Vitamin D3 receptor

Details

Name
Vitamin D3 receptor
Synonyms
  • 1,25-dihydroxyvitamin D3 receptor
  • NR1I1
  • Nuclear receptor subfamily 1 group I member 1
  • VDR
Gene Name
VDR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001554|Vitamin D3 receptor
MEAMAASTSLPDPGDFDRNVPRICGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTC
PFNGDCRITKDNRRHCQACRLKRCVDIGMMKEFILTDEEVQRKREMILKRKEEEALKDSL
RPKLSEEQQRIIAILLDAHHKTYDPTYSDFCQFRPPVRVNDGGGSHPSRPNSRHTPSFSG
DSSSSCSDHCITSSDMMDSSSFSNLDLSEEDSDDPSVTLELSQLSMLPHLADLVSYSIQK
VIGFAKMIPGFRDLTSEDQIVLLKSSAIEVIMLRSNESFTMDDMSWTCGNQDYKYRVSDV
TKAGHSLELIEPLIKFQVGLKKLNLHEEEHVLLMAICIVSPDRPGVQDAALIEAIQDRLS
NTLQTYIRCRHPPPGSHLLYAKMIQKLADLRSLNEEHSKQYRCLSFQPECSMKLTPLVLE
VFGNEIS
Number of residues
427
Molecular Weight
48288.64
Theoretical pI
6.5
GO Classification
Functions
calcitriol binding / calcitriol receptor activity / DNA binding / lithocholic acid binding / lithocholic acid receptor activity / retinoid X receptor binding / sequence-specific DNA binding / steroid hormone receptor activity / zinc ion binding
Processes
bile acid signaling pathway / calcium ion transport / cell morphogenesis / cellular calcium ion homeostasis / decidualization / gene expression / intestinal absorption / lactation / mammary gland branching involved in pregnancy / negative regulation of cell proliferation / negative regulation of keratinocyte proliferation / negative regulation of transcription from RNA polymerase II promoter / negative regulation of transcription, DNA-templated / positive regulation of apoptotic process involved in mammary gland involution / positive regulation of gene expression / positive regulation of keratinocyte differentiation / positive regulation of transcription from RNA polymerase II promoter / positive regulation of vitamin D 24-hydroxylase activity / regulation of calcidiol 1-monooxygenase activity / signal transduction / skeletal system development / transcription initiation from RNA polymerase II promoter / vitamin D receptor signaling pathway
Components
nucleoplasm / nucleus / receptor complex / RNA polymerase II transcription factor complex
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0010550|Vitamin D3 receptor (VDR)
ATGGAGGCAATGGCGGCCAGCACTTCCCTGCCTGACCCTGGAGACTTTGACCGGAACGTG
CCCCGGATCTGTGGGGTGTGTGGAGACCGAGCCACTGGCTTTCACTTCAATGCTATGACC
TGTGAAGGCTGCAAAGGCTTCTTCAGGCGAAGCATGAAGCGGAAGGCACTATTCACCTGC
CCCTTCAACGGGGACTGCCGCATCACCAAGGACAACCGACGCCACTGCCAGGCCTGCCGG
CTCAAACGCTGTGTGGACATCGGCATGATGAAGGAGTTCATTCTGACAGATGAGGAAGTG
CAGAGGAAGCGGGAGATGATCCTGAAGCGGAAGGAGGAGGAGGCCTTGAAGGACAGTCTG
CGGCCCAAGCTGTCTGAGGAGCAGCAGCGCATCATTGCCATACTGCTGGACGCCCACCAT
AAGACCTACGACCCCACCTACTCCGACTTCTGCCAGTTCCGGCCTCCAGTTCGTGTGAAT
GATGGTGGAGGGAGCCATCCTTCCAGGCCCAACTCCAGACACACTCCCAGCTTCTCTGGG
GACTCCTCCTCCTCCTGCTCAGATCACTGTATCACCTCTTCAGACATGATGGACTCGTCC
AGCTTCTCCAATCTGGATCTGAGTGAAGAAGATTCAGATGACCCTTCTGTGACCCTAGAG
CTGTCCCAGCTCTCCATGCTGCCCCACCTGGCTGACCTGGTCAGTTACAGCATCCAAAAG
GTCATTGGCTTTGCTAAGATGATACCAGGATTCAGAGACCTCACCTCTGAGGACCAGATC
GTACTGCTGAAGTCAAGTGCCATTGAGGTCATCATGTTGCGCTCCAATGAGTCCTTCACC
ATGGACGACATGTCCTGGACCTGTGGCAACCAAGACTACAAGTACCGCGTCAGTGACGTG
ACCAAAGCCGGACACAGCCTGGAGCTGATTGAGCCCCTCATCAAGTTCCAGGTGGGACTG
AAGAAGCTGAACTTGCATGAGGAGGAGCATGTCCTGCTCATGGCCATCTGCATCGTCTCC
CCAGATCGTCCTGGGGTGCAGGACGCCGCGCTGATTGAGGCCATCCAGGACCGCCTGTCC
AACACACTGCAGACGTACATCCGCTGCCGCCACCCGCCCCCGGGCAGCCACCTGCTCTAT
GCCAAGATGATCCAGAAGCTAGCCGACCTGCGCAGCCTCAATGAGGAGCACTCCAAGCAG
TACCGCTGCCTCTCCTTCCAGCCTGAGTGCAGCATGAAGCTAACGCCCCTTGTGCTCGAA
GTGTTTGGCAATGAGATCTCCTGA
Chromosome Location
12
Locus
12q13.11
External Identifiers
ResourceLink
UniProtKB IDP11473
UniProtKB Entry NameVDR_HUMAN
GenBank Protein ID340203
GenBank Gene IDJ03258
GenAtlas IDVDR
HGNC IDHGNC:12679
General References
