AKR1C3

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 reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Full Name

Aldo-Keto Reductase Family 1 Member C3

Function

Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone (PubMed:10622721, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:9927279). 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, PubMed:11165022). Acts preferentially as a 17-ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone (PubMed:20036328). Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol (PubMed:15047184, PubMed:20036328, PubMed:10622721, PubMed:11165022, PubMed:10998348, PubMed:19010934). 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) (PubMed:10998348, PubMed:14672942, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:10557352). Displays also retinaldehyde reductase activity toward 9-cis-retinal (PubMed:21851338).

Biological Process

Cellular response to cadmium ion Source: UniProtKB
Cellular response to calcium ion Source: UniProtKB
Cellular response to corticosteroid stimulus Source: UniProtKB
Cellular response to jasmonic acid stimulus Source: UniProtKB
Cellular response to prostaglandin D stimulus Source: UniProtKB
Cellular response to prostaglandin stimulus Source: UniProtKB
Cellular response to reactive oxygen species Source: UniProtKB
Cellular response to starvation Source: UniProtKB
Cyclooxygenase pathway Source: Reactome
Daunorubicin metabolic process Source: UniProtKB
Doxorubicin metabolic process Source: UniProtKB
Farnesol catabolic process Source: UniProtKB
G protein-coupled receptor signaling pathway Source: UniProtKB
Keratinocyte differentiation Source: UniProtKB
Macromolecule metabolic process Source: UniProtKB
Male gonad development Source: UniProtKB
Negative regulation of retinoic acid biosynthetic process Source: UniProtKB
Positive regulation of cell death Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of endothelial cell apoptotic process Source: UniProtKB
Positive regulation of protein kinase B signaling Source: UniProtKB
Positive regulation of reactive oxygen species metabolic process Source: UniProtKB
Progesterone metabolic process Source: UniProtKB
Prostaglandin metabolic process Source: UniProtKB
Regulation of retinoic acid receptor signaling pathway Source: UniProtKB
Regulation of testosterone biosynthetic process Source: UniProtKB
Renal absorption Source: UniProtKB
Response to nutrient Source: UniProtKB
Retinal metabolic process Source: UniProtKB
Retinoid metabolic process Source: Reactome
Retinol metabolic process Source: GOC
Steroid metabolic process Source: UniProtKB
Testosterone biosynthetic process Source: UniProtKB

Cellular Location

Cytoplasm