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Details on Person UniProt:P42330-2 AKR1C3

Class:IdReferenceIsoform:8977282
_chainChangeLogchain:1-323 added on Fri February 17 2017
_displayNameUniProt:P42330-2 AKR1C3
_timestamp2026-02-20 22:40:49
chainchain:1-323
checksum86A7690D9498C6FD
commentFUNCTION 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).CATALYTIC ACTIVITY a 17beta-hydroxy steroid + NADP(+) = a 17-oxo steroid + NADPH + H(+)CATALYTIC ACTIVITY a 3alpha-hydroxysteroid + NADP(+) = a 3-oxosteroid + NADPH + H(+)CATALYTIC ACTIVITY testosterone + NADP(+) = androst-4-ene-3,17-dione + NADPH + H(+)CATALYTIC ACTIVITY androsterone + NADPH + H(+) = 5alpha-androstane-3alpha,17beta-diol + NADP(+)CATALYTIC ACTIVITY 5alpha-androstane-3alpha,17beta-diol + NADP(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADPH + H(+)CATALYTIC ACTIVITY 5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADPH + H(+)CATALYTIC ACTIVITY androst-4-ene-3,11,17-trione + NADPH + H(+) = 17beta-hydroxyandrost-4-ene-3,11-dione + NADP(+)CATALYTIC ACTIVITY 5alpha-androstan-3,11,17-trione + NADPH + H(+) = 17beta-hydroxy-5alpha-androstan-3,11-dione + NADP(+)CATALYTIC ACTIVITY 3alpha-hydroxy-5alpha-androstan-11,17-dione + NADPH + H(+) = 3alpha,17beta-dihydroxy-5alpha-androstan-11-one + NADP(+)CATALYTIC ACTIVITY 17beta-estradiol + NADP(+) = estrone + NADPH + H(+)CATALYTIC ACTIVITY (20S)-hydroxypregn-4-en-3-one + NADP(+) = progesterone + NADPH + H(+)CATALYTIC ACTIVITY prostaglandin F2alpha + NADP(+) = prostaglandin D2 + NADPH + H(+)CATALYTIC ACTIVITY prostaglandin F2alpha + NADP(+) = prostaglandin H2 + NADPH + H(+)CATALYTIC ACTIVITY prostaglandin D2 + NADPH + H(+) = 11beta-prostaglandin F2 + NADP(+)CATALYTIC ACTIVITY prostaglandin D2-ethanolamide + NADPH + H(+) = 11beta-prostaglandin F2-ethanolamide + NADP(+)CATALYTIC ACTIVITY 9-cis-retinol + NADP(+) = 9-cis-retinal + NADPH + H(+)CATALYTIC ACTIVITY testosterone + NAD(+) = androst-4-ene-3,17-dione + NADH + H(+)CATALYTIC ACTIVITY 17beta-estradiol + NAD(+) = estrone + NADH + H(+)CATALYTIC ACTIVITY (20S)-hydroxypregn-4-en-3-one + NAD(+) = progesterone + NADH + H(+)CATALYTIC ACTIVITY 5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADH + H(+)CATALYTIC ACTIVITY 5alpha-androstane-3alpha,17beta-diol + NAD(+) = androsterone + NADH + H(+)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).BIOPHYSICOCHEMICAL PROPERTIES kcat is 0.044 min(-1) for testosterone oxydation (PubMed:10998348). kcat is 13 min(-1) for 9-cis-retinal as substrate (PubMed:21851338). kcat is 4.18 min(-1) for 17beta-hydroxy-5alpha-androstan-3-one reduction (PubMed:10998348). kcat is 0.37 min(-1) for 3alpha-hydroxy-5alpha-androstan-17-one reduction (PubMed:10998348). kcat is 0.046 min(-1) for 17beta-hydroxy-5alpha-androstan-3-one oxydation (PubMed:10998348).INTERACTION Expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate and testis. High expression in prostate and mammary gland. In the prostate, higher levels in epithelial cells than in stromal cells. In the brain, expressed in medulla, spinal cord, frontotemporal lobes, thalamus, subthalamic nuclei and amygdala. Weaker expression in the hippocampus, substantia nigra and caudate.SIMILARITY Belongs to the aldo/keto reductase family.SEQUENCE CAUTION Truncated N-terminus.
created[InstanceEdit:8964659] Weiser, JD
descriptionrecommendedName: fullName evidence="27 28 30"Aldo-keto reductase family 1 member C3 ecNumber evidence="5 6 7 8 14 18 21 22"1.1.1.- ecNumber evidence="8"1.1.1.210 ecNumber evidence="6 8"1.1.1.53 ecNumber evidence="6"1.1.1.62 alternativeName: fullName evidence="24"17-beta-hydroxysteroid dehydrogenase type 5 shortName: 17-beta-HSD 5 alternativeName: 3-alpha-HSD type II, brain alternativeName: fullName evidence="36 37"3-alpha-hydroxysteroid dehydrogenase type 2 shortName evidence="36 37"3-alpha-HSD type 2 ecNumber evidence="7 18 21 22"1.1.1.357 alternativeName: Chlordecone reductase homolog HAKRb alternativeName: Dihydrodiol dehydrogenase 3 shortName: DD-3 shortName: DD3 alternativeName: Dihydrodiol dehydrogenase type I alternativeName: HA1753 alternativeName: fullName evidence="23"Prostaglandin F synthase shortName evidence="23"PGFS ecNumber evidence="5 7 18 21 22"1.1.1.188 alternativeName: fullName evidence="37"Testosterone 17-beta-dehydrogenase 5 ecNumber evidence="6 7 21 22"1.1.1.239 ecNumber evidence="6 7 14 21 22"1.1.1.64
geneNameAKR1C3
DDH1
HSD17B5
KIAA0119
PGFS
identifierP42330
isoformParent
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
Cytoplasm
Lipid metabolism
NAD
NADP
Oxidoreductase
Proteomics identification
Reference proteome
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameAKR1C3
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8962252] ENSEMBL:ENSG00000196139 AKR1C3 [Homo sapiens]
secondaryIdentifierAK1C3_HUMAN
A8K2V0
B4DL37
Q5T2L1
Q96DJ1
Q96KI8
Q99530
Q9UCX1
Q9UII3
Q9UKL9
sequenceLength323
species[Species:48887] Homo sapiens
variantIdentifierP42330-2
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No pathways have been reviewed or authored by UniProt:P42330-2 AKR1C3 (8977282)
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