Constitutive Androstane Receptor-2 (CAR-2; NR1I3i2)
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 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. CAR exists as three predominant splice variants in humans depicted as CAR-1, CAR-2 and CAR-3. Each has unique biological properties. These splice variants do not exist in rat and mouse.
Unlike CAR-1, CAR-2 is
It is noteworthy, and a source of experimental confusion, that a number of xenobiotics characterized as activators of human CAR (including phenobarbital) actually modulate the receptor's activity
For more information on CAR, visit the Nuclear Receptor Resource.
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Print PDF View Full Size Research conducted by: Koji Toyokawa (1), Ewa Maddox (1), Jack Vanden Huevel (1,2), & Bruce Sherf (1) (1) INDIGO Biosciences, Inc., 1981 Pine Hall Rd, State College, PA, USA (2) Center for Molecular Toxicology and Carcinogenesis, 325 Life Sciences Building, Penn State University, University Park, PA 16802, USA Date of Publication:
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