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Bile acid receptor (Farnesoid X-activated receptor) (Farnesol receptor HRR-1) (Nuclear receptor subfamily 1 group H member 4) (Retinoid X receptor-interacting protein 14) (RXR-interacting protein 14)

 NR1H4_HUMAN             Reviewed;         486 AA.
Q96RI1; A1L4K5; B7Z412; B7ZM06; F8VYG8; Q8NFP5; Q8NFP6; Q92943;
27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
26-APR-2004, sequence version 2.
25-OCT-2017, entry version 178.
RecName: Full=Bile acid receptor;
AltName: Full=Farnesoid X-activated receptor;
AltName: Full=Farnesol receptor HRR-1;
AltName: Full=Nuclear receptor subfamily 1 group H member 4;
AltName: Full=Retinoid X receptor-interacting protein 14;
Short=RXR-interacting protein 14;
Name=NR1H4; Synonyms=BAR, FXR, HRR1, RIP14;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
Papetti M., Wood N., Lohmar P.D., Bowman M.R.;
"The identification of the cDNA coding for HRR-1, a novel human
farnesol receptor.";
Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Han J.-I., Bok S.-H., Jeong T.-S.;
"Functional analysis of human farnesol receptor (NR1H4) splicing
variant.";
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND ALTERNATIVE
SPLICING (ISOFORMS 3 AND 4).
PubMed=12062799; DOI=10.1016/S0378-1119(02)00557-7;
Huber R.M., Murphy K., Miao B., Link J.R., Cunningham M.R.,
Rupar M.J., Gunyuzlu P.L., Haws T.F. Jr., Kassam A., Powell F.,
Hollis G.F., Young P.R., Mukherjee R., Burn T.C.;
"Generation of multiple farnesoid-X-receptor isoforms through the use
of alternative promoters.";
Gene 290:35-43(2002).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Colon;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16541075; DOI=10.1038/nature04569;
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
Kucherlapati R., Weinstock G., Gibbs R.A.;
"The finished DNA sequence of human chromosome 12.";
Nature 440:346-351(2006).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
FUNCTION IN BA HOMEOSTASIS.
PubMed=10514450; DOI=10.1074/jbc.274.42.29749;
Grober J., Zaghini I., Fujii H., Jones S.A., Kliewer S.A.,
Willson T.M., Ono T., Besnard P.;
"Identification of a bile acid-responsive element in the human ileal
bile acid-binding protein gene. Involvement of the farnesoid X
receptor/9-cis-retinoic acid receptor heterodimer.";
J. Biol. Chem. 274:29749-29754(1999).
[9]
FUNCTION IN BA HOEMOSTASIS.
PubMed=10334992; DOI=10.1126/science.284.5418.1362;
Makishima M., Okamoto A.Y., Repa J.J., Tu H., Learned R.M., Luk A.,
Hull M.V., Lustig K.D., Mangelsdorf D.J., Shan B.;
"Identification of a nuclear receptor for bile acids.";
Science 284:1362-1365(1999).
[10]
FUNCTION IN BA HOEMOSTASIS.
PubMed=10334993; DOI=10.1126/science.284.5418.1365;
Parks D.J., Blanchard S.G., Bledsoe R.K., Chandra G., Consler T.G.,
Kliewer S.A., Stimmel J.B., Willson T.M., Zavacki A.M., Moore D.D.,
Lehmann J.M.;
"Bile acids: natural ligands for an orphan nuclear receptor.";
Science 284:1365-1368(1999).
[11]
FUNCTION IN LIPID HOMEOSTASIS.
PubMed=11579204; DOI=10.1210/mend.15.10.0712;
Kast H.R., Nguyen C.M., Sinal C.J., Jones S.A., Laffitte B.A.,
Reue K., Gonzalez F.J., Willson T.M., Edwards P.A.;
"Farnesoid X-activated receptor induces apolipoprotein C-II
transcription: a molecular mechanism linking plasma triglyceride
levels to bile acids.";
Mol. Endocrinol. 15:1720-1728(2001).
[12]
FUNCTION IN LIPID HOMEOSTASIS.
PubMed=11927623; DOI=10.1172/JCI0214505;
Claudel T., Sturm E., Duez H., Torra I.P., Sirvent A., Kosykh V.,
Fruchart J.C., Dallongeville J., Hum D.W., Kuipers F., Staels B.;
"Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-
I transcription via a negative FXR response element.";
J. Clin. Invest. 109:961-971(2002).
[13]
FUNCTION IN BA HOMEOSTASIS.
PubMed=12815072; DOI=10.1101/gad.1083503;
Holt J.A., Luo G., Billin A.N., Bisi J., McNeill Y.Y., Kozarsky K.F.,
Donahee M., Wang D.Y., Mansfield T.A., Kliewer S.A., Goodwin B.,
Jones S.A.;
"Definition of a novel growth factor-dependent signal cascade for the
suppression of bile acid biosynthesis.";
Genes Dev. 17:1581-1591(2003).
[14]
FUNCTION IN BA HOMEOSTASIS.
PubMed=12806625; DOI=10.1016/S0016-5085(03)00388-3;
Barbier O., Torra I.P., Sirvent A., Claudel T., Blanquart C.,
Duran-Sandoval D., Kuipers F., Kosykh V., Fruchart J.C., Staels B.;
"FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism
of negative feedback control of FXR activity.";
Gastroenterology 124:1926-1940(2003).
[15]
FUNCTION IN LIPID HOMEOSTASIS.
