Mineralocorticoid receptor

Details

Name
Mineralocorticoid receptor
Kind
protein
Synonyms
  • MCR
  • MLR
  • MR
  • Nuclear receptor subfamily 3 group C member 2
Gene Name
NR3C2
UniProtKB Entry
P08235Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0055786|Mineralocorticoid receptor
METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNST
QGSSKEKQELLPCLQQDNNRPGILTSDIKTELESKELSATVAESMGLYMDSVRDADYSYE
QQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAV
VKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPN
VENRGSRSHSPAHASNVGSPLSSPLSSMKSSISSPPSHCSVKSPVSSPNNVTLRSSVSSP
ANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVP
SPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSD
SSFSVPIKQESTKHSCSGTSFKGNPTVNPFPFMDGSYFSFMDDKDYYSLSGILGPPVPGF
DGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSAR
DQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPS
KICLVCGDEASGCHYGVVTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRL
QKCLQAGMNLGARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEEGTTYIAPAKEPSVN
TALVPQLSTISRALTPSPVMVLENIEPEIVYAGYDSSKPDTAENLLSTLNRLAGKQMIQV
VKWAKVLPGFKNLPLEDQITLIQYSWMCLSSFALSWRSYKHTNSQFLYFAPDLVFNEEKM
HQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTIPKDGLKSQAAFEEMRTNYI
KELRKMVTKCPNNSGQSWQRFYQLTKLLDSMHDLVSDLLEFCFYTFRESHALKVEFPAML
VEIISDQLPKVESGNAKPLYFHRK
Number of residues
984
Molecular Weight
107080.615
Theoretical pI
7.42
GO Classification
Functions
steroid binding / zinc ion binding
Processes
signal transduction
Components
endoplasmic reticulum membrane / nucleoplasm / receptor complex
General 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
Specific Function
DNA-binding transcription factor activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0020476|Mineralocorticoid receptor (NR3C2)
ATGGAGACCAAAGGCTACCACAGTCTCCCTGAAGGTCTAGATATGGAAAGACGGTGGGGT
CAAGTTTCTCAGGCTGTGGAGCGTTCTTCCCTGGGACCTACAGAGAGGACCGATGAGAAT
AACTACATGGAGATTGTCAACGTAAGCTGTGTTTCCGGTGCTATTCCAAACAACAGTACT
CAAGGAAGCAGCAAAGAAAAACAAGAACTACTCCCTTGCCTTCAGCAAGACAATAATCGG
CCTGGGATTTTAACATCTGATATTAAAACTGAGCTGGAATCTAAGGAACTTTCAGCAACT
GTAGCTGAGTCCATGGGTTTATATATGGATTCTGTAAGAGATGCTGACTATTCCTATGAG
CAGCAGAACCAACAAGGAAGCATGAGTCCAGCTAAGATTTATCAGAATGTTGAACAGCTG
GTGAAATTTTACAAAGGAAATGGCCATCGTCCTTCCACTCTAAGTTGTGTGAACACGCCC
TTGAGATCATTTATGTCTGACTCTGGGAGCTCCGTGAATGGTGGCGTCATGCGCGCCGTT
GTTAAAAGCCCTATCATGTGTCATGAGAAAAGCCCGTCTGTTTGCAGCCCTCTGAACATG
ACATCTTCGGTTTGCAGCCCTGCTGGAATCAACTCTGTGTCCTCCACCACAGCCAGCTTT
GGCAGTTTTCCAGTGCACAGCCCAATCACCCAGGGAACTCCTCTGACATGCTCCCCTAAT
GTTGAAAATCGAGGCTCCAGGTCGCACAGCCCTGCACATGCTAGCAATGTGGGCTCTCCT
CTCTCAAGTCCGTTAAGTAGCATGAAATCCTCAATTTCCAGCCCTCCAAGTCACTGCAGT
GTAAAATCTCCAGTCTCCAGTCCCAATAATGTCACTCTGAGATCCTCTGTGTCTAGCCCT
GCAAATATTAACAACTCAAGGTGCTCTGTTTCCAGCCCTTCGAACACTAATAACAGATCC
