Protein:VDR |
Protein Summary |
 Gene summary |
| Gene name: VDR | ASpdb.0 ID: 7421 | Gene | Gene symbol | VDR | Gene ID | 7421 |
| Gene name | vitamin D receptor |
| Synonyms | NR1I1|PPP1R163 |
| Cytomap | 12q13.11 |
| Type of gene | protein-coding |
| Description | vitamin D3 receptor1,25-dihydroxyvitamin D3 receptornuclear receptor subfamily 1 group I member 1protein phosphatase 1, regulatory subunit 163vitamin D (1,25- dihydroxyvitamin D3) receptor |
| Modification date | 20240416 |
| UniProtAcc | P11473 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | VDR | GO:0000122 | negative regulation of transcription by RNA polymerase II | 17426122 |
| Gene | VDR | GO:0003677 | DNA binding | 11891224 |
| Gene | VDR | GO:0003700 | DNA-binding transcription factor activity | 17426122 |
| Gene | VDR | GO:0004879 | nuclear receptor activity | 12016314|16549446|17082781|32354638 |
| Gene | VDR | GO:0005634 | nucleus | 16207705 |
| Gene | VDR | GO:0005634 | nucleus | 15589699|17082781 |
| Gene | VDR | GO:0005654 | nucleoplasm | - |
| Gene | VDR | GO:0005829 | cytosol | - |
| Gene | VDR | GO:0008285 | negative regulation of cell population proliferation | 16549446 |
| Gene | VDR | GO:0010980 | positive regulation of vitamin D 24-hydroxylase activity | 16549446 |
| Gene | VDR | GO:0035435 | phosphate ion transmembrane transport | 32354638 |
| Gene | VDR | GO:0038183 | bile acid signaling pathway | 12016314 |
| Gene | VDR | GO:0038186 | bile acid nuclear receptor activity | 12016314 |
| Gene | VDR | GO:0042789 | mRNA transcription by RNA polymerase II | 20171278 |
| Gene | VDR | GO:0043235 | receptor complex | 17426122 |
| Gene | VDR | GO:0045892 | negative regulation of DNA-templated transcription | 11891224 |
| Gene | VDR | GO:0045944 | positive regulation of transcription by RNA polymerase II | 20171278 |
| Gene | VDR | GO:0046965 | nuclear retinoid X receptor binding | 28698609 |
| Gene | VDR | GO:0070561 | vitamin D receptor signaling pathway | 16549446 |
| Gene | VDR | GO:0070564 | positive regulation of vitamin D receptor signaling pathway | 20171278 |
| Gene | VDR | GO:0070644 | vitamin D response element binding | 17426122 |
| Gene | VDR | GO:0090575 | RNA polymerase II transcription regulator complex | 17426122 |
| Gene | VDR | GO:1902098 | calcitriol binding | 10678179|12016314 |
| Gene | VDR | GO:1902121 | lithocholic acid binding | 12016314 |
| Gene | VDR | GO:1903412 | response to bile acid | 12016314|32354638 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P11473-1 | P11473-1_1ie9_A.pdb | 1IE9 | X-ray | 1.4 | A | 118 | 423 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P11473 | VDR | P11473-1 | P11473-2 | 427 | 477 | 1 | 1 | Substitution | M | MEWRNKKRSDWLSMVLRTAGVEEAFGSEVSVRPHRRAPLGSTYLPPAPSGM | 1 | 51 |
| Multiple sequence alignment of our canonical and alternatively spliced VDR |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of VDR |
| UniProt-id | ENSG | ENST | ENSP |
| P11473-1 | ENSG00000111424.12 | ENST00000395324.6 | ENSP00000378734.2 |
| P11473-1 | ENSG00000111424.12 | ENST00000549336.6 | ENSP00000449573.2 |
| P11473-2 | ENSG00000111424.12 | ENST00000550325.5 | ENSP00000447173.1 |
| UniProt-id | NM ID | NP ID |
| P11473-1 | NM_000376.2 | NP_000367.1 |
| P11473-1 | NM_001017535.1 | NP_001017535.1 |
| P11473-2 | NM_001017536.1 | NP_001017536.1 |
| Amino acid sequences of our canonical and alternatively spliced VDR |
| accession_id | Protein sequence |
| P11473-1 | MEAMAASTSLPDPGDFDRNVPRICGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTCPFNGDCRITKDNRRHCQACRLKRCVDIGMM KEFILTDEEVQRKREMILKRKEEEALKDSLRPKLSEEQQRIIAILLDAHHKTYDPTYSDFCQFRPPVRVNDGGGSHPSRPNSRHTPSFSG DSSSSCSDHCITSSDMMDSSSFSNLDLSEEDSDDPSVTLELSQLSMLPHLADLVSYSIQKVIGFAKMIPGFRDLTSEDQIVLLKSSAIEV IMLRSNESFTMDDMSWTCGNQDYKYRVSDVTKAGHSLELIEPLIKFQVGLKKLNLHEEEHVLLMAICIVSPDRPGVQDAALIEAIQDRLS |
