Search Results
Overview
| Uniprot ID | P52895 |
|---|---|
| Protein Name | Aldo-keto reductase family 1 member C2 |
| Gene Name | AKR1C2 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 161 | CKDAGLAKSIGVSNF |
| 179 | LLEMILNKPGLKYKP |
| 183 | ILNKPGLKYKPVCNQ |
| 185 | NKPGLKYKPVCNQVE |
| 246 | PVLCALAKKHKRTPA |
| 33 | PAEVPKSKALEAVKL |
| 84 | EDIFYTSKLWSNSHR |
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 3alpha-hydroxysteroids, but also 3beta-, 17beta- and 20alpha-hydroxysteroids (PubMed:8920937, PubMed:9716498, PubMed:10998348, PubMed:12416991, PubMed:11995921, PubMed:12604236, PubMed:14672942, PubMed:19218247, PubMed:21802064, PubMed:11514561, PubMed:15929998, PubMed:17034817, PubMed:17442338, PubMed:24434280). Required for male sex determination as a component of the 'backdoor' androgen biosynthesis pathway that generates 5alpha-dihydrotestosterone (5alpha-DHT) via pregnanes. Acts together with AKR1C4 to convert 5alpha-dihydroprogesterone (5alpha-DHP) to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP/allopregnanolone), leading to 5alpha-DHT secretion necessary for embryonic gonad differentiation into testis (PubMed:12416991, PubMed:21802064). In androgen catabolism, may predominantly act as a phase I enzyme by introducing a hydroxyl group prior to conjugation. It can nevertheless participate in the alternative phase II pathway by directly reducing sulfate- or glucuronide-conjugated androgens (PubMed:10998348, PubMed:11514561, PubMed:14672942, PubMed:15929998, PubMed:19218247, PubMed:24434280). In neurosteroid biosynthesis, may preferentially reduce 5alpha-dihydroprogesterone (5-alpha-DHP) and 5alpha-dihydrodeoxycorticosterone (5-alpha-DHDOC) precursors to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP/allopregnanolone) and 3alpha,21-dihydroxy-5alpha-pregnane-20-one (3alpha,5alpha-THDOC) neuroactive steroids known to alter neural excitability via allosteric activation of gamma-aminobutyric acid type A receptors (GABAAR) (PubMed:11995921, PubMed:12416991, PubMed:12604236). Regulates ligand availability for steroid hormone receptors. Catalyzes the inactivation of 5alpha-DHT and progesterone converting them into 3alpha/beta-androstanediols and (20S)-hydroxypregn-4-en-3-one, respectively (PubMed:10998348, PubMed:24434280). Can form 17beta-hydroxysteroids such as testosterone and estradiol albeit with lower efficiency when compared to AKR1C3 (PubMed:10998348). May contribute to the metabolism of adrenal-derived androgens via reduction of 11-keto-5alpha-androstane-3,17-dione (11K-Adione) into 11-ketoandrosterone (11KAST) and of 11-ketodihydrotestosterone (11KDHT) into 11-keto-5alpha-androstane-3alpha/beta,17beta-diol (11K-A3alphadiol) (PubMed:31926269). May also play a role in prostaglandin (PG) metabolism by reducing PGD2 to 11beta-PGF2 (PubMed:9716498). Also able to metabolize xenobiotics (S)-indan-1-ol and trans-1,2-dihydrobenzene-1,2-diols (PubMed:8573067, PubMed:9716498). 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:14672942, PubMed:21802064)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005829 | cytosol |
| Molecular Function | GO:0140169 | 3-alpha-hydroxysteroid 3-dehydrogenase [NAD(P)+] activity |
| Molecular Function | GO:0004032 | aldose reductase (NADPH) activity |
| Molecular Function | GO:0047023 | androsterone dehydrogenase [NAD(P)+] activity |
| Molecular Function | GO:0032052 | bile acid binding |
| Molecular Function | GO:0031406 | carboxylic acid binding |
| Molecular Function | GO:0004303 | estradiol 17-beta-dehydrogenase [NAD(P)+] activity |
| Molecular Function | GO:0047718 | indanol dehydrogenase 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:0047045 | testosterone dehydrogenase (NADP+) activity |
| Molecular Function | GO:0047115 | trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity |
| Biological Process | GO:0071395 | cellular response to jasmonic acid stimulus |
| Biological Process | GO:0071799 | cellular response to prostaglandin D stimulus |
| Biological Process | GO:0044597 | daunorubicin metabolic process |
| Biological Process | GO:0007586 | digestion |
| Biological Process | GO:0044598 | doxorubicin metabolic process |
| Biological Process | GO:0030855 | epithelial cell differentiation |
| Biological Process | GO:0007186 | G protein-coupled receptor signaling pathway |
| Biological Process | GO:0008284 | positive regulation of cell population proliferation |
| Biological Process | GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| Biological Process | GO:0042448 | progesterone metabolic process |
| Biological Process | GO:0006693 | prostaglandin metabolic process |
| Biological Process | GO:0008202 | steroid metabolic process |
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] 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.