Vitamin D3 receptor

Function

Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells. Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Plays a central role in calcium homeostasis (By similarity). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites.

Classification

Family (Pfam)

PF00104 Hormone_recep, PF00105 zf-C4

InterPro

DBD_VDR, NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR1, Nuclear_hrmn_rcpt, VitD_rcpt, Znf_hrmn_rcpt, Znf_NHR/GATA

Functional cluster

Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 52

• 1DB1 X-ray 1.80A
• 1IE8 X-ray 1.52A
• 1IE9 X-ray 1.40A
• 1KB2 X-ray 2.70A
• 1KB4 X-ray 2.80A
• 1KB6 X-ray 2.70A
• 1S0Z X-ray 2.50A
• 1S19 X-ray 2.10A
• 1TXI X-ray 1.90A
• 1YNW X-ray 3.00A
• 2HAM X-ray 1.90A
• 2HAR X-ray 1.90A
• … and 40 more

A predicted model is available from AlphaFold.

Gene Ontology · 37

• GO:0000785 chromatin
• GO:0005737 cytoplasm
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0043235 receptor complex
• GO:0090575 RNA polymerase II transcription regulator complex
• GO:0038186 bile acid nuclear receptor activity
• GO:1902098 calcitriol binding
• GO:0003677 DNA binding
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:1902121 lithocholic acid binding
• GO:0004879 nuclear receptor activity
• GO:0046965 nuclear retinoid X receptor binding
• GO:0003707 nuclear steroid receptor activity
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0005499 vitamin D binding
• GO:0008270 zinc ion binding
• GO:0030154 cell differentiation
• GO:0000902 cell morphogenesis
• GO:0046697 decidualization
• GO:0030522 intracellular receptor signaling pathway
• GO:0042789 mRNA transcription by RNA polymerase II
• GO:0008285 negative regulation of cell population proliferation
• GO:0045892 negative regulation of DNA-templated transcription
• GO:0010839 negative regulation of keratinocyte proliferation
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0038185 nuclear receptor-mediated bile acid signaling pathway
• GO:0035435 phosphate ion transmembrane transport
• GO:0030501 positive regulation of bone mineralization
• GO:0010628 positive regulation of gene expression
• GO:0045618 positive regulation of keratinocyte differentiation
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0070564 positive regulation of vitamin D receptor signaling pathway
• GO:1903412 response to bile acid
• GO:0048384 retinoic acid receptor signaling pathway
• GO:0042359 vitamin D metabolic process
• GO:0070561 vitamin D receptor signaling pathway

Disease associations

• vitamin D-dependent rickets, type 2A MONDO:0010186
• Mycobacterium tuberculosis, susceptibility MONDO:0000070

Drugs targeting this protein · 18

• CHOLECALCIFEROL agonist
• PARICALCITOL agonist
• CALCIPOTRIENE agonist
• DOXERCALCIFEROL agonist
• ERGOCALCIFEROL agonist
• ALFACALCIDOL agonist
• SEOCALCITOL agonist
• BECOCALCIDIOL agonist
• INECALCITOL agonist
• LUNACALCIPOL agonist
• DIHYDROTACHYSTEROL agonist
• ILX23-7553 agonist
• CALCIFEDIOL agonist
• ELOCALCITOL agonist
• PEFCALCITOL agonist
• ELDECALCITOL agonist
• DP001 agonist
• CALCITRIOL agonist

Related proteins · sequence + function similarity

• Vitamin D3 receptor 1.00
• Vitamin D3 receptor 0.98
• Vitamin D3 receptor 0.98
• Vitamin D3 receptor 0.98
• Vitamin D3 receptor 0.98
• Vitamin D3 receptor A 0.97
• Vitamin D3 receptor 0.96
• Vitamin D3 receptor 0.96
• Vitamin D3 receptor 0.96
• Vitamin D3 receptor B 0.95
• Thyroid hormone receptor alpha 0.92
• Thyroid hormone receptor alpha 0.92

Co-cited proteins · studied together in the literature

• Vitamin D3 receptor 2 shared papers
• Iroquois-class homeodomain protein IRX-4 1 shared papers
• Tyrosine-protein kinase BAZ1B 2 shared papers
• Importin-4 1 shared papers
• Retinoic acid receptor RXR-alpha 4 shared papers
• SNW domain-containing protein 1 1 shared papers
• Thyroid hormone receptor alpha 1 shared papers
• Vitamin D3 receptor 1 shared papers
• Retinoic acid receptor alpha 3 shared papers
• Bile acid receptor 1 shared papers
• Hepatocyte nuclear factor 4-alpha 1 shared papers
• Nuclear receptor coactivator 6 1 shared papers

Literature · 40 cited papers

• UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability. Mol. Cell · 2023
• Lithocholic acid increases intestinal phosphate and calcium absorption in a vitamin D receptor dependent but transcellular pathway independent manner. Kidney Int. · 2020
• Nuclear hormone receptors: Ancient 9aaTAD and evolutionally gained NCoA activation pathways. J. Steroid Biochem. Mol. Biol. · 2019
• Functional analyses of a novel missense and other mutations of the vitamin D receptor in association with alopecia. Sci. Rep. · 2017
• Retraction: 'Ligand-induced transrepression by VDR through association of WSTF with acetylated histones'. EMBO J. · 2014
• IRX4 at 5p15 suppresses prostate cancer growth through the interaction with vitamin D receptor, conferring prostate cancer susceptibility. Hum. Mol. Genet. · 2012
• A novel mutation in the VDR gene in hereditary vitamin D-resistant rickets. Br. J. Dermatol. · 2008
• 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
• The finished DNA sequence of human chromosome 12. Nature · 2006
• Promoter and 3'-untranslated-region haplotypes in the vitamin D receptor gene predispose to osteoporotic fracture: the Rotterdam study. Am. J. Hum. Genet. · 2005
• Ligand-induced transrepression by VDR through association of WSTF with acetylated histones. EMBO J. · 2005
• Importin 4 is responsible for ligand-independent nuclear translocation of vitamin D receptor. J. Biol. Chem. · 2005
• … and 28 more in the literature graph