Receptor vitamina D

Receptor vitamina D
Vitamin D (1,25- dihidroksivitamin D3) receptor
(427 aminokiselina)
Identifikatori
SimbolVDR Name = Receptor vitamina D
InterPro12679
SCOPvezan je sa vitaminom D; Heterodimer VDR+RXRA Homodimer; vezan je sa vitaminom D; Heterodimer VDR+RXRA
SUPERFAMILYvezan je sa vitaminom D; Heterodimer VDR+RXRA Homodimer; vezan je sa vitaminom D; Heterodimer VDR+RXRA
OPM superfamilija[https://www.rcsb.org/structure/1YY1 1YY1​, ABCD​ 1YY1​, ABCD​]
vitamin D receptor
Identifikatori
Alijasi
Spoljašnji IDGeneCards: [1]
Obrazac RNK izražavanja
More reference expression data
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VrsteČovekMiš
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RefSeq (mRNA)

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RefSeq (protein)

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Kalcitriolni receptor – poznat i kao receptor vitamina D (VDR) i NR1 I 1 (potporodica nuklearnih receptora 1, grupa I, član 1) – član je porodice nuklearnih receptora transkripcijskih faktora.[1] Nakon aktivacije vitamina D, VDR formira heterodimer sa retinoidnim X receptorom i veže se za elemente hormonskog odgovora na DNK. To dovodi do ispoljavanja ili transrepresije specifičnih genskih proizvoda. VDR-i ne regulišu samo transkripcioni odgovor, već učestvuju i u posttranskripcijskom mehanizmu koje usmerava mikroRNK.[2] Kod ljudi, receptor vitamina D je kodiran genom VDR.[3]

Glukokortikoidi su poznati po smanjivanju ekspresije VDR, što se ispoljava u većini tkiva, a u probavnom traktu regulišu transport kalcijuma, gvožđa i ostalih minerala.[4]

Funkcija

Sinteza receptora vitamina vitamina D3 je genetički kontrolisana. Ovaj receptor istovremeno funkcioniše i kao receptor za sekundarnu žučnu i litoholinsku kiselinu. Receptor pripada porodici of trans-aktivnih transkripcionih regulatornih faktora i pokazuje sličnost sekvence sa receptorima steroidnih i tiroidnih hormona.[5]

Nizvodni ciljevi ovog nuklearnog hormonskog receptora su uglavnom obuhvaćeni metabolizamom minerala, iako receptor reguliše i niz drugih metaboličkih puteva, kao što su oni koji učestvuju u imunim odgovorima i raku.[6]

Mutacije u ovom genu su povezane sa rezistentnošću rahitisa na vitamin D, tipa II. Jednonukleotidni polimorfizam u inicijacijskom kodonu dovodi do izmenjene translacije startnog mesta, tri kodona nizvodno. Alternativno splajsovanje RNK se javlja kod više transkribovanih varijanti, koje kodiraju isti protein.[7]

Receptor vitamina D ima važnu ulogu u regulisanju ciklusa rasta dlake. Gubitak gena VDR je, kod ekperimentalnih životinja, povezan sa gubitkom dlake.[8] Experimentalna proučavanja pokazuju da neligandirani VDR stupa u interakciju sa ragulatornim regionom gena cWnt (wnt signalni put) i slušnog ježa, i da je neophodan za pokretanje ovih puteva tokom postnatalnog ciklusa rasta dlake.[9] Ove studije su otkrile nove akcije neligandskih VDR u regulisanju post-morfogenog ciklusa dlake.

