Property Summary

NCBI Gene PubMed Count 62
PubMed Score 410.81
PubTator Score 154.14

Knowledge Summary


No data available


  Differential Expression (1)

Disease log2 FC p
non-small cell lung cancer 1.051 4.4e-05

 GO Component (1)

Protein-protein Interaction (5)

Gene RIF (42)

26351209 Identify two novel factors, AKR1C2 (positive factor) and NF1 (negative factor), as the AEG-1 downstream players in the process of metastasis in liver cancer.
26318406 We identified two powerful genes in the liver cancer metastasis process, AEG-1 and AKR1C2.
26244607 The endogenous HMOX1 gene but not the AKR1C2 gene is strongly repressed by Bach1 in HaCaT keratinocytes.
25463305 In model cell lines of endometrial cancer, AKR1C2 and SRD5A1 have crucial roles in progesterone metabolism.
24434280 The V54L mutation significantly decreases the 3alpha-hydroxysteroid dehydrogenase activity of DDH2 for the reduction of dihydrotestosterone.
24244276 Significantly higher levels of SRD5A1, AKR1C2, AKR1C3, and HSD17B10 mRNA were however found in bone metastases than in non-malignant and/or malignant prostate tissue
22534668 DDH2 expression might be a potential predictor and monitor of cisplatin efficacy in advanced NSCLC patients.
22275760 Data suggest that modulation of AKR1C2 by glucocorticoids (dexamethasone in this study) locally modifies exposure of adipose cells to endogenous androgens; thus, AKR1C2 activation/inactivation may be involved in regional fat deposition.
22064385 Data suggest that interleukin-1beta facilitates progesterone metabolism in cervical fibroblasts by regulating expression of AKR1C1 and AKR1C2.
21521174 role of AKR1C2 in the metabolism of testosterone and progesterone via the 5beta-reductase pathway.
21280124 The folding initiation mechanism of human bile acid-binding protein (BABP) has been examined by (19) F NMR.
21232532 enhanced metabolism of progesterone by SRD5A1 and the 20alpha-HSD and 3alpha/beta-HSD activities of AKR1C1, AKR1C2 and AKR1C3
21217827 analysis of single nucleotide polymorphisms of AKR1C1 and AKR1C2
20840669 Overexpression of aldo-keto reductase 1C2 is associated with disease progression in patients with prostatic cancer
20734064 Observational study of gene-disease association. (HuGE Navigator)
20689807 Observational study of gene-disease association. (HuGE Navigator)
20056642 We investigated associations between single nucleotide polymorphisms in genes HSD3B1, SRD5A1/2, and AKR1C2 and prostate cancer risk
20056642 Observational study of gene-disease association. (HuGE Navigator)
19846565 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19846565 The researchers found an increased risk of breast cancer in women with AKR1C2 who carried 1 or 2 alleles and who used estrogen-progesterone therapy.
19754879 The disulfide bridge does not modify the protein-binding stoichiometry, but has a key role in modulating recognition at both sites, inducing site selectivity for glycocholic and glycochenodeoxycholic acid.
19487289 AKR1C isoforms as a novel target of jasmonates in cancer cells.
19320734 AKR1C subfamily genes are stress-inducible and might function as survival factors in keratinocytes.
19258517 The results show that several naturally occurring single nucleotide polymorphisms in AKR1C2 result in reduced enzyme activities. These variant AKR1C2 alleles may represent one factor involved in the variable degradation of dihydrotestosterone in vivo.
18984855 Higher mRNA levels of enzymes synthesizing and inactivating androgens are found in differentiated adipocytes, consistent with higher androgen-processing rates in these cells.
18654764 Incubations of normal human bronchial epithelial cells with individual heavy metals showed that the upregulation of AKR1C1 and AKR1C2 was predominantly caused by lead.
18396902 Results describe cathepsin D and aldo-keto reductase 1C2 and 1B10 dysregulation in Barrett's esophagus and esophageal adenocarcinoma.
18251165 The inhibition of activation of the beta-catenin/TCF-signaling pathway is believed to be one mechanism by which AKR1C2 siRNA exerts a gatekeeper function during hepatocarcinogenesis.
17432832 Wild-type ileal BABP undergoes a slow conformational change after both bile-salt binding sites become occupied, a kinetic step that is missing in mutants that lack positive cooperativity.
17203165 continual intake of arsenic in drinking water might provoke AKR1C2 expression that could in turn induce drug resistance in bladder cancer, and AKR1C2 may have a role in development of bladder cancer
16478829 The regulation of AKR1C2 by antioxidant response element suggests that AKR1C2 detoxifies products of reactive oxidant injury.
16411748 human ileal bile acid binding protein has a high degree of selectivity in its interactions with glycocholate and glycochenodeoxycholate brought on by the conformation of its ternary complex
16216911 Results suggest that 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 3 might play slightly different roles in zebrafish compared with human although testosterone itself is likely to have similar functions in both organisms.
15492289 Loss of AKR1C1 and AKR1C2 in breast cancer results in decreased progesterone catabolism, which, in combination with increased PR expression, may augment progesterone signaling by its nuclear receptors.
15383625 metabolizes tibolone
15212687 Expression of SRD5A1 (5alphaR1) and SRD5A2 (5alphaR2) is elevated, and expression of AKR1C1 (20alpha-HSO), AKR1C2 (3alpha-HSO3) and AKR1C3 (3alpha-HSO2) is reduced in tumorous as compared to normal breast tissue.
15188492 Akr1c2 which is up-regulated in esophageal squamous cell carcinoma probably plays an important role in tumor development of esophagus and may be proposed as a potential molecular target treatments.
14671194 expression and activity of type 5 17beta-hydroxysteroid dehydrogenase and type 3 3alpha-hydroxysteroid dehydrogenase in female subcutaneous tissue and omental adipose tissue and in preadipocytes
13678667 Glaucomatous optic nerve head astrocytes express a higher level of 3alpha-HSD isoform AKR1C2 and its mRNA than normal astrocytes.
12810547 in prostate cells AKR1C2 acts as a 3-ketosteroid reductase to eliminate 5alpha-DHT and prevents activation of the androgen receptor.
12416991 The kinetics of 3-alpha-HSD type III indicates an ordered ternary complex mechanism characterized by allopregnanolone formation, with NAD cofactor binding before the steroid substrate and dissociating after release of the steroid product.
11854486 human ileal bile acid binding protein binds two molecules of glycocholic acid with low intrinsic affinity but an extraordinarily high degree of positive cooperativity

