Pregnane X Receptor (PXR)

NR1I2; SAR; PAR1; PAR2; PRR; BXR; ONR1; PAR; PARq; SXR; Nuclear Receptor Subfamily 1,Group I,Member 2; Steroid and xenobiotic receptor; Pregnane X receptor

SPN	S839
HGNC	7968
MGI	1337040
PubMed	12372848
RGD	69057
UniProt	O75469
Wiki	PXR

PXRbelongs 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.

Reference

"SXR, a novel steroid and xenobiotic-sensing nuclear receptor."
Genes Dev. 12:3195-3205(1998) [PubMed] [Europe PMC] [Abstract]

"The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions."
J. Clin. Invest. 102:1016-1023(1998) [PubMed] [Europe PMC] [Abstract]

"Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction."
Proc. Natl. Acad. Sci. U.S.A. 95:12208-12213(1998) [PubMed] [Europe PMC] [Abstract]

"The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants."
Pharmacogenetics 11:555-572(2001) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin."
J. Biol. Chem. 276:14581-14587(2001) [PubMed] [Europe PMC] [Abstract]

"Molecular mechanism of nuclear translocation of an orphan nuclear receptor, SXR."
Mol. Pharmacol. 63:524-531(2003) [PubMed] [Europe PMC] [Abstract]

"Human CYP3A4 and murine Cyp3A11 are regulated by equol and genistein via the pregnane X receptor in a species-specific manner."
J. Nutr. 139:898-904(2009) [PubMed] [Europe PMC] [Abstract]

"The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity."
Science 292:2329-2333(2001) [PubMed] [Europe PMC] [Abstract]

"2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin."
Biochemistry 42:1430-1438(2003) [PubMed] [Europe PMC] [Abstract]

"Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor."
J. Mol. Biol. 331:815-828(2003) [PubMed] [Europe PMC] [Abstract]

"Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic rifampicin."
Mol. Endocrinol. 19:1125-1134(2005) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the PXR-T1317 complex provides a scaffold to examine the potential for receptor antagonism."
Bioorg. Med. Chem. 15:2156-2166(2007) [PubMed] [Europe PMC] [Abstract]

"Structural basis of human pregnane X receptor activation by the hops constituent colupulone."
Mol. Pharmacol. 74:1512-1520(2008) [PubMed] [Europe PMC] [Abstract]

"Eleven novel single nucleotide polymorphisms in the NR1I2 (PXR) gene, four of which induce non-synonymous amino acid alterations."
Drug Metab. Pharmacokinet. 17:561-565(2002) [PubMed] [Europe PMC] [Abstract]