Mineralocorticoid receptor
Short name=MR
Alternative name(s):
Nuclear receptor subfamily 3 group C member 2
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. Ref.1
Subunit structure
Heteromultimeric cytoplasmic complex with HSP90, HSP70, and FKBP4, in the absence of ligand. After ligand binding, it translocates to the nucleus and binds to DNA as a homodimer and as a heterodimer with NR3C1. May interact with HSD11B2 in the absence of ligand. Binds the coactivators NCOA1, NCOA2, TIF1 and NRIP1. Ref.18
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. Ref.7 Ref.15 Ref.16
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. Ref.2 Ref.10
Domain
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Post-translational modification
Phosphorylated. Ref.7
Involvement in disease
Pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:177735]: A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.21 Ref.24 Ref.25 Ref.27
Early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:605115]: Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.17 Ref.19 Ref.22
Sequence similarities
Belongs to the nuclear hormone receptor family. NR3 subfamily.
Contains 1 nuclear receptor DNA-binding domain.
