Mineralokortikoidni receptor

Nuklearni receptor potfamilije 3, grupa C, član 2
Nuklearni receptor potfamilije 3, grupa C, član 2
	PDB prikaz baziran na PDB: 1gdc.
Dostupne strukture
	1Y9R, 1YA3, 2A3I, 2AA2, 2AA5, 2AA6, 2AA7, 2AAX, 2AB2, 2ABI, 2OAX, 3VHU, 3VHV, 3WFF, 3WFG
Identifikatori
Simboli	NR3C2; MCR; MLR; MR; NR3C2VIT
Vanjski ID	OMIM: 600983 MGI: 99459 HomoloGene: 121495 IUPHAR: GeneCards: NR3C2 Gene
Ontologija gena
Molekularna funkcija	• za sekvencu specifično dejstvo DNK vezujućeg transkripcionog faktora; • aktivnost steroidnog hormonskg receptora; • steroidno vezivanje;
Celularna komponenta	• nukleoplazma; • membrana endoplazmatičnog retikuluma;
Biološki proces	• transkriptiona inicijacija iz promotera RNK polimeraze II; • homeostaza ćelijskog jona natrijuma; • ćelijska transdukcija;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	4306
Ensembl	ENSG00000151623
UniProt	P08235
RefSeq (mRNA)	NM_000901
RefSeq (protein)	NP_000892
Lokacija (UCSC)	Chr 4:; 149 - 149.37 Mb
PubMed pretraga	[1]

Mineralokortikoidni receptor (MR, MLR, MCR, aldosteronski receptor, nuklearni receptor putfamilije 3, grupa C, član 2, NR3C2) protein je koji je kod čoveka kodiran NR3C2 genom lociranom na hromozomu 4q31.1-31.2.^[1]

MR je receptor sa jednakim afinitetom za mineralokortikoide i glukokortikoide. On pripada familiji citosolnih receptora. Ligand se difuzijom unosi u ćelije, formira interakciju sa receptorom i to dovodi do prenosa signala što utiče na izražavanje specifičnog gena u jedru.

Funkcija

MR je izražen u mnogim tkivima, kao što su bubrezi, creva, srce, centralni nervni sistem (hipokampus), smeđe adipozno tkivo i znojne žlezde. U epitelnim tkivima, njegova aktivacija dovodi do izražavanja proteina koji regulišu transport jona i vode (uglavnom epitelni natrijumski kanal ili ENaC, Na+/K+ pumpa, serumom i glukokortikoidom indukovana kinaza ili SGK1) te dolazi do reapsopcije natrijuma, i konsekventno povećanja ektracelularne zapremine, povećanja krvnog pritiska, i izlučivanja kalijuma radi održavanja normalne koncentracije soli u telu.

Ovaj receptor aktiviraju mineralokortikoidi, kao što je aldosteron, i deoksikortikosteron kao i glukokortikoidi, poput kortizola. U životinjama, mineralokortikoidni receptor je „zaštićen“ od glukokortikoida putem kolokalizacije enzima, kortikosteroid 11-beta-dehidrogenaza izozim 2 (aka 11-β-hidroksisteroidna dehidrogenaza 2; 11ß-HSD2), koja konvertuje kortizol do neaktivnog kortizona. On je takođe responsivan na pojedine progestine. Spironolakton i eplerenon su antagonisti mineralokortikoidnog receptora.

