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UniProt functional annotation for P42330 | ||
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| UniProt code: P42330. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone (PubMed:10622721, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:9927279). Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH (PubMed:14672942, PubMed:11165022). Acts preferentially as a 17- ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone (PubMed:20036328). Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol (PubMed:15047184, PubMed:20036328, PubMed:10622721, PubMed:11165022, PubMed:10998348, PubMed:19010934). Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:10998348, PubMed:14672942, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:10557352). Displays also retinaldehyde reductase activity toward 9-cis-retinal (PubMed:21851338). {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:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}. |
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| Catalytic activity: | |
Reaction=a 3alpha-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+) + NADPH; Xref=Rhea:RHEA:34783, ChEBI:CHEBI:15378, ChEBI:CHEBI:36835, ChEBI:CHEBI:47788, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.357; Evidence={ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}; |
| Catalytic activity: | |
Reaction=a 3alpha-hydroxysteroid + NAD(+) = a 3-oxosteroid + H(+) + NADH; Xref=Rhea:RHEA:34779, ChEBI:CHEBI:15378, ChEBI:CHEBI:36835, ChEBI:CHEBI:47788, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.357; Evidence={ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}; |
| Catalytic activity: | |
Reaction=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin D2; Xref=Rhea:RHEA:10140, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404, ChEBI:CHEBI:57406, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.188; Evidence={ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}; |
| Catalytic activity: | |
Reaction=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin H2; Xref=Rhea:RHEA:45312, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404, ChEBI:CHEBI:57405, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:15047184, ECO:0000269|PubMed:19010934}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45314; Evidence={ECO:0000305|PubMed:15047184, ECO:0000305|PubMed:19010934}; |
| Catalytic activity: | |
Reaction=H(+) + NADPH + prostaglandin D2 = 11beta-prostaglandin F2 + NADP(+); Xref=Rhea:RHEA:45316, ChEBI:CHEBI:15378, ChEBI:CHEBI:57406, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:85173; Evidence={ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:15047184, ECO:0000269|PubMed:20036328}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45317; Evidence={ECO:0000305|PubMed:10622721, ECO:0000305|PubMed:20036328}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45318; Evidence={ECO:0000305|PubMed:10622721}; |
| Catalytic activity: | |
Reaction=H(+) + NADPH + prostaglandin D2-ethanolamide = 11beta- prostaglandin F2-ethanolamide + NADP(+); Xref=Rhea:RHEA:45308, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:85174, ChEBI:CHEBI:85175; Evidence={ECO:0000269|PubMed:15047184}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45309; Evidence={ECO:0000305|PubMed:15047184}; |
| Catalytic activity: | |
Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422, ChEBI:CHEBI:17347, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.239; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930; Evidence={ECO:0000305|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14931; Evidence={ECO:0000305|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=NADP(+) + testosterone = androst-4-ene-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:14981, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422, ChEBI:CHEBI:17347, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.64; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:20036328, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14982; Evidence={ECO:0000305|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14983; Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:20036328}; |
| Catalytic activity: | |
Reaction=17beta-estradiol + NADP(+) = estrone + H(+) + NADPH; Xref=Rhea:RHEA:24616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:17263, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.62; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:20036328}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24617; Evidence={ECO:0000305|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618; Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:20036328}; |
| Catalytic activity: | |
Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH; Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613; Evidence={ECO:0000305|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24614; Evidence={ECO:0000305|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=(20S)-hydroxypregn-4-en-3-one + NADP(+) = H(+) + NADPH + progesterone; Xref=Rhea:RHEA:42112, ChEBI:CHEBI:15378, ChEBI:CHEBI:17026, ChEBI:CHEBI:28453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:20036328}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42113; Evidence={ECO:0000305|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42114; Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:20036328}; |