PubMed=12891557; DOI=10.1016/S0016-5085(03)00896-5;
Claudel T., Inoue Y., Barbier O., Duran-Sandoval D., Kosykh V.,
Fruchart J., Fruchart J.C., Gonzalez F.J., Staels B.;
"Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII
expression.";
Gastroenterology 125:544-555(2003).
[16]
FUNCTION IN LIPID HOMEOSTASIS.
PubMed=12660231; DOI=10.1074/jbc.M302505200;
Anisfeld A.M., Kast-Woelbern H.R., Meyer M.E., Jones S.A., Zhang Y.,
Williams K.J., Willson T., Edwards P.A.;
"Syndecan-1 expression is regulated in an isoform-specific manner by
the farnesoid-X receptor.";
J. Biol. Chem. 278:20420-20428(2003).
[17]
FUNCTION IN BA HOMEOSTASIS.
PubMed=12754200; DOI=10.1074/jbc.M302128200;
Pircher P.C., Kitto J.L., Petrowski M.L., Tangirala R.K.,
Bischoff E.D., Schulman I.G., Westin S.K.;
"Farnesoid X receptor regulates bile acid-amino acid conjugation.";
J. Biol. Chem. 278:27703-27711(2003).
[18]
FUNCTION IN LIPID HOMEOSTASIS.
PubMed=12554753; DOI=10.1210/me.2002-0120;
Pineda Torra I., Claudel T., Duval C., Kosykh V., Fruchart J.C.,
Staels B.;
"Bile acids induce the expression of the human peroxisome
proliferator-activated receptor alpha gene via activation of the
farnesoid X receptor.";
Mol. Endocrinol. 17:259-272(2003).
[19]
INTERACTION WITH PPARGC1A.
PubMed=15202934; DOI=10.1042/BJ20040432;
Kanaya E., Shiraki T., Jingami H.;
"The nuclear bile acid receptor FXR is activated by PGC-1alpha in a
ligand-dependent manner.";
Biochem. J. 382:913-921(2004).
[20]
INTERACTION WITH NCOA1, AND LIGAND-BINDING.
PubMed=14684751; DOI=10.1074/jbc.M306422200;
Lew J.L., Zhao A., Yu J., Huang L., De Pedro N., Pelaez F.,
Wright S.D., Cui J.;
"The farnesoid X receptor controls gene expression in a ligand- and
promoter-selective fashion.";
J. Biol. Chem. 279:8856-8861(2004).
[21]
FUNCTION IN BA HOEMOSTASIS.
PubMed=15239098; DOI=10.1002/hep.20295;
Neimark E., Chen F., Li X., Shneider B.L.;
"Bile acid-induced negative feedback regulation of the human ileal
bile acid transporter.";
Hepatology 40:149-156(2004).
[22]
INTERACTION WITH MED1.
PubMed=15187081; DOI=10.1074/jbc.M405126200;
Pineda Torra I., Freedman L.P., Garabedian M.J.;
"Identification of DRIP205 as a coactivator for the Farnesoid X
receptor.";
J. Biol. Chem. 279:36184-36191(2004).
[23]
FUNCTION IN LIPID HOMEOSTASIS.
PubMed=15337761; DOI=10.1074/jbc.M404255200;
Hirokane H., Nakahara M., Tachibana S., Shimizu M., Sato R.;
"Bile acid reduces the secretion of very low density lipoprotein by
repressing microsomal triglyceride transfer protein gene expression
mediated by hepatocyte nuclear factor-4.";
J. Biol. Chem. 279:45685-45692(2004).
[24]
FUNCTION IN BA HOMEOSTASIS, AND INTERACTION WITH CARM1.
PubMed=15471871; DOI=10.1074/jbc.M410021200;
Ananthanarayanan M., Li S., Balasubramaniyan N., Suchy F.J.,
Walsh M.J.;
"Ligand-dependent activation of the farnesoid X-receptor directs
arginine methylation of histone H3 by CARM1.";
J. Biol. Chem. 279:54348-54357(2004).
[25]
INTERACTION WITH PRMT1.
PubMed=15911693; DOI=10.1124/mol.105.012104;
Rizzo G., Renga B., Antonelli E., Passeri D., Pellicciari R.,
Fiorucci S.;
"The methyl transferase PRMT1 functions as co-activator of farnesoid X
receptor (FXR)/9-cis retinoid X receptor and regulates transcription
of FXR responsive genes.";
Mol. Pharmacol. 68:551-558(2005).
[26]
FUNCTION IN BA HOEMOSTASIS.
PubMed=16269519; DOI=10.1152/ajpgi.00430.2005;
Landrier J.-F., Eloranta J.J., Vavricka S.R., Kullak-Ublick G.A.;
"The nuclear receptor for bile acids, FXR, transactivates human
organic solute transporter-alpha and -beta genes.";
Am. J. Physiol. 290:G476-G485(2006).
[27]
FUNCTION IN BA HOEMOSTASIS.
PubMed=16946559; DOI=10.2133/dmpk.21.315;
Miyata M., Matsuda Y., Tsuchiya H., Kitada H., Akase T., Shimada M.,
Nagata K., Gonzalez F.J., Yamazoe Y.;
"Chenodeoxycholic acid-mediated activation of the farnesoid X receptor
negatively regulates hydroxysteroid sulfotransferase.";
Drug Metab. Pharmacokinet. 21:315-323(2006).
[28]
POSSIBLE INVOLVEMENT IN INTRAHEPATIC CHOLESTASIS OF PREGNANCY.
