AKR1C4
entrez
1109
canonical
uniprot
P17516
canonical
ensembl
ENSG00000198610
resolver
ensp
ENSP00000263126
resolver
ensp
ENSP00000369814
resolver
enst
ENST00000263126
resolver
enst
ENST00000380448
resolver
genesymbol
AKR1C4
resolver
genesymbol_syn
CHDR
resolver
hgnc
HGNC:387
resolver
uniprot
Q5T6A3
resolver
uniprot
Q8WW84
resolver
uniprot
Q9NS54
resolver
uniprot_entry
AK1C4_HUMAN
resolver
uniprot_sec
Q5T6A3
resolver
uniprot_sec
Q8WW84
resolver
uniprot_sec
Q9NS54
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by nonsteroidal the anti-inflammatory drugs (NSAID) flufenamic (PubMed:14672942). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942). {ECO:0000269|PubMed:14672942}.
uniprot
proteins
amino_acid_sequence
MDPKYQRVELNDGHFMPVLGFGTYAPPEVPRNRAVEVTKLAIEAGFRHIDSAYLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWCTFFQPQMVQPALESSLKKLQLDYVDLYLLHFPMALKPGETPLPKDENGKVIFDTVDLSATWEVMEKCKDAGLAKSIGVSNFNCRQLEMILNKPGLKYKPVCNQVECHPYLNQSKLLDFCKSKDIVLVAHSALGTQRHKLWVDPNSPVLLEDPVLCALAKKHKQTPALIALRYQLQRGVVVLAKSYNEQRIRENIQVFEFQLTSEDMKVLDGLNRNYRYVVMDFLMDHPDYPFSDEY
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 gene represented in this entry may act as a disease modifier. A splicing mutation resulting in loss of AKR1C4 exon 2 has been found in affected individuals carrying a causative mutation in AKR1C2 (PubMed:21802064). These patients manifest a more severe disease phenotype than individuals only carrying mutations in AKR1C2. {ECO:0000269|PubMed:21802064}.
uniprot
proteins
ec_number
1.1.1.-
uniprot
proteins
ec_number
1.1.1.209
uniprot
proteins
ec_number
1.1.1.210
uniprot
proteins
ec_number
1.1.1.225
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
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/beta-, 17beta- and 20alpha-hydroxysteroids (PubMed:10634139, PubMed:10998348, PubMed:11158055, PubMed:14672942, PubMed:1530633, PubMed:12604236, PubMed:19218247, PubMed:21802064, PubMed:7650035). 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 AKR1C2 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:21802064). May regulate the concentrations of circulating neurosteroids. Reduces 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: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:11158055, PubMed:14672942). 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-A3diol) (PubMed:31926269). Catalyzes the reduction of estrone into 17beta-estradiol but with low efficiency (PubMed:14672942). 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). Catalyzes the biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol, leading to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route (PubMed:2427522). 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:10634139, ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11158055, ECO:0000269|PubMed:12604236, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:1530633, ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:21802064, ECO:0000269|PubMed:2427522, ECO:0000269|PubMed:31926269, ECO:0000269|PubMed:7650035}.
uniprot
proteins
mass_dalton
37067
uniprot
proteins
pathway_participation
PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:14672942}.
uniprot
proteins
post_translational_modification
PTM: The N-terminus is blocked.
uniprot
proteins
protein_family
Aldo/keto reductase family
uniprot
proteins
pubmed
10634139
uniprot
proteins
pubmed
10672042
uniprot
proteins
pubmed
10998348
uniprot
proteins
pubmed
11158055
uniprot
proteins
pubmed
12604236
uniprot
proteins
pubmed
14672942
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
1530633
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19218247
uniprot
proteins
pubmed
21802064
uniprot
proteins
pubmed
2187532
uniprot
proteins
pubmed
24189185
uniprot
proteins
pubmed
2427522
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
31926269
uniprot
proteins
pubmed
7626489
uniprot
proteins
pubmed
7650035
uniprot
proteins
pubmed
8172617
uniprot
proteins
pubmed
8274401
uniprot
proteins
sequence_length
323
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q04828}.
uniprot
proteins