Constitutive androstane receptor

Nuclear receptor subfamily 1, group I, member 3
PDB rendering based on 1xv9.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1xv9​, 1xvp​
Identifiers
Symbols	NR1I3 ; CAR; CAR1; MB67; MGC150433; MGC97144; MGC97209
External IDs	Template:OMIM5 Template:MGI HomoloGene: 3759
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

The constitutive androstane receptor (CAR), also known as NR1I3 (nuclear receptor subfamily 1, group I, member 3), is a nuclear hormone receptor with activity similar to that seen in other steroid receptors such as estrogen or progesterone but more similar in form to PPAR, LXR and RXR. CAR functions somewhat differently from other steroid receptors and its activity is still being elucidated. It is known to act in concert with PXR to detoxify xenobiotics.

CAR is encoded by the NR1I3 gene. This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs. Multiple transcript variants encoding different isoforms have been found for this gene.

Further reading

• Masuno M, Shimozawa N, Suzuki Y; et al. (1994). "Assignment of the human peroxisome assembly factor-1 gene (PXMP3) responsible for Zellweger syndrome to chromosome 8q21.1 by fluorescence in situ hybridization". Genomics. 20 (1): 141–2. doi:10.1006/geno.1994.1144. PMID 8020947.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Baes M, Gulick T, Choi HS; et al. (1994). "A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements". Mol. Cell. Biol. 14 (3): 1544–52. PMID 8114692.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Choi HS, Seol W, Moore DD (1996). "A component of the 26S proteasome binds on orphan member of the nuclear hormone receptor superfamily". J. Steroid Biochem. Mol. Biol. 56 (1-6 Spec No): 23–30. PMID 8603043.CS1 maint: Multiple names: authors list (link)
• Seol W, Choi HS, Moore DD (1996). "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors". Science. 272 (5266): 1336–9. PMID 8650544.CS1 maint: Multiple names: authors list (link)
• Choi HS, Chung M, Tzameli I; et al. (1997). "Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR". J. Biol. Chem. 272 (38): 23565–71. PMID 9295294.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Seol W, Hanstein B, Brown M, Moore DD (1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Mol. Endocrinol. 12 (10): 1551–7. PMID 9773978.CS1 maint: Multiple names: authors list (link)
• Forman BM, Tzameli I, Choi HS; et al. (1998). "Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta". Nature. 395 (6702): 612–5. doi:10.1038/26996. PMID 9783588.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Gonzalez MM, Carlberg C (2002). "Cross-repression, a functional consequence of the physical interaction of non-liganded nuclear receptors and POU domain transcription factors". J. Biol. Chem. 277 (21): 18501–9. doi:10.1074/jbc.M200205200. PMID 11891224.
• Min G, Kim H, Bae Y; et al. (2002). "Inhibitory cross-talk between estrogen receptor (ER) and constitutively activated androstane receptor (CAR). CAR inhibits ER-mediated signaling pathway by squelching p160 coactivators". J. Biol. Chem. 277 (37): 34626–33. doi:10.1074/jbc.M205239200. PMID 12114525.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Goodwin B, Hodgson E, D'Costa DJ; et al. (2002). "Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor". Mol. Pharmacol. 62 (2): 359–65. PMID 12130689.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ferguson SS, LeCluyse EL, Negishi M, Goldstein JA (2002). "Regulation of human CYP2C9 by the constitutive androstane receptor: discovery of a new distal binding site". Mol. Pharmacol. 62 (3): 737–46. PMID 12181452.CS1 maint: Multiple names: authors list (link)
• Zhang J, Huang W, Chua SS; et al. (2002). "Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR". Science. 298 (5592): 422–4. doi:10.1126/science.1073502. PMID 12376703.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Chang TK, Bandiera SM, Chen J (2003). "Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels". Drug Metab. Dispos. 31 (1): 7–10. PMID 12485946.CS1 maint: Multiple names: authors list (link)
• Pascussi JM, Busson-Le Coniat M, Maurel P, Vilarem MJ (2003). "Transcriptional analysis of the orphan nuclear receptor constitutive androstane receptor (NR1I3) gene promoter: identification of a distal glucocorticoid response element". Mol. Endocrinol. 17 (1): 42–55. PMID 12511605.CS1 maint: Multiple names: authors list (link)
• Shiraki T, Sakai N, Kanaya E, Jingami H (2003). "Activation of orphan nuclear constitutive androstane receptor requires subnuclear targeting by peroxisome proliferator-activated receptor gamma coactivator-1 alpha. A possible link between xenobiotic response and nutritional state". J. Biol. Chem. 278 (13): 11344–50. doi:10.1074/jbc.M212859200. PMID 12551939.CS1 maint: Multiple names: authors list (link)
• Maglich JM, Parks DJ, Moore LB; et al. (2003). "Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes". J. Biol. Chem. 278 (19): 17277–83. doi:10.1074/jbc.M300138200. PMID 12611900.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Xie W, Yeuh MF, Radominska-Pandya A; et al. (2003). "Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 4150–5. doi:10.1073/pnas.0438010100. PMID 12644700.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Huang W, Zhang J, Chua SS; et al. (2003). "Induction of bilirubin clearance by the constitutive androstane receptor (CAR)". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 4156–61. doi:10.1073/pnas.0630614100. PMID 12644704.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Auerbach SS, Ramsden R, Stoner MA; et al. (2003). "Alternatively spliced isoforms of the human constitutive androstane receptor". Nucleic Acids Res. 31 (12): 3194–207. PMID 12799447.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

External links

• constitutive+androstane+receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.