Search Results
Overview
| Uniprot ID | P17516 |
|---|---|
| Protein Name | Aldo-keto reductase family 1 member C4 |
| Gene Name | AKR1C4 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 161 | CKDAGLAKSIGVSNF |
| 183 | ILNKPGLKYKPVCNQ |
| 185 | NKPGLKYKPVCNQVE |
| 207 | SKLLDFCKSKDIVLV |
| 209 | LLDFCKSKDIVLVAH |
| 225 | ALGTQRHKLWVDPNS |
| 246 | PVLCALAKKHKQTPA |
| 39 | NRAVEVTKLAIEAGF |
| 4 | ****MDPKYQRVELN |
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/beta-, 17beta- and 20alpha-hydroxysteroids (PubMed:10634139, PubMed:10998348, PubMed:11158055, PubMed:14672942, PubMed:1530633, PubMed:12604236, PubMed:19218247, PubMed:21802064, PubMed:7650035). 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 AKR1C2 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:21802064). May regulate the concentrations of circulating neurosteroids. Reduces 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: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:11158055, PubMed:14672942). 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-A3diol) (PubMed:31926269). Catalyzes the reduction of estrone into 17beta-estradiol but with low efficiency (PubMed:14672942). 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:19218247). Catalyzes the biotransformation of the pesticide chlordecone (kepone) to its corresponding alcohol, leading to increased biliary excretion of the pesticide and concomitant reduction of its neurotoxicity since bile is the major excretory route (PubMed:2427522). 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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Biological Process | GO:0015721 | bile acid and bile salt transport |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0070062 | extracellular exosome |
| 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: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:0015125 | bile acid transmembrane transporter activity |
| Molecular Function | GO:0047743 | chlordecone reductase activity |
| Molecular Function | GO:0009055 | electron transfer activity |
| Molecular Function | GO:0004303 | estradiol 17-beta-dehydrogenase [NAD(P)+] 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:0001758 | retinal dehydrogenase (NAD+) activity |
| Molecular Function | GO:0047035 | testosterone dehydrogenase (NAD+) activity |
| Molecular Function | GO:0047045 | testosterone dehydrogenase (NADP+) activity |
| Biological Process | GO:0008209 | androgen metabolic process |
| Biological Process | GO:0006699 | bile acid biosynthetic process |
| Biological Process | GO:0071395 | cellular response to jasmonic acid stimulus |
| Biological Process | GO:0044597 | daunorubicin metabolic process |
| Biological Process | GO:0044598 | doxorubicin metabolic process |
| Biological Process | GO:0042448 | progesterone metabolic process |
| Biological Process | GO:0006693 | prostaglandin metabolic process |
| Biological Process | GO:0001523 | retinoid 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] 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.