Constitutive androstane receptor
Encyclopedia
The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein
that in humans is encoded by the NR1I3 gene
. CAR is a member of the nuclear receptor
superfamily and along with PXR
functions as a sensor of endobiotic and xenobiotic
substances and in response upregulates the expression
of proteins responsible for the metabolism
and excretion
of these substances. Hence CAR (and PXR) are important in the detoxification of foreign substances such as drugs.
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 agonist
s and inverse agonist
s. 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the NR1I3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. CAR is a member of the nuclear receptor
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
superfamily and along with PXR
Pregnane X receptor
In the field of molecular biology, the pregnane X receptor , also known as the steroid and xenobiotic sensing nuclear receptor or nuclear receptor subfamily 1, group I, member 2 is a protein that in humans is encoded by the NR1I2 gene.PXR is a nuclear receptor whose primary function is to sense...
functions as a sensor of endobiotic and xenobiotic
Xenobiotic
A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual...
substances and in response upregulates the expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of proteins responsible for the metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
and excretion
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
of these substances. Hence CAR (and PXR) are important in the detoxification of foreign substances such as drugs.
Function
CAR is 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 receptorRetinoid X receptor
The retinoid X receptor is a type of nuclear receptor that is activated by 9-cis retinoic acid. There are three retinoic X receptors : RXR-alpha, RXR-beta, and RXR-gamma, encoded by the , , genes, respectively....
and regulates the transcription of target genes involved in drug metabolism and bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
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 agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
s and inverse agonist
Inverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....
s. 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.