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vitamin D3 receptor; VDR; 1,25-dihydroxyvitamin D3 receptor; nuclear receptor subfamily 1 group I member 1 (VDR, NR1I1)

Function: - nuclear hormone receptor - transcription factor - mediates action of vitamin D3 by controlling expression of hormone sensitive genes - binds to DNA (via enhancer element VDRE) as heterodimer with RXR - cytoplasmic anchoring associated with hsp90 - role in Ca+2 homeostasis - interacts with SMAD3 - interacts with MED1, NCOA1, NCOA2, NCOA3 & NCOA6 coactivators, increasing transcription of target genes Structure: - homodimer in the absence of bound vitamin D3. - heterodimer with RXRA after vitamin D3 binding - composed of three domains: a) modulating N-terminal domain b) DNA-binding domain c) C-terminal steroid-binding domain - belongs to the nuclear hormone receptor family, NR1 subfamily - contains 1 nuclear receptor DNA-binding domain Compartment: nucleus Polymorphism: - genetic variations in VDR may determine Mycobacterium tuberculosis susceptibility - polymorphisms of VDR may influence individual susceptibility to developing actinic keratosis [6] - polymorphisms in VDR may increase risk of cutaneous melanoma [7] - polymorphisms in VDR may be associated with increased susceptibility to hip fracture & myocardial infarction [8] Pathology: - defects in VDR are the cause of rickets type 2A Notes: uncertain whether Met-1 or Met-4 is the initiator

Interactions

molecular events

Related

calcitriol; 1,25-dihydroxycholcalciferol; 1,25-dihydroxyvitamin D3 cholecalciferol; vitamin D3 heat shock protein [hsp]-90 retinoid X receptor (RXR) vitamin D response element (VDRE)

General

nuclear hormone receptor NR1 subfamily

Properties

SIZE: MW = 48 kD entity length = 427 aa COMPARTMENT: cytoplasm MOTIF: DNA-binding motif SITE: 24-89 MOTIF: Zn finger C4-type SITE: 24-84 EFFECTOR-BOUND: Zn+2 Zn finger C4-type SITE: 60-84 EFFECTOR-BOUND: Zn+2 hinge region {90-191} ligand-binding site SITE: 192-427 FOR-BINDING-OF: calcitriol

Database Correlations

OMIM correlations MORBIDMAP 601769 UniProt P11473 PFAM correlations Kegg hsa:7421

References

  1. Alberts et al Molecular Biology of the Cell, 2nd ed. 1989, pg 704
  2. Green S. Nuclear hormone receptors. Promiscuous liaisons. Nature. 1993 Feb 18;361(6413):590-1. PMID: 8382343
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=VDR
  4. SHMPD; The Singapore human mutation andvpolymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=VDR
  5. UniProt :accession P11473
  6. Carless MA et al Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin. Br J Dermatol 2008 Sep; 159:804. PMID: 18647306
  7. Mocellin S and Nitti D. Vitamin D receptor polymorphisms and the risk of cutaneous melanoma: A systematic review and meta-analysis. Cancer 2008 Nov; 113:2398. PMID: 18647306
  8. Levin GP et al Genetic Variants and Associations of 25-Hydroxyvitamin D Concentrations With Major Clinical Outcomes. JAMA. 2012;308(18):1898-1905 PMID: 23150009 http://jama.jamanetwork.com/article.aspx?articleid=1391914

Component-of

molecular complex