AKR1C4
Function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Liver specific enzyme that acts as an NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain (PubMed:10634139, PubMed:10998348, PubMed:11158055, PubMed:14672942, PubMed:1530633, PubMed:19218247, PubMed:7650035). Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH (PubMed:14672942). Acts preferentially as a 3-alpha-hydroxysteroid dehydrogenase (HSD) with a subsidiary 3-beta-HSD activity (PubMed:14672942). Catalyzes efficiently the transformation of the potent androgen 5-alpha-dihydrotestosterone (5alpha-DHT or 17beta-hydroxy-5alpha-androstan-3-one) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:10998348, PubMed:11158055, PubMed:14672942). Catalyzes the reduction of estrone into 17beta-estradiol but with low efficiency (PubMed:14672942). Metabolizes a broad spectrum of natural and synthetic therapeutic steroid and plays an important role in metabolism of androgens, estrogens, progestereone and conjugated steroids (PubMed:10998348, PubMed:14672942, PubMed:19218247). Catalyzes the biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leading to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route (PubMed:2427522).
Involvement in disease
46,XY sex reversal 8
SRXY8
A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.
None
The gene represented in this entry may act as a disease modifier. A splicing mutation resulting in loss of AKR1C4 exon 2 has been found in affected individuals carrying a causative mutation in AKR1C2 (PubMed:21802064). These patients manifest a more severe disease phenotype than individuals only carrying mutations in AKR1C2.
Pathway
Steroid metabolism.
Post-translational modifications
The N-terminus is blocked.
Sequence Similarities
Belongs to the aldo/keto reductase family.
Tissue Specificity
Liver specific.
Cellular localization
- Cytoplasm
- Cytosol
Alternative names
CHDR, AKR1C4, Aldo-keto reductase family 1 member C4, 3-alpha-hydroxysteroid dehydrogenase type I, 3alpha-hydroxysteroid 3-dehydrogenase, Chlordecone reductase, Dihydrodiol dehydrogenase 4, HAKRA, 3-alpha-HSD1, CDR, DD-4, DD4