AKR1C3
entrez
8644
canonical
uniprot
P42330
canonical
ensembl
ENSG00000196139
resolver
ensp
ENSP00000369927
resolver
ensp
ENSP00000401327
resolver
enst
ENST00000439082
resolver
genesymbol
AKR1C3
resolver
genesymbol_syn
DDH1
resolver
genesymbol_syn
HSD17B5
resolver
genesymbol_syn
KIAA0119
resolver
genesymbol_syn
PGFS
resolver
hgnc
HGNC:386
resolver
uniprot
A0A0A0MSS8
resolver
uniprot
A8K2V0
resolver
uniprot
B4DKT3
resolver
uniprot
B4DL37
resolver
uniprot
Q5T2L1
resolver
uniprot
Q96DJ1
resolver
uniprot
Q96KI8
resolver
uniprot
Q99530
resolver
uniprot
Q9UCX1
resolver
uniprot
Q9UII3
resolver
uniprot
Q9UKL9
resolver
uniprot_entry
A0A0A0MSS8_HUMAN
resolver
uniprot_entry
AK1C3_HUMAN
resolver
uniprot_entry
B4DKT3_HUMAN
resolver
uniprot_sec
A8K2V0
resolver
uniprot_sec
B4DL37
resolver
uniprot_sec
Q5T2L1
resolver
uniprot_sec
Q96DJ1
resolver
uniprot_sec
Q96KI8
resolver
uniprot_sec
Q99530
resolver
uniprot_sec
Q9UCX1
resolver
uniprot_sec
Q9UII3
resolver
uniprot_sec
Q9UKL9
resolver
activity_regulation
ACTIVITY REGULATION: Strongly inhibited by nonsteroidal anti-inflammatory drugs (NSAID) including flufenamic acid and indomethacin. Also inhibited by the flavinoid, rutin, and by selective serotonin inhibitors (SSRIs) (PubMed:10557352, PubMed:14979715, PubMed:14996743). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942). {ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:14979715, ECO:0000269|PubMed:14996743}.
uniprot
proteins
amino_acid_sequence
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPMSLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLDRNLHYFNSDSFASHPNYPYSDEY
uniprot
proteins
ec_number
1.1.1.-
uniprot
proteins
ec_number
1.1.1.188
uniprot
proteins
ec_number
1.1.1.210
uniprot
proteins
ec_number
1.1.1.239
uniprot
proteins
ec_number
1.1.1.357
uniprot
proteins
ec_number
1.1.1.53
uniprot
proteins
ec_number
1.1.1.62
uniprot
proteins
ec_number
1.1.1.64
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 17beta-hydroxysteroids, but also 3alpha- and 20alpha-hydroxysteroids (PubMed:10998348, PubMed:11165022, PubMed:20036328, PubMed:9415401, PubMed:9927279, PubMed:10998348, PubMed:9927279). Produces potent androgens via classical and 'backdoor'/alternative pathways. In the classical androgen metabolic pathway (biosynthesis of 5alpha-dihydrotestosterone (5alpha-DHT) via testosterone), catalyzes the reduction of delta4-androstenedione to form testosterone (PubMed:10998348, PubMed:11165022, PubMed:20036328, PubMed:9415401, PubMed:9927279). In the 'backdoor' androgen metabolic pathway (biosynthesis of 5alpha-dihydrotestosterone (5alpha-DHT) via pregnanes), reduces androsterone to 5alpha-androstane-3alpha,17beta-diol preceding 5alpha-DHT secretion (PubMed:10557352, PubMed:10998348, PubMed:9415401). Reduces 5alpha-DHT to less potent androgen 5alpha-androstane-3alpha,17beta-diol, likely regulating ligand availability for androgen receptors (PubMed:10557352, PubMed:10998348, PubMed:11165022, PubMed:14672942, PubMed:7650035, PubMed:9415401). May contribute to the metabolism of adrenal-derived androgen precursors. Reduces 11-keto-4-androstene-3,17-dione (11KA4) and 11-keto-5alpha-androstane-3,17-dione (11K-Adione) into potent androgens 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT), respectively (PubMed:31926269). In estrogen metabolism, catalyzes the conversion of estrone to potent estrogen 17beta-estradiol (PubMed:10998348, PubMed:11165022, PubMed:20036328). Acts as a prostaglandin (PG) F2alpha synthase. Displays 11-ketoreductase and 9,11-endoperoxide reductase activities and reduces PGD2 to 11beta-PGF2alpha and PGH2 to PGF2alpha (PubMed:10622721, PubMed:11165022, PubMed:15047184, PubMed:19010934, PubMed:20036328, PubMed:7650035, PubMed:9415401, PubMed:9927279). Also displays retinaldehyde reductase activity toward 9-cis-retinal (PubMed:21851338). 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:11165022, PubMed:14672942). In addition, it is able to reduce in vitro various carbonyl compounds like menadione, phenanthrenequinone and nitrobenzaldehyde (By similarity). {ECO:0000250|UniProtKB:P05980, ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:15047184, ECO:0000269|PubMed:19010934, ECO:0000269|PubMed:20036328, ECO:0000269|PubMed:21851338, ECO:0000269|PubMed:31926269, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}.
uniprot
proteins
mass_dalton
36853
uniprot
proteins
mutagenesis
MUTAGEN 75; /note="K->E: No effect on 17beta-HSD activity."; /evidence="ECO:0000269|PubMed:9927279"; MUTAGEN 226; /note="R->P: Decreases in the retinaldehyde reductase activity. 3-fold decrease in the kcat value, whereas the KM value does not vary."; /evidence="ECO:0000269|PubMed:21851338"; MUTAGEN 226; /note="R->Q: Decrease in the retinaldehyde reductase activity. Exhibits changes in both KM and kcat values."; /evidence="ECO:0000269|PubMed:21851338
uniprot
proteins
protein_family
Aldo/keto reductase family
uniprot
proteins
pubmed
10557352
uniprot
proteins
pubmed
10622721
uniprot
proteins
pubmed
10672042
uniprot
proteins
pubmed
10998348
uniprot
proteins
pubmed
11165022
uniprot
proteins
pubmed
14672942
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14979715
uniprot
proteins
pubmed
14996743
uniprot
proteins
pubmed
15047184
uniprot
proteins
pubmed
15087468
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19010934
uniprot
proteins
pubmed
20036328
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21851338
uniprot
proteins
pubmed
24189185
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
31926269
uniprot
proteins
pubmed
7626489
uniprot
proteins
pubmed
7650035
uniprot
proteins
pubmed
7788527
uniprot
proteins
pubmed
8274401
uniprot
proteins
pubmed
9415401
uniprot
proteins
pubmed
9927279
uniprot
proteins
sequence_length
323
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10622721}.
uniprot
proteins