AKR1C3
AKR1C3 (aldo-keto reductase family 1 member C3, also known as HSD17B5, PGFS, DDX, HAKRB and KIAA0119) is a cytosolic NADPH-dependent reductase. It converts ketosteroids to hydroxysteroids and acts as a prostaglandin F2alpha synthase. Browse Assay Genie's current range of AKR1C3 research reagents below, or read on for the biology behind the target.
AKR1C3 is a cytosolic aldo-keto reductase that catalyses the NADPH-dependent reduction of ketosteroids to hydroxysteroids. It shows broad substrate specificity with distinct positional and stereochemical preferences, mainly generating 17beta-hydroxysteroids but also 3alpha- and 20alpha-hydroxysteroids. The enzyme produces potent androgens through both the classical pathway, where it reduces delta4-androstenedione to testosterone, and the 'backdoor' pathway, where it reduces androsterone to 5alpha-androstane-3alpha,17beta-diol ahead of 5alpha-dihydrotestosterone (5alpha-DHT) secretion. It can also reduce 5alpha-DHT to a less potent androgen, which may help regulate ligand availability for androgen receptors, and it reduces 11-ketoandrostenedione and 11-keto-5alpha-androstanedione to 11-ketotestosterone and 11-ketodihydrotestosterone.
Beyond androgens, AKR1C3 converts estrone to 17beta-estradiol in oestrogen metabolism. It acts as a prostaglandin F2alpha synthase, with 11-ketoreductase and 9,11-endoperoxide reductase activities that reduce PGD2 to 11beta-PGF2alpha and PGH2 to PGF2alpha. It also shows retinaldehyde reductase activity toward 9-cis-retinal and can reduce carbonyl compounds such as menadione, phenanthrenequinone and nitrobenzaldehyde. In vitro it can work in both directions with NADPH/NADP(+) or NADH/NAD(+), but in vivo reductase activity prevails because NADPH inhibits NAD(+)-dependent oxidation.
The AKR1C3 gene belongs to the aldo/keto reductase superfamily, which comprises more than 40 enzymes that convert aldehydes and ketones to alcohols. It shares high sequence identity with three other genes and is clustered with them on chromosome 10p15-p14, and three transcript variants encoding different isoforms have been reported. NCBI notes a possible role in allergic diseases such as asthma and in the control of cell growth and differentiation. Earlier names include hydroxysteroid (17-beta) dehydrogenase 5 and 3-alpha hydroxysteroid dehydrogenase, type II.
AKR1C3 generates testosterone and 5alpha-DHT through classical and backdoor pathways, making it central to studies of androgen production and receptor ligand availability.
The enzyme converts estrone to 17beta-estradiol, linking it to studies of local oestrogen production and steroid hormone balance.
As a prostaglandin F2alpha synthase that reduces PGD2 and PGH2, AKR1C3 is relevant to prostaglandin pathway and allergic disease research.
Overlapping but distinct substrate specificities among aldo-keto reductases make AKR1C3 a useful subject for comparing family members and their roles.
AKR1C3 is a cytosolic enzyme that reduces ketosteroids to hydroxysteroids using NADPH. It produces testosterone and other potent androgens, converts estrone to 17beta-estradiol, and acts as a prostaglandin F2alpha synthase. It also reduces 9-cis-retinal and several carbonyl compounds.
AKR1C3 is also known as HSD17B5, PGFS, DDX, HAKRB and KIAA0119. Earlier names were hydroxysteroid (17-beta) dehydrogenase 5 and 3-alpha hydroxysteroid dehydrogenase, type II. NCBI reports three transcript variants encoding different isoforms.
AKR1C3 belongs to the aldo/keto reductase family and shares high sequence identity with three other genes clustered with it at chromosome 10p15-p14. These enzymes have overlapping but distinct substrate specificities. Check the datasheet of any product for its validated reactivity.
Other aldo-keto reductases, including the closely clustered AKR1C enzymes, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P42330; product specifications from Assay Genie datasheets.