DEFINITION
A short protein description with the molecular wheight, isoforms, etc...
Use, when available, the link to Wikipedia (Es Trypsin)
External links not available on Wikipedia have to be added here
THE GENE
Wikigenes includes links to
- NCBI Gene
- NCBI SNP
- iHOP resource
- OMIM
- SNPedia
- UniProt
- Ensembl
- HGNC
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
Protein Aminoacids Percentage (Width 700 px)
Low Trp in VDR (like IL-6 and TNFalpha)
tryptophan vdr
SYNTHESIS AND TURNOVER
VDR synthesis
Evidence for the impairment of the vitamin D activation pathway by cyclosporine A
VDR phosphorylation
Upon ligand binding the 1alpha,25-dihydroxy Vitamin D3 receptor (VDR) undergoes a conformational change that allows interaction with coactivator proteins including p160/SRC family members and the multimeric DRIP complex through the DRIP205 subunit. Casein kinase II (CKII) phosphorylates VDR both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of VDR to bind DNA, but increases its ability to transactivate target promoters (Arriagada, 2007).
Human vitamin D receptor phosphorylation by casein kinase II at Ser-208 potentiates transcriptional activation.
Human vitamin D receptor is selectively phosphorylated by protein kinase C on serine 51, a residue crucial to its trans-activation function.
Integration of hormone signaling in the regulation of human 25(OH)D3 24-hydroxylase transcription.
Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns.
Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells.
Induction of apoptosis by 1,25-dihydroxyvitamin D3 in MCF-7 Vitamin D3-resistant variant can be sensitized by TPA.
mRNA synthesis
protein synthesis
post-translational modifications
Translocation
VDR nuclear import
VDR nuclear translocation
degradation
CELLULAR FUNCTIONS
cellular localization,
biological function
- Cell signaling and Ligand transport
- Structural proteins
REGULATION
DIAGNOSTIC USE
VDR polymorphysm and diseases
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| OMIM | URL |
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Vitamin D3 compounds offer an alternative approach to anti-hormonal therapies for human breast cancer. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) acts through the nuclear Vitamin D3 receptor (VDR), a phosphoprotein and ligand-dependent transcription factor. Our lab has shown that 1,25-(OH)2D3 induces apoptosis in MCF-7 cells by disruption of mitochondrial function which is associated with Bax translocation to mitochondria, cytochrome c release, and production of reactive oxygen species (ROS). TPA, a protein kinase C (PKC) activator, does not induce cytochrome c release or Bax translocation, thus demonstrating that it has no effect on mitochondria and apoptosis on its own. However, when the MCF-7D3Res cells (a Vitamin D3-resistant variant) are treated with 1,25-(OH)2D3 in the presence of TPA, the cells displayed apoptotic morphology and redistribution of both cytochrome c and Bax. TPA pretreatment greatly enhances 1,25-(OH)2D3 stimulated 24-hydroxylase luciferase activity and VDR protein expression, although transactivation is lower in the MCF-7D3Res cells compared to the parental cell line. The observation that the phorbol ester TPA sensitizes the Vitamin D3-resistant variant to the effects of 1,25-(OH)2D3 suggests an important role for phosphorylation in dictating sensitivity to Vitamin D3-mediated apoptosis. This study demonstrates that the effects of 1,25-(OH)2D3 on mitochondrial disruption might be sensitized through activators of PKC.(Nervaez CJ)
Association of vitamin D receptor (Fok-I) polymorphism with the clinical presentation of calcium urolithiasis
Vitamin D receptor polymorphisms and diseases.
Abstract Additive effects of the chemokine receptor 2, vitamin D receptor, interleukin-6 polymorphisms and cardiovascular risk factors on the prevalence of myocardial infarction in patients below 65 years.
Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states.
INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-5 INTERACTS WITH THE VITAMIN D RECEPTOR AND MODULATES THE VITAMIN D RESPONSE IN OSTEOBLASTS. 2007
Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. 2005
VDRE Controlled genes table 2
VDRE Controlled genes table 3
VDRE Controlled genes table 4
Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells. 2005
Phytoestrogens regulate transcription and translation of vitamin D receptor in colon cancer celLS 2006
Three cell lines established from patients with VDDR-II (Rh-VDR, Sh-VDR, and Ab-VDR) (Lymphocyte cell lines from vitamin D-dependent rickets type II show functional defects in the 1 alpha,25-dihydroxyvitamin D3 receptor. 1990) showed no specific binding of 1,25(OH)2D3 to a receptor and treatment of the cultured cells with 1,25(OH)2D3 did not stimulate production of 24,25-dihydroxy-vitamin D3 (24,25(OH)2D3), a response which is diagnostic of the presence of a functional 1,25(OH)2D3 receptor.
