 2 enzyme in the zebrafish. The Journal of steroid biochemistry and molecular biology. 103(1):35-43.
Abstract
Among the family of 17beta-hydroxysteroid dehydrogenases, the type 2 (17beta-HSD 2) is the main enzyme responsible for inactivation of estrogens and androgens, catalyzing the oxidation of the C17 hydroxyl group. 17beta-HSD 2 has been studied only in mammals, its occurrence and function in other vertebrates hardly known. We investigated the presence of homologs in non-mammalian species and found sequences of 17beta-HSD 2 and its closest homolog 11beta-HSD 2 in zebrafish (Danio rerio), Takifugu rubripes, Tetraodon nigroviridis, Xenopus tropicalis and chicken databases. Furthermore, we cloned zebrafish 17beta-HSD 2 from ovarian tissue and found high expression also in the testis of adult fish and throughout embryogenesis. The enzyme, though, is inactive likely due to a non-sense N-terminal region including a dysfunctional cofactor binding motif. Replacement of the affected part by the corresponding human 17beta-HSD 2 sequence fully restored enzymatic activity. Comparison of all retrieved 17beta-HSD 2 sequences indicates that this functional loss may have occurred only in zebrafish, where steroid inactivation at position C17 seems to pursue without the protein studied. The closely related 11beta-HSD 2 is unlikely to substitute for 17beta-HSD 2 since in our hands it did not catalyze the respective oxidation of testosterone or estradiol.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping