Molecular Target
Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Cellline Data Matrix
Gene Expression
Gene Copy Number Variation
RNA Interference
Mutations

Molecular Target Synopsis - VDR (P11473) - Overview

Protein


VDR, Vitamin D3 receptor
UniProt P11473

Also Known as VDR_HUMAN, VDR, NR1I1

Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis. Homodimer in the absence of bound vitamin D3. Heterodimer with RXRA after vitamin D3 binding. Interacts with SMAD3. Interacts with MED1, NCOA1, NCOA2, NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts (in a ligand-dependent manner) with BAZ1B/WSTF. Interacts with SNW1. Interacts with IRX4, the interaction doesn't affect its transactivation activity.

Variants and Isoforms


P11473-1, P11473-2

Drugs


VDR is targeted by Approved Drugs Calcitriol, Cholecalciferol, Calcifediol, Calcipotriene, Ergocalciferol, Paricalcitol, Doxercalciferol. (see details)

Sub-cellular localization


UniProt: VDR is active in the following subcellular-locations: Nucleus.



UniProt
GO terms

Mutations in Cancer


Please click the link to see mutations reported in Cancer Gene Census

Please click the link to see mutations reported in ICGC

According to the Cosmic, VDR has 1 reported mutations in cell lines ....p.R274C (1)

The mutation data was obtained from the Sanger Institute Catalogue Of Somatic Mutations In Cancer web site, http://www.sanger.ac.uk/cosmic
Bamford et al (2004) The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer, 91,355-358.
Please click the link to see mutations reported in MoKCa

(see details)

Gene Copy Number Variation


VDR has an absolute copy number > 7 in 4 cell lines, the highest copy numbers are in cell lines : RH18, CHAGOK1, NCIH2342, NCIH295. (see details)

Gene Expression


In the NCI - NCI 60 Reference panel, the highest expressing cell lines are: HCT116, OVCAR8. (see details)

RNA Interference


VDR was reported in the following RNAI studies:

Science - Cancer proliferation gene discovery through functional genomics, the highest RNAi cell lines are: HMECS. (see details)

AACR Journals - Results of primary druggable genome v2 (DG2) Achilles heel siRNA screen in KMS11 multiple myeloma cells, the highest RNAi cell lines are: KMS11. (see details)

3D Structures


There are 39 structures (42 chains) solved for VDR
33 are solved in complex with at least one small molecule ligand
2 are solved with an approved drug

VDR is solved in complex with the approved drug(s) VDX/Calcitriol (1DB1_A,1IE9_A,1RK3_A,2HC4_A,2ZLC_A).
(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


VDR has been screened with 719 compounds (1391 bioactivities), 198 compounds have bioactivities that show binding affinity of <= 500nM (275 bioactivities). (see details)