Pregnane X receptor
Nuclear receptor subfamily 1, group I, member 2
|PDB rendering based on 1ilg.|
|Available structures:, , , , ,|
|RNA expression pattern|
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In the field of molecular biology, the pregnane X receptor (PXR), also known as NR1I2 (nuclear receptor subfamily 1, group I, member 2), 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 detoxification and clearance of these substance from the body.
PXR is encoded by the NR1I2 gene. The product of this gene belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. The encoded protein is a transcriptional regulator of the cytochrome P450 gene 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 dexamethasone and rifampicin. Several alternatively spliced transcripts encoding different isoforms, some of which use non-AUG (CUG) translation initiation codon, have been described for this gene. Additional transcript variants exist, however, they have not been fully characterized.
PXR is activated by a large number of endogenous and exogenous chemicals including steroids, antibiotics, antimycotics, bile acids, and hyperforin, a constituent of the herbal antidepressant St. John's Wort.
In addition, PXR up regulates the expression of phase II conjugating enzymes such as glutathione S-transferase and phase III transport uptake and efflux proteins such as OATP2 (SLCO2A1 ) and MDR1 (ABCB1).
- ↑ Kliewer S, Goodwin B, Willson T (2002). "The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism". Endocr. Rev. 23 (5): 687-702. PMID 12372848.
- ↑ Entrez Gene: NR1I2 nuclear receptor subfamily 1, group I, member 2.
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Transcription factors and intracellular receptors
|(1) Basic domains|
|(2) Zinc finger|
|(4) β-Scaffold factors with|
minor groove contacts
| (0) Other|
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