گیرنده ایکس فارنزوئید

NR1H4
ساختارهای موجود
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1OSH, 3BEJ, 3DCT, 3DCU, 3FLI, 3FXV, 3GD2, 3HC5, 3HC6, 3L1B, 3OKH, 3OKI, 3OLF, 3OMK, 3OMM, 3OOF, 3OOK, 3RUT, 3RUU, 3RVF, 3P88, 3P89, 4OIV, 4WVD, 4QE6, 4QE8
معین‌کننده‌ها
نام‌های دیگر	NR1H4, BAR, FXR, HRR-1, HRR1, RIP14, nuclear receptor subfamily 1 group H member 4, PFIC5
شناسه‌های بیرونی	OMIM: 603826 MGI: 1352464 HomoloGene: 3760 GeneCards: NR1H4
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)[1]
End	89,533,585 bp[1]
الگوی گسترش RNA
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • sequence-specific DNA binding; • DNA binding; • GO:0001106 transcription corepressor activity; • GO:0001131، GO:0001151، GO:0001130، GO:0001204 DNA-binding transcription factor activity; • GO:0001105 transcription coactivator activity; • zinc ion binding; • GO:0001077، GO:0001212، GO:0001213، GO:0001211، GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • metal ion binding; • retinoid X receptor binding; • steroid hormone receptor activity; • bile acid binding; • GO:0001948 پیوند پروتئینی; • nuclear receptor binding; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • chenodeoxycholic acid binding; • GO:0000975 transcription cis-regulatory region binding; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • GO:0038050، GO:0004886، GO:0038051 nuclear receptor activity; • bile acid receptor activity; • GO:0001200، GO:0001133، GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • transcription factor binding; • nuclear receptor coactivator activity; • signaling receptor activity;
ترکیبات سلولی	• نوکلئوپلاسم; • هسته یاخته; • RNA polymerase II transcription regulator complex;
فرایند زیستی	• Notch signaling pathway; • cellular triglyceride homeostasis; • cellular response to organonitrogen compound; • regulation of insulin secretion involved in cellular response to glucose stimulus; • positive regulation of ammonia assimilation cycle; • toll-like receptor 4 signaling pathway; • immune system process; • histone H3-R17 methylation; • regulation of transcription by RNA polymerase II; • positive regulation of glutamate metabolic process; • intracellular bile acid receptor signaling pathway; • negative regulation of apoptotic process; • negative regulation of transcription by RNA polymerase II; • transcription, DNA-templated; • regulation of low-density lipoprotein particle clearance; • regulation of bile acid biosynthetic process; • regulation of cholesterol metabolic process; • regulation of urea metabolic process; • intracellular receptor signaling pathway; • negative regulation of bile acid biosynthetic process; • cellular response to fatty acid; • bile acid and bile salt transport; • nitrogen catabolite activation of transcription from RNA polymerase II promoter; • transcription initiation from RNA polymerase II promoter; • inflammatory response; • دستگاه ایمنی ذاتی; • ورارسانی پیام; • steroid hormone mediated signaling pathway; • fatty acid homeostasis; • positive regulation of insulin receptor signaling pathway; • cellular response to lipopolysaccharide; • negative regulation of interleukin-2 production; • positive regulation of insulin secretion involved in cellular response to glucose stimulus; • negative regulation of inflammatory response; • glucose homeostasis; • negative regulation of NF-kappaB transcription factor activity; • positive regulation of adipose tissue development; • cell-cell junction assembly; • toll-like receptor 9 signaling pathway; • negative regulation of monocyte chemotactic protein-1 production; • bile acid metabolic process; • negative regulation of I-kappaB kinase/NF-kappaB signaling; • negative regulation of tumor necrosis factor-mediated signaling pathway; • defense response to bacterium; • negative regulation of interleukin-1 production; • negative regulation of tumor necrosis factor production; • negative regulation of interleukin-6 production; • triglyceride homeostasis; • negative regulation of interferon-gamma production; • regulation of transcription, DNA-templated; • bile acid signaling pathway; • positive regulation of transcription by RNA polymerase II; • positive regulation of phosphatidic acid biosynthetic process; • cholesterol homeostasis; • lipid metabolism; • multicellular organism development; • دگرگونی یاخته‌; • lipid homeostasis; • cellular glucose homeostasis;
	Sources:آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	9971
	20186
	ENSG00000012504
	ENSMUSG00000047638
	Q96RI1
	Q60641
	NM_001206978، NM_001206979، NM_001206992، NM_001206993، NM_005123، XM_006719719، XM_011539040، XM_011539041، XM_011539042، NR_135146 NM_001206977، NM_001206978، NM_001206979، NM_001206992، NM_001206993، NM_005123، XM_006719719، XM_011539040، XM_011539041، XM_011539042، NR_135146
	NM_001163700، NM_009108، XM_006513391، XM_006513393، XR_001779493، XM_030244963 NM_001163504، NM_001163700، NM_009108، XM_006513391، XM_006513393، XR_001779493، XM_030244963
	NP_001193907، NP_001193908، NP_001193921، NP_001193922، NP_005114، XP_006719782، XP_011537342، XP_011537343، XP_011537344 NP_001193906، NP_001193907، NP_001193908، NP_001193921، NP_001193922، NP_005114، XP_006719782، XP_011537342، XP_011537343، XP_011537344; NP_001193908.1، XP_011537342.1 NP_001193906.1، NP_001193908.1، XP_011537342.1
	NP_001157172، NP_033134، XP_006513454، XP_030100823، NP_001372640 NP_001156976، NP_001157172، NP_033134، XP_006513454، XP_030100823، NP_001372640
	ویکی‌داده
مشاهده/ویرایش Human	View/Edit Mouse

