Mineralocorticoid receptor

NR3C2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Y9R, 1YA3, 2A3I, 2AA2, 2AA5, 2AA6, 2AA7, 2AAX, 2AB2, 2ABI, 2OAX, 3VHU, 3VHV, 3WFF, 3WFG, 4PF3, 4TNT, 4UDB, 4UDA, 5HCV
Identifiers
Aliases	NR3C2, MCR, MLR, MR, NR3C2VIT, nuclear receptor subfamily 3 group C member 2
External IDs	OMIM: 600983 MGI: 99459 HomoloGene: 121495 GeneCards: NR3C2
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q31.23 Start 148,078,762 bp[1] End 148,444,698 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 C1|8 36.34 cM Start 77,626,070 bp[2] End 77,971,641 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell rectum middle temporal gyrus Brodmann area 23 Achilles tendon jejunal mucosa renal medulla Region I of hippocampus proper parotid gland frontal pole Top expressed in Region I of hippocampus proper hippocampus proper left colon dentate gyrus facial motor nucleus ciliary body subiculum olfactory tubercle otolith organ utricle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sequence-specific DNA binding DNA binding DNA-binding transcription factor activity zinc ion binding metal ion binding steroid hormone receptor activity steroid binding protein binding lipid binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm endoplasmic reticulum membrane membrane receptor complex endoplasmic reticulum nucleus nucleoplasm cytosol Biological process regulation of transcription, DNA-templated transcription, DNA-templated transcription initiation from RNA polymerase II promoter signal transduction steroid hormone mediated signaling pathway regulation of transcription by RNA polymerase II positive regulation of NIK/NF-kappaB signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4306 110784 Ensembl ENSG00000151623 ENSMUSG00000031618 UniProt P08235 Q8VII8 RefSeq (mRNA) NM_000901 NM_001166104 NM_001354819 NM_001083906 RefSeq (protein) NP_000892 NP_001159576 NP_001341748 n/a Location (UCSC) Chr 4: 148.08 – 148.44 Mb Chr 8: 77.63 – 77.97 Mb PubMed search [3] [4]
Wikidata
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The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.^[5]

MR is a receptor with equal affinity for mineralocorticoids and glucocorticoids. It belongs to the nuclear receptor family where the ligand diffuses into cells, interacts with the receptor and results in a signal transduction affecting specific gene expression in the nucleus. The selective response of some tissues and organs to mineralocorticoids over glucocorticoids occurs because mineralocorticoid-responsive cells express Corticosteroid 11-beta-dehydrogenase isozyme 2, an enzyme which selectively inactivates glucocorticoids more readily than mineralocorticoids.

Function

MR is expressed in many tissues, such as the kidney, colon, heart, central nervous system (hippocampus), brown adipose tissue and sweat glands. In epithelial tissues, its activation leads to the expression of proteins regulating ionic and water transports (mainly the epithelial sodium channel or ENaC, Na+/K+ pump, serum and glucocorticoid induced kinase or SGK1) resulting in the reabsorption of sodium, and as a consequence an increase in extracellular volume, increase in blood pressure, and an excretion of potassium to maintain a normal salt concentration in the body.

The receptor is activated by mineralocorticoids such as aldosterone and its precursor deoxycorticosterone as well as glucocorticoids like cortisol. In intact animals, the mineralocorticoid receptor is "protected" from glucocorticoids by co-localization of an enzyme, corticosteroid 11-beta-dehydrogenase isozyme 2 (a.k.a. 11β-hydroxysteroid dehydrogenase 2; 11β-HSD2), that converts cortisol to inactive cortisone.^[6]

Activation of the mineralocorticoid receptor, upon the binding of its ligand aldosterone, results in its translocation to the cell nucleus, homodimerization and binding to hormone response elements present in the promoter of some genes. This results in the complex recruitment of the transcriptional machinery and the transcription into mRNA of the DNA sequence of the activated genes.^[7]

An activating mutation in the NR3C2 gene (S810L) results in constitutive activity of the mineralocorticoid receptor, leading to severe early-onset hypertension that is exacerbated by pregnancy. In a family known to harbor the S810L mutation, 3 individuals carrying the mutation died of chronic heart failure before age 50.^[8] Additional studies have shown that this activated version of MR can positively respond to ligands that are traditionally antagonists, such as endogenous hormones like progesterone, and the diuretic drugs spironolactone and eplerenone.^[8]

Ligands

Aldosterone, 11-deoxycorticosterone, and cortisol are endogenous agonists of the MR. Fludrocortisone is a synthetic agonist of the MR which is used clinically. Progesterone is a potent endogenous antagonist of the MR.^[9] Synthetic antagonists of the MR include the steroidal compounds spironolactone, canrenone, eplerenone, and drospirenone and the nonsteroidal compounds apararenone, esaxerenone, and finerenone.

Interactions

Mineralocorticoid receptor has been shown to interact with:

• Glucocorticoid receptor^[10] and
• TRIM24.^[10][11][12]

See also

• Aldosterone
• Glucocorticoid
• Mineralocorticoid

References

Further reading

External links

• Mineralocorticoid+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)