Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.
Gene References into Functions
- Role of mineralocorticoid receptor activation in cardiac diastolic dysfunction. PMID: 27989961
- MiR-135b-5p, maybe a novel therapeutic target for pancreatic cancer, promoted migration, invasion and EMT of pancreatic cancer cells by targeting NR3C2. PMID: 29196101
- Our findings indicate that genetic variants associated with enhanced mineralocorticoid receptor expression facilitate a stress-induced shift from hippocampal toward dorsal striatal learning, most likely via impaired hippocampal processing and reduced amygdala-hippocampus cross talk, allowing the dorsal striatum to guide behavior under stress. PMID: 29147678
- We genotyped 4 SNPs on the NR3C2 gene (rs6810951, rs4635799, rs11099695, rs2070950. Haplotype analyses revealed significant effects of NR3C2 (p = 0.034) on cortisol stress response.NR3C2 also influenced attentional performance via an interaction with stress-induced cortisol response (p < 0.001). Neither NR3C1 haplotype nor NR3C2 haplotype was associated with reasoning abilities. PMID: 29100174
- Corticosterone coordinates via mineralocorticoid receptor the networks underlying how an individual copes with stress, and this action is complemented by the widely distributed lower affinity glucocorticoid receptor involved in the subsequent management of stress adaptation. PMID: 26970338
- The MR-genotype moderates the influence of E2 and P4 on emotional information processing. PMID: 27936434
- SUMOylation of 11beta-HSD2 at residue K266 modulates cortisol-mediated MR nuclear translocation independently of effects on transactivation. PMID: 28938454
- haplotype TAAT of GR might be a protective factor against aggressive behavior, while gene-gene interactions between GR (NR3C1) rs1800445 and MR (NR3C2) rs2070951 might be a risk factor for aggressive behavior in the Central South Chinese Han population PMID: 28686058
- Polymorphisms of the glucocorticoid receptor gene influenced both the basal state of the hypothalamus-pituitary-adrenal axis as well as self-perceived stress. The mineralocorticoid receptor gene only associated with self-perceived stress and 5-HTT only with the cortisol awakening response. PMID: 27427534
- Low NR3C2 expression is associated with Pancreatic Cancer. PMID: 27197190
- the variant rs2070951 and the GA haplotype in NR3C2 were associated with an increased risk for cCSC. Results of this genetic study support a possible role for the mineralocorticoid receptor in the pathogenesis of cCSC. PMID: 28334414
- Glucocorticoid receptor (GR) and Mineralocorticoid Receptor (MR) actions on NFkappaB - and AP-1-dependent signaling were compared in a standardized cellular context where GR or MR could be specifically expressed in the absence of other nuclear receptors. Like GR, MR was found to repress NFkappaB-driven transcription in these cells. PMID: 27650495
- The inhibitory effect of phosphorylation on MR acts in a dominant-negative manner, effectively amplifying its functional effect on gene transactivation. PMID: 27422824
- The new frameshift mutation decreased the expression of MR, but not NR3C2 mRNA, and led to decreased MR function, with no dominant negative effect. PMID: 27725360
- dysregulation of GR, MR, FKBP5, and PTGES3 in autistic spectrum disorder (ASD) and suggest a possible role of inflammation in altered GR function in ASD. PMID: 25912394
- hyperactive hypothalamo-pituitary-adrenocortical axis in overweight diabetic subjects may be associated with downregulation of 11beta-HSD1, MR, and GR in the brain. PMID: 26212138
- MR C3514G and MR C4582A single nucleotide polymorphism exhibited no association with the development of coronary artery disease in Taiwanese. PMID: 26941570
- Our current findings demonstrate that Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression. Our work provides a hint for the drug discovery against cardiovascular disease PMID: 26446917
- Data show that both mineralcorticoid receptor (MR) and G-protein estrogen receptor (GPER) contribute to the proliferation and migration of breast and endothelial cancer cells by sodium-hydrogen exchanger 1 protein (NHE-1) upon aldosterone exposure. PMID: 26646587
- rs5522 polymorphism might affect cardiac remodeling and aldosterone levels in resistant hypertension PMID: 26049084
- Data show that aldosterone via the mineralocorticoid receptor (MR) reduces microRNA miR-29b in vivo in murine aorta and in human primary and cultured vascular smooth muscle cells (VSMCs). PMID: 26728178
- Roles of individual amino acids in human mineralocorticoid and glucocorticoid receptors in the transactivation of downstream genes in response to cortisol and aldosterone. PMID: 26907965
- NR3C2 was found to be significantly associated with longitudinal systolic Blood Pressure change in a Han Chinese population. PMID: 25820244
- Findings indicate that CS-3150 is a selective and highly potent mineralocorticoid receptor antagonist with long-lasting oral activity. PMID: 26073023
- Among the class II HDACs, HDAC4 interacted with both MR and HDAC3 after aldosterone stimulation. The nuclear translocation of HDAC4 was mediated by protein kinase A (PKA) and protein phosphatases (PP) PMID: 26305553
- This review will focus on recent advances in our knowledge of MR function with an emphasis on these models. [review] PMID: 26136532
- CBP and p300 as lysine acetyltransferases responsible for the regulation of MR PMID: 25707758
- Data indicate that finerenone inhibits mineralocorticoid receptor (MR), steroid receptor coactivator-1 binding at the regulatory sequence. PMID: 26203193
- There were no consistent associations between GR and MR gene polymorphisms, interactions between GR and MR haplotypes and stressful conditions and recurrence of major depressive disorder. PMID: 25765757
- MR expression was decreased in PTSD patients with low HPA axis reactivity compared to PTSD patients with high HPA axis reactivity. PMID: 25745955
- These findings indicate that GEMIN4 functions as a novel coregulator of the MR. PMID: 25555524
- Data suggest that NR3C2 activation plays role in pathogenesis of cardiovascular diseases; targeted drug therapy with NR3C2 antagonists may prevent progression of cardiovascular diseases to acute situations such as sudden cardiac arrest. [REVIEW] PMID: 25707577
- Vascular mineralocorticoid receptor and blood pressure regulation PMID: 25733376
- The article reviews recent findings on the involvement of aldosterone but also of MR on energy metabolism and discusses the therapeutic potential of manipulating MR signaling for the management of metabolic disorders in humans. [review] PMID: 25436733
- This study showed that association of the NR3C2 gene and childhood trauma with negative memory bias was found in depressed patients in remission. PMID: 25714450
- new insights into aldosterone MR-mediated renal signaling PMID: 26054365
- An association between mineralocorticoid receptor gene polymorphisms, rs17484063 and rs2883929, and preterm birth. PMID: 26260058
- Carriers of mineralocorticoid receptor haplotype 1 or 3 were sensitive to the impact of oral contraceptives on the recognition of sad and fearful faces and on emotional memory, whereas MR haplotype 2 carriers were not. PMID: 25497375
- Vascular MCR signaling plays an important role in inflammatory and immune responses and development of aortic and femoral artery stiffening secondary to consumption of a Western diet. PMID: 26015449
- Expression of MR in visceral adipose tissue and prostaglandin D2 synthase is strongly correlated in adipose tissues from obese patients. PMID: 25966493
- The found of this study suggest that MR-2G/C polymorphism may partially explain the plastic brain vulnerability to traumatic events. PMID: 25241277
- Putative upstream open reading frames from the 5' untranslated regions in NR3C1. PMID: 25771224
- EEF1A1, SSRP1, and XRCC6 are novel interacting partners of the mineralocorticoid receptor PMID: 25000480
- NR3C2 rs5522 affects blood pressure response to enalapril treatment and may serve as a useful pharmacogenomic marker of antihypertensive response to enalapril in essential hypertension patients. PMID: 24059494
- Our data confirmed that treatment-resistant depression is associated with hypercortisolism and possible mineralocorticoid receptor malfunctioning, such as a down regulation PMID: 23904409
- These results suggest that rs5522 G allele carriers might be vulnerable to stressful life events. PMID: 25220664
- PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins. PMID: 24355684
- Haploinsufficiency of MR in pseudohypoaldosteronism type 1 causes hypothalamo-pituitary adrenal (HPA) axis activation, providing genetic evidence that MR contributes to negative feedback in the human HPA axis. PMID: 24712576
- Variations in NR3C2 are associated with negative memory bias and this relationship appears to be influenced by life adversity. PMID: 24485490
- results indicate a regulatory influence of MR signaling on human T-cell migration and suggest a role for endogenous aldosterone in the redistribution of T-cell subsets to lymph nodes, involving CD62L, CCR7, and CXCR4. PMID: 24595810
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Involvement in disease
Pseudohypoaldosteronism 1, autosomal dominant (PHA1A); Early-onset hypertension with severe exacerbation in pregnancy (EOHSEP)
Subcellular Location
Cytoplasm. Nucleus. Endoplasmic reticulum membrane; Peripheral membrane protein. Note=Cytoplasmic and nuclear in the absence of ligand; nuclear after ligand-binding. When bound to HSD11B2, it is found associated with the endoplasmic reticulum membrane.
Protein Families
Nuclear hormone receptor family, NR3 subfamily
Tissue Specificity
Ubiquitous. Highly expressed in distal tubules, convoluted tubules and cortical collecting duct in kidney, and in sweat glands. Detected at lower levels in cardiomyocytes, in epidermis and in colon enterocytes.
