FXR Protein, Human (His, StrepⅡ)

FXR is a ligand-activated transcription factor that serves as a receptor for bile acids (BAs), including chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA), and allocholic acid (ACA). It plays a crucial role in BA homeostasis by regulating genes involved in BA synthesis, conjugation, and enterohepatic circulation. Additionally, FXR modulates lipid and glucose metabolism and participates in innate immune responses. The FXR-RXR heterodimer primarily binds to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' (IR-1), with lower affinity for tandem repeat DR1 sites. In the liver, FXR activates transcription of the corepressor NR0B2, indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) through epigenetic repression mediated by histone demethylase KDM1A. It also activates genes such as SLC10A1/NTCP (BA uptake), SLC27A5/BACS, BAAT (BA conjugation), ABCB11/BSEP (bile salt export), ABCC2/MRP2, and ABCB4 (phosphatidylcholine secretion). In the intestine, FXR induces FGF19 expression, which suppresses hepatic CYP7A1. Furthermore, FXR regulates lipid metabolism by modulating SREBF1, PLTP, SCARB1, APOE, and other genes, and influences glucose homeostasis via NR0B2/SHP-mediated repression. FXR also contributes to intestinal innate immunity by suppressing inflammatory cytokines and maintaining epithelial barrier integrity. By similarity: FXR transcriptional activity is modulated by monomeric nuclear receptors (e.g., NR5A2/LRH-1) binding to coregulatory NRE half-sites; it coordinates FGF19 action through hepatic KLB/beta-klotho induction; regulates glycogen synthesis; inhibits bacterial overgrowth in the gut; and exhibits anti-inflammatory effects in liver inflammation.