Ca prostata e polimorfismi nelle etnie
Le interazioni fra il gene del recettore nucleare della vitamina D (VDR) ed il gene SRD5A2 che codifica per un enzima nella cascata del DHT influenzano la proliferazione delle cellule prostatiche, ma la combinazione di varianti di questi due geni influenzano il rischio di tumore prostatico negli uomini di razza bianca ed in quelli di razza ispanica. La normale crescita prostatica è promossa da interazioni fra la vitamina D e la cascata che converte il testosterone in DHT. La vitamina D inibisce la proliferazione delle cellule prostatiche in vitro, e la diminuzione dei livelli sierici di vitamina D è associata ad un elevato rischio di tumore prostatico. Oltre alle influenze genetiche, il rischio deriva anche da fattori correlati all'etnia, come la dieta, che potrebbero interagire con i geni per influenzare il rischio, ma si tratta di un fattore molto delicato da esaminare. In ogni caso, ignorare differenze genetiche che esistono davvero significa rinunciare ad informazioni potenzialmente valide che possono aiutare ad identificare aree in cui migliorare rilevamento, trattamento e sopravivenza di malattie gravi come il tumore prostatico. E' necessario prestare attenzione nell'uso di queste differenze per migliorare lo stato di salute senza oggettivizzare nessuno. (Clin Cancer Res 2008; 14: 3223-9)
if serum 1,25(OH)2D3 is high, cells are resistant ?
Deletion of Deoxyribonucleic Acid Binding Domain of the Vitamin D Receptor Abrogates Genomic and Nongenomic Functions of Vitamin D 2002
Papers cGMP VDR
Papers cAMP VDR
Papers p53 VDR
VDR homodimer
The vitamin D receptor represses transcription of the pituitary transcription factor Pit-1 gene without involvement of the retinoid X receptor. 2006
Nuclear receptor coactivators facilitate vitamin D receptor homodimer action on direct repeat hormone response elements. 2000
Identification of a vitamin D3 response element in the fibronectin gene that is bound by a vitamin D3 receptor homodimer. 1996
Identification of a vitamin D receptor homodimer-type response element in the rat calcitriol 24-hydroxylase gene promoter. 1994
Vitamin D regulates the phenotype of human breast cancer cells. 2007
VDR heterodimer
High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. 2011
Lancet. 2011 Jan 15;377(9761):242-50. Epub 2011 Jan 5.
Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, Packe GE, Moore-Gillon JC, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Woodward NJ, Venton TR, Barnes KE, Mullett CJ, Coussens AK, Rutterford CM, Mein CA, Davies GR, Wilkinson RJ, Nikolayevskyy V, Drobniewski FA, Eldridge SM, Griffiths CJ.
Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK. a.martineau@qmul.ac.uk
Comment in:
* Lancet. 2011 Jan 15;377(9761):189-90.
Abstract
BACKGROUND: Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent.
METHODS: We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3). This trial is registered with ClinicalTrials.gov number NCT00419068.
FINDINGS: 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90-2·16; p=0.14). TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (p(interaction)=0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36-48·01; p=0·02). FokI genotype did not modify the effect of vitamin D supplementation (p(interaction)=0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6-88·2; p<0·0001).
INTERPRETATION: Administration of four doses of 2·5 mg vitamin D(3) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism.
1,25-Dihydroxyvitamin D decreases HTRA1 promoter activity in the rhesus monkey--a plausible explanation for the influence of vitamin D on age-related macular degeneration?, 2013
- Age-related macular degeneration is the major cause of blindness in the elderly worldwide and the risk is influenced by both environmental and genetic risk factors. One important disease-associated region in humans is located on 10q26 and includes the two candidate genes ARMS2 and HTRA1. However, determination of the causative gene has not yet been possible and examining the situation in the rhesus monkey may help understand the situation in humans. In a recent paper, we characterized the rhesus monkey 10q26-orthologue region on chromosome 9 in detail and identified the drusen-associated HTRA1 promoter SNP rs196357513 as a putative risk factor. In this study, we predicted 9 binding sites for the vitamin D-dependent transcription factor vitamin D receptor in the rhesus HTRA1 promoter, one of which is destroyed by the rs196357513-risk allele. As patients with vitamin D deficit are at increased risk for age-related macular degeneration, a luciferase assay in transiently transfected ARPE19-cells was performed to evaluate the influence of the SNP rs196357513 and of 1,25-dihydroxyvitamin D on the rhesus monkey HTRA1 promoter activity. This revealed that the luciferase activity of the promoter construct containing the rs196357513 wild type allele was significantly reduced after vitamin D stimulation. An in silico analysis and literature search imply that this regulation could also play a role in human HTRA1 expression. Moreover, HTRA1 promoter activity of the construct containing the rs196357513 risk allele appeared diminished in comparison to the construct with the wild type allele, albeit this difference was not significant. The lower promoter activity due to the rhesus monkey rs196357513 risk allele apparently contradicts the common hypothesis for the human HTRA1 promoter risk allele of SNP rs11200638, for which a higher promoter activity has been observed. Our data point to a yet unexpected effect of decreased HTRA1 expression on drusen pathogenesis. Thus not only a higher HTRA1 expression, but an imbalance of HTRA1 might be disease-relevant. Both findings require closer analysis, but if relevance for humans proves true, it would impact current age-related macular degeneration research and treatment.