AA Sequence


Text Mined References (66)

PMID Year Title
26351209 2014 AEG-1 Promotes Metastasis Through Downstream AKR1C2 and NF1 in Liver Cancer.
26318406 2016 High-Content Functional Screening of AEG-1 and AKR1C2 for the Promotion of Metastasis in Liver Cancer.
26244607 2015 Dual regulation of skin sensitizer-induced HMOX1 expression by Bach1 and Nrf2: Comparison to regulation of the AKR1C2-ARE element in the KeratinoSens cell line.
25463305 2015 Important roles of the AKR1C2 and SRD5A1 enzymes in progesterone metabolism in endometrial cancer model cell lines.
24434280 2014 Human 3-alpha hydroxysteroid dehydrogenase type 3 (3?-HSD3): the V54L mutation restricting the steroid alternative binding and enhancing the 20?-HSD activity.
24244276 2013 Characterization of prostate cancer bone metastases according to expression levels of steroidogenic enzymes and androgen receptor splice variants.
22534668 2012 Proteomics-based identification of secreted protein dihydrodiol dehydrogenase 2 as a potential biomarker for predicting cisplatin efficacy in advanced NSCLC patients.
22275760 2012 Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes.
22064385 2012 Interleukin 1? regulates progesterone metabolism in human cervical fibroblasts.
21851338 2011 Retinaldehyde is a substrate for human aldo-keto reductases of the 1C subfamily.
21802064 2011 Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation.
21521174 2011 Stereospecific reduction of 5?-reduced steroids by human ketosteroid reductases of the AKR (aldo-keto reductase) superfamily: role of AKR1C1-AKR1C4 in the metabolism of testosterone and progesterone via the 5?-reductase pathway.
21492153 2011 Analysis of proteomic changes induced upon cellular differentiation of the human intestinal cell line Caco-2.
21280124 2011 Residual interactions in unfolded bile acid-binding protein by 19F NMR.
21232532 2011 Aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 may enhance progesterone metabolism in ovarian endometriosis.
21217827 2010 Modeling single nucleotide polymorphisms in the human AKR1C1 and AKR1C2 genes: implications for functional and genotyping analyses.
20840669 2010 Overexpression of aldo-keto reductase 1C2 is associated with disease progression in patients with prostatic cancer.
20837989 2010 Naturally occurring variants of human aldo-keto reductases with reduced in vitro metabolism of daunorubicin and doxorubicin.
20734064 2010 A large-scale candidate gene association study of age at menarche and age at natural menopause.
20689807 2010 Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer.
20056642 2010 Genetic variation of genes involved in dihydrotestosterone metabolism and the risk of prostate cancer.
19846565 2009 Genetic variation in the progesterone receptor and metabolism pathways and hormone therapy in relation to breast cancer risk.
19754879 2009 Disulfide bridge regulates ligand-binding site selectivity in liver bile acid-binding proteins.
19487289 2009 AKR1C isoforms represent a novel cellular target for jasmonates alongside their mitochondrial-mediated effects.
19320734 2009 Aldo-keto reductase 1C subfamily genes in skin are UV-inducible: possible role in keratinocytes survival.
19258517 2009 The effect of allelic variation in aldo-keto reductase 1C2 on the in vitro metabolism of dihydrotestosterone.
18984855 2009 Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis.
18654764 2008 Cadmium, cobalt and lead cause stress response, cell cycle deregulation and increased steroid as well as xenobiotic metabolism in primary normal human bronchial epithelial cells which is coordinated by at least nine transcription factors.
18508192 2008 AKR1C2 and AKR1C3 mediated prostaglandin D2 metabolism augments the PI3K/Akt proliferative signaling pathway in human prostate cancer cells.
18396902 2008 Proteomic screening of a cell line model of esophageal carcinogenesis identifies cathepsin D and aldo-keto reductase 1C2 and 1B10 dysregulation in Barrett's esophagus and esophageal adenocarcinoma.
