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UniProt functional annotation for Q04828 | ||
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| UniProt code: Q04828. |
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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 (PubMed:19218247). Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH (PubMed:14672942). Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens (PubMed:10998348). May also reduce conjugated steroids such as 5alpha- dihydrotestosterone sulfate (PubMed:19218247). Displays affinity for bile acids (PubMed:8486699). {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:8486699}. |
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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:10998348, ECO:0000269|PubMed:11013348}; |
| 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:10998348, ECO:0000269|PubMed:11013348}; |
| Catalytic activity: | |
Reaction=17alpha,20alpha-dihydroxypregn-4-en-3-one + NADP(+) = 17alpha- hydroxyprogesterone + H(+) + NADPH; Xref=Rhea:RHEA:15857, ChEBI:CHEBI:15378, ChEBI:CHEBI:17252, ChEBI:CHEBI:36726, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.149; Evidence={ECO:0000305|PubMed:11013348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15859; Evidence={ECO:0000305|PubMed:11013348}; |
| Catalytic activity: | |
Reaction=17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(+) = 17alpha- hydroxyprogesterone + H(+) + NADH; Xref=Rhea:RHEA:15853, ChEBI:CHEBI:15378, ChEBI:CHEBI:17252, ChEBI:CHEBI:36726, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.149; Evidence={ECO:0000305|PubMed:11013348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15855; Evidence={ECO:0000305|PubMed:11013348}; |
| 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:11013348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42113; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42114; Evidence={ECO:0000269|PubMed:10998348}; |
| 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:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42110; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348}; |
| Catalytic activity: | |
Reaction=(1R,2R)-1,2-dihydrobenzene-1,2-diol + NADP(+) = catechol + H(+) + NADPH; Xref=Rhea:RHEA:16729, ChEBI:CHEBI:10702, ChEBI:CHEBI:15378, ChEBI:CHEBI:18135, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.20; Evidence={ECO:0000269|PubMed:8486699, ECO:0000269|PubMed:8573067}; |
| Catalytic activity: | |
Reaction=(S)-indan-1-ol + NAD(+) = H(+) + indan-1-one + NADH; Xref=Rhea:RHEA:16317, ChEBI:CHEBI:15378, ChEBI:CHEBI:17404, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:156384; EC=1.1.1.112; Evidence={ECO:0000269|PubMed:8573067}; |
| Catalytic activity: | |
Reaction=(S)-indan-1-ol + NADP(+) = H(+) + indan-1-one + NADPH; Xref=Rhea:RHEA:16321, ChEBI:CHEBI:15378, ChEBI:CHEBI:17404, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:156384; EC=1.1.1.112; Evidence={ECO:0000269|PubMed:8573067}; |
| 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:10998348, ECO:0000269|PubMed:14672942}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42118; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|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, ECO:0000269|PubMed:19218247}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16299; Evidence={ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:19218247}; |
| 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:0000269|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = 5alpha- androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:42120, ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42121; Evidence={ECO:0000269|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NADP(+) = 5alpha- androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:20377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.209; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20378; Evidence={ECO:0000269|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:10998348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42157; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42158; Evidence={ECO:0000269|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}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42125; Evidence={ECO:0000269|PubMed:10998348}; |
| 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}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24617; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618; Evidence={ECO:0000269|PubMed:10998348}; |
| 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:0000269|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24614; Evidence={ECO:0000269|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=1.1.1.51; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14982; Evidence={ECO:0000269|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=20alpha-hydroxy-5beta-pregnan-3-one + NADP(+) = 5beta-pregnan- 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:42168, ChEBI:CHEBI:15378, ChEBI:CHEBI:30154, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78666; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42169; Evidence={ECO:0000269|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=3beta-hydroxy-5beta-pregnane-20-one + NADP(+) = 5beta-pregnan- 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:22944, ChEBI:CHEBI:15378, ChEBI:CHEBI:16229, ChEBI:CHEBI:30154, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=3beta-hydroxy-5beta-pregnane-20-one + H(+) + NADPH = 3beta,20alpha-dihydroxy-5beta-pregnane + NADP(+); Xref=Rhea:RHEA:65496, ChEBI:CHEBI:15378, ChEBI:CHEBI:16229, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:156526; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65497; Evidence={ECO:0000269|PubMed:10998348}; |
| Catalytic activity: | |
Reaction=(3beta,5alpha,17beta)-3-hydroxyandrostan-17-yl sulfate + NADP(+) = 5alpha-dihydrotestosterone sulfate + H(+) + NADPH; Xref=Rhea:RHEA:53120, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:136982, ChEBI:CHEBI:136983; Evidence={ECO:0000269|PubMed:19218247}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53122; Evidence={ECO:0000269|PubMed:19218247}; |
| 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). {ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:8573067}. |
| Biophysicochemical properties: | |
Kinetic parameters: KM=5 uM for (s)-tetralol {ECO:0000269|PubMed:8573067}; KM=38 uM for (s)-indan-1-ol {ECO:0000269|PubMed:8573067}; KM=580 uM for benzene dihydrodiol ((1R,2R)-1,2-dihydrobenzene-1,2- diol) {ECO:0000269|PubMed:8573067}; KM=3 uM for 5-beta-pregnane-3-alpha,20-alpha-diol {ECO:0000269|PubMed:8573067}; KM=3 uM for 5-beta-pregnan-20-alpha-ol-3-one {ECO:0000269|PubMed:8573067}; KM=12 uM for 4-pregnen-20-alpha-ol-3-one {ECO:0000269|PubMed:8573067}; KM=133 uM for 9-alpha,11-beta-prostaglandin F(2) {ECO:0000269|PubMed:8573067}; KM=2 uM for 5-beta-pregnan-3-alpha-ol-20-one {ECO:0000269|PubMed:8573067}; KM=1 uM for 5-beta-androstane-3,17-dione {ECO:0000269|PubMed:8573067}; KM=12 uM for prostaglandin D(2) {ECO:0000269|PubMed:8573067}; KM=2.65 uM for progesterone (in the reduction assay) {ECO:0000269|PubMed:10998348}; KM=16.2 uM for 3beta-hydroxy-5beta-pregnane-20-one (in the reduction assay) {ECO:0000269|PubMed:10998348}; KM=14.7 uM for (20S)-hydroxypregn-4-en-3-one (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=80.6 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the reduction assay) {ECO:0000269|PubMed:10998348}; KM=4.2 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the reduction assay) {ECO:0000269|PubMed:19218247}; KM=31.7 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=6.77 uM for 5alpha-androstan-3,17-dione (in the reduction assay) {ECO:0000269|PubMed:10998348}; KM=41.7 uM for 3alpha-hydroxy-5alpha-androstan-17-one/androsterone (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=21.0 uM for 3alpha-hydroxy-5alpha-androstan-17-one/androsterone (in the reduction assay) {ECO:0000269|PubMed:10998348}; KM=39.8 uM for testosterone (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=19.4 uM for 20alpha-hydroxy-5beta-pregnan-3-one (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=5.2 uM for 5alpha-dihydrotestosterone sulfate (in the reduction assay) {ECO:0000269|PubMed:19218247}; Vmax=7.85 nmol/min/mg enzyme for the reduction of progesterone {ECO:0000269|PubMed:10998348}; Vmax=29.7 nmol/min/mg enzyme for the reduction of 3beta-hydroxy- 5beta-pregnane-20-one {ECO:0000269|PubMed:10998348}; Vmax=31.9 nmol/min/mg enzyme for the oxidation of (20S)-hydroxypregn- 4-en-3-one {ECO:0000269|PubMed:10998348}; Vmax=18.0 nmol/min/mg enzyme for the reduction of 17beta-hydroxy- 5alpha-androstan-3-one {ECO:0000269|PubMed:10998348}; Vmax=0.72 nmol/min/mg enzyme for the oxidation of 17beta-hydroxy- 5alpha-androstan-3-one {ECO:0000269|PubMed:10998348}; Vmax=12.8 nmol/min/mg enzyme for the reduction of 5alpha-androstan- 3,17-dione {ECO:0000269|PubMed:10998348}; Vmax=1.59 nmol/min/mg enzyme for the oxidation of 3alpha-hydroxy- 5alpha-androstan-17-one/androsterone {ECO:0000269|PubMed:10998348}; Vmax=4.79 nmol/min/mg enzyme for the reduction of 3alpha-hydroxy- 5alpha-androstan-17-one/androsterone {ECO:0000269|PubMed:10998348}; Vmax=1.2 nmol/min/mg enzyme for the oxidation of testosterone {ECO:0000269|PubMed:10998348}; Vmax=87.5 nmol/min/mg enzyme for the oxidation of 20alpha-hydroxy- 5beta-pregnan-3-one {ECO:0000269|PubMed:10998348}; Note=kcat is 0.29 min-1 for the reduction of progesterone (PubMed:10998348). kcat is 1.1 min-1 for the reduction of 3beta- hydroxy-5beta-pregnane-20-one (PubMed:10998348). kcat is 1.2 min-1 for the oxidation of (20S)-hydroxypregn-4-en-3-one (PubMed:10998348). kcat is 0.66 min-1 for the reduction of 17beta-hydroxy-5alpha- androstan-3-one (PubMed:10998348). kcat is 0.026 min-1 for the oxidation of 17beta-hydroxy-5alpha-androstan-3-one (PubMed:10998348). kcat is 0.47 min-1 for the reduction of 5alpha-androstan-3,17-dione (PubMed:10998348). kcat is 0.06 min-1 for the oxidation of 3alpha- hydroxy-5alpha-androstan-17-one/androsterone (PubMed:10998348). kcat is 0.18 min-1 for the reduction of 3alpha-hydroxy-5alpha-androstan- 17-one/androsterone (PubMed:10998348). kcat is 0.044 min-1 for the oxidation of testosterone (PubMed:10998348). kcat is 3.23 min-1 for the oxidation of 20alpha-hydroxy-5beta-pregnan-3-one (PubMed:10998348). kcat is 0.74 min-1 for the reduction of 17beta- hydroxy-5alpha-androstan-3-one (PubMed:19218247). kcat is 0.75 min-1 for the reduction of 5alpha-dihydrotestosterone sulfate (PubMed:19218247). {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:19218247}; |
| Pathway: | |
Steroid metabolism. {ECO:0000269|PubMed:14672942}. |
| Subunit: | |
Monomer. {ECO:0000269|PubMed:12899831, ECO:0000269|PubMed:21414777}. |
| Subcellular location: | |
Cytoplasm, cytosol {ECO:0000269|PubMed:8486699}. |
| Tissue specificity: | |
Expressed in all tissues tested including liver, prostate, testis, adrenal gland, brain, uterus, mammary gland and keratinocytes. Highest levels found in liver, mammary gland and brain. {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348}. |
| Similarity: | |
Belongs to the aldo/keto reductase family. {ECO:0000305}. |
Annotations taken from UniProtKB at the EBI.