AKR1C2
entrez
1646
canonical
uniprot
P52895
canonical
ensembl
ENSG00000151632
resolver
ensp
ENSP00000370129
resolver
ensp
ENSP00000392694
resolver
ensp
ENSP00000408440
resolver
enst
ENST00000421196
resolver
genesymbol
AKR1C2
resolver
genesymbol_syn
DDH2
resolver
hgnc
HGNC:385
resolver
uniprot
A8K2N9
resolver
uniprot
B4DK69
resolver
uniprot
B4DKR9
resolver
uniprot
F6Q7U0
resolver
uniprot
Q14133
resolver
uniprot
Q5SR16
resolver
uniprot
Q7M4N1
resolver
uniprot
Q96A71
resolver
uniprot_entry
AK1C2_HUMAN
resolver
uniprot_entry
B4DK69_HUMAN
resolver
uniprot_entry
F6Q7U0_HUMAN
resolver
uniprot_sec
A8K2N9
resolver
uniprot_sec
B4DKR9
resolver
uniprot_sec
Q14133
resolver
uniprot_sec
Q5SR16
resolver
uniprot_sec
Q7M4N1
resolver
uniprot_sec
Q96A71
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by bile acids such as lithocholic acid with an IC(50) of 0.07 uM, ursodeoxycholic acid with an IC(50) of 0.08 uM and chenodeoxycholic acid with an IC(50) of 0.13 uM. Inhibited by anti-inflammatory drugs such as flufenamic acid with an IC(50) of 0.9 uM, indomethacin with an IC(50) of 75 uM and ibuprofen with an IC(50) of 6.9 uM. Inhibited by aromatic synthetic compounds such as hexestrol with an IC(50) of 2.8 uM, 1,10-phenanthroline with an IC(50) of 2100 uM and 1,7-phenanthroline with an IC(50) of 1500 uM (PubMed:8573067, PubMed:12416991, PubMed:9716498). Not affected by fluoxetine, paroxetine, sertraline, norfluoxetine, carbamazepine, clozapine, flurbiprofen, or bromosulfophthalein (PubMed:12416991). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942). Inhibited by anti-anxiety drugs benzodiazepines (PubMed:11995921). {ECO:0000269|PubMed:11995921, ECO:0000269|PubMed:12416991, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:8573067}.
uniprot
proteins
amino_acid_sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHIDSAHVYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFNHRLLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
uniprot
proteins
disease_involvement
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. {ECO:0000269|PubMed:21802064}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.1.1.112
uniprot
proteins
ec_number
1.1.1.209
uniprot
proteins
ec_number
1.1.1.357
uniprot
proteins
ec_number
1.1.1.51
uniprot
proteins
ec_number
1.1.1.62
uniprot
proteins
ec_number
1.3.1.20
uniprot
proteins
function
FUNCTION: Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids. Displays broad substrate specificity with distinct positional and stereochemistry, primarily generating 3alpha-hydroxysteroids, but also 3beta-, 17beta- and 20alpha-hydroxysteroids (PubMed:8920937, PubMed:9716498, PubMed:10998348, PubMed:12416991, PubMed:11995921, PubMed:12604236, PubMed:14672942, PubMed:19218247, PubMed:21802064, PubMed:11514561, PubMed:15929998, PubMed:17034817, PubMed:17442338, PubMed:24434280). Required for male sex determination as a component of the 'backdoor' androgen biosynthesis pathway that generates 5alpha-dihydrotestosterone (5alpha-DHT) via pregnanes. Acts together with AKR1C4 to convert 5alpha-dihydroprogesterone (5alpha-DHP) to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP/allopregnanolone), leading to 5alpha-DHT secretion necessary for embryonic gonad differentiation into testis (PubMed:12416991, PubMed:21802064). In androgen catabolism, may predominantly act as a phase I enzyme by introducing a hydroxyl group prior to conjugation. It can nevertheless participate in the alternative phase II pathway by directly reducing sulfate- or glucuronide-conjugated androgens (PubMed:10998348, PubMed:11514561, PubMed:14672942, PubMed:15929998, PubMed:19218247, PubMed:24434280). In neurosteroid biosynthesis, may preferentially reduce 5alpha-dihydroprogesterone (5-alpha-DHP) and 5alpha-dihydrodeoxycorticosterone (5-alpha-DHDOC) precursors to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP/allopregnanolone) and 