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
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q13.33 Start 119,780,484 bp[1] End 119,818,487 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 B3 Start 38,068,685 bp[2] End 38,115,186 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver jejunal mucosa duodenum rectum gallbladder cecum appendix smooth muscle tissue hypothalamus lymph node Top expressed in duodenum jejunum crypt of lieberkuhn of small intestine colon left colon left lobe of liver ileum female urethra intestinal villus stomach More reference expression data BioGPS 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 Species Human Mouse Entrez 8856 18171 Ensembl ENSG00000144852 ENSMUSG00000022809 UniProt O75469 O54915 RefSeq (mRNA) NM_033013 NM_003889 NM_022002 NM_001098404 NM_010936 RefSeq (protein) NP_003880 NP_071285 NP_148934 NP_001091874 NP_035066 Location (UCSC) Chr 3: 119.78 – 119.82 Mb Chr 16: 38.07 – 38.12 Mb PubMed search [3] [4]
Wikidata
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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]

See also

• Constitutive androstane receptor
• Farnesoid X receptor

References

Further reading

External links

• pregnane+X+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Nuclear Receptor Resource Page Archived 2016-06-10 at the Wayback Machine

This article incorporates text from the United States National Library of Medicine, which is in the public domain.