Mineralokortikoidni receptor

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

edit

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[uredi | uredi kod]

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[uredi | uredi kod]

Mineralokortikoidni receptor formira interakcije sa:

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

Reference[uredi | uredi kod]

↑ 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. DOI:10.1159/000132846. PMID 2558856.
↑ Fuller PJ, Young MJ (2005). „Mechanisms of mineralocorticoid action”. Hypertension 46 (6): 1227–35. DOI:10.1161/01.HYP.0000193502.77417.17. PMID 16286565.
↑ ^3,0 ^3,1 Savory, J G; Préfontaine G G, Lamprecht C, Liao M, Walther R F, Lefebvre Y A, Haché R J (February 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. DOI:10.1128/MCB.21.3.781-793.2001. ISSN 0270-7306. PMC 86670. PMID 11154266. Greška u referenci: Nevaljana oznaka <ref>; naziv "pmid11154266" je zadan više puta s različitim sadržajem
↑ Zennaro MC, Souque A, Viengchareun S, Poisson E, Lombès M (September 2001). „A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action”. Mol. Endocrinol. 15 (9): 1586–98. DOI:10.1210/me.15.9.1586. PMID 11518808.
↑ Thénot S, Henriquet C, Rochefort H, Cavaillès V (May 1997). „Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1”. J. Biol. Chem. 272 (18): 12062–8. DOI:10.1074/jbc.272.18.12062. PMID 9115274.

Literatura[uredi | uredi kod]

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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.
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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. DOI:10.1159/000132846. PMID 2558856.
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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. DOI:10.1210/jc.82.5.1345. PMID 9141514.
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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. DOI:10.1210/me.14.8.1210. PMID 10935545.
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