Vitamin D receptor pathway (WP2877)

Homo sapiens

The vitamin D receptor (VDR, a.k.a. NR1I1) is a nuclear receptor that responds to binding of vitamin D and subsequently forms a dimer with RXR to induce transcription of its target genes. It mainly regulates genes cytochrome P450 genes involved in xenobiotic biotransformation. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2877 CPTAC Assay Portal].

Authors

Rianne Fijten , Kristina Hanspers , Friederike Ehrhart , Egon Willighagen , Kim de Nooijer , Martina Summer-Kutmon , Alex Pico , Eric Weitz , and Alvin Kho

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

vitamin D signaling pathway

Participants

Label Type Compact URI Comment
Ligand Metabolite chebi:48705
VDR ligand Metabolite chebi:48705 T3
Ligand Metabolite chebi:48705
BCL6 GeneProduct ncbigene:604
STS GeneProduct ncbigene:412
LRRC25 GeneProduct ncbigene:126364
TREM1 GeneProduct ncbigene:54210
LPGAT1 GeneProduct ncbigene:9926
ITGAM GeneProduct ncbigene:3684
VDR GeneProduct ncbigene:7421 vitamin D (1,25- dihydroxyvitamin D3) receptor
RXRA GeneProduct ncbigene:6256 retinoid X receptor, alpha
VDR GeneProduct ncbigene:7421 vitamin D (1,25- dihydroxyvitamin D3) receptor
RXRA GeneProduct ncbigene:6256 retinoid X receptor, alpha
VDR GeneProduct ncbigene:7421 vitamin D (1,25- dihydroxyvitamin D3) receptor
IRF4 GeneProduct ncbigene:3662
HLA-DRB1 GeneProduct ncbigene:3123
CLEC16A GeneProduct ncbigene:23274
HSD17B2 GeneProduct ncbigene:3294
CDKAL1 GeneProduct ncbigene:54901
Col13A1 GeneProduct ncbigene:1305
TNFAIP3 GeneProduct ncbigene:7128
FGF23 GeneProduct ncbigene:8074
CYP24A1 GeneProduct ncbigene:1591
CST6 GeneProduct ncbigene:1474
DEFB4A GeneProduct ncbigene:1673
CD40 GeneProduct ncbigene:958
PRKCQ GeneProduct ncbigene:5588
IRF5 GeneProduct ncbigene:3663
IL1RL1 GeneProduct ncbigene:9173
HLA-DQA1 GeneProduct ncbigene:3117
CLPTM1L GeneProduct ncbigene:81037
CAMP GeneProduct ncbigene:820
TNFSF4 GeneProduct ncbigene:7292
STAM GeneProduct ncbigene:8027
HIF1A GeneProduct ncbigene:3091
CTLA4 GeneProduct ncbigene:1493
CLMN GeneProduct ncbigene:79789
MXD1 GeneProduct ncbigene:4084
PTH GeneProduct ncbigene:5741
TRPV5 GeneProduct ncbigene:56302
TRPV6 GeneProduct ncbigene:55503
CYP27B1 GeneProduct ncbigene:1594
PTGER4 GeneProduct ncbigene:5734
TNFSF11 GeneProduct ncbigene:8600
PRDM1 GeneProduct ncbigene:639
RASGRP1 GeneProduct ncbigene:10125
SLC34A2 GeneProduct ncbigene:10568
