Pregnane X receptor

NR1I2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1ILG, 1ILH, 1M13, 1NRL, 1SKX, 2O9I, 2QNV, 3CTB, 3HVL, 3R8D, 4J5W, 4J5X, 4NY9, 4S0S, 4S0T, 4XHD, 4X1F, 4X1G, 4XAO, 5A86
Identifiers
Aliases	NR1I2, BXR, ONR1, PAR, PAR1, PAR2, PARq, PRR, PXR, SAR, SXR, nuclear receptor subfamily 1 group I member 2
External IDs	OMIM: 603065; MGI: 1337040; HomoloGene: 40757; GeneCards: NR1I2; OMA:NR1I2 - orthologs
Gene location (Human)
Chr.	Chromosome 3 (human)
End	119,818,487 bp
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	38,115,186 bp
RNA expression pattern
	Top expressed in
	right lobe of liver; ; jejunal mucosa; ; mucosa of transverse colon; ; duodenum; ; rectum; ; mucosa of ileum; ; mucosa of sigmoid colon; ; gallbladder; ; cecum; ; appendix;
	Top expressed in
	duodenum; ; jejunum; ; crypt of lieberkuhn of small intestine; ; colon; ; left colon; ; left lobe of liver; ; ileum; ; female urethra; ; lumbar subsegment of spinal cord; ; intestinal villus;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	DNA binding; sequence-specific DNA binding; RNA polymerase II transcription regulatory region sequence-specific DNA binding; DNA-binding transcription factor activity; DNA-binding transcription activator activity, RNA polymerase II-specific; transcription coactivator activity; zinc ion binding; metal ion binding; steroid hormone receptor activity; nuclear receptor activity; protein binding; DNA-binding transcription factor activity, RNA polymerase II-specific; transcription cis-regulatory region binding; transcription factor binding; nuclear receptor coactivator activity; signaling receptor activity;
Cellular component	nucleus; nucleoplasm; nuclear body; intermediate filament cytoskeleton; RNA polymerase II transcription regulator complex;
Biological process	steroid metabolic process; regulation of transcription, DNA-templated; xenobiotic transport; xenobiotic export; transcription, DNA-templated; positive regulation of transcription, DNA-templated; positive regulation of gene expression; xenobiotic metabolic process; transcription initiation from RNA polymerase II promoter; negative regulation of transcription, DNA-templated; signal transduction; steroid hormone mediated signaling pathway; positive regulation of transcription by RNA polymerase II; intracellular receptor signaling pathway; multicellular organism development; cell differentiation;
	Sources:Amigo / QuickGO
Orthologs
	8856
	18171
	ENSG00000144852
	ENSMUSG00000022809
	O75469
	O54915
	NM_033013; NM_003889; NM_022002
	NM_001098404; NM_010936
	NP_003880; NP_071285; NP_148934
	NP_001091874; NP_035066
	Wikidata
View/Edit Human	View/Edit Mouse

In the field of 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 protein that in humans is encoded by the NR1I2 (nuclear Receptor subfamily 1, group I, member 2) gene.^[5]^[6]^[7]

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 detoxification and clearance of these substances from the body.^[8] PXR belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. PXR 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.^[7]^[9]

Ligands

Agonists

PXR is activated by a large number of endogenous and exogenous chemicals^[8] including steroids (e.g., progesterone, 17α-hydroxyprogesterone, 17α-hydroxypregnenolone, 5α-dihydroprogesterone, 5β-dihydroprogesterone, allopregnanolone, corticosterone, cyproterone acetate, spironolactone, dexamethasone, mifepristone), antibiotics (e.g., rifampicin, rifaximin), antimycotics, bile acids, hyperforin (a constituent of St. John's Wort), and other compounds such as meclizine, paclitaxel, cafestol,^[10] and forskolin.^[11]^[12]

Antagonists

Ketoconazole is an example of one of the relatively few-known antagonists of the PXR.^[13]^[14] SPA70 (also known as LC-1) was recently identified and characterized as a potent and selective PXR antagonist.^[15]^[16]

Mechanism

Like other type II nuclear receptors, when activated, it forms a heterodimer with the retinoid X receptor, and binds to hormone response elements on DNA which elicits expression of gene products.^[8]

One of the primary targets of PXR activation is the induction of CYP3A4, an important phase I oxidative enzyme that is responsible for the metabolism of many drugs.^[6]^[7] In addition, PXR up regulates the expression of phase II conjugating enzymes such as glutathione S-transferase^[17] and phase III transport uptake and efflux proteins such as OATP2^[18] and MDR1.^[19]^[20]