Interakcije

Kalcitriolni receptor formira interakcije protein-protein sa:

  • BAG1,[10]
  • BAZ1B,[11]
  • CAV3,[12]
  • MED1,[11][13]
  • MED12,[11][11][13]
  • NCOR1,[14]
  • NCOR2,[14][15]
  • NCOA2,[11][16][17][18]
  • RXRA,[17][19]
  • RUNX1,[15]
  • RUNX1T1,[15]
  • SNW1,[17][19]
  • STAT1,[20] and
  • Cinkov prst i ZBTB16.[15][21]

Vidi još

Reference

  1. ^ Moore DD, Kato S, Xie W, Mangelsdorf DJ, Schmidt DR, Xiao R, Kliewer SA (2006). „International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor”. Pharmacol. Rev. 58 (4): 742—59. PMID 17132852. doi:10.1124/pr.58.4.6. 
  2. ^ Lisse TS, Chun RF, Rieger S, Adams JS, Hewison M (2013). „Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts”. J Bone Miner Res. 28 (6): 1478—14788. PMID 23362149. doi:10.1002/jbmr.1882. 
  3. ^ Szpirer J, Szpirer C, Riviere M, Levan G, Marynen P, Cassiman JJ, Wiese R, DeLuca HF (1991). „The Sp1 transcription factor gene (SP1) and the 1,25-dihydroxyvitamin D3 receptor gene (VDR) are colocalized on human chromosome arm 12q and rat chromosome 7”. Genomics. 11 (1): 168—73. PMID 1662663. doi:10.1016/0888-7543(91)90114-T. 
  4. ^ Fleet JC, Schoch RD (2010). „Molecular Mechanisms for Regulation of Intestinal Calcium Absorption by Vitamin D and Other Factors”. Crit Rev Clin Lab Sci. 47 (4): 181—195. PMID 21182397. doi:10.3109/10408363.2010.536429. 
  5. ^ Germain P, Staels B, Dacquet C, Spedding M, Laudet V (2006). „Overview of nomenclature of nuclear receptors”. Pharmacol. Rev. 58 (4): 685—704. PMID 17132848. doi:10.1124/pr.58.4.2. 
  6. ^ Adorini L, Daniel KC, Penna G (2006). „Vitamin D receptor agonists, cancer and the immune system: an intricate relationship”. Curr Top Med Chem. 6 (12): 1297—301. PMID 16848743. doi:10.2174/156802606777864890. 
  7. ^ „Entrez Gene: VDR vitamin D (1,25- dihydroxyvitamin D3) receptor”. 
  8. ^ Luderer HF, Demay MB (2010). „The vitamin D receptor, the skin and stem cells”. J. Steroid Biochem. Mol. Biol. 121 (1–2): 314—6. PMID 20138991. doi:10.1016/j.jsbmb.2010.01.015. 
  9. ^ Lisse TS, Saini V, Zhao H, Luderer HF, Gori F, Demay MB (2014). „The Vitamin D Receptor Is Required for Activation of cWnt and Hedgehog Signaling in Keratinocytes”. Mol. Endocrinol. 28 (10): 1698—1706. PMID 25180455. doi:10.1210/me.2014-1043. 
  10. ^ Guzey M, Takayama S, Reed JC (2000). „BAG1L enhances trans-activation function of the vitamin D receptor”. J. Biol. Chem. 275 (52): 40749—56. PMID 10967105. doi:10.1074/jbc.M004977200. 
  11. ^ а б в г д Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S (2003). „The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome”. Cell. 113 (7): 905—17. PMID 12837248. doi:10.1016/S0092-8674(03)00436-7. 
