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a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
the 24th letter of the Roman alphabet (同)x, ex

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=sense organ / 受信装置
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/29 21:49:05」(JST)

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The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4) is a nuclear receptor that is encoded by the NR1H4 gene in humans.^[1]^[2]

Function

FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear 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 up- or down-regulates the expression of certain genes.^[2]

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 are already high. FXR has also been found to be important in regulation of hepatic triglyceride levels.^[3] Studies have also shown the FXR to regulate the expression and activity of epithelial transport proteins involved in fluid homestasis in the intestine, such as the cystic fibrosis conductance transmembrane regulator (CFTR).^[4]

Interactions

Farnesoid X receptor has been shown to interact with:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha^[5] and
Retinoid X receptor alpha.^[6]

Ligands

A number of ligands for FXR are known, of both natural and synthetic origin.^[7]^[8]^[9]

Agonists

Cafestol^[10]
Chenodeoxycholic acid
Obeticholic acid
Fexaramine

Antagonists

Guggulsterone

References

^ "Entrez Gene: NR1H4 nuclear receptor subfamily 1, group H, member 4".
^ ^a ^b Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, Evans RM, Weinberger C (Jun 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.
^ Jiao Y, Lu Y, Li XY (Jan 2015). "Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis". Acta Pharmacologica Sinica 36 (1): 44–50. doi:10.1038/aps.2014.116. PMID 25500875.
^ Mroz MS, Keating N, Ward JB, Sarker R, Amu S, Aviello G, Donowitz M, Fallon PG, Keely SJ (May 2014). "Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo". Gut 63 (5): 808–17. doi:10.1136/gutjnl-2013-305088. PMID 23916961.
^ Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA (Jan 2004). "Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR". Genes & Development 18 (2): 157–69. doi:10.1101/gad.1138104. PMC 324422. PMID 14729567.
^ Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Molecular Endocrinology 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. PMID 7760852.
^ Fiorucci S, Zampella A, Distrutti E (2012). "Development of FXR, PXR and CAR agonists and antagonists for treatment of liver disorders". Current Topics in Medicinal Chemistry 12 (6): 605–24. doi:10.2174/156802612799436678. PMID 22242859.
^ Fiorucci S, Mencarelli A, Distrutti E, Zampella A (May 2012). "Farnesoid X receptor: from medicinal chemistry to clinical applications". Future Medicinal Chemistry 4 (7): 877–91. doi:10.4155/fmc.12.41. PMID 22571613.
^ Vaz B, de Lera ÁR (Nov 2012). "Advances in drug design with RXR modulators". Expert Opinion on Drug Discovery 7 (11): 1003–16. doi:10.1517/17460441.2012.722992. PMID 22954251.
^ Ricketts ML, Boekschoten MV, Kreeft AJ, Hooiveld GJ, Moen CJ, Müller M, Frants RR, Kasanmoentalib S, Post SM, Princen HM, Porter JG, Katan MB, Hofker MH, Moore DD (Jul 2007). "The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors". Molecular Endocrinology 21 (7): 1603–16. doi:10.1210/me.2007-0133. PMID 17456796.

External links

"Farnesoid X Receptor (NR1H4)". Nuclear Receptor Resource.
farnesoid X-activated receptor at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 急性前骨髄球性白血病の分子生物学 molecular biology of acute promyelocytic leukemia
2. 甲状腺ホルモンの作用 thyroid hormone action
3. 分化（レチノイン酸）症候群 differentiation retinoic acid syndrome
4. 中枢性甲状腺機能低下症 central hypothyroidism
5. 甲状腺ホルモンとの薬物相互作用 drug interactions with thyroid hormones

English Journal

Bile Acids Increase Independently From Hypocaloric Restriction After Bariatric Surgery.

Jahansouz C1, Xu H, Hertzel AV, Serrot FJ, Kvalheim N, Cole A, Abraham A, Luthra G, Ewing K, Leslie DB, Bernlohr DA, Ikramuddin S.
Annals of surgery.Ann Surg.2016 Dec;264(6):1022-1028.
OBJECTIVES: To measure changes in the composition of serum bile acids (BA) and the expression of Takeda G-protein-coupled receptor 5 (TGR5) acutely after bariatric surgery or caloric restriction.SUMMARY BACKGROUND DATA: Metabolic improvement after bariatric surgery occurs before substantial weight l
PMID 26655924

Conformational modulation of the farnesoid X receptor by prenylflavonoids: Insights from hydrogen deuterium exchange mass spectrometry (HDX-MS), fluorescence titration and molecular docking studies.

