AKR1C4 Antibody – Rabbit Polyclonal

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]

Function: 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.

Catalytic activity: Chlordecone alcohol + NADP+ = chlordecone + NADPH.A 3-alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H.

Subunit structure: Monomer.

Subcellular location: Cytoplasm.

Tissue specificity: Liver specific. Ref.2 Ref.6

Post-translational modification: The N-terminus is blocked.

Polymorphism: The allele with Cys-145/Val-311 shows a three- to five-fold decrease in catalytic efficiency for xenobiotic and steroidal substrates compared to the Ser-145/Leu-311 allele.

Involvement in disease: 46,XY sex reversal 8 (SRXY8) [MIM:614279]: A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.Note: 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 (Ref.12). These patients manifest a more severe disease phenotype than individuals only carrying mutations in AKR1C2. Ref.12

Sequence similarities: Belongs to the aldo/keto reductase family.

Sequence caution: The sequence AAA35658.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.