  12. ^ Zhao G, Simpson RU (2010). „Membrane Localization, Caveolin-3 Association and Rapid Actions of Vitamin D Receptor in Cardiac Myocytes”. Steroids. 75 (8–9): 555—9. PMC 2885558 Слободан приступ. PMID 20015453. doi:10.1016/j.steroids.2009.12.001. 
  13. ^ а б Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (1999). „Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators”. Mol. Cell. 3 (3): 361—70. PMID 10198638. doi:10.1016/S1097-2765(00)80463-3. 
  14. ^ а б Tagami T, Lutz WH, Kumar R, Jameson JL (1998). „The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators”. Biochem. Biophys. Res. Commun. 253 (2): 358—63. PMID 9878542. doi:10.1006/bbrc.1998.9799. 
  15. ^ а б в г Puccetti E, Obradovic D, Beissert T, Bianchini A, Washburn B, Chiaradonna F, Boehrer S, Hoelzer D, Ottmann OG, Pelicci PG, Nervi C, Ruthardt M (2002). „AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor”. Cancer Res. 62 (23): 7050—8. PMID 12460926. 
  16. ^ Herdick M, Steinmeyer A, Carlberg C (2000). „Antagonistic action of a 25-carboxylic ester analogue of 1alpha, 25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators”. J. Biol. Chem. 275 (22): 16506—12. PMID 10748178. doi:10.1074/jbc.M910000199. 
  17. ^ а б в Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN (2001). „Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription”. J. Biol. Chem. 276 (44): 40614—20. PMID 11514567. doi:10.1074/jbc.M106263200. 
  18. ^ He B, Wilson EM (2003). „Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs”. Mol. Cell. Biol. 23 (6): 2135—50. PMC 149467 Слободан приступ. PMID 12612084. doi:10.1128/MCB.23.6.2135-2150.2003. 
  19. ^ а б Baudino TA, Kraichely DM, Jefcoat SC, Winchester SK, Partridge NC, MacDonald PN (1998). „Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription”. J. Biol. Chem. 273 (26): 16434—41. PMID 9632709. doi:10.1074/jbc.273.26.16434. 
  20. ^ Vidal M, Ramana CV, Dusso AS (2002). „Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription”. Mol. Cell. Biol. 22 (8): 2777—87. PMC 133712 Слободан приступ. PMID 11909970. doi:10.1128/MCB.22.8.2777-2787.2002. 
  21. ^ Ward JO, McConnell MJ, Carlile GW, Pandolfi PP, Licht JD, Freedman LP (2001). „The acute promyelocytic leukemia-associated protein, promyelocytic leukemia zinc finger, regulates 1,25-dihydroxyvitamin D(3)-induced monocytic differentiation of U937 cells through a physical interaction with vitamin D(3) receptor”. Blood. 98 (12): 3290—300. PMID 11719366. doi:10.1182/blood.V98.12.3290. 