PubMed=17681172; DOI=10.1053/j.gastro.2007.05.015;
Van Mil S.W., Milona A., Dixon P.H., Mullenbach R., Geenes V.L.,
Chambers J., Shevchuk V., Moore G.E., Lammert F., Glantz A.G.,
Mattsson L.A., Whittaker J., Parker M.G., White R., Williamson C.;
"Functional variants of the central bile acid sensor FXR identified in
intrahepatic cholestasis of pregnancy.";
Gastroenterology 133:507-516(2007).
[29]
FUNCTION IN BA HOEMOSTASIS, AND INTERACTION WITH GPS2.
PubMed=17895379; DOI=10.1073/pnas.0706736104;
Sanyal S., Baavner A., Haroniti A., Nilsson L.M., Lundaasen T.,
Rehnmark S., Witt M.R., Einarsson C., Talianidis I., Gustafsson J.A.,
Treuter E.;
"Involvement of corepressor complex subunit GPS2 in transcriptional
pathways governing human bile acid biosynthesis.";
Proc. Natl. Acad. Sci. U.S.A. 104:15665-15670(2007).
[30]
PHOSPHORYLATION, AND MUTAGENESIS OF THR-456.
PubMed=18668687; DOI=10.1002/hep.22431;
Frankenberg T., Miloh T., Chen F.Y., Ananthanarayanan M., Sun A.Q.,
Balasubramaniyan N., Arias I., Setchell K.D., Suchy F.J.,
Shneider B.L.;
"The membrane protein ATPase class I type 8B member 1 signals through
protein kinase C zeta to activate the farnesoid X receptor.";
Hepatology 48:1896-1905(2008).
[31]
POSSIBLE INVOLVEMENT IN CHOLESTEROL CHOLELITHIASIS.
PubMed=17931734; DOI=10.1016/j.jhep.2007.07.027;
Kovacs P., Kress R., Rocha J., Kurtz U., Miquel J.F., Nervi F.,
Mendez-Sanchez N., Uribe M., Bock H.H., Schirin-Sokhan R.,
Stumvoll M., Moessner J., Lammert F., Wittenburg H.;
"Variation of the gene encoding the nuclear bile salt receptor FXR and
gallstone susceptibility in mice and humans.";
J. Hepatol. 48:116-124(2008).
[32]
PHOSPHORYLATION AT SER-145 AND SER-164, INTERACTION WITH PPARGC1A, AND
MUTAGENESIS OF SER-145 AND SER-164.
PubMed=18755856; DOI=10.1210/me.2008-0092;
Gineste R., Sirvent A., Paumelle R., Helleboid S., Aquilina A.,
Darteil R., Hum D.W., Fruchart J.C., Staels B.;
"Phosphorylation of farnesoid X receptor by protein kinase C promotes
its transcriptional activity.";
Mol. Endocrinol. 22:2433-2447(2008).
[33]
INTERACTION WITH XRCC5 AND XRCC6.
PubMed=19833092; DOI=10.1016/j.bbrc.2009.10.040;
Ohno M., Kunimoto M., Nishizuka M., Osada S., Imagawa M.;
"Ku proteins function as corepressors to regulate farnesoid X
receptor-mediated gene expression.";
Biochem. Biophys. Res. Commun. 390:738-742(2009).
[34]
TISSUE SPECIFICITY.
PubMed=19393742; DOI=10.1016/j.bbadis.2009.04.004;
Renga B., Migliorati M., Mencarelli A., Fiorucci S.;
"Reciprocal regulation of the bile acid-activated receptor FXR and the
interferon-gamma-STAT-1 pathway in macrophages.";
Biochim. Biophys. Acta 1792:564-573(2009).
[35]
ACETYLATION AT LYS-167 AND LYS-227 BY EP300.
PubMed=19883617; DOI=10.1016/j.cmet.2009.09.009;
Kemper J.K., Xiao Z., Ponugoti B., Miao J., Fang S., Kanamaluru D.,
Tsang S., Wu S.Y., Chiang C.M., Veenstra T.D.;
"FXR acetylation is normally dynamically regulated by p300 and SIRT1
but constitutively elevated in metabolic disease states.";
Cell Metab. 10:392-404(2009).
[36]
FUNCTION IN INTESTINAL INNATE IMMUNITY, TISSUE SPECIFICITY,
SUBCELLULAR LOCATION, AND SUMOYLATION.
PubMed=19864602; DOI=10.4049/jimmunol.0803978;
Vavassori P., Mencarelli A., Renga B., Distrutti E., Fiorucci S.;
"The bile acid receptor FXR is a modulator of intestinal innate
immunity.";
J. Immunol. 183:6251-6261(2009).
[37]
FUNCTION IN BA HOMEOSTASIS.
PubMed=19085950; DOI=10.1002/hep.22627;
Song K.H., Li T., Owsley E., Strom S., Chiang J.Y.;
"Bile acids activate fibroblast growth factor 19 signaling in human
hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene
expression.";
Hepatology 49:297-305(2009).
[38]
INTERACTION WITH SMARCA4.
PubMed=19805516; DOI=10.1128/MCB.00825-09;
Miao J., Fang S., Lee J., Comstock C., Knudsen K.E., Kemper J.K.;
"Functional specificities of Brm and Brg-1 Swi/Snf ATPases in the
feedback regulation of hepatic bile acid biosynthesis.";
Mol. Cell. Biol. 29:6170-6181(2009).
[39]
INTERACTION WITH PAGR1 AND NCOA6.
PubMed=19556342; DOI=10.1210/me.2009-0099;
Kim D.H., Lee J., Lee B., Lee J.W.;
"ASCOM controls farnesoid X receptor transactivation through its
associated histone H3 lysine 4 methyltransferase activity.";
Mol. Endocrinol. 23:1556-1562(2009).
