Aldo-Keto Reductase Family 1 Member C4 (AKR1C4) Human Active Protein

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, Jul 2008]

AKR1C4: Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha- androstan-3-alpha,17-beta-diol (3-alpha-diol). Also has some 20- alpha-hydroxysteroid dehydrogenase activity. The biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol leads to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route. Defects in AKR1C4 are a cause of 46,XY sex reversal type 8 (SRXY8). A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. AKR1C4 mutations may act as modifier of disease severity in SRXY8 patients. A splicing mutation resulting in loss of exon 2 has been found in affected individuals also carrying mutation Val-79 in AKR1C2 (PubMed:21802064). Belongs to the aldo/keto reductase family.

Protein type: EC 1.1.1.357; Lipid Metabolism - C21-steroid hormone; Lipid Metabolism - androgen and estrogen; Xenobiotic Metabolism - metabolism by cytochrome P450; Lipid Metabolism - primary bile acid biosynthesis; EC 1.1.1.225; Oxidoreductase

Chromosomal Location of Human Ortholog: 10p15.1

Cellular Component: cytoplasm; cytosol

Molecular Function: oxidoreductase activity, acting on NADH or NADPH, quinone or similar compound as acceptor; electron carrier activity; aldo-keto reductase activity; chlordecone reductase activity; bile acid transmembrane transporter activity; 3(or 17)-alpha-hydroxysteroid dehydrogenase activity; retinal dehydrogenase activity

Biological Process: bile acid and bile salt transport; steroid metabolic process; bile acid biosynthetic process; phototransduction, visible light; bile acid metabolic process; androgen metabolic process; retinoid metabolic process

Disease: 46,xy Sex Reversal 8