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Farnesoid X receptor: Wikis


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Nuclear receptor subfamily 1, group H, member 4

PDB rendering based on 1osh.
Available structures
1osh, 1osv, 1ot7
Symbols NR1H4; BAR; FXR; HRR-1; HRR1; MGC163445; RIP14
External IDs OMIM603826 MGI1352464 HomoloGene3760 GeneCards: NR1H4 Gene
RNA expression pattern
PBB GE NR1H4 206340 at tn.png
More reference expression data
Species Human Mouse
Entrez 9971 20186
Ensembl ENSG00000012504 n/a
UniProt Q96RI1 n/a
RefSeq (mRNA) NM_005123 NM_009108
RefSeq (protein) NP_005114 NP_033134
Location (UCSC) Chr 12:
99.39 - 99.48 Mb
PubMed search [1] [2]

The farnesoid X receptor (FXR), also known as NR1H4 (nuclear receptor subfamily 1, group H, member 4) is a nuclear hormone receptor with activity similar to that seen in other steroid receptors such as estrogen or progesterone but more similar in form to PPAR, LXR and RXR. FXR is encoded by the NR1H4 gene.[1]

FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Like other steroid receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA which elicits expression or transrepression of gene products.

One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP) which then functions to inhibit transcription of the CYP7A1 gene. In this way a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels all already high.



Farnesoid X receptor has been shown to interact with PPARGC1A[2] and Retinoid X receptor alpha.[3]


  1. ^ "Entrez Gene: NR1H4 nuclear receptor subfamily 1, group H, member 4".  
  2. ^ Zhang, Yanqiao; Castellani Lawrence W, Sinal Christopher J, Gonzalez Frank J, Edwards Peter A (Jan. 2004). "Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR". Genes Dev. (United States) 18 (2): 157–69. doi:10.1101/gad.1138104. ISSN 0890-9369. PMID 14729567.  
  3. ^ Seol, W; Choi H S, Moore D D (Jan. 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Mol. Endocrinol. (UNITED STATES) 9 (1): 72–85. ISSN 0888-8809. PMID 7760852.  

Further reading

  • Kalaany NY, Mangelsdorf DJ (2006). "LXRS and FXR: the yin and yang of cholesterol and fat metabolism.". Annu. Rev. Physiol. 68: 159–91. doi:10.1146/annurev.physiol.68.033104.152158. PMID 16460270.  
  • Kuipers F, Stroeve JH, Caron S, Staels B (2007). "Bile acids, farnesoid X receptor, atherosclerosis and metabolic control.". Curr. Opin. Lipidol. 18 (3): 289–97. doi:10.1097/MOL.0b013e3281338d08. PMID 17495603.  
  • Seol W, Choi HS, Moore DD (1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors.". Mol. Endocrinol. 9 (1): 72–85. doi:10.1210/me.9.1.72. PMID 7760852.  
  • Forman BM, Goode E, Chen J, et al. (1995). "Identification of a nuclear receptor that is activated by farnesol metabolites.". Cell 81 (5): 687–93. doi:10.1016/0092-8674(95)90530-8. PMID 7774010.  
  • Zavacki AM, Lehmann JM, Seol W, et al. (1997). "Activation of the orphan receptor RIP14 by retinoids.". Proc. Natl. Acad. Sci. U.S.A. 94 (15): 7909–14. doi:10.1073/pnas.94.15.7909. PMID 9223286.  
  • Makishima M, Okamoto AY, Repa JJ, et al. (1999). "Identification of a nuclear receptor for bile acids.". Science 284 (5418): 1362–5. doi:10.1126/science.284.5418.1362. PMID 10334992.  
  • Parks DJ, Blanchard SG, Bledsoe RK, et al. (1999). "Bile acids: natural ligands for an orphan nuclear receptor.". Science 284 (5418): 1365–8. doi:10.1126/science.284.5418.1365. PMID 10334993.  
  • Bramlett KS, Yao S, Burris TP (2001). "Correlation of farnesoid X receptor coactivator recruitment and cholesterol 7alpha-hydroxylase gene repression by bile acids.". Mol. Genet. Metab. 71 (4): 609–15. doi:10.1006/mgme.2000.3106. PMID 11136553.  
  • Stegh AH, Barnhart BC, Volkland J, et al. (2002). "Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator protein.". J. Biol. Chem. 277 (6): 4351–60. doi:10.1074/jbc.M108947200. PMID 11733517.  
  • Cui J, Heard TS, Yu J, et al. (2002). "The amino acid residues asparagine 354 and isoleucine 372 of human farnesoid X receptor confer the receptor with high sensitivity to chenodeoxycholate.". J. Biol. Chem. 277 (29): 25963–9. doi:10.1074/jbc.M200824200. PMID 12004058.  
  • Huber RM, Murphy K, Miao B, et al. (2002). "Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters.". Gene 290 (1-2): 35–43. doi:10.1016/S0378-1119(02)00557-7. PMID 12062799.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • Pineda Torra I, Claudel T, Duval C, et al. (2003). "Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor.". Mol. Endocrinol. 17 (2): 259–72. doi:10.1210/me.2002-0120. PMID 12554753.  
  • Anisfeld AM, Kast-Woelbern HR, Meyer ME, et al. (2003). "Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor.". J. Biol. Chem. 278 (22): 20420–8. doi:10.1074/jbc.M302505200. PMID 12660231.  
  • Pircher PC, Kitto JL, Petrowski ML, et al. (2003). "Farnesoid X receptor regulates bile acid-amino acid conjugation.". J. Biol. Chem. 278 (30): 27703–11. doi:10.1074/jbc.M302128200. PMID 12754200.  
  • Zhao A, Lew JL, Huang L, et al. (2003). "Human kininogen gene is transactivated by the farnesoid X receptor.". J. Biol. Chem. 278 (31): 28765–70. doi:10.1074/jbc.M304568200. PMID 12761213.  
  • Barbier O, Torra IP, Sirvent A, et al. (2003). "FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity.". Gastroenterology 124 (7): 1926–40. doi:10.1016/S0016-5085(03)00388-3. PMID 12806625.  
  • Holt JA, Luo G, Billin AN, et al. (2003). "Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis.". Genes Dev. 17 (13): 1581–91. doi:10.1101/gad.1083503. PMID 12815072.  
  • Claudel T, Inoue Y, Barbier O, et al. (2003). "Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression.". Gastroenterology 125 (2): 544–55. doi:10.1016/S0016-5085(03)00896-5. PMID 12891557.  
  • Hsiao PW, Fryer CJ, Trotter KW, et al. (2003). "BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation.". Mol. Cell. Biol. 23 (17): 6210–20. doi:10.1128/MCB.23.17.6210-6220.2003. PMID 12917342.  

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