18251165 AKR1C2 small interfering RNA (siRNA) inhibited beta-catenin expression and transcriptional activation in human liver cancer cell line QGY7701.
17442338 2007 Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids differently from other aldo-keto reductases: identification and characterization of amino acid residues critical for substrate binding.
17432832 2007 Kinetic mechanism of ligand binding in human ileal bile acid binding protein as determined by stopped-flow fluorescence analysis.
17203165 2007 Overexpression of aldo-keto reductase 1C2 as a high-risk factor in bladder cancer.
17034817 2006 Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase (apoenzyme and enzyme-NADP(H) binary complex): identification of molecular determinants responsible for the unique 17alpha-reductive activity of this enzyme.
16478829 2006 Induction of AKR1C2 by phase II inducers: identification of a distal consensus antioxidant response element regulated by NRF2.
16411748 2006 Determinants of cooperativity and site selectivity in human ileal bile acid binding protein.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16216911 2005 Androgen metabolism via 17beta-hydroxysteroid dehydrogenase type 3 in mammalian and non-mammalian vertebrates: comparison of the human and the zebrafish enzyme.
15929998 2005 Comparison of crystal structures of human type 3 3alpha-hydroxysteroid dehydrogenase reveals an "induced-fit" mechanism and a conserved basic motif involved in the binding of androgen.
15492289 2004 Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15383625 2004 Tibolone is metabolized by the 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four human isozymes of the aldo-keto reductase 1C subfamily: inversion of stereospecificity with a delta5(10)-3-ketosteroid.
15212687 2004 Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma.
15188492 2004 Differential gene expression between squamous cell carcinoma of esophageus and its normal epithelium; altered pattern of mal, akr1c2, and rab11a expression.
15164054 2004 The DNA sequence and comparative analysis of human chromosome 10.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14671194 2003 Local androgen inactivation in abdominal visceral adipose tissue.
13678667 2003 Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes.
12810547 2003 Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12416991 2002 Kinetics of allopregnanolone formation catalyzed by human 3 alpha-hydroxysteroid dehydrogenase type III (AKR1C2).
11514561 2001 Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution.
11513593 2001 Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase/bile acid binding protein complexed with NADP(+) and ursodeoxycholate.
10672042 2000 Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes.
9716498 1998 Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA.
8920937 1996 Molecular cloning of human type 3 3 alpha-hydroxysteroid dehydrogenase that differs from 20 alpha-hydroxysteroid dehydrogenase by seven amino acids.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8573067 1996 Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells.
8486699 1993 cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family.
8274401 1993 Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase.
8011662 1994 cDNA and deduced amino acid sequences of a human colon dihydrodiol dehydrogenase.
7959017 1994 Structure of a gene coding for human dihydrodiol dehydrogenase/bile acid-binding protein.
7789999 1995 Localization of multiple human dihydrodiol dehydrogenase (DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome 10 by the polymerase chain reaction and fluorescence in situ hybridization.
4352099 1972 Steroid 17,20-desmolase deficiency: a new cause of male pseudohermaphroditism.
2187532 1990 Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase.