| UniProt functional annotation for P52895 | |||
| UniProt code: P52895. |
| Organism: | Homo sapiens (Human). | |
| Taxonomy: | Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. | |
| 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). Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3- alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha- androstane-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:15929998, PubMed:17034817, PubMed:17442338, PubMed:8573067). Also specifically able to produce 17beta-hydroxy-5alpha-androstan-3-one/5alphaDHT (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:15929998, ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338, ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:8486699, ECO:0000269|PubMed:8573067}. | |
| 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:15929998, ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338, ECO:0000269|PubMed:8573067}; | |
| 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:15929998, ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338, 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, ECO:0000269|PubMed:19218247}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42117; Evidence={ECO:0000269|PubMed:10998348}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42118; Evidence={ECO:0000269|PubMed:10998348, 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, ECO:0000269|PubMed:14672942}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42005; Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006; 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:14672942}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42125; Evidence={ECO:0000269|PubMed:14672942}; | |
| 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=(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}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42113; Evidence={ECO:0000269|PubMed:10998348}; 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}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42110; 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=(3beta,5alpha,17beta)-3-hydroxy-androstan-17-yl sulfate + NADP(+) = 5alpha-dihydrotestosterone sulfate + H(+) + NADPH; Xref=Rhea:RHEA:53136, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133105, ChEBI:CHEBI:136982; Evidence={ECO:0000269|PubMed:19218247}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53138; Evidence={ECO:0000269|PubMed:19218247}; | |
| 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: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}; | |
| Activity regulation: | Inhibited by hexestrol with an IC(50) of 2.8 uM, 1,10-phenanthroline with an IC(50) of 2100 uM, 1,7-phenanthroline with an IC(50) of 1500 uM, flufenamic acid with an IC(50) of 0.9 uM, indomethacin with an IC(50) of 75 uM, ibuprofen with an IC(50) of 6.9 uM, lithocholic acid with an IC(50) of 0.07 uM, ursodeoxycholic acid with an IC(50) of 0.08 uM and chenodeoxycholic acid with an IC(50) of 0.13 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=260 uM for (s)-tetralol {ECO:0000269|PubMed:8573067}; KM=520 uM for (s)-indan-1-ol {ECO:0000269|PubMed:8573067}; KM=5000 uM for benzene dihydrodiol {ECO:0000269|PubMed:8573067}; KM=1 uM for 5-beta-pregnane-3-alpha,20-alpha-diol {ECO:0000269|PubMed:8573067}; KM=208 uM for 9-alpha,11-beta-prostaglandin F(2) {ECO:0000269|PubMed:8573067}; KM=0.3 uM for 5-beta-androstane-3,17-dione {ECO:0000269|PubMed:8573067}; KM=79 uM for prostaglandin D2 {ECO:0000269|PubMed:8573067}; KM=26 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the reduction assay) {ECO:0000269|PubMed:10998348}; KM=2.9 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the reduction assay) {ECO:0000269|PubMed:19218247}; KM=6.26 uM for 5alpha-androstan-3,17-dione (in the reduction assay) {ECO:0000269|PubMed:10998348}; KM=9.73 uM for 3alpha-hydroxy-5alpha-androstan-17-one/androsterone (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=22.0 uM for 5alpha-androstane-3alpha,17beta-diol (in the oxidation assay) {ECO:0000269|PubMed:10998348}; KM=4.2 uM for 5alpha-dihydrotestosterone sulfate (in the reduction assay) {ECO:0000269|PubMed:19218247}; Vmax=6.24 nmol/min/mg enzyme for the reduction of 17beta-hydroxy- 5alpha-androstan-3-one {ECO:0000269|PubMed:10998348}; Vmax=37.8 nmol/min/mg enzyme for the reduction of 5alpha-androstan- 3,17-dione {ECO:0000269|PubMed:10998348}; Vmax=11.3 nmol/min/mg enzyme for the oxidation of 3alpha-hydroxy- 5alpha-androstan-17-one/androsterone {ECO:0000269|PubMed:10998348}; Vmax=6.58 nmol/min/mg enzyme for the oxidation of 5alpha-androstane- 3alpha,17beta-diol {ECO:0000269|PubMed:10998348}; Note=kcat is 0.66 min-1 for the reduction of 17beta-hydroxy-5alpha- androstan-3-one (PubMed:10998348). kcat is 1.98 min-1 for the reduction of 17beta-hydroxy-5alpha-androstan-3-one (PubMed:19218247). kcat is 1.39 min-1 for the reduction of 5alpha-androstan-3,17-dione (PubMed:10998348). kcat is 0.42 min-1 for the oxidation of 3alpha- hydroxy-5alpha-androstan-17-one/androsterone (PubMed:10998348). kcat is 0.24 min-1 for the oxidation of 5alpha-androstane-3alpha,17beta- diol (PubMed:10998348). kcat is 1.0 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}. | |
| Subcellular location: | Cytoplasm, cytosol {ECO:0000305|PubMed:8486699}. | |
| Tissue specificity: | Expressed in fetal testes. Expressed in fetal and adult adrenal glands. {ECO:0000269|PubMed:21802064}. | |
| 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 disease is caused by variants affecting the gene represented in this entry. | |
| Similarity: | Belongs to the aldo/keto reductase family. {ECO:0000305}. | |
Annotations taken from UniProtKB at the EBI.