3alpha,21-dihydroxy-5alpha-pregnane-20-one (3alpha,5alpha-THDOC) neuroactive steroids known to alter neural excitability via allosteric activation of gamma-aminobutyric acid type A receptors (GABAAR) (PubMed:11995921, PubMed:12416991, PubMed:12604236). Regulates ligand availability for steroid hormone receptors. Catalyzes the inactivation of 5alpha-DHT and progesterone converting them into 3alpha/beta-androstanediols and (20S)-hydroxypregn-4-en-3-one, respectively (PubMed:10998348, PubMed:24434280). Can form 17beta-hydroxysteroids such as testosterone and estradiol albeit with lower efficiency when compared to AKR1C3 (PubMed:10998348). May contribute to the metabolism of adrenal-derived androgens via reduction of 11-keto-5alpha-androstane-3,17-dione (11K-Adione) into 11-ketoandrosterone (11KAST) and of 11-ketodihydrotestosterone (11KDHT) into 11-keto-5alpha-androstane-3alpha/beta,17beta-diol (11K-A3alphadiol) (PubMed:31926269). May also play a role in prostaglandin (PG) metabolism by reducing PGD2 to 11beta-PGF2 (PubMed:9716498). Also able to metabolize xenobiotics (S)-indan-1-ol and trans-1,2-dihydrobenzene-1,2-diols (PubMed:8573067, PubMed:9716498). In vitro can efficiently catalyze bidirectional conversion between ketosteroids and hydroxysteroids using NADPH/NADP(+) or NADH/NAD(+) as cofactors. In vivo however, the reductase activity prevails since the major reducing cofactor NADPH inhibits NAD(+)-dependent oxidase activity (PubMed:14672942, PubMed:21802064). {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11514561, ECO:0000269|PubMed:11995921, ECO:0000269|PubMed:12416991, ECO:0000269|PubMed:12604236, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:15929998, ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338, ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:21802064, ECO:0000269|PubMed:24434280, ECO:0000269|PubMed:31926269, ECO:0000269|PubMed:8573067, ECO:0000269|PubMed:8920937, ECO:0000269|PubMed:9716498}.
uniprot
proteins
mass_dalton
36735
uniprot
proteins
mutagenesis
MUTAGEN 24; /note="Y->A: Partially switches the stereospecificity of the reductase activity from 17beta to 17alpha. Acquires the capacity to metabolize androstenedione into epitestosterone. Decreases the affinity for androstenedione."; /evidence="ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338"; MUTAGEN 54; /note="V->L: 17-fold reduction in 3alpha hydroxysteroid dehydrogenase activity toward 5alpha-DHT. 4.4-fold increase in 20alpha hydroxysteroid dehydrogenase activity toward progesterone."; /evidence="ECO:0000269|PubMed:24434280"; MUTAGEN 301; /note="R->A: Decreases 3-alpha-hydroxysteroid reductase activity about 50-fold."; /evidence="ECO:0000269|PubMed:15929998"; MUTAGEN 304; /note="R->A: Decreases 3-alpha-hydroxysteroid reductase activity about 500-fold."; /evidence="ECO:0000269|PubMed:15929998
uniprot
proteins
pathway_participation
PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:14672942}.
uniprot
proteins
protein_family
Aldo/keto reductase family
uniprot
proteins
pubmed
10672042
uniprot
proteins
pubmed
10998348
uniprot
proteins
pubmed
11513593
uniprot
proteins
pubmed
11514561
uniprot
proteins
pubmed
11995921
uniprot
proteins
pubmed
12416991
uniprot
proteins
pubmed
12604236
uniprot
proteins
pubmed
14672942
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15929998
uniprot
proteins
pubmed
17034817
uniprot
proteins
pubmed
17442338
uniprot
proteins
pubmed
19218247
uniprot
proteins
pubmed
21802064
uniprot
proteins
pubmed
24189185
uniprot
proteins
pubmed
24434280
uniprot
proteins
pubmed
31926269
uniprot
proteins
pubmed
7959017
uniprot
proteins
pubmed
8011662
uniprot
proteins
pubmed
8274401
uniprot
proteins
pubmed
8486699
uniprot
proteins
pubmed
8573067
uniprot
proteins
pubmed
8920937
uniprot
proteins
pubmed
9716498
uniprot
proteins
sequence_length
323
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:8486699}.
uniprot
proteins