Farnesoid X Receptor (FXR; NR1H4)

This gene encodes a ligand-activated transcription factor, which shares structural features in common with nuclear hormone receptor family, such as a DNA-binding domain that targets the receptor to specific DNA sequences, and a ligand-binding domain, which interacts directly with the ligand and contains a ligand-dependent transcriptional activation domain. This protein functions as a receptor for bile acids, and when bound to bile acids, regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

[provided byRefSeq, Aug 2011]

NRR Pathway

nr1h4-pathway

Farnesoid X Receptor Structure

mmdbimage-5_med

(From Structure)

Link

 

(From Aceview)

There are 99 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (Breast Neoplasms; Cholestasis; Cholesterol, HDL/blood*; Coronary Artery Disease; Dyslipidemias; hyperlipidemia, familial combined; Liver Cirrhosis; Xanthomatosis, Cerebrotendinous), proposed to participate in a pathway (FXR and LXR Regulation of Cholesterol Metabolism) and processes (bile acid metabolic process, digestive tract development, negative regulation of transcription from RNA polymerase II promoter, positive regulation of transcription from RNA polymerase II promoter, regulation of carbohydrate metabolic process, response to glucose stimulus, response to lipopolysaccharide). Proteins are expected to have molecular functions (bile acid binding, double-stranded DNA binding, metal ion binding, peptide binding and 4 others) and to localize in nucleus. Putative protein interactors have been described (CASP8, ESR1, NCAPD2ANDGAPDH, NCOA1, NCOR2, PPARGC1A, RXRA, RXRG, SMARCD1, SMARCD3). 

(From HuGENavigator)

  • Lung Neoplasms 
  • Pregnancy Complications 
  • Inflammatory Bowel Diseases 
  • Insulin Resistance 
  • Liver Cirrhosis 
  • Cholestasis, Intrahepatic 
  • Colitis, Ulcerative 
  • Coronary Artery Disease 
  • Coronary Disease 
  • Crohn Disease 
  • Diabetes Complications 
  • Diarrhea 
  • Disease Progression 
  • Dyslipidemias 
  • Fatty Liver 
  • Gallstones 
  • Alzheimer Disease 
  • Atherosclerosis 
  • Biliary Tract Diseases 
  • Calcinosis 
  • Carcinoma, Squamous Cell 
  • Cardiovascular Diseases 
  • Cholangiocarcinoma 
  • Cholestasis 
  • Liver Diseases 
  • Irritable Bowel Syndrome 
  • Hepatitis C, Chronic 
  • Hyperglycemia 
  • Hyperlipidemia, Familial Combined 
  • Hyperlipidemias 
  • Inflammation 
  • Pulmonary Disease, Chronic Obstructive 
  • Urinary Bladder Neoplasms 
  • Metabolic Syndrome X 
  • Neoplasms 
  • Osteoporosis 
  • Overweight 

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.

FXR 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 farnesoid x receptor. This kit product is an all-inclusive assay system that includes, in addition to FXR 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.

BAR; FXR; HRR1; HRR-1; RIP14

(From Aceview)

The gene contains 20 distinct gt-ag introns. Transcription produces 13 different mRNAs, 11 alternatively spliced variants and 2 unspliced forms. There are 2 probable alternative 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, presence or absence of 4 cassette exons, overlapping exons with different boundaries. Note that mRNA .hAug10 was found in vivo, although it is a predicted target of nonsense mediated mRNA decay (NMD). 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 cAug10, dAug10, eAug10). 

image-14_med

(From STRINGS)

CASP8, ESR1, NCAPD2ANDGAPDH, NCOA1, NCOR2, PPARGC1A, RXRA, RXRG, SMARCD1, SMARCD3

(From KEGG)

  • Chenodeoxycholic acid
  • Turofexorate isopropyl
  • Obeticholic acid

(From BioGPS)

206340_at_med