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mineralocorticoid receptor; MR; nuclear receptor subfamily 3 group C member 2 (NR3C2, MCR, MLR)

Function: - receptor for both mineralocorticoids & glucocorticoids - binds to mineralocorticoid response elements (MRE) & transactivates target genes - effect is to increase ion & water transport & thus raise extracellular fluid volume & blood pressure & lower K+ levels - cytoplasmic anchoring &/or assembly; a) heteromultimeric cytoplasmic complex with HSP90, HSP70, & FKBP4, in the absence of ligand b) after ligand binding, it translocates to the nucleus & binds to DNA as a homodimer & as a heterodimer with NR3C1 - may interact with HSD11B2 in the absence of ligand. - binds the coactivators NCOA1, NCOA2, TIF1 & NRIP1 - phosphorylated Structure: 1) composed of three domains: a) modulating N-terminal domain b) DNA-binding domain c) C-terminal steroid-binding domain 2) belongs to the nuclear hormone receptor family, NR3 subfamily 3) contains 1 nuclear receptor DNA-binding domain Compartment: - cytoplasm, nucleus, endoplasmic reticulum membrane - cytoplasmic & nuclear in the absence of ligand - nuclear after ligand-binding - when bound to HSD11B2, it is found associated with the endoplasmic reticulum membrane Alternative splicing: named isoforms=4 Additional isoforms seem to exist Expression: - ubiquitous - highly expressed in distal tubules, convoluted tubules & cortical collecting duct in kidney, & in sweat glands - detected at lower levels in cardiomyocytes, in epidermis & in colon enterocytes Pathology: - defects in NR3C2 are a cause of a) autosomal dominant pseudohypoaldosteronism type 1 b) early onset hypertension with severe exacerbation in pregnancy Comparative biology: - type I corticosteroid receptor (rat).

Interactions

molecular events

Related

mineralocorticoid mineralocorticoid receptor activation

General

steroid receptor

Properties

SIZE: MW = 107 kD entity length = 984 aa COMPARTMENT: cytoplasm MOTIF: allosteric site SITE: N-TERMINAL DNA-binding motif SITE: 603-668 MOTIF: Zn finger C4-type SITE: 603-623 EFFECTOR-BOUND: Zn+2 kxffkr NAME: kxffkr SITE: 624-629 FOR-BINDING-OF: calreticulin FORM: kxffkr Zn finger C4-type SITE: 639-663 EFFECTOR-BOUND: Zn+2 hinge region {669-732} ligand-binding site SITE: 733-984 FOR-BINDING-OF: mineralocorticoid

Database Correlations

OMIM correlations MORBIDMAP 600983 UniProt P08235 PFAM correlations Kegg hsa:4306

References

  1. Alberts et al Molecular Biology of the Cell, 2nd ed. 1989, pg 704
  2. Journal Watch 20(16):130, 2000 Geller DS et al Science 289:119, 2000
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=NR3C2
  4. Wikipedia; Note: mineralocorticoid receptor entry http://en.wikipedia.org/wiki/mineralocorticoid_receptor
  5. UniProt :accession P08235