AKR1C4

This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq]

aldo-keto reductase family 1, member C4 (chlordecone reductase; 3-alpha hydroxysteroid dehydrogenase, type I; dihydrodiol dehydrogenase 4)

Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Liver specific enzyme that acts as NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain (PubMed:14672942, PubMed:10998348, PubMed:7650035, PubMed:1530633, PubMed:11158055, PubMed:10634139, PubMed:19218247). 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:11158055, PubMed:10998348, 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).

Androgen metabolic process Source: ProtInc
Bile acid and bile salt transport Source: ProtInc
Bile acid biosynthetic process Source: Reactome
Cellular response to jasmonic acid stimulus Source: UniProtKB
Daunorubicin metabolic process Source: UniProtKB
Doxorubicin metabolic process Source: UniProtKB
Progesterone metabolic process Source: GO_Central
Prostaglandin metabolic process Source: GO_Central
Retinoid metabolic process Source: Reactome
Steroid metabolic process

Cytosol

46,XY sex reversal 8 (SRXY8): 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. A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.

The N-terminus is blocked.