| Catalytic activity: | |
Reaction=(20S)-hydroxypregn-4-en-3-one + NAD(+) = H(+) + NADH + progesterone; Xref=Rhea:RHEA:42108, ChEBI:CHEBI:15378, ChEBI:CHEBI:17026, ChEBI:CHEBI:28453, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42109; Evidence={ECO:0000305|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42110; Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:20036328}; |
| Catalytic activity: | |
Reaction=5alpha-androstane-3alpha,17beta-diol + NADP(+) = 17beta- hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:42116, ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42118; Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:14672942}; |
| Catalytic activity: | |
Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta- hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004, ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006; Evidence={ECO:0000305|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=3alpha-hydroxy-5alpha-androstan-17-one + H(+) + NADPH = 5alpha-androstane-3alpha,17beta-diol + NADP(+); Xref=Rhea:RHEA:42156, ChEBI:CHEBI:15378, ChEBI:CHEBI:16032, ChEBI:CHEBI:36713, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:9415401}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42157; Evidence={ECO:0000305|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42158; Evidence={ECO:0000305|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 3alpha- hydroxy-5alpha-androstan-17-one + H(+) + NADH; Xref=Rhea:RHEA:42124, ChEBI:CHEBI:15378, ChEBI:CHEBI:16032, ChEBI:CHEBI:36713, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:9415401}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42125; Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:14672942}; |
| Catalytic activity: | |
Reaction=5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta- hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:16297, ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:18329, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.210; Evidence={ECO:0000269|PubMed:14672942}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16299; Evidence={ECO:0000305|PubMed:14672942}; |
| Catalytic activity: | |
Reaction=9-cis-retinol + NADP(+) = 9-cis-retinal + H(+) + NADPH; Xref=Rhea:RHEA:54916, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273; Evidence={ECO:0000269|PubMed:21851338}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:54918; Evidence={ECO:0000305|PubMed:21851338}; |
| 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:14979715, PubMed:14996743, PubMed:10557352). 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}. |
| Biophysicochemical properties: | |
Kinetic parameters: KM=11.9 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=26.2 uM for 17beta-hydroxy-5alpha-androstan-3-one {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022}; KM=19 uM for 17beta-hydroxy-5alpha-androstan-3-one {ECO:0000269|PubMed:9415401}; KM=8.96 uM for 3alpha-hydroxy-5alpha-androstan-17-one (in the reduction assay) {ECO:0000269|PubMed:10998348}; KM=17.5 uM for prostaglandin H2 {ECO:0000269|PubMed:19010934}; KM=0.3 uM for 9-cis-retinol {ECO:0000269|PubMed:21851338}; KM=0.4 uM for 9-cis-retinal {ECO:0000269|PubMed:21851338}; KM=142.1 uM for progesterone {ECO:0000269|PubMed:10557352}; KM=2.37 uM for 17beta-hydroxy-5alpha-androstan-3-one {ECO:0000269|PubMed:10557352}; KM=1.0 uM for androstanediol {ECO:0000269|PubMed:10557352}; KM=5 uM for 5alpha-androstan-3,17-dione {ECO:0000269|PubMed:10998348}; KM=24.3 uM for testosterone (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=27.2 uM for 5alpha-androstane-3alpha,17beta-diol {ECO:0000269|PubMed:10998348}; Vmax=3.9 nmol/min/mg enzyme with prostaglandin H2 as substrate {ECO:0000269|PubMed:19010934}; Vmax=20.1 nmol/min/mg enzyme with progesterone as substrate {ECO:0000269|PubMed:10557352}; Vmax=2.45 nmol/min/mg enzyme for 7beta-hydroxy-5alpha-androstan-3-one {ECO:0000269|PubMed:9415401}; Vmax=1.8 nmol/min/mg enzyme with 17beta-hydroxy-5alpha-androstan-3- one as substrate {ECO:0000269|PubMed:10557352}; Vmax=4.18 nmol/min/mg enzyme for 17beta-hydroxy-5alpha-androstan-3- one reduction {ECO:0000269|PubMed:10998348}; Vmax=3.99 nmol/min/mg enzyme for 5alpha-androstane-3alpha,17beta-diol oxidation {ECO:0000269|PubMed:10998348}; Vmax=48.4 nmol/min/mg enzyme for 5alpha-androstan-3,17-dione reduction {ECO:0000269|PubMed:10998348}; Vmax=10.2 nmol/min/mg enzyme for 3alpha-hydroxy-5alpha-androstan-17- one reduction {ECO:0000269|PubMed:10998348}; Vmax=1.34 nmol/min/mg enzyme for testosterone oxydation {ECO:0000269|PubMed:10998348}; Vmax=4.4 nmol/min/mg enzyme with androstanediol as substrate {ECO:0000269|PubMed:10557352}; Note=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). {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:21851338}; |
| Pathway: | |
Steroid metabolism. {ECO:0000269|PubMed:14672942}. |
| Subcellular location: | |
Cytoplasm {ECO:0000269|PubMed:10622721}. |
| Tissue specificity: | |
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. {ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}. |
| Similarity: | |
Belongs to the aldo/keto reductase family. {ECO:0000305}. |
| Sequence caution: | |
Sequence=BAA04619.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; |
Annotations taken from UniProtKB at the EBI.