  1. Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O'Malley BW: Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U S A. 1988 May;85(10):3294-8. [PubMed:2835767]
  2. Goto H, Chen KS, Prahl JM, DeLuca HF: 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. 1992 Aug 17;1132(1):103-8. [PubMed:1324736]
  3. Miyamoto K, Kesterson RA, Yamamoto H, Taketani Y, Nishiwaki E, Tatsumi S, Inoue Y, Morita K, Takeda E, Pike JW: Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol. 1997 Jul;11(8):1165-79. [PubMed:9212063]
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  7. Yu XP, Mocharla H, Hustmyer FG, Manolagas SC: Vitamin D receptor expression in human lymphocytes. Signal requirements and characterization by western blots and DNA sequencing. J Biol Chem. 1991 Apr 25;266(12):7588-95. [PubMed:1850412]
  8. Fang Y, van Meurs JB, d'Alesio A, Jhamai M, Zhao H, Rivadeneira F, Hofman A, van Leeuwen JP, Jehan F, Pols HA, Uitterlinden AG: Promoter and 3'-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the rotterdam study. Am J Hum Genet. 2005 Nov;77(5):807-23. Epub 2005 Sep 26. [PubMed:16252240]
  9. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80. [PubMed:9267036]
  10. Baudino TA, Kraichely DM, Jefcoat SC Jr, Winchester SK, Partridge NC, MacDonald PN: Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription. J Biol Chem. 1998 Jun 26;273(26):16434-41. [PubMed:9632709]
  11. Mahajan MA, Samuels HH: A new family of nuclear receptor coregulators that integrate nuclear receptor signaling through CREB-binding protein. Mol Cell Biol. 2000 Jul;20(14):5048-63. [PubMed:10866662]
  12. Fujiki R, Kim MS, Sasaki Y, Yoshimura K, Kitagawa H, Kato S: Ligand-induced transrepression by VDR through association of WSTF with acetylated histones. EMBO J. 2005 Nov 16;24(22):3881-94. Epub 2005 Oct 27. [PubMed:16252006]
  13. Nguyen HH, Takata R, Akamatsu S, Shigemizu D, Tsunoda T, Furihata M, Takahashi A, Kubo M, Kamatani N, Ogawa O, Fujioka T, Nakamura Y, Nakagawa H: IRX4 at 5p15 suppresses prostate cancer growth through the interaction with vitamin D receptor, conferring prostate cancer susceptibility. Hum Mol Genet. 2012 May 1;21(9):2076-85. doi: 10.1093/hmg/dds025. Epub 2012 Feb 8. [PubMed:22323358]
  14. Rochel N, Wurtz JM, Mitschler A, Klaholz B, Moras D: The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell. 2000 Jan;5(1):173-9. [PubMed:10678179]
  15. Tocchini-Valentini G, Rochel N, Wurtz JM, Mitschler A, Moras D: Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5491-6. [PubMed:11344298]
  16. Shaffer PL, Gewirth DT: Structural basis of VDR-DNA interactions on direct repeat response elements. EMBO J. 2002 May 1;21(9):2242-52. [PubMed:11980721]
  17. Tocchini-Valentini G, Rochel N, Wurtz JM, Moras D: Crystal structures of the vitamin D nuclear receptor liganded with the vitamin D side chain analogues calcipotriol and seocalcitol, receptor agonists of clinical importance. Insights into a structural basis for the switching of calcipotriol to a receptor antagonist by further side chain modification. J Med Chem. 2004 Apr 8;47(8):1956-61. [PubMed:15055995]
  18. Shaffer PL, Gewirth DT: Structural analysis of RXR-VDR interactions on DR3 DNA. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):215-9. [PubMed:15225774]
  19. Eelen G, Verlinden L, Rochel N, Claessens F, De Clercq P, Vandewalle M, Tocchini-Valentini G, Moras D, Bouillon R, Verstuyf A: Superagonistic action of 14-epi-analogs of 1,25-dihydroxyvitamin D explained by vitamin D receptor-coactivator interaction. Mol Pharmacol. 2005 May;67(5):1566-73. Epub 2005 Feb 22. [PubMed:15728261]
  20. Hourai S, Fujishima T, Kittaka A, Suhara Y, Takayama H, Rochel N, Moras D: Probing a water channel near the A-ring of receptor-bound 1 alpha,25-dihydroxyvitamin D3 with selected 2 alpha-substituted analogues. J Med Chem. 2006 Aug 24;49(17):5199-205. [PubMed:16913708]
