Pregnane X receptor

In the field of is_associated_with::molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a is_associated_with::protein that in humans is encoded by the NR1I2 (nuclear Receptor subfamily 1, group I, member 2) gene.

Function
PXR is a nuclear receptor whose primary function is to sense the presence of foreign toxic substances and in response up regulate the expression of proteins involved in the is_associated_with::detoxification and clearance of these substances from the body. PXR belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a is_associated_with::DNA-binding domain. The encoded protein is a transcriptional regulator of the is_associated_with::cytochrome P450 gene is_associated_with::CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including is_associated_with::dexamethasone and is_associated_with::rifampicin.

PXR is activated by a large number of is_associated_with::endogenous and is_associated_with::exogenous chemicals including is_associated_with::steroids, is_associated_with::antibiotics, is_associated_with::antimycotics, is_associated_with::bile acids, is_associated_with::hyperforin, a constituent of the herbal antidepressant is_associated_with::St. John's Wort, and many other herbal compounds.

Mechanism
Like other type II nuclear receptors, when activated, it forms a heterodimer with the is_associated_with::retinoid X receptor, and binds to is_associated_with::hormone response elements on DNA which elicits expression of is_associated_with::gene products.

One of the primary targets of PXR activation is the induction of is_associated_with::CYP3A4, an important phase I oxidative is_associated_with::enzyme that is responsible for the is_associated_with::metabolism of many is_associated_with::drugs. In addition, PXR up regulates the expression of phase II conjugating enzymes such as is_associated_with::glutathione S-transferase and phase III transport uptake and efflux proteins such as OATP2 and MDR1.