[40]
FUNCTION IN GLUCOSE HOMEOSTASIS, AND TISSUE SPECIFICITY.
PubMed=20447400; DOI=10.1016/j.febslet.2010.04.068;
Popescu I.R., Helleboid-Chapman A., Lucas A., Vandewalle B.,
Dumont J., Bouchaert E., Derudas B., Kerr-Conte J., Caron S.,
Pattou F., Staels B.;
"The nuclear receptor FXR is expressed in pancreatic beta-cells and
protects human islets from lipotoxicity.";
FEBS Lett. 584:2845-2851(2010).
[41]
REVIEW.
PubMed=21383957; DOI=10.1621/nrs.08005;
Modica S., Gadaleta R.M., Moschetta A.;
"Deciphering the nuclear bile acid receptor FXR paradigm.";
Nucl. Recept. Signal. 8:E005-E005(2010).
[42]
FUNCTION IN INTESTINAL INFLAMMATION.
PubMed=21242261; DOI=10.1136/gut.2010.212159;
Gadaleta R.M., van Erpecum K.J., Oldenburg B., Willemsen E.C.,
Renooij W., Murzilli S., Klomp L.W., Siersema P.D., Schipper M.E.,
Danese S., Penna G., Laverny G., Adorini L., Moschetta A.,
van Mil S.W.;
"Farnesoid X receptor activation inhibits inflammation and preserves
the intestinal barrier in inflammatory bowel disease.";
Gut 60:463-472(2011).
[43]
FUNCTION IN LIPID HOMEOSTASIS.
PubMed=21804189; DOI=10.1172/JCI45277;
Chennamsetty I., Claudel T., Kostner K.M., Baghdasaryan A., Kratky D.,
Levak-Frank S., Frank S., Gonzalez F.J., Trauner M., Kostner G.M.;
"Farnesoid X receptor represses hepatic human APOA gene expression.";
J. Clin. Invest. 121:3724-3734(2011).
[44]
REVIEW.
PubMed=22820415; DOI=10.1016/j.bbalip.2012.07.004;
Hollman D.A., Milona A., van Erpecum K.J., van Mil S.W.;
"Anti-inflammatory and metabolic actions of FXR: insights into
molecular mechanisms.";
Biochim. Biophys. Acta 1821:1443-1452(2012).
[45]
METHYLATION AT LYS-220 BY SETD7.
PubMed=22345554; DOI=10.1152/ajpgi.00441.2011;
Balasubramaniyan N., Ananthanarayanan M., Suchy F.J.;
"Direct methylation of FXR by Set7/9, a lysine methyltransferase,
regulates the expression of FXR target genes.";
Am. J. Physiol. 302:G937-G947(2012).
[46]
POSSIBLE INVOLVEMENT IN PRIMARY BILIARY CIRRHOSIS.
PubMed=23235576; DOI=10.1002/14651858.CD000551.pub3;
Rudic J.S., Poropat G., Krstic M.N., Bjelakovic G., Gluud C.;
"Ursodeoxycholic acid for primary biliary cirrhosis.";
Cochrane Database Syst. Rev. 12:CD000551-CD000551(2012).
[47]
TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION.
PubMed=23928191; DOI=10.1016/j.bcp.2013.07.022;
Vaquero J., Monte M.J., Dominguez M., Muntane J., Marin J.J.;
"Differential activation of the human farnesoid X receptor depends on
the pattern of expressed isoforms and the bile acid pool
composition.";
Biochem. Pharmacol. 86:926-939(2013).
[48]
SUMOYLATION AT LYS-132 AND LYS-289, AND MUTAGENESIS OF LYS-132;
LYS-289 AND GLU-291.
PubMed=23546875; DOI=10.1074/jbc.M112.443937;
Balasubramaniyan N., Luo Y., Sun A.Q., Suchy F.J.;
"SUMOylation of the farnesoid X receptor (FXR) regulates the
expression of FXR target genes.";
J. Biol. Chem. 288:13850-13862(2013).
[49]
MUTAGENESIS OF LYS-132; LYS-167; LYS-220; LYS-227; LYS-353 AND
LYS-474, AND INTERACTION WITH RXRA AND SETD7.
PubMed=23462506; DOI=10.1124/mol.113.084772;
Sun A.Q., Luo Y., Backos D.S., Xu S., Balasubramaniyan N., Reigan P.,
Suchy F.J.;
"Identification of functionally relevant lysine residues that modulate
human farnesoid X receptor activation.";
Mol. Pharmacol. 83:1078-1086(2013).
[50]
INVOLVEMENT IN PFIC5, VARIANT PFIC5 LYS-149 INS, CHARACTERIZATION OF
VARIANT PFIC5 LYS-149 INS (ISOFORM 4), AND FUNCTION (ISOFORM 4).
PubMed=26888176; DOI=10.1038/ncomms10713;
Gomez-Ospina N., Potter C.J., Xiao R., Manickam K., Kim M.S.,
Kim K.H., Shneider B.L., Picarsic J.L., Jacobson T.A., Zhang J.,
He W., Liu P., Knisely A.S., Finegold M.J., Muzny D.M., Boerwinkle E.,
Lupski J.R., Plon S.E., Gibbs R.A., Eng C.M., Yang Y.,
Washington G.C., Porteus M.H., Berquist W.E., Kambham N., Singh R.J.,
Xia F., Enns G.M., Moore D.D.;
"Mutations in the nuclear bile acid receptor FXR cause progressive
familial intrahepatic cholestasis.";
Nat. Commun. 7:10713-10713(2016).
[51]
X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 258-476 IN COMPLEX WITH
SYNTHETIC AGONIST FEXARAMINE, FUNCTION, AND INTERACTION WITH NCOA1.
PubMed=12718892; DOI=10.1016/S1097-2765(03)00104-7;
Downes M., Verdecia M.A., Roecker A.J., Hughes R., Hogenesch J.B.,
Kast-Woelbern H.R., Bowman M.E., Ferrer J.L., Anisfeld A.M.,
Edwards P.A., Rosenfeld J.M., Alvarez J.G., Noel J.P., Nicolaou K.C.,
Evans R.M.;
"A chemical, genetic, and structural analysis of the nuclear bile acid
receptor FXR.";
Mol. Cell 11:1079-1092(2003).
[52]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 241-469 IN COMPLEXES WITH
CHENODEOXYCHOLIC ACID ANALOGS AND NCOA2 COACTIVATOR PEPTIDE.
PubMed=12718893; DOI=10.1016/S1097-2765(03)00112-6;
Mi L.Z., Devarakonda S., Harp J.M., Han Q., Pellicciari R.,
Willson T.M., Khorasanizadeh S., Rastinejad F.;
"Structural basis for bile acid binding and activation of the nuclear
receptor FXR.";
Mol. Cell 11:1093-1100(2003).
[53]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 252-486 IN COMPLEX WITH
SYNTHETIC AGONIST, FUNCTION, AND INTERACTION WITH NCOA1.
PubMed=18621523; DOI=10.1016/j.bmcl.2008.06.073;
Akwabi-Ameyaw A., Bass J.Y., Caldwell R.D., Caravella J.A., Chen L.,
Creech K.L., Deaton D.N., Jones S.A., Kaldor I., Liu Y., Madauss K.P.,
Marr H.B., McFadyen R.B., Miller A.B., Iii F.N., Parks D.J.,
Spearing P.K., Todd D., Williams S.P., Wisely G.B.;
"Conformationally constrained farnesoid X receptor (FXR) agonists:
Naphthoic acid-based analogs of GW 4064.";
Bioorg. Med. Chem. Lett. 18:4339-4343(2008).
[54]
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 249-486 IN COMPLEX WITH
STEROID ANALOG MFA-1 AND NCOA1 PEPTIDE, INTERACTION WITH NCOA1, AND
DOMAIN.
PubMed=18391212; DOI=10.1073/pnas.0710981105;
Soisson S.M., Parthasarathy G., Adams A.D., Sahoo S., Sitlani A.,
Sparrow C., Cui J., Becker J.W.;
"Identification of a potent synthetic FXR agonist with an unexpected
mode of binding and activation.";
Proc. Natl. Acad. Sci. U.S.A. 105:5337-5342(2008).
[55]
X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 260-486 IN COMPLEX WITH
SYNTHETIC AGONIST, FUNCTION, AND INTERACTION WITH NCOA1.
PubMed=19410460; DOI=10.1016/j.bmcl.2009.04.047;
Bass J.Y., Caldwell R.D., Caravella J.A., Chen L., Creech K.L.,
Deaton D.N., Madauss K.P., Marr H.B., McFadyen R.B., Miller A.B.,
Parks D.J., Todd D., Williams S.P., Wisely G.B.;
"Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist
GW4064.";
Bioorg. Med. Chem. Lett. 19:2969-2973(2009).
[56]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 257-486 IN COMPLEX WITH
SYNTHETIC AGONIST, FUNCTION, AND INTERACTION WITH NCOA1.
PubMed=19586769; DOI=10.1016/j.bmcl.2009.06.062;
Akwabi-Ameyaw A., Bass J.Y., Caldwell R.D., Caravella J.A., Chen L.,
Creech K.L., Deaton D.N., Madauss K.P., Marr H.B., McFadyen R.B.,
Miller A.B., Navas F. III, Parks D.J., Spearing P.K., Todd D.,
Williams S.P., Bruce Wisely G.;
"FXR agonist activity of conformationally constrained analogs of GW
4064.";
Bioorg. Med. Chem. Lett. 19:4733-4739(2009).
[57]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 258-486 IN COMPLEX WITH
SYNTHETIC AGONIST.
PubMed=19159286; DOI=10.1021/jm8014124;
Flatt B., Martin R., Wang T.L., Mahaney P., Murphy B., Gu X.H.,
Foster P., Li J., Pircher P., Petrowski M., Schulman I., Westin S.,
Wrobel J., Yan G., Bischoff E., Daige C., Mohan R.;
"Discovery of XL335 (WAY-362450), a highly potent, selective, and
orally active agonist of the farnesoid X receptor (FXR).";
J. Med. Chem. 52:904-907(2009).
[58]
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 248-476 IN COMPLEX WITH
SYNTHETIC AGONIST.
PubMed=20095622; DOI=10.1021/jm901650u;
Lundquist J.T., Harnish D.C., Kim C.Y., Mehlmann J.F., Unwalla R.J.,
Phipps K.M., Crawley M.L., Commons T., Green D.M., Xu W., Hum W.T.,
Eta J.E., Feingold I., Patel V., Evans M.J., Lai K.,
Borges-Marcucci L., Mahaney P.E., Wrobel J.E.;
"Improvement of physiochemical properties of the
tetrahydroazepinoindole series of farnesoid X receptor (FXR) agonists:
beneficial modulation of lipids in primates.";
J. Med. Chem. 53:1774-1787(2010).
-!- FUNCTION: Ligand-activated transcription factor. Receptor for bile
acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic
acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a
essential role in BA homeostasis through the regulation of genes
involved in BA synthesis, conjugation and enterohepatic
circulation. Also regulates lipid and glucose homeostasis and is
involved innate immune response (PubMed:10334992, PubMed:10334993,
PubMed:21383957, PubMed:22820415). The FXR-RXR heterodimer binds
predominantly to farnesoid X receptor response elements (FXREs)
containing two inverted repeats of the consensus sequence 5'-
AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1)
but also to tandem repeat DR1 sites with lower affinity, and can
be activated by either FXR or RXR-specific ligands. It is proposed
that monomeric nuclear receptors such as NR5A2/LRH-1 bound to
coregulatory nuclear responsive element (NRE) halfsites located in
close proximity to FXREs modulate transcriptional activity (By
similarity). In the liver activates transcription of the
corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1
(involved in BA synthesis) implicating at least in part histone
demethylase KDM1A resulting in epigenomic repression, and
SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs).
Activates transcription of the repressor MAFG (involved in
regulation of BA synthesis) (By similarity). Activates
transcription of SLC27A5/BACS and BAAT (involved in BA
conjugation), ABCB11/BSEP (involved in bile salt export) by
directly recruiting histone methyltransferase CARM1, and
ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4
(involved in secretion of phosphatidylcholine in the small
intestine) (PubMed:12754200, PubMed:15471871, PubMed:17895379).
Activates transcription of SLC27A5/BACS and BAAT (involved in BA
conjugation), ABCB11/BSEP (involved in bile salt export) by
directly recruiting histone methyltransferase CARM1, and
ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4
(involved in secretion of phosphatidylcholine in the small
intestine) (PubMed:10514450, PubMed:15239098, PubMed:16269519). In
the intestine activates FGF19 expression and secretion leading to
hepatic CYP7A1 repression (PubMed:12815072, PubMed:19085950). The
function also involves the coordinated induction of hepatic
KLB/beta-klotho expression (By similarity). Regulates
transcription of liver UGT2B4 and SULT2A1 involved in BA
detoxification; binding to the UGT2B4 promoter seems to imply a
monomeric transactivation independent of RXRA (PubMed:12806625,
PubMed:16946559). Modulates lipid homeostasis by activating liver
NR0B2/SHP-mediated repression of SREBF1 (involved in de novo
lipogenesis), expression of PLTP (involved in HDL formation),
SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA
(involved in beta-oxidation of fatty acids), VLDLR and SDC1
(involved in the hepatic uptake of LDL and IDL remnants), and
inhibiting expression of MTTP (involved in VLDL assembly
(PubMed:12660231, PubMed:12554753, PubMed:15337761). Increases
expression of APOC2 (promoting lipoprotein lipase activity
implicated in triglyceride clearance) (PubMed:11579204).
Transrepresses APOA1 involving a monomeric competition with NR2A1
for binding to a DR1 element (PubMed:11927623, PubMed:21804189).
Also reduces triglyceride clearance by inhibiting expression of
ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein
lipase) (PubMed:12891557). Involved in glucose homeostasis by
modulating hepatic gluconeogenesis through activation of
NR0B2/SHP-mediated repression of respective genes. Modulates
glycogen synthesis (inducing phosphorylation of glycogen synthase
kinase-3) (By similarity). Modulates glucose-stimulated insulin
secretion and is involved in insulin resistance (PubMed:20447400).
Involved in intestinal innate immunity. Plays a role in protecting
the distal small intestine against bacterial overgrowth and
preservation of the epithelial barrier (By similarity). Down-
regulates inflammatory cytokine expression in several types of
immune cells including macrophages and mononuclear cells
(PubMed:21242261). Mediates trans-repression of TLR4-induced
cytokine expression; the function seems to require its sumoylation
and prevents N-CoR nuclear receptor corepressor clearance from
target genes such as IL1B and NOS2 (PubMed:19864602). Involved in
the TLR9-mediated protective mechanism in intestinal inflammation.
Plays an anti-inflammatory role in liver inflammation; proposed to
inhibit proinflammatory (but not antiapoptotic) NF-kappa-B
signaling) (By similarity). {ECO:0000250|UniProtKB:Q60641,
ECO:0000250|UniProtKB:Q62735, ECO:0000269|PubMed:10334992,
ECO:0000269|PubMed:10334993, ECO:0000269|PubMed:10514450,
ECO:0000269|PubMed:11579204, ECO:0000269|PubMed:11927623,
ECO:0000269|PubMed:12554753, ECO:0000269|PubMed:12660231,
ECO:0000269|PubMed:12718892, ECO:0000269|PubMed:12754200,
ECO:0000269|PubMed:12806625, ECO:0000269|PubMed:12815072,
ECO:0000269|PubMed:12891557, ECO:0000269|PubMed:14684751,
ECO:0000269|PubMed:15239098, ECO:0000269|PubMed:15337761,
ECO:0000269|PubMed:15471871, ECO:0000269|PubMed:16269519,
ECO:0000269|PubMed:16946559, ECO:0000269|PubMed:17895379,
ECO:0000269|PubMed:18621523, ECO:0000269|PubMed:19085950,
ECO:0000269|PubMed:19410460, ECO:0000269|PubMed:19586769,
ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:20447400,
ECO:0000269|PubMed:21242261, ECO:0000269|PubMed:21804189,
ECO:0000269|PubMed:23928191, ECO:0000305|PubMed:21383957,
ECO:0000305|PubMed:22820415}.
-!- FUNCTION: Isoform 1: Promotes transcriptional activation of target
genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB
(inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low
activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and
ACA); not inducible by taurine- and glycine-amidated CDCA.
{ECO:0000269|PubMed:23928191}.
-!- FUNCTION: Isoform 2: Promotes transcriptional activation of target
genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA),
NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA),
SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and
FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA.
{ECO:0000269|PubMed:23928191}.
-!- FUNCTION: Isoform 3: Promotes transcriptional activation of target
genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB
(inducible by unconjugated CDCA and DCA) and IBAP; low activity
for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not
inducible by taurine- and glycine-amidated CDCA.
{ECO:0000269|PubMed:23928191}.
-!- FUNCTION: Isoform 4: Promotes transcriptional activation of target
genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA),
NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA),
SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and
FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3;
not inducible by taurine- and glycine-amidated CDCA.
{ECO:0000269|PubMed:23928191, ECO:0000269|PubMed:26888176}.
-!- SUBUNIT: Binds DNA predominantly as a heterodimer with RXRA. After
activation by agonist binding interacts with coactivators.
Interacts with NCOA1, NCOA2, PPARGC1A, CARM1, SETD7, PRMT1, GPS2,
SMARCA4 and MED1 (PubMed:15202934, PubMed:14684751,
PubMed:15187081, PubMed:15471871, PubMed:15911693,
PubMed:17895379, PubMed:18755856, PubMed:19805516,
PubMed:23462506, PubMed:12718892, PubMed:12718893,
PubMed:18621523, PubMed:18391212, PubMed:19410460,
PubMed:19586769). Interacts with EP300 and SMARCD1 (By
similarity). Interacts with XRCC5 and XRCC6; decreasing NR1H4/FXR
transactivation activity towards ABCB11/BSEP (PubMed:19833092).
Interacts with PAGR1 AND NCOA6; indicative for an association with
an MLL2/MLL3 complex (ASCOM) (PubMed:19556342).
{ECO:0000250|UniProtKB:Q60641, ECO:0000250|UniProtKB:Q62735,
ECO:0000269|PubMed:12718892, ECO:0000269|PubMed:12718893,
ECO:0000269|PubMed:14684751, ECO:0000269|PubMed:15187081,
ECO:0000269|PubMed:15202934, ECO:0000269|PubMed:15471871,
ECO:0000269|PubMed:15911693, ECO:0000269|PubMed:17895379,
ECO:0000269|PubMed:18391212, ECO:0000269|PubMed:18621523,
ECO:0000269|PubMed:19159286, ECO:0000269|PubMed:19410460,
ECO:0000269|PubMed:19556342, ECO:0000269|PubMed:19586769,
ECO:0000269|PubMed:19805516, ECO:0000269|PubMed:19833092,
ECO:0000269|PubMed:23462506}.
-!- INTERACTION:
P03372:ESR1; NbExp=2; IntAct=EBI-10921781, EBI-78473;
Q15788:NCOA1; NbExp=5; IntAct=EBI-9640524, EBI-455189;
P78527:PRKDC; NbExp=4; IntAct=EBI-9640524, EBI-352053;
Q8WTS6:SETD7; NbExp=5; IntAct=EBI-1250177, EBI-1268586;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19864602,
ECO:0000305}.
-!- SUBCELLULAR LOCATION: Isoform 1: Nucleus
{ECO:0000269|PubMed:23928191}.
-!- SUBCELLULAR LOCATION: Isoform 2: Nucleus
{ECO:0000269|PubMed:23928191}.
-!- SUBCELLULAR LOCATION: Isoform 3: Nucleus
{ECO:0000269|PubMed:23928191}.
-!- SUBCELLULAR LOCATION: Isoform 4: Nucleus
{ECO:0000269|PubMed:23928191}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative promoter usage, Alternative splicing; Named isoforms=5;
Name=1; Synonyms=FXRalpha2(+), FXRalpha1, FXRbeta1;
IsoId=Q96RI1-3; Sequence=Displayed;
Note=Produced by alternative promoter usage.;
Name=2; Synonyms=FXRalpha2(-), FXRalpha4, FXRbeta2;
IsoId=Q96RI1-4; Sequence=VSP_003665;
Note=Produced by alternative splicing of isoform 1.;
Name=3; Synonyms=FXRalpha1(+), FXRalpha1;
IsoId=Q96RI1-1; Sequence=VSP_010135;
Note=Produced by alternative promoter usage.;
Name=4; Synonyms=FXRalpha1(-), FXRalpha2;
IsoId=Q96RI1-2; Sequence=VSP_010135, VSP_003665;
Note=Produced by alternative splicing of isoform 3.;
Name=5;
IsoId=Q96RI1-5; Sequence=VSP_010135, VSP_044547;
Note=Produced by alternative splicing of isoform 3. No
experimental confirmation available.;
-!- TISSUE SPECIFICITY: Liver and hepatocyte-related cells express
mainly FXRalpha1-type isoforms with isoform 3 and isoform 4 in
approximately equal proportions. In intestine and kidney mainly
FXRalpha2-type isoforms are expressed with isoform 1 and isoform 2
in approximately equal proportions. Expressed in pancreatic beta
cells and macrophages. {ECO:0000269|PubMed:19393742,
ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:20447400,
ECO:0000269|PubMed:23928191}.
-!- PTM: Acetylated by EP300. Lys-227 as is the major acetylation site
for EP300; the dynamicly regulated acetylation inhibits
heterodimerization with RXRA and transactivation activity.
Deacetylated by SIRT1. {ECO:0000269|PubMed:18755856}.
