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Validated All-in-One™ qPCR Primer for NR1I3(NM_005122.4) Search again
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
Summary
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.
Gene References into function
- CAR antagonizes ER-mediated transcriptional activity by squelching limiting amounts of p160 coactivators, such as SRC-1 and GRIP-1.
- Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor.
- Regulation of human CYP2C9 by the constitutive androstane receptor: discovery of a new distal binding site.
- identified as a key regulator of acetaminophen metabolism and hepatotoxicity
- Substantial interindividual differences exist in hepatic constitutive androstane receptor expression; a 240-fold interindividual variability in hepatic mRNA levels has been detected.
- A distal glucocorticoid response element located within the CAR promoter is described, and evidence is presented that this element is capable of of conferring transcriptional activation via the glucocorticoid pathway.
- activation requires subnuclear targeting by peroxisome proliferator-activated receptor gamma coactivator-1 alpha
- control of steroid, heme, and carcinogen metabolism by this protein in transgenic mice
- Induces bilirubin clearance when expressed in transgenic mice
- Alternatively spliced isoforms of the constitutive androstane receptor.
- CAR-RXR heterodimers and CAR monomers can contribute to the gene activating function of phenobarbital response enhancer modules in CAR target genes
- stabilization of helix 12 by a contact between its C terminus and the lysine of helix 4 has the same impact in human and mouse constitutive androstane receptor (CAR)
- pregnane X receptor (PXR) and constitutively activated receptor (CAR) mediate induction of CYP3A5 in human liver and intestine
- The antiemetic meclizine is both an agonist ligand for mouse CAR and an inverse agonist for human CAR.
- negative regulation of CAR, a glucocorticoid-responsive gene, via proinflammatory cytokine interleukin 1beta (IL-1beta)
- The two cis-acting elements, the distal PBREM and the proximal OARE, within the chromatin structure are both regulated by CAR in response to okadaic acid and TCPOBOP to maximally induce the CYP2B6 promoter.
- studies identified several amino acids within helices 3 (Asn(165)), 5 (Val(199)), 11 (Tyr(326), Ile(330), and Gln(331)), and 12 (Leu(343) and Ile(346)) that contribute to the high basal activity of human CAR
- NR1I3 has a role in regulating both liver homeostasis and tumorigenesis in response to xenobiotic stresses
- there is cross talk between distal CAR/PXR sites and HNF4alpha binding sites in the CYP2C9 promoter and that the HNF4alpha sites are required for maximal induction of the CYP2C9 promoter.
- role in transcriptional regulation of CYP2C8
- hCAR mediates the methotrexate induction of hSULT2A1.
- observations suggest that HNF4alpha1 positively regulates hCAR expression in normal developing and adult livers, whereas HNF4alpha7 represses hCAR gene expression in hepatocellular carcinoma
- interindividual variation in the expression level of CAR probably determines variation in expression and activity of a broad scope of xenobiotic metabolism genes
- Role of aryl hydrocarbon receptor in drug metabolism demonstrates in vivo up-regulation of androstane receptor through chemical exposure.
- Inter-individual/inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of CAR cannot account for this variability.
- the human cathepsin E gene is regulated by the constitutive androstane receptor
- PPARalpha ligands not only serve as PPARalpha agonists but possibly act as CAR antagonists.
- genetic polymorphisms in CAR may have an indirect effect on drug disposition--REVIEW
- R16A at the membrane may mediate the PB signal to initiate CAR nuclear translocation, through a mechanism including its dimerization and inhibition of PP1beta activity.
- CAR requires early growth response 1 to activate the human cytochrome P450 2B6 gene
- In this review, constitutive active/androstane receptor (CAR) is a nuclear receptor that plays a critical role in modulating hepatic energy metabolism.
- CAR may influence the expression of genes involved in not only the metabolism of endogenous and exogenous substances but also in the cell proliferation.
- ATF5 is abundant in the liver, activates CYP2B6, and cooperates with CAR in sustaining the hepatic-specific expression of this P450 in human hepatocytes and hepatoma cells.