| P11473-2 | MEWRNKKRSDWLSMVLRTAGVEEAFGSEVSVRPHRRAPLGSTYLPPAPSGMEAMAASTSLPDPGDFDRNVPRICGVCGDRATGFHFNAMT CEGCKGFFRRSMKRKALFTCPFNGDCRITKDNRRHCQACRLKRCVDIGMMKEFILTDEEVQRKREMILKRKEEEALKDSLRPKLSEEQQR IIAILLDAHHKTYDPTYSDFCQFRPPVRVNDGGGSHPSRPNSRHTPSFSGDSSSSCSDHCITSSDMMDSSSFSNLDLSEEDSDDPSVTLE LSQLSMLPHLADLVSYSIQKVIGFAKMIPGFRDLTSEDQIVLLKSSAIEVIMLRSNESFTMDDMSWTCGNQDYKYRVSDVTKAGHSLELI EPLIKFQVGLKKLNLHEEEHVLLMAICIVSPDRPGVQDAALIEAIQDRLSNTLQTYIRCRHPPPGSHLLYAKMIQKLADLRSLNEEHSKQ |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| VDR (go to UniProt):P11473 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
Gene Isoform Structures and Expression Levels for VDR |
| Gene structures of our canonical and alternative spliced genes of VDR * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P11473-1 |
| 3D view using mol* of P11473-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P11473-1 |
 |
| pLDDT distribution across the protein length of P11473-2 |
 |
Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P11473-1 |
 |
Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P11473-1 | 1.257 | 177 | 1.315 | 301.84 | 0.269 | 0.96 | 1.205 | 2.639 | 0.616 | 4.284 | 2.104 | 142,143,144,147,227,230,231,233,234,236,237,240,26 8,271,272,274,275,278,286,288,295,300,303,305,309, 313,317,397,401,404,414,418,422 |
| P11473-2 | 1.249 | 187 | 1.302 | 300.468 | 0.294 | 0.96 | 1.188 | 2.591 | 0.658 | 3.939 | 1.953 | 192,193,194,197,277,280,281,283,284,286,287,290,31 8,321,322,324,325,328,336,338,345,350,353,355,359, 363,447,451,454,464,468,472 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P11473-1_P11473-1_1ie9_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P11473-1_1ie9_A_P11473-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P11473-1_P11473-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P11473-1_vs_P11473-2.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P11473-1_vs_P11473-2.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to VDR |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P11473 | VDR | DB08742 | 1,3-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) | experimental | |
| P11473 | VDR | DB00169 | Cholecalciferol | approved, nutraceutical | agonist |
| P11473 | VDR | DB01436 | Alfacalcidol | approved, nutraceutical | agonist |
| P11473 | VDR | DB04891 | Becocalcidiol | investigational | |
| P11473 | VDR | DB05295 | Eldecalcitol | investigational | |
| P11473 | VDR | DB01070 | Dihydrotachysterol | approved | agonist |
| P11473 | VDR | DB03451 | Lexacalcitol | experimental | |
| P11473 | VDR | DB04540 | Cholesterol | approved, investigational | |
| P11473 | VDR | 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-diol | experimental | |
| P11473 | VDR | DB00153 | Ergocalciferol | approved, nutraceutical | agonist |
| P11473 | VDR | DB06194 | Elocalcitol | investigational | |
| P11473 | VDR | DB04258 | Seocalcitol | investigational | |
| P11473 | VDR | DB04796 | Inecalcitol | investigational | |
| P11473 | VDR | DB00136 | Calcitriol | approved, nutraceutical | agonist |
| P11473 | VDR | DB11094 | Vitamin D | approved, nutraceutical, vet_approved | |
| P11473 | VDR | DB05024 | CTA018 | investigational | |
| P11473 | VDR | DB00910 | Paricalcitol | approved, investigational | agonist |
| P11473 | VDR | DB14635 | Curcumin sulfate | experimental | |
| P11473 | VDR | DB00146 | Calcifediol | approved, nutraceutical | agonist |
| P11473 | VDR | DB11672 | Curcumin | approved, investigational | |
| P11473 | VDR | DB06410 | Doxercalciferol | approved | suppressor |
| P11473 | VDR | DB02300 | Calcipotriol | approved | antagonist |
Related Diseases to VDR |
