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bile acid receptor; nuclear receptor subfamily 1 group H member 4; farnesoid X-activated receptor; farnesol receptor HRR-1; retinoid X receptor-interacting protein 14; RXR-interacting protein 14 (NR1H4, BAR, FXR, HRR1, RIP14)

Function: 1) receptor for bile acids a) chenodeoxycholic acid b) lithocholic acid c) deoxycholic acid 2) transcriptional repression of CYP7A1 gene 3) activates intestinal bile acid-binding protein (IBABP) 4) bile acid/FXR complex forms nuclear heterodimer with RXR - bile acid/FXR/RXR complex activates - CYP7A1 gene - IBABP gene - FGF19 gene 5) interacts with CARM1 & SMARD1 6) upregulates expression of ACE2 (receptor for SARS-Cov2) [8] Structure: - belongs to the nuclear hormone receptor family, NR1 subfamily - contains 1 nuclear receptor DNA-binding domain Compartment: - cytoplasm, nucleus - binds to bile acid in the cytoplasm - the bile acid/FXR receptor complex migrates into the cell nucleus Alternative splicing: named isoforms=4 Pharmacology: - binds to & is inhibited by ursodiol - upregulates ACE2 (receptor for SARS Cov2) in lung & intestine - inhibition by ursodiol may inhibit Covid-19 infection [8] Comparative biology: - in mice, binding of bile acids to the nuclear receptor FXR plays a role in benefits of vertical sleeve gastrectomy [3] - higher levels of circulating bile acids

General

DNA-binding protein nuclear hormone receptor family zinc finger protein

Properties

SIZE: MW = 56 kD entity length = 486 aa COMPARTMENT: cytoplasm MOTIF: DNA-binding motif SITE: 134-209 MOTIF: Zn finger C4-type SITE: 137-157 EFFECTOR-BOUND: Zn+2 Zn finger C4-type SITE: 173-197 EFFECTOR-BOUND: Zn+2 binding site SITE: 256-474 FOR-BINDING-OF: ligand

Database Correlations

OMIM 603826 UniProt Q96RI1 PFAM correlations Kegg hsa:9971

References

  1. UniProt :accession Q96RI1
  2. Wikipedia; farnesoid X receptor entry http://en.wikipedia.org/wiki/farnesoid_X_receptor
  3. Ryan KK et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 2014 May 8; 509:183 PMID: 24670636
  4. Wang H, Chen J, Hollister K, Sowers LC, Forman BM Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell. 1999 May;3(5):543-53. PMID: 10360171
  5. Claudel T, Sturm E, Kuipers F, Staels B The farnesoid X receptor: a novel drug target? Expert Opin Investig Drugs. 2004 Sep;13(9):1135-48. PMID: 15330745
  6. Downes M, Verdecia MA, Roecker AJ et al A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell. 2003 Apr;11(4):1079-92 PMID: 12718892
  7. Biocarta: FXR and LXR Regulation of Cholesterol Metabolism http://www.biocarta.com/pathfiles/m_fxrpathway.asp
  8. Brevini T, Maes M, Webb GJ et al FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature 2022. Dec 5. PMID: 36470304 https://www.nature.com/articles/s41586-022-05594-0