Aktivacija mineralokortikoidnog receptora, nakon vezivanja liganda aldosterona, dovodi do njegove translokacije u ćelijsko jedro, homodimerizacije i vezivanja za hormonske responsne elemente prisutne u promoterima pojedinih gena. Rezultat je kompleksno regrutovanje transkripcione mašinerije i transkripcije DNK sekvence aktiviranih gena u iRNK.^[2]

Interakcije

Mineralokortikoidni receptor formira interakcije sa:

Glukokortikoidni receptor^[3] i
TRIM24.^[3]^[4]^[5]

Reference

^ Fan YS, Eddy RL, Byers MG, Haley LL, Henry WM, Nowak NJ, Shows TB (1989). „The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2”. Cytogenet. Cell Genet. 52 (1-2): 83—4. PMID 2558856. doi:10.1159/000132846.
^ Fuller PJ, Young MJ (2005). „Mechanisms of mineralocorticoid action”. Hypertension. 46 (6): 1227—35. PMID 16286565. doi:10.1161/01.HYP.0000193502.77417.17.
^ ^а ^б Savory, J G; Préfontaine G G; et al. (2001). „Glucocorticoid receptor homodimers and glucocorticoid-mineralocorticoid receptor heterodimers form in the cytoplasm through alternative dimerization interfaces”. Mol. Cell. Biol. UNITED STATES. 21 (3): 781—93. ISSN 0270-7306. PMC 86670 . PMID 11154266. doi:10.1128/MCB.21.3.781-793.2001.
^ Zennaro MC, Souque A, Viengchareun S, Poisson E, Lombès M (2001). „A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action”. Mol. Endocrinol. 15 (9): 1586—98. PMID 11518808. doi:10.1210/me.15.9.1586.
^ 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. doi:10.1074/jbc.272.18.12062.

Literatura

Hellal-Levy C, Fagart J, Souque A, Rafestin-Oblin ME (2000). „Mechanistic aspects of mineralocorticoid receptor activation.”. Kidney Int. 57 (4): 1250—5. PMID 10760050. doi:10.1046/j.1523-1755.2000.00958.x.
Sheppard KE (2002). „Nuclear receptors. II. Intestinal corticosteroid receptors.”. Am. J. Physiol. Gastrointest. Liver Physiol. 282 (5): G742—6. PMID 11960770. doi:10.1152/ajpgi.00531.2001.
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. doi:10.1007/BF00276340.
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. doi:10.1159/000132846.
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. doi:10.1126/science.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. doi:10.1016/0960-0760(95)00162-S.
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. doi:10.1016/0014-5793(96)00295-5.
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. doi:10.1074/jbc.272.18.12062.
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. doi:10.1210/jc.82.5.1345.
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. PMID 9662404. doi:10.1038/966.
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. PMID 9724527. doi:10.1021/bi980593e.
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. PMID 10391210. doi:10.1038/10297.
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. PMC 316379 . 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. doi:10.1126/science.289.5476.119.
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. doi:10.1210/me.14.8.1210.
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. doi:10.1016/S0304-3940(00)01325-2.

Spoljašnje veze

Mineralocorticoid+Receptors на US National Library of Medicine Medical Subject Headings (MeSH)

[pmid2558856-1] Fan YS, Eddy RL, Byers MG, Haley LL, Henry WM, Nowak NJ, Shows TB (1989). „The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2”. Cytogenet. Cell Genet. 52 (1-2): 83—4. PMID 2558856. doi:10.1159/000132846.

[pmid16286565-2] Fuller PJ, Young MJ (2005). „Mechanisms of mineralocorticoid action”. Hypertension. 46 (6): 1227—35. PMID 16286565. doi:10.1161/01.HYP.0000193502.77417.17.

[pmid11154266-3] а ^б Savory, J G; Préfontaine G G; et al. (2001). „Glucocorticoid receptor homodimers and glucocorticoid-mineralocorticoid receptor heterodimers form in the cytoplasm through alternative dimerization interfaces”. Mol. Cell. Biol. UNITED STATES. 21 (3): 781—93. ISSN 0270-7306. PMC 86670 . PMID 11154266. doi:10.1128/MCB.21.3.781-793.2001.

[pmid11518808-4] Zennaro MC, Souque A, Viengchareun S, Poisson E, Lombès M (2001). „A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action”. Mol. Endocrinol. 15 (9): 1586—98. PMID 11518808. doi:10.1210/me.15.9.1586.

[pmid9115274-5] 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. doi:10.1074/jbc.272.18.12062.

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