Mineralokortikoidni receptor

Izvor: Wikipedia
edit
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 OMIM600983 MGI99459 HomoloGene121495 IUPHAR: GeneCards: NR3C2 Gene
Pregled RNK izražavanja
PBB GE NR3C2 205259 at tn.png
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 4306 110784
Ensembl ENSG00000151623 ENSMUSG00000031618
UniProt P08235 Q8VII8
RefSeq (mRNA) NM_000901 NM_001083906
RefSeq (protein) NP_000892 NP_001077375
Lokacija (UCSC) Chr 4:
149 - 149.37 Mb
Chr 8:
76.9 - 77.25 Mb
PubMed pretraga [1] [2]

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 - уреди]

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 - уреди]

Mineralokortikoidni receptor formira interakcije sa:

Reference[uredi - уреди]

  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. doi:10.1159/000132846. PMID 2558856. 
  2. 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. 3.0 3.1 Savory, J G; Préfontaine G G, Lamprecht C, Liao M, Walther R F, Lefebvre Y A, Haché R J (Feb. 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. 
  4. 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. 
  5. 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 - уреди]

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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. 
  • 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. doi:10.1007/BF00276340. 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. doi:10.1159/000132846. 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. doi:10.1126/science.3037703. 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. doi:10.1016/0960-0760(95)00162-S. 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. doi:10.1016/0014-5793(96)00295-5. 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. doi:10.1074/jbc.272.18.12062. 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. doi:10.1210/jc.82.5.1345. 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. 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. doi:10.1126/science.289.5476.119. 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. doi:10.1210/me.14.8.1210. 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. doi:10.1016/S0304-3940(00)01325-2. PMID 10936692. 

Spoljašnje veze[uredi - уреди]