Farnesoid X Receptor

Farnesoid X receptors (FXRs), members of the nuclear receptor (NR) superfamily, are encoded by two FXR genes: FXRα and FXRβ. Significantly, FXRβ is a pseudogene in humans, although it serves as a lanosterol sensor and encodes a functional protein in rodents, rabbits and dogs. FXRs share a common architecture with other metabolic NRs: a ligand-independent transcriptional activation domain (AF1), a core DNA-binding domain (DBD), a hinge region, a C-terminal ligand-binding domain (LBD) and a ligand-dependent activation function domain (AF2). Specific bile acids (BAs), such as chenodeoxycholic acid (CDCA) and cholic acid (CA), are endogenous ligands for FXRs. After ligand binding, FXRs can bind to and activate or repress through a large variety of DNA elements, called FXR response elements (FXREs), either as a monomer or as a FXR/RXR heterodimer. FXRs are expressed in high amounts in body tissues that participate in bilirubin metabolism including the liver, intestines, and kidneys.