| Previous studies relating to the alternative splicing of VDR and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| VDR | 19819974 | Modulation of vitamin d receptor activity by the corepressor hairless: differential effects of hairless isoforms. | The vitamin D receptor (VDR) and its corepressor Hairless (HR) are thought to regulate key steps in the hair cycle because mutations in VDR or HR cause alopecia in humans and mice. Many mammalian cells express two major HR isoforms due to alternative splicing of exon 17. HR isoform-a encodes an 1189-amino acid protein (full-length HR), and isoform-b encodes an 1134-amino acid protein (HRDelta1072-1126). We demonstrated that both HR isoforms are expressed in primary human keratinocytes and in the human keratinocyte cell line HaCaT. In transfected COS-7 cells, the full-length HR repressed VDR-mediated transactivation. In contrast, HRDelta1072-1126 failed to suppress and even stimulated VDR-mediated transactivation. In coimmunoprecipitation, both HR isoforms interacted with the VDR, but only the full-length HR interacted with histone deacetylase 1 (HDAC1). Alanine mutagenesis of two conserved glutamic acids residues (E1100A/E1101A) encoded by exon 17 completely eliminated HR corepressor activity and interactions with HDAC1. When the two HR isoforms were coexpressed in COS-7 cells, the corepressor activity of the full-length HR was not antagonized by the HRDelta1072-1126 isoform. When transfected into HaCaT cells, the full-length HR inhibited endogenous CYP24A1 basal gene expression as well as 1,25-dihydroxyvitamin D3-stimulated CYP24A1 expression. HRDelta1072-1126 failed to suppress basal or 1,25-dihydroxyvitamin D3-stimulated CYP24A1 gene expression. In conclusion, we have demonstrated that both HR isoforms are expressed in keratinocytes and that the HRDelta1072-1126 isoform lacks corepressor activity and is unable to bind HDACs. HRDelta1072-1126 may function as a coactivator in some settings by inhibiting HDAC recruitment to the VDR transcriptional complex. | D000505 | Alopecia |
| VDR | 20403997 | Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer. | Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol synthesis, modifies the effect of statins on serum cholesterol levels. Long-term use of statins is associated with a reduced risk of colorectal cancer (CRC) in some, but not all, studies. We genotyped variants in 40 candidate genes important for cholesterol synthesis and metabolism in a population-based case-control study of CRC involving 2,138 incident cases and 2,049 population-based controls. We identified a single-nucleotide polymorphism in the HMGCR gene that significantly modified the protective association between statins and CRC risk. Compared with nonusers, the unadjusted odds ratio of CRC among statin users with the A/A genotype of rs12654264 in HMGCR was 0.3 (95% confidence interval, 0.18-0.51) and among statin users with the T/T genotype was 0.66 (95% confidence interval, 0.41-1.06; P-interaction = 0.0012). This genetic variant (A/A genotype of rs12654264) also was associated with lower serum levels of low-density lipoprotein among all cases and controls. In colon cancer cell lines, the reduction in cholesterol levels after statin treatment was substantially stronger in cells carrying the A/A genotype, and this difference was related to alternative splicing involving the HMGCR statin-binding domain. We anticipate that these data may advance the development of personalized statin use for reducing the risk of cancer as well as cardiovascular disease among the approximately 25 million people currently using statins worldwide. | D015179 | Colorectal Neoplasms |
Clinically important variants in VDR |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |