Pregnane X Receptor (PXR; NR1I2)

This gene product 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.

[provided by RefSeq, Jul 2008]

NRR Pathway

pxr-pathway

Pregnane X Receptor Structure

(From Structure)

Link

(From Aceview)

There are 138 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (Asthma; Breast Neoplasms; Coronary Artery Disease; Osteomalacia) and proposed to participate in a process (regulation of transcription, DNA-dependent). Proteins are expected to have molecular functions (metal ion binding, protein binding, sequence-specific DNA binding, steroid hormone receptor activity and 2 others) and to localize in various compartments (cytoplasm, nucleus). Putativeprotein interactors have been described (ACTN2, NCOA1, NCOA3, NCOR2, NR1I2, NUCB2, POU1F1, PPARGC1A, PSMC5, RXRA, RXRB, RXRG, SRC). 

(From HuGENavigator)

  • HIV Infections 
  • Breast Neoplasms 
  • Colitis, Ulcerative 
  • Crohn Disease 
  • Inflammatory Bowel Diseases 
  • Neutropenia 
  • Acquired Immunodeficiency Syndrome 
  • Colorectal Neoplasms 
  • Epilepsy 
  • Drug-Induced Liver Injury 
  • Kidney Neoplasms 
  • Carcinoma, Renal Cell 
  • Cardiovascular Diseases 
  • Carcinoma 
  • Multiple Myeloma 
  • Pregnancy Complications 
  • Prostatic Neoplasms 
  • Recurrence 
  • Respiratory Tract Neoplasms 
  • Thyroid Neoplasms 
  • Tobacco Use Disorder 
  • Translocation, Genetic 
  • Viremia 
  • Myocardial Infarction 
  • Neoplasm Recurrence, Local 
  • Neoplasms, Second Primary 
  • Hypertriglyceridemia 
  • Hypospadias 
  • Head and Neck Neoplasms 
  • Hearing Loss 
  • Osteoporosis, Postmenopausal 
  • Kidney Failure, Chronic 
  • Carcinoma, Non-Small-Cell Lung 
  • Colonic Neoplasms 
  • Cryptorchidism 
  • Delayed Graft Function 
  • Dementia 
  • Diabetes Mellitus, Type 2 
  • Cholangitis, Sclerosing 
  • Cholestasis, Intrahepatic 
  • Chronic Periodontitis 
  • Adenocarcinoma 
  • Anemia 
  • Asthma 
  • Barrett Esophagus 
  • Birth Weight 
  • Bone Neoplasms 
  • Leukemia, Myelocytic, Acute 
  • Leukopenia 
  • Liver Cirrhosis 
  • Liver Cirrhosis, Biliary 
  • Liver Neoplasms 
  • Lung Neoplasms 
  • Lymphatic Metastasis 
  • Lymphoma 
  • Edema 
  • Coronary Artery Disease 
  • Esophageal Neoplasms 
  • Esophagitis, Peptic 
  • Fatty Liver

Assay Kits and Services are available from INDIGO Biosciences.

Kits are offered in different assay formats to accommodate researchers’ needs: 3x 32, 1x 96, and 1x 384 assay formats for screening small numbers of test compounds, as well as custom bulk reagents for HTS applications. Assay systems are all inclusive, providing reporter cells, optimized growth media, media for diluting test compounds, a positive-control agonist, luciferase detection reagent, a white assay plate, a detailed protocol, and a protocol quick guide. All kits are shipped on dry ice.

PXR Reporter Cells are prepared using INDIGO’s proprietary CryoMite™ process. This cryo-preservation method yields high cell viability post-thaw, and provides the convenience of immediately dispensing healthy, division-competent reporter cells into assay plates. There is no need for intermediate spin-and-wash steps, viability determinations, or cell titer adjustments.

The principle application of this assay product is in the screening of test samples to quantify functional activities, either agonist or antagonist, that they may exert against the pregnane x receptor. This kit product is an all-inclusive assay system that includes, in addition to PXR Reporter Cells, two optimized media for use during cell culture and (optionally) in diluting the test samples, a reference agonist, Luciferase Detection Reagent, a cell culture-ready assay plate, and a detailed protocol.

BXR; PAR; PRR; PXR; SAR; SXR; ONR1; PAR1; PAR2; PARq

(From Aceview)

The gene contains 12 distinct gt-ag introns. Transcription produces 9 different mRNAs, 7 alternatively spliced variants and 2 unspliced forms. There are 5 probablealternative promotors, 2 non overlapping alternative last exons and 4 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5′ end, truncation of the 3′ end, overlapping exons with different boundaries. Efficacy of translation may be reduced by the presence of a shorter translated product (uORF) initiating at an AUG upstream of the main open reading frame (in variant dAug10). 

Gene NR112

(From STRINGS)

ACTN2, NCOA1, NCOA3, NCOR2, NR1I2, NUCB2, POU1F1, PPARGC1A, PSMC5, RXRA, RXRB, RXRG, SRC

(From WikiPedia)

Agonists

5α-Dihydroprogesterone 5β-Dihydroprogesterone 17α-Hydroxypregnenolone 17α-Hydroxyprogesterone Δ4-Androstenedione Δ5-Androstenediol Δ5-Androstenedione AA-861 Allopregnanolone Alpha-Lipoic acid Ambrisentan AMI-193 Amlodipine besylate Antimycotics Artemisinin Aurothioglucose Bile acids Bithionol Bosentan Bumecaine Cafestol Cephaloridine Cephradine Chlorpromazine Ciglitazone Clindamycin Clofenvinfos Chloroxine Clotrimazole Colforsin Corticosterone Cyclophosphamide Cyproterone acetate Demecolcine Dexamethasone DHEA DHEA-S Dibunate sodium Diclazuril Dicloxacillin Dimercaprol Dinaline Docetaxel Docusate calcium Dodecylbenzenesulfonic acid Dronabinol Droxidopa Eburnamonine Ecopipam Enzacamene Epothilone B Erythromycin Famprofazone Febantel Felodipine Fenbendazole Fentanyl Flucloxacillin Fluorometholone Griseofulvin Haloprogin Hetacillin potassium Hyperforin (Hypericum perforatum) Indinavir sulfate Lasalocid sodium Levothyroxine Linolenic acid LOE-908 Loratadine Lovastatin Meclizine Methacycline Methylprednisolone Metyrapone Mevastatin Mifepristone Nafcillin Nicardipine Nicotine Nifedipine Nilvadipine Nisoldipine Norelgestromin Omeprazole Orlistat Oxatomide Paclitaxel Phenobarbital Piperine Plicamycin Prednisolone Pregnanolone Pregnenolone Pregnenolone 16α-carbonitrile Proadifen Progesterone Reserpine Reverse triiodothyronine Rifampicin Rifaximin Rimexolone Riodipine Ritonavir Simvastatin Sirolimus Spironolactone Spiroxatrine SR-12813 Suberoylanilide Sulfisoxazole Suramin Tacrolimus Tenylidone Terconazole Testosterone isocaproate Tetracycline Thiamylal sodium Thiothixene Thonzonium bromide Tianeptine Troglitazone Troleandomycin Tropanyl 3,5-dimethulbenzoate Zafirlukast Zearalanol

Antagonists

Ketoconazole

(From BioGPS)

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