Search Results
Overview
| Uniprot ID | P42330 |
|---|---|
| Protein Name | Aldo-keto reductase family 1 member C3 |
| Gene Name | AKR1C3 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 104 | PALENSLKKAQLDYV |
| 179 | QLEMILNKPGLKYKP |
| 183 | ILNKPGLKYKPVCNQ |
| 185 | NKPGLKYKPVCNQVE |
| 201 | HPYFNRSKLLDFCKS |
| 207 | SKLLDFCKSKDIVLV |
| 246 | PVLCALAKKHKRTPA |
| 33 | PPEVPRSKALEVTKL |
| 4 | ****MDSKHQCVKLN |
| 84 | EDIFYTSKLWSTFHR |
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 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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005737 | cytoplasm |
| Molecular Function | GO:0004303 | estradiol 17-beta-dehydrogenase [NAD(P)+] activity |
| Molecular Function | GO:0045550 | geranylgeranyl reductase activity |
| Molecular Function | GO:0045703 | ketoreductase activity |
| Molecular Function | GO:0047086 | ketosteroid monooxygenase activity |
| Molecular Function | GO:0016655 | oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor |
| Molecular Function | GO:0036131 | prostaglandin D2 11-ketoreductase activity |
| Molecular Function | GO:0047017 | prostaglandin F synthase activity |
| Molecular Function | GO:0036130 | prostaglandin H2 endoperoxidase reductase activity |
| Molecular Function | GO:0001758 | retinal dehydrogenase (NAD+) activity |
| Molecular Function | GO:0047035 | testosterone dehydrogenase (NAD+) activity |
| Molecular Function | GO:0047045 | testosterone dehydrogenase (NADP+) activity |
| Biological Process | GO:0071277 | cellular response to calcium ion |
| Biological Process | GO:0071384 | cellular response to corticosteroid stimulus |
| Biological Process | GO:0071395 | cellular response to jasmonic acid stimulus |
| Biological Process | GO:0071799 | cellular response to prostaglandin D stimulus |
| Biological Process | GO:0071379 | cellular response to prostaglandin stimulus |
| Biological Process | GO:0009267 | cellular response to starvation |
| Biological Process | GO:0044597 | daunorubicin metabolic process |
| Biological Process | GO:0044598 | doxorubicin metabolic process |
| Biological Process | GO:0016488 | farnesol catabolic process |
| Biological Process | GO:0007186 | G protein-coupled receptor signaling pathway |
| Biological Process | GO:0030216 | keratinocyte differentiation |
| Biological Process | GO:0043170 | macromolecule metabolic process |
| Biological Process | GO:0008584 | male gonad development |
| Biological Process | GO:1900053 | negative regulation of retinoic acid biosynthetic process |
| Biological Process | GO:0008284 | positive regulation of cell population proliferation |
| Biological Process | GO:2000353 | positive regulation of endothelial cell apoptotic process |
| Biological Process | GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| Biological Process | GO:2000379 | positive regulation of reactive oxygen species metabolic process |
| Biological Process | GO:0042448 | progesterone metabolic process |
| Biological Process | GO:0006693 | prostaglandin metabolic process |
| Biological Process | GO:0046457 | prostanoid biosynthetic process |
| Biological Process | GO:0048385 | regulation of retinoic acid receptor signaling pathway |
| Biological Process | GO:2000224 | regulation of testosterone biosynthetic process |
| Biological Process | GO:0070293 | renal absorption |
| Biological Process | GO:0007584 | response to nutrient |
| Biological Process | GO:0042574 | retinal metabolic process |
| Biological Process | GO:0001523 | retinoid metabolic process |
| Biological Process | GO:0008202 | steroid metabolic process |
| Biological Process | GO:0061370 | testosterone biosynthetic process |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0005634 | nucleus |
| Molecular Function | GO:0047020 | 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity |
| Molecular Function | GO:0140169 | 3-alpha-hydroxysteroid 3-dehydrogenase [NAD(P)+] activity |
| Molecular Function | GO:0047024 | 5-alpha-androstane-3-beta,17-beta-diol dehydrogenase (NADP+) activity |
| Molecular Function | GO:0008106 | alcohol dehydrogenase (NADP+) activity |
| Molecular Function | GO:0004032 | aldose reductase (NADPH) activity |
| Molecular Function | GO:0004745 | all-trans-retinol dehydrogenase (NAD+) activity |
| Molecular Function | GO:0052650 | all-trans-retinol dehydrogenase (NADP+) activity |
| Molecular Function | GO:0047044 | androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity |
| Molecular Function | GO:0047023 | androsterone dehydrogenase [NAD(P)+] activity |
| Molecular Function | GO:0032052 | bile acid binding |
| Molecular Function | GO:0047787 | Delta4-3-oxosteroid 5beta-reductase activity |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.