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Description

Mineralocorticoid receptor (UniProt P22199, also known as MR, Nuclear receptor subfamily 3 group C member 2) is encoded by the Nr3c2 (also known as MCR, Mlr) gene (Gene ID 25672) in rats. Mineralocorticoid receptor (MR) is expressed in multiple tissues, including renal epithelia, smooth muscle, endothelium, cardiomyocytes, and hippocampal neurons, where it mediates diverse functions. MR is activated by aldosterone and also by cortisol in cells that do not express 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2). MR is normally activated by aldosterone, which is produced by adrenal glomerulosa in response to intravascular volume depletion and hyperkalemia. Consistently, gain of function mutations in MR lead to severe hypertension, often with hypokalemia, while loss of function mutations result in neonatal hypotension. Ser843 phosphorylation in the MR ligand-binding domain is reported to prevent MR ligand binding and activation. MR pS843 is found exclusively in intercalated cells of the distal nephrons in the kidney. Intravascular volume depletion, angiotensin II and WNK4 signaling reduce MR pS843 levels, whereas hyperkalemia increases MR pS843.