FXR (Farnesoid-X-activated Receptor)

 Farnesoid-X-receptor (FXR) was originally identified and cloned in rat as an orphan nuclear hormone receptor based on hybridization with a degenerate oligonucleotide designed from the highly conserved nuclear hormone receptor DNA binding domain (1). FXR functions as a heterodimer with RXR and binds to sequence elements in the promoters of target genes. The FXR/RXR heterodimer binds with highest affinity to inverted repeats separated by 1 bp (IR-1) and with low affinity to direct repeats separated by 4 and 5 bp (DR-4 and DR-5) (1, 2). As is the case for other nuclear hormone receptors, FXR regulates target gene activity in response to ligand. While initial studies suggested that farnesol and retinoid metabolites were likely ligands for FXR, current data support the notion that FXR is a bile acid sensor that plays an integral role in bile acid synthesis and transport (1, 3-6). In the small intestine, FXR regulates bile acid uptake through the upregulation of the ileal bile acid binding protein gene via binding to an upstream response element (7). The FXR/RXR heterodimer can be activated by the bile salt chenodeoxycholic acid (CDCA) and FXR is required for the bile salt-dependent transcriptional control of the human ABCB11 gene (the bile salt export pump) (8). In addition, FXR has been shown to inhibit the cholesterol 7-hydrolase gene (CYP7A1) transcription (9).
Recombinant His tagged FXR is isolated from an E. coli strain that carries the coding sequence of the human FXR under the control of a T7 promoter.
FXR has been applied in DNA and protein-protein interactions assays.
The purified recombinant protein is greater than 95% homogeneous based on SDS-PAGE analysis.
1 unit equals 1 nanogram purified protein. 20 units are sufficient for a gel-mobility shift assay and 100 units are sufficient for a protein-protein interaction assay.
variable in different lots
1x dilution buffer A: 20 mM Tris-Cl (pH 8.0), 20% Glycerol, 100 mM KCl, 1 mM DTT and 0.2 mM EDTA
 
References:
1. Forman et al., (1995) Cell 81, 687-693
2. Seol et al., (1995) Mol. Endocrinol. 9, 72-85
3. Zavacki et al., (1997) Proc. Natl. Acad. Sci. 94, 7909-7914
4. Makishima et al., (1999) Science 284, 1362-1365
5. Parks et al., (1999) Science 284, 1365-1368
6. Wang et al., (1999) Mol. Cell 3, 543-553
7. Grober et al., (1999) J. Biol. Chem. 274, 29749-29754
8. Plass et al., (2002) Hepatology 35, 589-596
9. Chiang et al., (2001) Gene 262, 257-265