CYP7A1 GeneProduct ncbigene:1581 cytochrome P450, family 7, subfamily A, polypeptide 1
CYP2B6 GeneProduct ncbigene:1555 cytochrome P450, family 2, subfamily B, polypeptide 6
CYP2C9 GeneProduct ncbigene:1559 cytochrome P450, family 2, subfamily C, polypeptide 9
THBD GeneProduct ncbigene:7056
KL GeneProduct ncbigene:9365
CASP5 GeneProduct ncbigene:838
TRAK1 GeneProduct ncbigene:22906
LRP5 GeneProduct ncbigene:4041
DUSP10 GeneProduct ncbigene:11221
SEMA3B GeneProduct ncbigene:7869
KLK6 GeneProduct ncbigene:5653
SULT2A1 GeneProduct ncbigene:6822
SERPINB1 GeneProduct ncbigene:1992
NRIP1 GeneProduct ncbigene:8204
CYP3A4 GeneProduct ncbigene:1576
SPP1 GeneProduct ncbigene:6696
CEACAM1 GeneProduct ncbigene:634
PTHLH GeneProduct ncbigene:5744
S100A2 GeneProduct ncbigene:6273
BGLAP GeneProduct ncbigene:632
ASAP2 GeneProduct ncbigene:8853
ID4 GeneProduct ncbigene:3400
SOSTDC1 GeneProduct ncbigene:25928
BTLA GeneProduct ncbigene:151888
CD14 GeneProduct ncbigene:929
KLF4 GeneProduct ncbigene:9314
ALOX5 GeneProduct ncbigene:240
IL12A GeneProduct ncbigene:3592
ADGRE5 GeneProduct ncbigene:976
SLC37A2 GeneProduct ncbigene:219855
SATB1 GeneProduct ncbigene:6304
CBS GeneProduct ncbigene:875
LRRC8A GeneProduct ncbigene:56262
MYO9B GeneProduct ncbigene:4650
BDKRB1 GeneProduct ncbigene:623
NINJ1 GeneProduct ncbigene:4814
NRIP1 GeneProduct ncbigene:8204
CD200 GeneProduct ncbigene:4345
CD9 GeneProduct ncbigene:928
TPM1 GeneProduct ncbigene:7168
ALPI GeneProduct ncbigene:248
SLC2A4 GeneProduct ncbigene:6517
CYP1A1 GeneProduct ncbigene:1543
S100G GeneProduct ncbigene:795
ATP2C2 GeneProduct ncbigene:9914
SLC8A1 GeneProduct ncbigene:6546
CALB1 GeneProduct ncbigene:12307
TGFB1 GeneProduct ncbigene:7040
STEAP4 GeneProduct ncbigene:79689
ADAMTS5 GeneProduct ncbigene:11096
TNFRSF11B GeneProduct ncbigene:4982
HILPDA GeneProduct ncbigene:29923
ALPG GeneProduct ncbigene:251
CLDN2 GeneProduct ncbigene:9075
ATP2B1 GeneProduct ncbigene:490
SULT1C2 GeneProduct ncbigene:6819
S100A9 GeneProduct ncbigene:6280
MED9 GeneProduct ncbigene:55090
LCE1F GeneProduct ncbigene:353137
ABCD1 GeneProduct ncbigene:215
CDX2 GeneProduct ncbigene:1045
DACT2 GeneProduct ncbigene:168002
KNG1 GeneProduct ncbigene:3827
IRF8 GeneProduct ncbigene:3394
MX2 GeneProduct ncbigene:4600
NOX1 GeneProduct ncbigene:27035
TGFB2 GeneProduct ncbigene:7042
ORM2 GeneProduct ncbigene:5005
EPHB4 GeneProduct ncbigene:2050
ABC B1 GeneProduct ncbigene:5243
JUNB GeneProduct ncbigene:3726
CYP2S1 GeneProduct ncbigene:29785
