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Mineralocorticoid receptor




Nuclear receptor subfamily 3, group C, member 2
PDB rendering based on 1gdc.
Available structures: 1gdc, 1rgd, 1y9r, 1ya3, 2a3i, 2aa2, 2aa5, 2aa6, 2aa7, 2aax, 2ab2, 2abi, 2gda
Identifiers
Symbol(s) NR3C2; MCR; MGC133092; MLR; MR
External IDs OMIM: 600983 MGI: 99459 Homologene: 694
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 4306 110784
Ensembl ENSG00000151623 ENSMUSG00000031618
Uniprot P08235 Q3UW58
Refseq NM_000901 (mRNA)
NP_000892 (protein) 		XM_899576 (mRNA)
XP_904669 (protein)
Location Chr 4: 149.22 - 149.58 Mb Chr 8: 79.8 - 80.14 Mb
Pubmed search [1] [2]

The mineralocorticoid receptor (or MR, MLR, MCR), also called aldosterone receptor, is officially labelled nuclear receptor subfamily 3, group C, member 2, (NR3C2) and is a receptor with high affinity for mineralocorticoids. It belongs to the steroid hormone 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 gene for the NR3C2 (located on chromosome 4q31.1-31.2) encodes for the 107 kDa MR protein. 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 reabsoprtion 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 deoxycorticosterone as well as glucocorticoids, like cortisol and cortison. It also responds to some progestins. Spironolactone and eplerenone are mineralocorticoid receptor antagonists.

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.[1]

Related receptors

Receptors with a similar structure include: the androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, thyroid hormone receptors, peroxisome proliferator-activated receptors, retinoic acid receptor, farnesoid x receptor, pregnane x receptor, liver X receptor, vitamin D receptor, retinoid x receptor and the constitutive androstane receptor.

References

  1. ^ Fuller PJ, Young MJ (2005). "Mechanisms of mineralocorticoid action". Hypertension 46 (6): 1227-35. doi:10.1161/01.HYP.0000193502.77417.17. PMID 16286565.

Further reading

  • Hellal-Levy C, Fagart J, Souque A, Rafestin-Oblin ME (2000). "Mechanistic aspects of mineralocorticoid receptor activation.". Kidney Int. 57 (4): 1250-5. doi:10.1046/j.1523-1755.2000.00958.x. PMID 10760050.
  • Sheppard KE (2002). "Nuclear receptors. II. Intestinal corticosteroid receptors.". Am. J. Physiol. Gastrointest. Liver Physiol. 282 (5): G742-6. doi:10.1152/ajpgi.00531.2001. PMID 11960770.
  • Kjellander CG (1975). "[The psychotherapeutic society--utopia or nightmare?]". Lakartidningen 72 (12): 1160-1. PMID 1134129.
  • Alnemri ES, Maksymowych AB, Robertson NM, Litwack G (1991). "Overexpression and characterization of the human mineralocorticoid receptor.". J. Biol. Chem. 266 (27): 18072-81. PMID 1655735.
  • Morrison N, Harrap SB, Arriza JL, et al. (1990). "Regional chromosomal assignment of the human mineralocorticoid receptor gene to 4q31.1.". Hum. Genet. 85 (1): 130-2. PMID 2162806.
  • Fan YS, Eddy RL, Byers MG, et al. (1990). "The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2.". Cytogenet. Cell Genet. 52 (1-2): 83-4. PMID 2558856.
  • Arriza JL, Weinberger C, Cerelli G, et al. (1987). "Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor.". Science 237 (4812): 268-75. PMID 3037703.
  • Bloem LJ, Guo C, Pratt JH (1996). "Identification of a splice variant of the rat and human mineralocorticoid receptor genes.". J. Steroid Biochem. Mol. Biol. 55 (2): 159-62. PMID 7495694.
  • Jalaguier S, Mornet D, Mesnier D, et al. (1996). "Human mineralocorticoid receptor interacts with actin under mineralocorticoid ligand modulation.". FEBS Lett. 384 (2): 112-6. PMID 8612804.
  • Thénot S, Henriquet C, Rochefort H, Cavaillès V (1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1.". J. Biol. Chem. 272 (18): 12062-8. PMID 9115274.
  • Zennaro MC, Farman N, Bonvalet JP, Lombès M (1997). "Tissue-specific expression of alpha and beta messenger ribonucleic acid isoforms of the human mineralocorticoid receptor in normal and pathological states.". J. Clin. Endocrinol. Metab. 82 (5): 1345-52. PMID 9141514.
  • Bruner KL, Derfoul A, Robertson NM, et al. (1998). "The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52.". Receptors & signal transduction 7 (2): 85-98. PMID 9392437.
  • Geller DS, Rodriguez-Soriano J, Vallo Boado A, et al. (1998). "Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I.". Nat. Genet. 19 (3): 279-81. doi:10.1038/966. PMID 9662404.
  • Lupo B, Mesnier D, Auzou G (1998). "Cysteines 849 and 942 of human mineralocorticoid receptor are crucial for steroid binding.". Biochemistry 37 (35): 12153-9. doi:10.1021/bi980593e. PMID 9724527.
  • Halushka MK, Fan JB, Bentley K, et al. (1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.". Nat. Genet. 22 (3): 239-47. doi:10.1038/10297. PMID 10391210.
  • Freeman BC, Felts SJ, Toft DO, Yamamoto KR (2000). "The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies.". Genes Dev. 14 (4): 422-34. PMID 10691735.
  • Geller DS, Farhi A, Pinkerton N, et al. (2000). "Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.". Science 289 (5476): 119-23. PMID 10884226.
  • Hellal-Levy C, Fagart J, Souque A, et al. (2001). "Crucial role of the H11-H12 loop in stabilizing the active conformation of the human mineralocorticoid receptor.". Mol. Endocrinol. 14 (8): 1210-21. PMID 10935545.
  • Watzka M, Beyenburg S, Blümcke I, et al. (2000). "Expression of mineralocorticoid and glucocorticoid receptor mRNA in the human hippocampus.". Neurosci. Lett. 290 (2): 121-4. PMID 10936692.
v • d • e
Corticosteroids - glucocorticoid/receptor and mineralocorticoid/receptor
(A07EA, C05AA, D07, D10AA, H02, R01AD, R03BA, S01BA, S02B, and S03B)
EndogenousAldosterone, Cortisone, Hydrocortisone/cortisol, Desoxycortone
OthersAlclometasone, Amcinonide, Beclometasone, Betamethasone, Budesonide, Ciclesonide, Clobetasol, Clobetasone, Clocortolone, Cloprednol, Cortivazol, Deflazacort, Deoxycorticosterone, Desonide, Desoximetasone, Dexamethasone, Diflorasone, Diflucortolone, Difluprednate, Fluclorolone, Fludrocortisone, Fludroxycortide, Flumetasone, Flunisolide, Fluocinolone acetonide, Fluocinonide, Fluocortin, Fluocortolone, Fluorometholone, Fluperolone, Fluprednidene, Fluticasone, Formocortal, Halcinonide, Halometasone, Hydrocortisone aceponate, Hydrocortisone buteprate, Hydrocortisone butyrate, Loteprednol, Medrysone, Meprednisone, Methylprednisolone,Methylprednisolone aceponate, Mometasone furoate, Paramethasone, Prednicarbate, Prednisone, Prednisolone, Prednylidene, Rimexolone, Tixocortol, Triamcinolone, Ulobetasol
v • d • e
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP) Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH) ATOH1 • AhR • AHRR • ARNT • ASCL1 • BMAL (ARNTL, ARNTL2) • CLOCK • HIF (1A, 3A) • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1
(1.3) bHLH-ZIP Myc • MITF • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH) AP-2
(2) Zinc finger
DNA-binding domains
(2.1) Nuclear receptor (Cys4) subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)
(2.2) Other Cys4 GATA (1, 2, 3, 4, 5, 6)
(2.3) Cys2His2 General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH: 1, 2) • GLI-Krüppel family (1, 2, 3, YY1) • KLF (2, 4, 5, 6, 10, 11, 12, 13) • Sp1 • zinc finger (3, 35, 43, 146, 148, 165, 217, 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6 HIVEP1
(3) Helix-turn-helix
domains
(3.1) Homeo domain ARX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C6, C8, C9, C13, D1, D3, D4, D9, D10, D11, D12, D13) • NANOG • NKX (2-1, 2-5, 3-1) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7)
(3.2) Paired box PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
(3.3) Fork head / winged helix E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, L2, M1, N3, O3, O4, P1, P2, P3)
(3.4) Heat Shock Factors HSF1
(3.5) Tryptophan clusters ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB
(3.6) TEA domain transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with
minor groove contacts
(4.1) Rel homology region NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4)
(4.2) STAT STAT (1, 2, 3, 4, 5, 6)
(4.3) p53 p53
(4.4) MADS box Mef2 (A, B, C, D) • SRF
(4.7) High mobility group HNF (1A, 1B) • LEF1 • SOX (3, 4, 6, 9, 10, 13, 18) • SRY • SSRP1
(4.10) Cold-shock domain CSDA
(4.11) Runt CBF (RUNX1, RUNX2, RUNX3)
(0) Other
transcription factors
(0.2) HMGI(Y) HMGA (1, 2)
(0.3) Pocket domain Rb • RBL1 • RBL2
(0.6) Miscellaneous ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Mineralocorticoid_receptor". A list of authors is available in Wikipedia.
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