ACGCTTTCCAGTCCGGCAGCCAGTACTGTGGGATCTATCTGTAGCCCTGTAAACAATGCC
TTCAGCTACACTGCTTCTGGCACCTCTGCTGGATCCAGTACATTGCGGGATGTGGTTCCC
AGTCCAGACACGCAGGAGAAAGGTGCTCAAGAGGTCCCTTTTCCTAAGACTGAGGAAGTA
GAGAGTGCCATCTCAAATGGTGTGACTGGCCAGCTTAATATTGTCCAGTACATAAAACCA
GAACCAGATGGAGCTTTTAGCAGCTCATGTCTAGGAGGAAATAGCAAAATAAATTCGGAT
TCTTCATTCTCAGTACCAATAAAGCAAGAATCAACCAAGCATTCATGTTCAGGCACCTCT
TTTAAAGGGAATCCAACAGTAAACCCGTTTCCATTTATGGATGGCTCGTATTTTTCCTTT
ATGGATGATAAAGACTATTATTCCCTATCAGGAATTTTAGGACCACCTGTGCCCGGCTTT
GATGGTAACTGTGAAGGCAGCGGATTCCCAGTGGGTATTAAACAAGAACCAGATGATGGG
AGCTATTACCCAGAGGCCAGCATCCCTTCCTCTGCTATTGTTGGGGTGAATTCAGGTGGA
CAGTCCTTCCACTACAGGATTGGTGCTCAAGGTACAATATCTTTATCACGATCGGCTAGA
GACCAATCTTTCCAACACCTGAGTTCCTTTCCTCCTGTCAATACTTTAGTGGAGTCATGG
AAATCACACGGCGACCTGTCGTCTAGAAGAAGTGATGGGTATCCGGTCTTAGAATACATT
CCAGAAAATGTATCAAGCTCTACTTTACGAAGTGTTTCTACTGGATCTTCAAGACCTTCA
AAAATATGTTTGGTGTGTGGGGATGAGGCTTCAGGATGCCATTATGGGGTAGTCACCTGT
GGCAGCTGCAAAGTTTTCTTCAAAAGAGCAGTGGAAGGGCAACACAACTATTTATGTGCT
GGAAGAAATGATTGCATCATTGATAAGATTCGACGAAAGAATTGTCCTGCTTGCAGACTT
CAGAAATGTCTTCAAGCTGGAATGAATTTAGGAGCACGAAAGTCAAAGAAGTTGGGAAAG
TTAAAAGGGATTCACGAGGAGCAGCCACAGCAGCAGCAGCCCCCACCCCCACCCCCACCC
CCGCAAAGCCCAGAGGAAGGGACAACGTACATCGCTCCTGCAAAAGAACCCTCGGTCAAC
ACAGCACTGGTTCCTCAGCTCTCCACAATCTCACGAGCGCTCACACCTTCCCCCGTTATG
GTCCTTGAAAACATTGAACCTGAAATTGTATATGCAGGCTATGACAGCTCAAAACCAGAT
ACAGCCGAAAATCTGCTCTCCACGCTCAACCGCTTAGCAGGCAAACAGATGATCCAAGTC
GTGAAGTGGGCAAAGGTACTTCCAGGATTTAAAAACTTGCCTCTTGAGGACCAAATTACC
CTAATCCAGTATTCTTGGATGTGTCTATCATCATTTGCCTTGAGCTGGAGATCGTACAAA
CATACGAACAGCCAATTTCTCTATTTTGCACCAGACCTAGTCTTTAATGAAGAGAAGATG
CATCAGTCTGCCATGTATGAACTATGCCAGGGGATGCACCAAATCAGCCTTCAGTTCGTT
CGACTGCAGCTCACCTTTGAAGAATACACCATCATGAAAGTTTTGCTGCTACTAAGCACA
ATTCCAAAGGATGGCCTCAAAAGCCAGGCTGCATTTGAAGAAATGAGGACAAATTACATC
AAAGAACTGAGGAAGATGGTAACTAAGTGTCCCAACAATTCTGGGCAGAGCTGGCAGAGG
TTCTACCAACTGACCAAGCTGCTGGACTCCATGCATGACCTGGTGAGCGACCTGCTGGAA
TTCTGCTTCTACACCTTCCGAGAGTCCCATGCGCTGAAGGTAGAGTTCCCCGCAATGCTG
GTGGAGATCATCAGCGACCAGCTGCCCAAGGTGGAGTCGGGGAACGCCAAGCCGCTCTAC
TTCCACCGGAAGTGA
Chromosome Location
4
Locus
4q31.23
External Identifiers
ResourceLink
UniProtKB IDP08235
UniProtKB Entry NameMCR_HUMAN
GenBank Protein ID307166
GenBank Gene IDM16801
GeneCard IDNR3C2
GenAtlas IDNR3C2
HGNC IDHGNC:7979
PDB ID(s)1Y9R, 1YA3, 2A3I, 2AA2, 2AA5, 2AA6, 2AA7, 2AAX, 2AB2, 2ABI, 2OAX, 3VHU, 3VHV, 3WFF, 3WFG, 4PF3, 4TNT, 4UDA, 4UDB, 5HCV, 5L7E, 5L7G, 5L7H, 5MWP, 5MWY, 6GEV, 6GG8, 6GGG, 6L88
KEGG IDhsa:4306
IUPHAR/Guide To Pharmacology ID626
NCBI Gene ID4306
General References
  1. Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM: Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987 Jul 17;237(4812):268-75. [Article]