G6PD GeneProduct ncbigene:2539
S100A8 GeneProduct ncbigene:6279
TIMP3 GeneProduct ncbigene:7078
CEBPA GeneProduct ncbigene:1050
CDC34 GeneProduct ncbigene:997
GXYLT2 GeneProduct ncbigene:727936
CYP3A5 GeneProduct ncbigene:1577
CASP14 GeneProduct ncbigene:23581
ORM1 GeneProduct ncbigene:5004
LCE1D GeneProduct ncbigene:353134
ABCA11 GeneProduct ncbigene:79963
EFNA5 GeneProduct ncbigene:1946
TIMP2 GeneProduct ncbigene:7077
KRTAP4-1 GeneProduct ncbigene:85285
KRT13 GeneProduct ncbigene:3860
KRT71 GeneProduct ncbigene:112802
KRTAP10-4 GeneProduct ncbigene:386672
S100A4 GeneProduct ncbigene:6275
SPRR1B GeneProduct ncbigene:6699
S100A6 GeneProduct ncbigene:6277
KRTAP10-2 GeneProduct ncbigene:386679
KRTAP5-4 GeneProduct ncbigene:387267
LCE2B GeneProduct ncbigene:26239
KRT34 GeneProduct ncbigene:3885
KRTAP5-1 GeneProduct ncbigene:387264
KRT16 GeneProduct ncbigene:3868
KRTAP10-7 GeneProduct ncbigene:386675
KRT38 GeneProduct ncbigene:8687
KRTAP8-1 GeneProduct ncbigene:337879
SALL4 GeneProduct ncbigene:57167
CRACR2B GeneProduct ncbigene:283229
HNF1A GeneProduct ncbigene:6927
CRACR2A GeneProduct ncbigene:84766
CYP2D6 GeneProduct ncbigene:1565
ID1 GeneProduct ncbigene:3397
KRTAP10-9 GeneProduct ncbigene:386676
DEFB109C GeneProduct ncbigene:100286963
KRTAP12-2 GeneProduct ncbigene:353323
DEFB132 GeneProduct ncbigene:400830
CREG2 GeneProduct ncbigene:200407
COLEC11 GeneProduct ncbigene:78989
ZNF257 GeneProduct ncbigene:113835
CST1 GeneProduct ncbigene:1469
CA9 GeneProduct ncbigene:768
PNOC GeneProduct ncbigene:5368
DNER GeneProduct ncbigene:92737
DND1 GeneProduct ncbigene:373863
CDKN1A GeneProduct ncbigene:1026
LGALS9 GeneProduct ncbigene:3965
CDKN1B GeneProduct ncbigene:1027
IL25 GeneProduct ncbigene:64806
SFRP1 GeneProduct ncbigene:6422
ADRA1B GeneProduct ncbigene:147
BMP6 GeneProduct ncbigene:654
IGSF9B GeneProduct ncbigene:22997
ADRB2 GeneProduct ncbigene:154
MEG8 GeneProduct ncbigene:79104
NFATC2 GeneProduct ncbigene:4773
CCND1 GeneProduct ncbigene:595
CDKN2D GeneProduct ncbigene:1032
GADD45A GeneProduct ncbigene:1647
CCNE1 GeneProduct ncbigene:898
CDKN2A GeneProduct ncbigene:1029
CDK2 GeneProduct ncbigene:1017
CDKN2B GeneProduct ncbigene:1030
CDKN2C GeneProduct ncbigene:1031
CCNC GeneProduct ncbigene:892
MYC GeneProduct ncbigene:4609
FOXO1 GeneProduct ncbigene:2308
IGFBP1 GeneProduct ncbigene:3484
IGFBP3 GeneProduct ncbigene:3486
PPARD GeneProduct ncbigene:5467
IGFBP5 GeneProduct ncbigene:3488
G0S2 GeneProduct ncbigene:50486