Yang L1, Broderick D1, Campbell Y2, Gombart AF2, Stevens JF3, Jiang Y4, Hsu VL5, Bisson WH6, Maier CS7.
Biochimica et biophysica acta.Biochim Biophys Acta.2016 Dec;1864(12):1667-1677. doi: 10.1016/j.bbapap.2016.08.019. Epub 2016 Sep 3.
We report on the molecular interactions of the farnesoid X receptor (FXR) with prenylflavonoids, an emerging class of FXR modulators. FXR is an attractive therapeutic target for mitigating metabolic syndromes (MetS) because FXR activates the inhibitory nuclear receptor, small heterodimer partner (SH
PMID 27596062

Sirtuin 1 activation alleviates cholestatic liver injury in a cholic acid-fed mouse model of cholestasis.

Kulkarni SR1, Soroka CJ1, Hagey LR2, Boyer JL1.
Hepatology (Baltimore, Md.).Hepatology.2016 Dec;64(6):2151-2164. doi: 10.1002/hep.28826. Epub 2016 Oct 28.
Sirtuin1 (Sirt1; mammalian homolog of Saccharomyces cerevisiae enzyme Sir2) is a transcriptional and transactivational regulator of murine farnesoid X receptor (Fxr), which is the primary bile acid (BA) sensor, and critical regulator of BA metabolism in physiological and pathophysiological condition
PMID 27639250

Japanese Journal

Cholestasis induces reversible accumulation of periplakin in mouse liver.

Ito Shinji,Satoh Junko,Matsubara Tsutomu,Shah Yatrik M,Ahn Sung-Hoon,Anderson Cherie R,Shan Weiwei,Peters Jeffrey M,Gonzalez Frank J
BMC gastroenterology 13, 2013-07
… Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis. …
NAID 120005307061

Critical role of farnesoid X receptor for hepatocellular carcinoma cell proliferation

Fujino Tomofumi,Takeuchi Airi,Maruko-Ohtake Akiko [他]
The journal of biochemistry 152(6), 577-586, 2012-12
NAID 40019523919

「ファルネソイドX受容体」

Nuclear receptor subfamily 1, group H, member 4
	PDB rendering based on 1osh.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1OSH, 1OSK, 3BEJ, 3DCT, 3DCU, 3FLI, 3FXV, 3GD2, 3HC5, 3HC6, 3L1B, 3OKH, 3OKI, 3OLF, 3OMK, 3OMM, 3OOF, 3OOK, 3P88, 3P89, 3RUT, 3RUU, 3RVF, 4OIV, 4WVD
Identifiers
Symbols	NR1H4 ; BAR; FXR; HRR-1; HRR1; RIP14
External IDs	OMIM: 603826 MGI: 1352464 HomoloGene: 3760 IUPHAR: 603 ChEMBL: 2047 GeneCards: NR1H4 Gene
Gene ontology
Molecular function	• RNA polymerase II distal enhancer sequence-specific DNA binding; • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; • transcriptional activator activity, RNA polymerase II transcription factor binding; • transcription factor activity, sequence-specific DNA binding; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • steroid hormone receptor activity; • transcription coactivator activity; • transcription corepressor activity; • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding; • thyroid hormone receptor activity; • protein binding; • zinc ion binding; • ligand-dependent nuclear receptor binding; • bile acid binding; • bile acid receptor activity; • sequence-specific DNA binding; • retinoid X receptor binding; • chenodeoxycholic acid binding;
Cellular component	• nucleoplasm; • nuclear euchromatin;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • nitrogen catabolite activation of transcription from RNA polymerase II promoter; • transcription initiation from RNA polymerase II promoter; • signal transduction; • bile acid metabolic process; • gene expression; • bile acid and bile salt transport; • intracellular receptor signaling pathway; • regulation of urea metabolic process; • intracellular bile acid receptor signaling pathway; • steroid hormone mediated signaling pathway; • small molecule metabolic process; • positive regulation of transcription from RNA polymerase II promoter; • regulation of bile acid biosynthetic process; • negative regulation of bile acid biosynthetic process; • cellular response to organonitrogen compound; • regulation of cholesterol metabolic process; • cellular response to bile acid; • positive regulation of glutamate metabolic process; • positive regulation of ammonia assimilation cycle;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;