Pregnane X receptor pathway (WP2876)

The Pregnane X receptor (PXR, a.k.a. NR1I2) is a nuclear receptor whose primary function is sensing xenobiotics. It regulates the gene expression of genes that encode proteins involved in detoxification and clearance of xenobiotics. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2876 CPTAC Assay Portal]
last edited

Authors

Riannefijten, MaintBot, Khanspers, Egonw, Fehrhart, AlexanderPico, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: xenobiotic metabolic pathway

Participants

Label Type Compact Identifier
Ligand Metabolite chebi:77318
SRC GeneProduct ensembl:ENSG00000197122
NCOA2 GeneProduct ensembl:ENSG00000140396
NCOA3 GeneProduct ensembl:ENSG00000124151
PSMC5 GeneProduct ensembl:ENSG00000087191
NRIP1 GeneProduct ensembl:ENSG00000180530
SRPX2 GeneProduct ensembl:ENSG00000102359
NR1I2 GeneProduct ensembl:ENSG00000144852
RXRA GeneProduct ensembl:ENSG00000186350
HSP90AA1 GeneProduct ensembl:ENSG00000080824
PPARGC1A GeneProduct ensembl:ENSG00000109819
NR1I2 GeneProduct ensembl:ENSG00000144852
Ligand Metabolite chebi:77318
HSP90AA1 GeneProduct ensembl:ENSG00000080824
RXRA GeneProduct ensembl:ENSG00000186350
NR1I2 GeneProduct ensembl:ENSG00000144852
Ligand Metabolite chebi:77318
DNAJC7 GeneProduct ensembl:ENSG00000168259
DNAJC7 GeneProduct ensembl:ENSG00000168259
CYP3A7 GeneProduct ensembl:ENSG00000160870
UGT1A6 GeneProduct ensembl:ENSG00000167165
UGT1A3 GeneProduct ensembl:ENSG00000243135
UGT1A9 GeneProduct ensembl:ENSG00000241119
CYP2A6 GeneProduct ensembl:ENSG00000255974
UGT1A4 GeneProduct ensembl:ENSG00000244474
SLCO1B1 GeneProduct ensembl:ENSG00000134538
SRPX2 GeneProduct ensembl:ENSG00000102359
NCOA3 GeneProduct ensembl:ENSG00000124151
FOXO1 GeneProduct ensembl:ENSG00000150907
CYP4F12 GeneProduct ensembl:ENSG00000186204
CYP3A4 GeneProduct ensembl:ENSG00000160868
UGT1A1 GeneProduct ensembl:ENSG00000241635
ABCC4 GeneProduct ensembl:ENSG00000125257
NRIP1 GeneProduct ensembl:ENSG00000180530
CYP2B6 GeneProduct ensembl:ENSG00000197408
GSTA2 GeneProduct ensembl:ENSG00000244067
PSMC5 GeneProduct ensembl:ENSG00000087191
PPARGC1A GeneProduct ensembl:ENSG00000109819
NCOA1 GeneProduct ensembl:ENSG00000084676
NCOA2 GeneProduct ensembl:ENSG00000140396
ABCB1 GeneProduct ensembl:ENSG00000085563
CYP2C9 GeneProduct ensembl:ENSG00000138109
CYP3A5 GeneProduct ensembl:ENSG00000106258
CYP2C19 GeneProduct ensembl:ENSG00000165841
SULT2A1 GeneProduct ensembl:ENSG00000105398
ABCC2 GeneProduct ensembl:ENSG00000023839
ABCC3 GeneProduct ensembl:ENSG00000108846

References

  1. Willson TM, Kliewer SA. PXR, CAR and drug metabolism. Nat Rev Drug Discov. 2002 Apr;1(4):259–66. PubMed Europe PMC Scholia
  2. Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, et al. Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J Biol Chem. 2003 May 9;278(19):17277–83. PubMed Europe PMC Scholia
  3. Kodama S, Koike C, Negishi M, Yamamoto Y. Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Mol Cell Biol. 2004 Sep;24(18):7931–40. PubMed Europe PMC Scholia
  4. Handschin C, Meyer UA. Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Arch Biochem Biophys. 2005 Jan 15;433(2):387–96. PubMed Europe PMC Scholia
  5. Timsit YE, Negishi M. CAR and PXR: the xenobiotic-sensing receptors. Steroids. 2007 Mar;72(3):231–46. PubMed Europe PMC Scholia
  6. Echchgadda I, Song CS, Oh T, Ahmed M, De La Cruz IJ, Chatterjee B. The xenobiotic-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4alpha in the regulation of human steroid-/bile acid-sulfotransferase. Mol Endocrinol. 2007 Sep;21(9):2099–111. PubMed Europe PMC Scholia
  7. Pavek P, Dvorak Z. Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Curr Drug Metab. 2008 Feb;9(2):129–43. PubMed Europe PMC Scholia
  8. Hariparsad N, Chu X, Yabut J, Labhart P, Hartley DP, Dai X, et al. Identification of pregnane-X receptor target genes and coactivator and corepressor binding to promoter elements in human hepatocytes. Nucleic Acids Res. 2009 Mar;37(4):1160–73. PubMed Europe PMC Scholia
  9. Bock KW. From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans. Biochem Pharmacol. 2011 Jul 1;82(1):9–16. PubMed Europe PMC Scholia
  10. Fijten RRR, Jennen DGJ, van Delft JHM. Pathways for ligand activated nuclear receptors to unravel the genomic responses induced by hepatotoxicants. Curr Drug Metab. 2013 Dec;14(10):1022–8. PubMed Europe PMC Scholia