  21. Hughes MR, Malloy PJ, Kieback DG, Kesterson RA, Pike JW, Feldman D, O'Malley BW: Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets. Science. 1988 Dec 23;242(4886):1702-5. [PubMed:2849209]
  22. Yagi H, Ozono K, Miyake H, Nagashima K, Kuroume T, Pike JW: 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. 1993 Feb;76(2):509-12. [PubMed:8381803]
  23. Saijo T, Ito M, Takeda E, Huq AH, Naito E, Yokota I, Sone T, Pike JW, Kuroda Y: 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. 1991 Sep;49(3):668-73. [PubMed:1652893]
  24. Sone T, Marx SJ, Liberman UA, Pike JW: A unique point mutation in the human vitamin D receptor chromosomal gene confers hereditary resistance to 1,25-dihydroxyvitamin D3. Mol Endocrinol. 1990 Apr;4(4):623-31. [PubMed:2177843]
  25. Malloy PJ, Weisman Y, Feldman D: 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. 1994 Feb;78(2):313-6. [PubMed:8106618]
  26. Kristjansson K, Rut AR, Hewison M, O'Riordan JL, Hughes MR: Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3. J Clin Invest. 1993 Jul;92(1):12-6. [PubMed:8392085]
  27. Rut AR, Hewison M, Kristjansson K, Luisi B, Hughes MR, O'Riordan JL: Two mutations causing vitamin D resistant rickets: modelling on the basis of steroid hormone receptor DNA-binding domain crystal structures. Clin Endocrinol (Oxf). 1994 Nov;41(5):581-90. [PubMed:7828346]
  28. Lin NU, Malloy PJ, Sakati N, al-Ashwal A, Feldman D: 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. 1996 Jul;81(7):2564-9. [PubMed:8675579]
  29. Whitfield GK, Selznick SH, Haussler CA, Hsieh JC, Galligan MA, Jurutka PW, Thompson PD, Lee SM, Zerwekh JE, Haussler MR: Vitamin D receptors from patients with resistance to 1,25-dihydroxyvitamin D3: point mutations confer reduced transactivation in response to ligand and impaired interaction with the retinoid X receptor heterodimeric partner. Mol Endocrinol. 1996 Dec;10(12):1617-31. [PubMed:8961271]
  30. Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D: Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest. 1997 Jan 15;99(2):297-304. [PubMed:9005998]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00910Paricalcitolapproved, investigationalyesagonistDetails
DB01070DihydrotachysterolapprovedyesagonistDetails
DB00136Calcitriolapproved, nutraceuticalyesantagonistDetails
DB00153Ergocalciferolapproved, nutraceuticalyesagonistDetails
DB034511-alpha, 25-dihydroxyl-20-epi-22-oxa-24, 26 ,27-trihomovitamin D3experimentalunknownDetails
DB04258SeocalcitolinvestigationalunknownDetails
DB02300CalcipotriolapprovedunknownantagonistDetails
DB05024CTA018investigationalunknownDetails
DB05295EldecalcitolinvestigationalunknownDetails
DB04796InecalcitolinvestigationalunknownDetails
DB06194ElocalcitolinvestigationalunknownDetails
DB00146Calcifediolapproved, nutraceuticalyesagonistDetails
DB00169Cholecalciferolapproved, nutraceuticalyesagonistDetails
DB07530(1R,3R)-5-[(2E)-3-{(1S,3R)-2,2,3-trimethyl-3-[6,6,6-trifluoro-5-hydroxy-5-(trifluoromethyl)hex-3-yn-1-yl]cyclopentyl}prop-2-en-1-ylidene]cyclohexane-1,3-diolexperimentalunknownDetails
DB04891BecocalcidiolinvestigationalunknownDetails
DB087421,3-CYCLOHEXANEDIOL, 4-METHYLENE-5-[(2E)-[(1S,3AS,7AS)-OCTAHYDRO-1-(5-HYDROXY-5-METHYL-1,3-HEXADIYNYL)-7A-METHYL-4H-INDEN-4-YLIDENE]ETHYLIDENE]-, (1R,3S,5Z)experimentalunknownDetails
DB01436Alfacalcidolapproved, nutraceuticalyesagonistDetails
DB06410DoxercalciferolapprovedunknownsuppressorDetails
DB04540Cholesterolapproved, investigationalunknownDetails
DB11672Curcuminapproved, experimental, investigationalunknownDetails
DB11094Vitamin Dapproved, nutraceutical, vet_approvedunknownDetails
DB14635Curcumin sulfateexperimentalunknownDetails