گیرنده ایکس فارنزوئید (انگلیسی: Farnesoid X receptor‎) یا به اختصار FXR که با نام گیرندهٔ اسید صفراوی نیز شناخته می‌شود، یک گیرنده هسته‌ای است که در انسان توسط ژن «NR1H4» کُدگذاری می‌شود.[4][5]

عملکرد

این پروتئین در مقادیر زیاد در کبد و روده‌ها بیان می‌شود. چنوداوکسی کولیک اسید و سایر انواع اسیدهای صفراوی لیگاندهای طبیعی FXR محسوب می‌شوند. یکی از وظایف اصلی این پروتئین، سرکوب کردن آنزیم کلسترول ۷ آلفا-هیدروکسیلاز (CYP7A1) است که یک آنزیم تعیین‌کننده سرعت در ساخت اسیدهای صفراوی از کلسترول است. این پروتئین مستقیماً به پروموتر CYP7A1 متصل نمی‌شود، بلکه باعث افزایش ساخت شریک کوچک هترودایمر (SHP) می‌شود که این نیز به نوبهٔ خود، رونویسی ژن CYP7A1 را مهار می‌کند.

پروتئین FXR نقش تنظیمی مهمی بر روی سطح تری‌گلیسرید در کبد دارد.[6] به‌ویژه آنکه فعال‌شدن FXR سبب سرکوب لیپوژنز و افزایش اکسیداسیون اسید چرب از طریق افزایش فعالیت گیرندهٔ «PPARA» می‌گردد.[6] پروتئین FXR همچنین در تنظیم تولید و فعالیت پروتئین‌های حمل‌کنندهٔ بافت پوششی روده‌ها همچون «CFTR» که در تعدیل هم‌ایستایی مایعات نقش دارند، نقش دارد.[7]

گوگولسترون

منابع

GRCm38: Ensembl release 89: ENSMUSG00000047638 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: NR1H4 nuclear receptor subfamily 1, group H, member 4".
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. PMC 4571315. 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.
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.

مشارکت‌کنندگان ویکی‌پدیا. «Farnesoid X receptor». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۵ آوریل ۲۰۲۰.

