InterPro domain: IPR001104

3-oxo-5-alpha-steroid 4-dehydrogenases, 1.3.99.5 catalyse the conversion of 3-oxo-5-alpha-steroid + acceptor to 3-oxo-delta(4)-steroid + reduced acceptor. The steroid 5-alpha-reductase enzyme is responsible for the formation of dihydrotestosterone, this hormone promotes the differentiation of male external genitalia and the prostate during foetal development [ 1 ]. In humans mutations in this enzyme can cause a form of male pseudohermaphorditism in which the external genitalia and prostate fail to develop normally. A related steroid reductase enzyme, DET2, is found in plants such as Arabidopsis. Mutations in this enzyme cause defects in light-regulated development [ 2 ]. This domain is present in both type 1 and type 2 [ 3 ] forms.

This domain is also found in polyprenol reductase (SRD5A3; 1.3.1.94 ), which is reduces the alpha-isoprene unit of polyprenol to form dolichol. Dolichol is required for the synthesis of a dolichol-linked monosaccharide and the oligosaccharide precursor used for N-glycosylation [ 4 ].

Another enzyme with this domain is very-long-chain enoyl-CoA reductase (TECR; 1.3.1.93 ), which catalyzes the last of the four reactions of the long-chain fatty acids elongation cycle by reducing the trans-2,3-enoyl-CoA fatty acid intermediate to an acyl-CoA that can be further elongated by entering a new cycle of elongation [ 5 ].

1. Characterization and chromosomal mapping of a human steroid 5 alpha-reductase gene and pseudogene and mapping of the mouse homologue. Genomics 11, 1102-12
2. A role for brassinosteroids in light-dependent development of Arabidopsis. Science 272, 398-401
3. Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature 354, 159-61
4. SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell 142, 203-17
5. Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade. J. Biol. Chem. 278, 7335-43