3-oxo-5-alpha-steroid 4-dehydrogenase 2

UniProt P31213 Organism Homo sapiens Gene SRD5A2 EC 1.3.1.22

Also known as: SRD5A2

Function

Catalyzes the irreversible stereospecific reduction of the delta 4,5 bond (double bond between carbons 4 and 5) of various 3-oxo steroids (3-keto steroids) producing their 5alpha dihydro-3-oxo forms. Converts testosterone into 5-alpha-dihydrotestosterone (DHT), the most active androgen in the prostate, as it is the preferred ligand for androgen receptor (AR) transactivation, making this reaction a key step in male sexual differentiation during development. Besides testosterone, it can also act on other steroids, including progesterone, producing metabolites with diverse roles. Hence, it plays a central role in sexual differentiation and androgen physiology.

Classification

Family (Pfam): PF02544 Steroid_dh
InterPro: 3-oxo-5-alpha-steroid_4-DH, 3-oxo-5_a-steroid_4-DH_C, SRD5A/TECR
Functional cluster: Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 1

7BW1 X-ray 2.80A

A predicted model is available from AlphaFold.

Gene Ontology · 28

Disease associations

46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency MONDO:0009923

Drugs targeting this protein · 3

DUTASTERIDE inhibitor
ABIRATERONE inhibitor
FINASTERIDE inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

3-oxo-5-alpha-steroid 4-dehydrogenase 1 1 shared papers
11-beta-hydroxysteroid dehydrogenase type 2 1 shared papers
Cytochrome P450 11B2, mitochondrial 1 shared papers
11-beta-hydroxysteroid dehydrogenase 1 1 shared papers
Cytochrome P450 11B1, mitochondrial 1 shared papers

Literature · 23 cited papers

11beta-hydroxyandrostenedione, the product of androstenedione metabolism in the adrenal, is metabolized in LNCaP cells by 5alpha-reductase yielding 11beta-hydroxy-5alpha-androstanedione. J. Steroid Biochem. Mol. Biol. · 2013
SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY subjects. Clin. Endocrinol. (Oxf.) · 2005
A novel missense mutation of 5-alpha reductase type 2 gene (SRD5A2) leads to severe male pseudohermaphroditism in a Turkish family. Urology · 2005
New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2. J. Mol. Med. · 2005
Clinical, biochemical and morphologic diagnostic markers in an infant male pseudohermaphrodite patient with compound heterozygous mutations (G115D/R246W) in SRD5A2 gene. Horm. Res. · 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Compound heterozygous mutations in the SRD5A2 gene exon 4 in a male pseudohermaphrodite patient of Chinese origin. J. Androl. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
Comprehensive evaluation of the association between prostate cancer and genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2. Eur. J. Hum. Genet. · 2004
Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients. J. Clin. Endocrinol. Metab. · 2003
Uniparental disomy in steroid 5-alpha-reductase 2 deficiency. J. Clin. Endocrinol. Metab. · 2000
Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II. Pharmacogenetics · 2000
… and 11 more in the literature graph

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