برای مطالعهٔ بیشتر

Kalaany NY, Mangelsdorf DJ (2006). "LXRS and FXR: the yin and yang of cholesterol and fat metabolism". Annual Review of Physiology. 68: 159–91. doi:10.1146/annurev.physiol.68.033104.152158. PMID 16460270.
Kuipers F, Stroeve JH, Caron S, Staels B (Jun 2007). "Bile acids, farnesoid X receptor, atherosclerosis and metabolic control". Current Opinion in Lipidology. 18 (3): 289–97. doi:10.1097/MOL.0b013e3281338d08. PMID 17495603.
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.
Zavacki AM, Lehmann JM, Seol W, Willson TM, Kliewer SA, Moore DD (Jul 1997). "Activation of the orphan receptor RIP14 by retinoids". Proceedings of the National Academy of Sciences of the United States of America. 94 (15): 7909–14. doi:10.1073/pnas.94.15.7909. PMC 21528. PMID 9223286.
Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B (May 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, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM (May 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 (Dec 2000). "Correlation of farnesoid X receptor coactivator recruitment and cholesterol 7alpha-hydroxylase gene repression by bile acids". Molecular Genetics and Metabolism. 71 (4): 609–15. doi:10.1006/mgme.2000.3106. PMID 11136553.
Stegh AH, Barnhart BC, Volkland J, Algeciras-Schimnich A, Ke N, Reed JC, Peter ME (Feb 2002). "Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator protein". The Journal of Biological Chemistry. 277 (6): 4351–60. doi:10.1074/jbc.M108947200. PMID 11733517.
Cui J, Heard TS, Yu J, Lo JL, Huang L, Li Y, Schaeffer JM, Wright SD (Jul 2002). "The amino acid residues asparagine 354 and isoleucine 372 of human farnesoid X receptor confer the receptor with high sensitivity to chenodeoxycholate". The Journal of Biological Chemistry. 277 (29): 25963–9. doi:10.1074/jbc.M200824200. PMID 12004058.
Huber RM, Murphy K, Miao B, Link JR, Cunningham MR, Rupar MJ, Gunyuzlu PL, Haws TF, Kassam A, Powell F, Hollis GF, Young PR, Mukherjee R, Burn TC (May 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.
Pineda Torra I, Claudel T, Duval C, Kosykh V, Fruchart JC, Staels B (Feb 2003). "Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor". Molecular Endocrinology. 17 (2): 259–72. doi:10.1210/me.2002-0120. PMID 12554753.
Anisfeld AM, Kast-Woelbern HR, Meyer ME, Jones SA, Zhang Y, Williams KJ, Willson T, Edwards PA (May 2003). "Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor". The Journal of Biological Chemistry. 278 (22): 20420–8. doi:10.1074/jbc.M302505200. PMID 12660231.
Pircher PC, Kitto JL, Petrowski ML, Tangirala RK, Bischoff ED, Schulman IG, Westin SK (Jul 2003). "Farnesoid X receptor regulates bile acid-amino acid conjugation". The Journal of Biological Chemistry. 278 (30): 27703–11. doi:10.1074/jbc.M302128200. PMID 12754200.
Zhao A, Lew JL, Huang L, Yu J, Zhang T, Hrywna Y, Thompson JR, de Pedro N, Blevins RA, Peláez F, Wright SD, Cui J (Aug 2003). "Human kininogen gene is transactivated by the farnesoid X receptor". The Journal of Biological Chemistry. 278 (31): 28765–70. doi:10.1074/jbc.M304568200. PMID 12761213.
Barbier O, Torra IP, Sirvent A, Claudel T, Blanquart C, Duran-Sandoval D, Kuipers F, Kosykh V, Fruchart JC, Staels B (Jun 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, Bisi J, McNeill YY, Kozarsky KF, Donahee M, Wang DY, Mansfield TA, Kliewer SA, Goodwin B, Jones SA (Jul 2003). "Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis". Genes & Development. 17 (13): 1581–91. doi:10.1101/gad.1083503. PMC 196131. PMID 12815072.
Claudel T, Inoue Y, Barbier O, Duran-Sandoval D, Kosykh V, Fruchart J, Fruchart JC, Gonzalez FJ, Staels B (Aug 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, Wang W, Archer TK (Sep 2003). "BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation". Molecular and Cellular Biology. 23 (17): 6210–20. doi:10.1128/MCB.23.17.6210-6220.2003. PMC 180928. PMID 12917342.
Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, Wilson-Pérez HE, Sandoval DA, Kohli R, Bäckhed F, Seeley RJ (May 2014). "FXR is a molecular target for the effects of vertical sleeve gastrectomy". Nature. 509 (7499): 183–8. doi:10.1038/nature13135. PMC 4016120. PMID 24670636.

پیوند به بیرون

farnesoid X-activated receptor در سرعنوان‌های موضوعی پزشکی (MeSH) در کتابخانهٔ ملی پزشکی ایالات متحدهٔ آمریکا

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000047638 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-4] "Entrez Gene: NR1H4 nuclear receptor subfamily 1, group H, member 4".

[pmid7774010-5] 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.

[pmid25500875-6] 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. PMC 4571315. PMID 25500875.

[pmid23916961-7] 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.

[pmid17456796-8] 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.

گیرنده ایکس فارنزوئید

عملکرد

لیگاندها

آگونیست‌ها

آنتاگونیست‌ها

منابع

برای مطالعهٔ بیشتر

پیوند به بیرون