AKR1C2
AKR1C2 (aldo-keto reductase family 1 member C2, also known as DD2, DDH2, BABP, HAKRD, MCDR2 and TDD) is a cytosolic NADPH-dependent reductase that converts ketosteroids to hydroxysteroids. It shapes ligand availability for steroid hormone receptors. Browse Assay Genie's current range of AKR1C2 research reagents below, or read on for the biology behind the target.
AKR1C2 is a cytosolic aldo-keto reductase that catalyses the NADPH-dependent reduction of ketosteroids to hydroxysteroids. It has broad substrate specificity with distinct positional and stereochemical preferences, primarily generating 3alpha-hydroxysteroids but also 3beta-, 17beta- and 20alpha-hydroxysteroids. In androgen catabolism it may act mainly as a phase I enzyme, introducing a hydroxyl group before conjugation, although it can also reduce sulfate- or glucuronide-conjugated androgens. It inactivates 5alpha-dihydrotestosterone and progesterone, and so regulates ligand availability for steroid hormone receptors.
The enzyme is required for male sex determination as part of the 'backdoor' androgen biosynthesis pathway, which generates 5alpha-dihydrotestosterone via pregnanes. Together with AKR1C4, it converts 5alpha-dihydroprogesterone to allopregnanolone, supporting the 5alpha-DHT secretion needed for embryonic gonad differentiation into testis. In neurosteroid biosynthesis it may reduce 5alpha-dihydroprogesterone and 5alpha-dihydrodeoxycorticosterone to neuroactive steroids that alter neural excitability through allosteric activation of GABAA receptors. It may also contribute to adrenal-derived androgen metabolism, reduce PGD2 to 11beta-PGF2, and metabolise xenobiotics such as (S)-indan-1-ol. In vitro the reaction runs in both directions with NADPH/NADP(+) or NADH/NAD(+), but in vivo reductase activity prevails.
The AKR1C2 gene encodes a member of the aldo/keto reductase superfamily, which catalyses the conversion of aldehydes and ketones to alcohols using NADH and/or NADPH. NCBI notes that the enzyme binds bile acid with high affinity, and that the gene shares high sequence identity with three other family members clustered with it on chromosome 10p15-p14. Three transcript variants encode two isoforms. Previous names include dihydrodiol dehydrogenase 2, bile acid binding protein and 3-alpha hydroxysteroid dehydrogenase, type III.
AKR1C2 is a component of the backdoor pathway to 5alpha-DHT and is required for male sex determination.
By inactivating 5alpha-DHT and progesterone, it regulates ligand availability for steroid hormone receptors.
It may reduce 5alpha-pregnane precursors to neuroactive steroids that modulate GABAA receptor-dependent neural excitability.
The enzyme reduces PGD2 to 11beta-PGF2 and metabolises xenobiotics such as (S)-indan-1-ol and trans-1,2-dihydrobenzene-1,2-diols.
AKR1C2 is a cytosolic enzyme that reduces ketosteroids to hydroxysteroids using NADPH, mainly forming 3alpha-hydroxysteroids. It inactivates 5alpha-DHT and progesterone, takes part in backdoor androgen synthesis needed for male sex determination, and may contribute to neurosteroid and prostaglandin metabolism.
Aliases include DD, DD2, DDH2, BABP, HAKRD, MCDR2 and TDD. Earlier names were dihydrodiol dehydrogenase 2, bile acid binding protein and 3-alpha hydroxysteroid dehydrogenase type III. Three transcript variants encoding two isoforms have been reported by NCBI.
AKR1C2 shares high sequence identity with three other genes clustered with it on chromosome 10p15-p14. It works with AKR1C4 in the backdoor pathway, and forms testosterone and estradiol less efficiently than AKR1C3. Orthologue information is not given in the source data.
Other aldo-keto reductases, including AKR1C family members involved in steroid metabolism, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P52895; product specifications from Assay Genie datasheets.