Constitutive androstane receptor pathway (WP2875)
Homo sapiens
The Constitutive Androstane Receptor (CAR) is a nuclear receptor and functions as a sensor for xenobiotics. It regulates transcription of genes encoding proteins in metabolism and excretion of xenobiotics. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2875 CPTAC Assay Portal]
Authors
Rianne Fijten , Egon Willighagen , Kristina Hanspers , Friederike Ehrhart , Martina Summer-Kutmon , Anders Riutta , Alex Pico , and Eric WeitzActivity
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Cited In
- Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor (2022).
- Prognostic and Diagnostic Values of Semaphorin 5B and Its Correlation With Tumor-Infiltrating Immune Cells in Kidney Renal Clear-Cell Carcinoma (2022).
- Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Phenotype (2016).
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
signaling pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Ligand | Metabolite | chebi:77326 | |
| NR1I3 | GeneProduct | ncbigene:9970 | nuclear receptor subfamily 1, group I, member 3 |
| RXRA | GeneProduct | ncbigene:6256 | retinoid X receptor, alpha |
| PPP2R4 | GeneProduct | ensembl:ENSG00000119383 | plays a role in translocation of CAR |
| HSP90AA1 | GeneProduct | ncbigene:3320 | heat shock protein 90kDa alpha (cytosolic), class A member 1 |
| DNAJC7 | GeneProduct | ncbigene:7266 | DnaJ (Hsp40) homolog, subfamily C, member 7 |
| NCOA6 | GeneProduct | ncbigene:23054 | nuclear receptor coactivator 6 |
| SP1 | GeneProduct | ncbigene:6667 | Sp1 transcription factor |
| NCOA1 | GeneProduct | ncbigene:8648 | nuclear receptor coactivator 1 |
| PPARGC1A | GeneProduct | ncbigene:10891 | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha |
| NCOA2 | GeneProduct | ncbigene:10499 | nuclear receptor coactivator 2 |
| SMC1A | GeneProduct | ncbigene:8243 | structural maintenance of chromosomes 1A |
| CYP2C9 | GeneProduct | ncbigene:1559 | cytochrome P450, family 2, subfamily C, polypeptide 9 |
| ABCB1 | GeneProduct | ncbigene:5243 | ATP-binding cassette, sub-family B (MDR/TAP), member 1 |
| UGT1A1 | GeneProduct | ensembl:ENSG00000241635 | |
| ABCC2 | GeneProduct | ncbigene:1244 | ATP-binding cassette, sub-family C (CFTR/MRP), member 2 |
| CYP2A6 | GeneProduct | ncbigene:1548 | cytochrome P450, family 2, subfamily A, polypeptide 6 |
| CYP4A11 | GeneProduct | ensembl:ENSG00000187048 | |
| CYP2C19 | GeneProduct | ncbigene:1557 | cytochrome P450, family 2, subfamily C, polypeptide 19 |
| SULT1A1 | GeneProduct | ensembl:ENSG00000196502 | during fasting |
| GSTA2 | GeneProduct | ncbigene:2939 | glutathione S-transferase alpha 2 |
| CYP3A5 | GeneProduct | ncbigene:1577 | cytochrome P450, family 3, subfamily A, polypeptide 5 |
| SULT2A1 | GeneProduct | ensembl:ENSG00000105398 | |
| CYP3A4 | GeneProduct | ncbigene:1576 | cytochrome P450, family 3, subfamily A, polypeptide 4 |
| ALAS1 | GeneProduct | ensembl:ENSG00000023330 | |
| EHHADH | GeneProduct | ensembl:ENSG00000113790 | |
| CYP2B6 | GeneProduct | ncbigene:1555 | cytochrome P450, family 2, subfamily B, polypeptide 6 |
| ABCC3 | GeneProduct | ncbigene:8714 | ATP-binding cassette, sub-family C (CFTR/MRP), member 3 |
| UGT1A4 | GeneProduct | ensembl:ENSG00000244474 | |
| UGT1A6 | GeneProduct | ensembl:ENSG00000167165 | |
| UGT1A9 | GeneProduct | ensembl:ENSG00000241119 | |
| UGT1A3 | GeneProduct | ensembl:ENSG00000243135 | |
| FOXO1 | GeneProduct | ensembl:ENSG00000150907 |
References
- The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Sugatani J, Kojima H, Ueda A, Kakizaki S, Yoshinari K, Gong QH, et al. Hepatology. 2001 May;33(5):1232–8. PubMed Europe PMC Scholia
- The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways. Cai Y, Konishi T, Han G, Campwala KH, French SW, Wan YJY. Eur J Pharm Sci. 2002 Feb;15(1):89–96. PubMed Europe PMC Scholia
- PXR, CAR and drug metabolism. Willson TM, Kliewer SA. Nat Rev Drug Discov. 2002 Apr;1(4):259–66. PubMed Europe PMC Scholia
- Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, et al. J Biol Chem. 2003 May 9;278(19):17277–83. PubMed Europe PMC Scholia
- The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. Maglich JM, Watson J, McMillen PJ, Goodwin B, Willson TM, Moore JT. J Biol Chem. 2004 May 7;279(19):19832–8. PubMed Europe PMC Scholia
- Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Kodama S, Koike C, Negishi M, Yamamoto Y. Mol Cell Biol. 2004 Sep;24(18):7931–40. PubMed Europe PMC Scholia
- 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
- A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer. Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, et al. Mol Cell. 2004 Dec 22;16(6):919–28. PubMed Europe PMC Scholia
- CAR and PXR: the xenobiotic-sensing receptors. Timsit YE, Negishi M. Steroids. 2007 Mar;72(3):231–46. PubMed Europe PMC Scholia
- 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. Echchgadda I, Song CS, Oh T, Ahmed M, De La Cruz IJ, Chatterjee B. Mol Endocrinol. 2007 Sep;21(9):2099–111. PubMed Europe PMC Scholia
- Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Pavek P, Dvorak Z. Curr Drug Metab. 2008 Feb;9(2):129–43. PubMed Europe PMC Scholia
- From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans. Bock KW. Biochem Pharmacol. 2011 Jul 1;82(1):9–16. PubMed Europe PMC Scholia
- 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