  2. Zennaro MC, Souque A, Viengchareun S, Poisson E, Lombes M: A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action. Mol Endocrinol. 2001 Sep;15(9):1586-98. [Article]
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  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP: Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat Genet. 1998 Jul;19(3):279-81. [Article]
  6. Alnemri ES, Maksymowych AB, Robertson NM, Litwack G: Overexpression and characterization of the human mineralocorticoid receptor. J Biol Chem. 1991 Sep 25;266(27):18072-81. [Article]
  7. Hanukoglu A: Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. J Clin Endocrinol Metab. 1991 Nov;73(5):936-44. [Article]
  8. Bloem LJ, Guo C, Pratt JH: Identification of a splice variant of the rat and human mineralocorticoid receptor genes. J Steroid Biochem Mol Biol. 1995 Nov;55(2):159-62. [Article]
  9. Zennaro MC, Farman N, Bonvalet JP, Lombes M: 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. 1997 May;82(5):1345-52. [Article]
  10. Bruner KL, Derfoul A, Robertson NM, Guerriero G, Fernandes-Alnemri T, Alnemri ES, Litwack G: The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52. Recept Signal Transduct. 1997;7(2):85-98. [Article]
  11. Lupo B, Mesnier D, Auzou G: Cysteines 849 and 942 of human mineralocorticoid receptor are crucial for steroid binding. Biochemistry. 1998 Sep 1;37(35):12153-9. [Article]
  12. Hellal-Levy C, Fagart J, Souque A, Rafestin-Oblin ME: Mechanistic aspects of mineralocorticoid receptor activation. Kidney Int. 2000 Apr;57(4):1250-5. [Article]
  13. Hellal-Levy C, Fagart J, Souque A, Wurtz JM, Moras D, Rafestin-Oblin ME: Crucial role of the H11-H12 loop in stabilizing the active conformation of the human mineralocorticoid receptor. Mol Endocrinol. 2000 Aug;14(8):1210-21. [Article]
  14. Odermatt A, Arnold P, Frey FJ: The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2. J Biol Chem. 2001 Jul 27;276(30):28484-92. Epub 2001 May 11. [Article]
  15. Shibata S, Nagase M, Yoshida S, Kawarazaki W, Kurihara H, Tanaka H, Miyoshi J, Takai Y, Fujita T: Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med. 2008 Dec;14(12):1370-6. doi: 10.1038/nm.1879. Epub 2008 Nov 23. [Article]
  16. Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP: A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor. J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. [Article]
  17. Li Y, Suino K, Daugherty J, Xu HE: Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor. Mol Cell. 2005 Aug 5;19(3):367-80. [Article]
  18. Fagart J, Huyet J, Pinon GM, Rochel M, Mayer C, Rafestin-Oblin ME: Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension. Nat Struct Mol Biol. 2005 Jun;12(6):554-5. Epub 2005 May 22. [Article]
  19. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [Article]
  20. Tajima T, Kitagawa H, Yokoya S, Tachibana K, Adachi M, Nakae J, Suwa S, Katoh S, Fujieda K: A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2000 Dec;85(12):4690-4. [Article]
  21. Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai FT, Sigler PB, Lifton RP: Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000 Jul 7;289(5476):119-23. [Article]
  22. Arai K, Nakagomi Y, Iketani M, Shimura Y, Amemiya S, Ohyama K, Shibasaki T: Functional polymorphisms in the mineralocorticoid receptor and amirolide-sensitive sodium channel genes in a patient with sporadic pseudohypoaldosteronism. Hum Genet. 2003 Jan;112(1):91-7. Epub 2002 Oct 25. [Article]
  23. Sartorato P, Lapeyraque AL, Armanini D, Kuhnle U, Khaldi Y, Salomon R, Abadie V, Di Battista E, Naselli A, Racine A, Bosio M, Caprio M, Poulet-Young V, Chabrolle JP, Niaudet P, De Gennes C, Lecornec MH, Poisson E, Fusco AM, Loli P, Lombes M, Zennaro MC: Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism. J Clin Endocrinol Metab. 2003 Jun;88(6):2508-17. [Article]
  24. Riepe FG, Finkeldei J, de Sanctis L, Einaudi S, Testa A, Karges B, Peter M, Viemann M, Grotzinger J, Sippell WG, Fejes-Toth G, Krone N: Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2006 Nov;91(11):4552-61. Epub 2006 Sep 5. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Fludrocortisoneapproved, investigationalyestargetagonistDetails
EplerenoneapprovedyestargetantagonistDetails
Desoxycorticosterone pivalateexperimental, vet_approvedyestargetagonistDetails
SpironolactoneapprovedyestargetantagonistDetails
Aldosteroneexperimental, investigationalyestargetagonistDetails
CorticosteroneexperimentalyestargetinhibitorDetails
Felodipineapproved, investigationalunknowntargetantagonistDetails
Nimodipineapproved, investigationalunknowntargetantagonistDetails
DrospirenoneapprovedyestargetantagonistDetails
Progesteroneapproved, vet_approvedyestargetantagonistagonistDetails
Fluticasone propionateapprovedunknowntargetantagonistDetails
Stanoloneillicit, investigationalunknowntargetDetails
MetriboloneexperimentalunknowntargetDetails
Testosteroneapproved, investigationalunknowntargetligandDetails
Testosterone cypionateapprovedunknowntargetDetails
Testosterone enanthateapprovedunknowntargetDetails
Stanolone acetateexperimentalunknowntargetDetails
Desoxycorticosterone acetateapprovedunknowntargetagonistDetails
Fluticasoneapproved, experimentalunknowntargetantagonistDetails
Fluticasone furoateapprovedunknowntargetantagonistDetails
Clobetasol propionateapprovedunknowntargetagonistDetails
Finerenoneapproved, investigationalyestargetantagonistDetails
Vamoroloneapproved, investigationalunknowntargetantagonistDetails
PF-03882845investigationalyestargetmodulatorDetails
LY-2623091investigationalyestargetantagonistDetails