References

  1. Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes. Drocourt L, Ourlin JC, Pascussi JM, Maurel P, Vilarem MJ. J Biol Chem. 2002 Jul 12;277(28):25125–32. PubMed Europe PMC Scholia
  2. The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Pascussi JM, Gerbal-Chaloin S, Drocourt L, Maurel P, Vilarem MJ. Biochim Biophys Acta. 2003 Feb 17;1619(3):243–53. PubMed Europe PMC Scholia
  3. Dehydroepiandrosterone sulfotransferase is a target for transcriptional induction by the vitamin D receptor. Echchgadda I, Song CS, Roy AK, Chatterjee B. Mol Pharmacol. 2004 Mar;65(3):720–9. PubMed Europe PMC Scholia
  4. C-jun N-terminal kinase modulates 1,25-dihydroxyvitamin D3-induced cytochrome P450 3A4 gene expression. Yasunami Y, Hara H, Iwamura T, Kataoka T, Adachi T. Drug Metab Dispos. 2004 Jul;32(7):685–8. PubMed Europe PMC Scholia
  5. Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Handschin C, Meyer UA. Arch Biochem Biophys. 2005 Jan 15;433(2):387–96. PubMed Europe PMC Scholia
  6. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Wang TT, Tavera-Mendoza LE, Laperriere D, Libby E, MacLeod NB, Nagai Y, et al. Mol Endocrinol. 2005 Nov;19(11):2685–95. PubMed Europe PMC Scholia
  7. Regulation of multiple insulin-like growth factor binding protein genes by 1alpha,25-dihydroxyvitamin D3. Matilainen M, Malinen M, Saavalainen K, Carlberg C. Nucleic Acids Res. 2005 Sep 26;33(17):5521–32. PubMed Europe PMC Scholia
  8. Vitamin D receptor regulation of the steroid/bile acid sulfotransferase SULT2A1. Chatterjee B, Echchgadda I, Song CS. Methods Enzymol. 2005;400:165–91. PubMed Europe PMC Scholia
  9. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Deeb KK, Trump DL, Johnson CS. Nat Rev Cancer. 2007 Sep;7(9):684–700. PubMed Europe PMC Scholia
  10. Mechanism of vitamin D receptor inhibition of cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes. Han S, Chiang JYL. Drug Metab Dispos. 2009 Mar;37(3):469–78. PubMed Europe PMC Scholia
  11. A genomic perspective on vitamin D signaling. Carlberg C, Seuter S. Anticancer Res. 2009 Sep;29(9):3485–93. PubMed Europe PMC Scholia
  12. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, et al. Genome Res. 2010 Oct;20(10):1352–60. PubMed Europe PMC Scholia
  13. Regulation of target gene expression by the vitamin D receptor - an update on mechanisms. Pike JW, Meyer MB, Bishop KA. Rev Endocr Metab Disord. 2012 Mar;13(1):45–55. PubMed Europe PMC Scholia
  14. Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)₂vitamin D₃: genomic and non-genomic mechanisms. Haussler MR, Jurutka PW, Mizwicki M, Norman AW. Best Pract Res Clin Endocrinol Metab. 2011 Aug;25(4):543–59. PubMed Europe PMC Scholia
  15. The first genome-wide view of vitamin D receptor locations and their mechanistic implications. Carlberg C, Seuter S, Heikkinen S. Anticancer Res. 2012 Jan;32(1):271–82. PubMed Europe PMC Scholia
  16. Molecular mechanisms of vitamin D action. Haussler MR, Whitfield GK, Kaneko I, Haussler CA, Hsieh D, Hsieh JC, et al. Calcif Tissue Int. 2013 Feb;92(2):77–98. PubMed Europe PMC Scholia
  17. Primary vitamin D target genes allow a categorization of possible benefits of vitamin D₃ supplementation. Carlberg C, Seuter S, de Mello VDF, Schwab U, Voutilainen S, Pulkki K, et al. PLoS One. 2013 Jul 29;8(7):e71042. PubMed Europe PMC Scholia
  18. The ASAP2 gene is a primary target of 1,25-dihydroxyvitamin D3 in human monocytes and macrophages. Seuter S, Ryynänen J, Carlberg C. J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:12–8. PubMed Europe PMC Scholia
  19. Gene regulatory scenarios of primary 1,25-dihydroxyvitamin d3 target genes in a human myeloid leukemia cell line. Ryynänen J, Seuter S, Campbell MJ, Carlberg C. Cancers (Basel). 2013 Oct 16;5(4):1221–41. PubMed Europe PMC Scholia
  20. Vitamin D and energy homeostasis: of mice and men. Bouillon R, Carmeliet G, Lieben L, Watanabe M, Perino A, Auwerx J, et al. Nat Rev Endocrinol. 2014 Feb;10(2):79–87. PubMed Europe PMC Scholia
  21. Pathways for ligand activated nuclear receptors to unravel the genomic responses induced by hepatotoxicants. Fijten RRR, Jennen DGJ, van Delft JHM. Curr Drug Metab. 2013 Dec;14(10):1022–8. PubMed Europe PMC Scholia
  22. VDR primary targets by genome-wide transcriptional profiling. Goeman F, De Nicola F, D’Onorio De Meo P, Pallocca M, Elmi B, Castrignanò T, et al. J Steroid Biochem Mol Biol. 2014 Sep;143:348–56. PubMed Europe PMC Scholia
  23. Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status in the hematopoietic system. Wilfinger J, Seuter S, Tuomainen TP, Virtanen JK, Voutilainen S, Nurmi T, et al. J Nutr Biochem. 2014 Aug;25(8):875–84. PubMed Europe PMC Scholia
  24. Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals. Ryynänen J, Neme A, Tuomainen TP, Virtanen JK, Voutilainen S, Nurmi T, et al. Mol Nutr Food Res. 2014 Oct;58(10):2036–45. PubMed Europe PMC Scholia