Fig. 1.

Current understanding of the FXR proteome. The liver in human and mice preferentially expresses FXRα2 to perform ligand-activated transcriptional activity. It is unknown which FXR isoform, FXRα3 or FXRα4, is preferentially expressed in the intestine. All FXR isoforms bind to the IR-1 motif while only FXR2 and FXR4 have been shown to bind the ER-2 DNA binding motifs. Identification of confirmed binding partners of the hepatic and intestinal FXR proteome, and studies on confirmed DNA binding motifs the FXR isoforms, may provide ideal targets for tissue-specific FXR therapeutics. Figure created with biorender.com and confirmed DNA binding motif sequences are repurposed with permission. ¹⁵