AKR1C1
entrez
1645
canonical
uniprot
Q04828
canonical
ensembl
ENSG00000187134
resolver
ensp
ENSP00000370254
resolver
enst
ENST00000380872
resolver
genesymbol
AKR1C1
resolver
genesymbol_syn
DDH
resolver
genesymbol_syn
DDH1
resolver
hgnc
HGNC:384
resolver
uniprot
P52896
resolver
uniprot
Q5SR15
resolver
uniprot
Q7M4N2
resolver
uniprot
Q9UCX2
resolver
uniprot_entry
AK1C1_HUMAN
resolver
uniprot_sec
P52896
resolver
uniprot_sec
Q5SR15
resolver
uniprot_sec
Q7M4N2
resolver
uniprot_sec
Q9UCX2
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by hexestrol with an IC(50) of 9.5 uM, 1,10-phenanthroline with an IC(50) of 55 uM, 1,7-phenanthroline with an IC(50) of 72 uM, flufenamic acid with an IC(50) of 6.0 uM, indomethacin with an IC(50) of 140 uM, ibuprofen with an IC(50) of 950 uM, lithocholic acid with an IC(50) of 25 uM, ursodeoxycholic acid with an IC(50) of 340 uM and chenodeoxycholic acid with an IC(50) of 570 uM (PubMed:8573067). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942). Inhibited by benzodiazepines. {ECO:0000269|PubMed:11995921, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:8573067}.
uniprot
proteins
amino_acid_sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRYLTLDIFAGPPNYPFSDEY
uniprot
proteins
ec_number
1.1.1.-
uniprot
proteins
ec_number
1.1.1.112
uniprot
proteins
ec_number
1.1.1.149
uniprot
proteins
ec_number
1.1.1.209
uniprot
proteins
ec_number
1.1.1.210
uniprot
proteins
ec_number
1.1.1.270
uniprot
proteins
ec_number
1.1.1.357
uniprot
proteins
ec_number
1.1.1.51
uniprot
proteins
ec_number
1.1.1.53
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 20alpha-hydroxysteroids, but also 3alpha/beta- and 17beta-hydroxysteroids (PubMed:10998348, PubMed:11013348, PubMed:14672942, PubMed:19218247, PubMed:11995921, PubMed:12604236). Involved in neurosteroid metabolism. Reduces 5alpha-dihydrodeoxycorticosterone (5-alpha-DHDOC) to neuroactive steroid 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) known to alter neural excitability via allosteric activation of gamma-aminobutyric acid type A (GABAAR) receptors. Inactivates 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) into less potent neurosteroid 3alpha,20alpha-dihydroxy-5alpha-pregnane (PubMed:11995921, PubMed:12604236). Catalyzes the reduction of progesterone to less potent progestogen (20S)-hydroxypregn-4-en-3-one likely regulating ligand availability for progesterone receptors (PubMed:10998348, PubMed:11013348, PubMed:12604236). 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:19218247). 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). {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348, ECO:0000269|PubMed:11995921, ECO:0000269|PubMed:12604236, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:8486699}.
uniprot
proteins
mass_dalton
36788
uniprot
proteins
mutagenesis
MUTAGEN 127; /note="E->D: 30-fold decrease in k(cat)/K(m) value for progesterone reduction; no effect on the K(m) value."; /evidence="ECO:0000269|PubMed:12899831"; MUTAGEN 222; /note="H->I: Marked decrease in k(cat)/K(m) value for progesterone; 24-fold decrease for progesterone reduction; 18-fold decrease for 20alpha-OHProg oxidation. 95-fold decrease in K(m) value for NADPH."; /evidence="ECO:0000269|PubMed:12899831"; MUTAGEN 222; /note="H->S: Marked decrease in k(cat)/K(m) value for progesterone; 10-fold decrease for progesterone reduction; 3-fold decrease for 20alpha-OHProg oxidation. 10-fold decrease in K(m) value for NADPH."; /evidence="ECO:0000269|PubMed:12899831"; MUTAGEN 304; /note="R->L: 70-fold decrease in progesterone reduction. No effect on DHT reduction."; /evidence="ECO:0000269|PubMed:12899831"; MUTAGEN 305; /note="Y->F: No effect on progesterone reduction."; /evidence="ECO:0000269|PubMed:12899831"; MUTAGEN 307; /note="T->V: No effect on progesterone reduction."; /evidence="ECO:0000269|PubMed:12899831"; MUTAGEN 309; /note="D->V: No effect on progesterone reduction."; /evidence="ECO:0000269|PubMed:12899831
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
11013348
uniprot
proteins
pubmed
11995921
uniprot
proteins
pubmed
12604236
uniprot
proteins
pubmed
12899831
uniprot
proteins
pubmed
14672942
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19218247
uniprot
proteins
pubmed
21414777
uniprot
proteins
pubmed
24189185
uniprot
proteins
pubmed
7515059
uniprot
proteins
pubmed
7626489
uniprot
proteins
pubmed
8132567
uniprot
proteins
pubmed
8172617
uniprot
proteins
pubmed
8274401
uniprot
proteins
pubmed
8486699
uniprot
proteins
pubmed
8573067
uniprot
proteins
sequence_length
323
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:8486699}.
uniprot
proteins