Literatura

  • Hosoi T (2002). „[Polymorphisms of vitamin D receptor gene]”. Nippon Rinsho. 60 Suppl 3: 106—10. PMID 11979895. 
  • Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP (2004). „Genetics and biology of vitamin D receptor polymorphisms”. Gene. 338 (2): 143—56. PMID 15315818. doi:10.1016/j.gene.2004.05.014. 
  • Norman AW (2007). „Minireview: vitamin D receptor: new assignments for an already busy receptor”. Endocrinology. 147 (12): 5542—8. PMID 16946007. doi:10.1210/en.2006-0946. 
  • Bollag WB (2007). „Differentiation of human keratinocytes requires the vitamin d receptor and its coactivators”. J. Invest. Dermatol. 127 (4): 748—50. PMID 17363957. doi:10.1038/sj.jid.5700692. 
  • Bugge TH, Pohl J, Lonnoy O, Stunnenberg HG (1992). „RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors”. EMBO J. 11 (4): 1409—18. PMC 556590 Слободан приступ. PMID 1314167. 
  • Goto H, Chen KS, Prahl JM, DeLuca HF (1992). „A single receptor identical with that from intestine/T47D cells mediates the action of 1,25-dihydroxyvitamin D-3 in HL-60 cells”. Biochim. Biophys. Acta. 1132 (1): 103—8. PMID 1324736. doi:10.1016/0167-4781(92)90063-6. 
  • Saijo T, Ito M, Takeda E, Huq AH, Naito E, Yokota I, Sone T, Pike JW, Kuroda Y (1991). „A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection”. Am. J. Hum. Genet. 49 (3): 668—73. PMC 1683124 Слободан приступ. PMID 1652893. 
  • Szpirer J, Szpirer C, Riviere M, Levan G, Marynen P, Cassiman JJ, Wiese R, DeLuca HF (1992). „The Sp1 transcription factor gene (SP1) and the 1,25-dihydroxyvitamin D3 receptor gene (VDR) are colocalized on human chromosome arm 12q and rat chromosome 7”. Genomics. 11 (1): 168—73. PMID 1662663. doi:10.1016/0888-7543(91)90114-T. 
  • Yu XP, Mocharla H, Hustmyer FG, Manolagas SC (1991). „Vitamin D receptor expression in human lymphocytes. Signal requirements and characterization by western blots and DNA sequencing”. J. Biol. Chem. 266 (12): 7588—95. PMID 1850412. 
  • Malloy PJ, Hochberg Z, Tiosano D, Pike JW, Hughes MR, Feldman D (1991). „The molecular basis of hereditary 1,25-dihydroxyvitamin D3 resistant rickets in seven related families”. J. Clin. Invest. 86 (6): 2071—9. PMC 329846 Слободан приступ. PMID 2174914. doi:10.1172/JCI114944. 
  • Sone T, Marx SJ, Liberman UA, Pike JW (1991). „A unique point mutation in the human vitamin D receptor chromosomal gene confers hereditary resistance to 1,25-dihydroxyvitamin D3”. Mol. Endocrinol. 4 (4): 623—31. PMID 2177843. doi:10.1210/mend-4-4-623. 
  • Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O'Malley BW (1988). „Cloning and expression of full-length cDNA encoding human vitamin D receptor”. Proc. Natl. Acad. Sci. U.S.A. 85 (10): 3294—8. PMC 280195 Слободан приступ. PMID 2835767. doi:10.1073/pnas.85.10.3294. 
  • Hughes MR, Malloy PJ, Kieback DG, Kesterson RA, Pike JW, Feldman D, O'Malley BW (1989). „Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets”. Science. 242 (4886): 1702—5. PMID 2849209. doi:10.1126/science.2849209. 
  • Rut AR, Hewison M, Kristjansson K, Luisi B, Hughes MR, O'Riordan JL (1995). „Two mutations causing vitamin D resistant rickets: modelling on the basis of steroid hormone receptor DNA-binding domain crystal structures”. Clin. Endocrinol. (Oxf). 41 (5): 581—90. PMID 7828346. doi:10.1111/j.1365-2265.1994.tb01822.x. 
  • Malloy PJ, Weisman Y, Feldman D (1994). „Hereditary 1 alpha,25-dihydroxyvitamin D-resistant rickets resulting from a mutation in the vitamin D receptor deoxyribonucleic acid-binding domain”. J. Clin. Endocrinol. Metab. 78 (2): 313—6. PMID 8106618. doi:10.1210/jc.78.2.313. 
  • Maruyama K, Sugano S (1994). „Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides”. Gene. 138 (1–2): 171—4. PMID 8125298. doi:10.1016/0378-1119(94)90802-8. 
  • Yagi H, Ozono K, Miyake H, Nagashima K, Kuroume T, Pike JW (1993). „A new point mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor in a kindred with hereditary 1,25-dihydroxyvitamin D-resistant rickets”. J. Clin. Endocrinol. Metab. 76 (2): 509—12. PMID 8381803. doi:10.1210/jc.76.2.509. 
  • Kristjansson K, Rut AR, Hewison M, O'Riordan JL, Hughes MR (1993). „Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3”. J. Clin. Invest. 92 (1): 12—6. PMC 293517 Слободан приступ. PMID 8392085. doi:10.1172/JCI116539. 
  • Jurutka PW, Hsieh JC, Nakajima S, Haussler CA, Whitfield GK, Haussler MR (1996). „Human vitamin D receptor phosphorylation by casein kinase II at Ser-208 potentiates transcriptional activation”. Proc. Natl. Acad. Sci. U.S.A. 93 (8): 3519—24. PMC 39642 Слободан приступ. PMID 8622969. doi:10.1073/pnas.93.8.3519. 
  • Lin NU, Malloy PJ, Sakati N, al-Ashwal A, Feldman D (1996). „A novel mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant rickets”. J. Clin. Endocrinol. Metab. 81 (7): 2564—9. PMID 8675579. doi:10.1210/jc.81.7.2564. 

Spoljašnje veze

  • Calcitriol+Receptors на US National Library of Medicine Medical Subject Headings (MeSH)
  • Nuclear Receptor Resource
  • Vitamin D Receptor: Molecule of the Month Архивирано на сајту Wayback Machine (16. октобар 2015)