-!- PTM: Methylation may increase transactivation of target genes.
{ECO:0000269|PubMed:22345554}.
-!- PTM: Phosphorylation by PKC/PRKCA increases transactivation
activity by promoting association with PPARGC1A.
{ECO:0000269|PubMed:18755856}.
-!- PTM: Sumoylated upon ligand binding. {ECO:0000269|PubMed:19864602,
ECO:0000269|PubMed:23546875}.
-!- DISEASE: Note=May be involved in intrahepatic cholestasis of
pregnancy. {ECO:0000305|PubMed:17681172}.
-!- DISEASE: Note=May be involved in cholesterol cholelithiasis.
{ECO:0000305|PubMed:17931734}.
-!- DISEASE: Cholestasis, progressive familial intrahepatic, 5 (PFIC5)
[MIM:617049]: A disorder characterized by early onset of
cholestasis that progresses to hepatic fibrosis, cirrhosis, and
end-stage liver disease before adulthood. PFIC5 is an autosomal
recessive, severe form characterized by onset of intralobular
cholestasis in the neonatal period. {ECO:0000269|PubMed:26888176}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- MISCELLANEOUS: Ursodeoxycholic (UDCA), a natural agonist of FXR,
is approved to treat primary biliary cirrhosis. However, effects
are discussed controversial. UDCA is also used to dissolve
(cholesterol) gallstones as alternative to surgery.
{ECO:0000305|PubMed:23235576}.
-!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
subfamily. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=BC144183; Type=Frameshift; Positions=156; Evidence={ECO:0000305};
-!- WEB RESOURCE: Name=Wikipedia; Note=Farnesoid X receptor entry;
URL="https://en.wikipedia.org/wiki/Farnesoid_X_receptor";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
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EMBL; U68233; AAB08107.1; -; mRNA.
EMBL; AF384555; AAK60271.1; -; mRNA.
EMBL; AF478445; AAM53550.1; -; mRNA.
EMBL; AF478446; AAM53551.1; -; mRNA.
EMBL; AK296612; BAH12398.1; -; mRNA.
EMBL; AC010200; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471054; EAW97639.1; -; Genomic_DNA.
EMBL; BC144183; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; BC144184; AAI44185.1; -; mRNA.
EMBL; BC130573; AAI30574.1; -; mRNA.
CCDS; CCDS55873.1; -. [Q96RI1-1]
CCDS; CCDS55874.1; -. [Q96RI1-5]
CCDS; CCDS55875.1; -. [Q96RI1-4]
CCDS; CCDS55876.1; -. [Q96RI1-3]
CCDS; CCDS9078.1; -. [Q96RI1-2]
RefSeq; NP_001193906.1; NM_001206977.1. [Q96RI1-1]
RefSeq; NP_001193907.1; NM_001206978.1. [Q96RI1-5]
RefSeq; NP_001193908.1; NM_001206979.1. [Q96RI1-1]
RefSeq; NP_001193921.1; NM_001206992.1. [Q96RI1-4]
RefSeq; NP_001193922.1; NM_001206993.1. [Q96RI1-3]
RefSeq; NP_005114.1; NM_005123.3. [Q96RI1-2]
RefSeq; XP_011537342.1; XM_011539040.2. [Q96RI1-1]
UniGene; Hs.282735; -.
UniGene; Hs.732506; -.
PDB; 1OSH; X-ray; 1.80 A; A=258-486.
PDB; 1OSK; Model; -; A=258-486.
PDB; 3BEJ; X-ray; 1.90 A; A/B=249-486.
PDB; 3DCT; X-ray; 2.50 A; A=252-486.
PDB; 3DCU; X-ray; 2.95 A; A=252-486.
PDB; 3FLI; X-ray; 2.00 A; A=258-486.
PDB; 3FXV; X-ray; 2.26 A; A=258-486.
PDB; 3GD2; X-ray; 3.20 A; A=260-486.
PDB; 3HC5; X-ray; 2.60 A; A=257-486.
PDB; 3HC6; X-ray; 3.20 A; A=257-486.
PDB; 3L1B; X-ray; 1.90 A; A=258-486.
PDB; 3OKH; X-ray; 2.50 A; A=258-486.
PDB; 3OKI; X-ray; 2.00 A; A/C=258-486.
PDB; 3OLF; X-ray; 1.90 A; A/C=258-486.
PDB; 3OMK; X-ray; 1.90 A; A/C=258-486.
PDB; 3OMM; X-ray; 2.10 A; A/C=258-486.
PDB; 3OOF; X-ray; 2.29 A; A/C=258-486.
PDB; 3OOK; X-ray; 2.29 A; A/C=258-486.
PDB; 3P88; X-ray; 2.95 A; A=258-486.
PDB; 3P89; X-ray; 2.30 A; A=258-486.
PDB; 3RUT; X-ray; 3.00 A; A=258-486.
PDB; 3RUU; X-ray; 2.50 A; A=258-486.
PDB; 3RVF; X-ray; 3.10 A; A=257-486.
PDB; 4OIV; X-ray; 1.70 A; A/B=258-483.
PDB; 4QE6; X-ray; 1.65 A; A=258-486.
PDB; 4QE8; X-ray; 2.62 A; A/B=258-486.
PDB; 4WVD; X-ray; 2.90 A; A/B=258-468.
PDB; 5IAW; X-ray; 2.58 A; A/B=259-486.
PDB; 5ICK; X-ray; 2.47 A; A/B=258-486.
PDB; 5Q0I; X-ray; 1.70 A; A=258-486.
PDB; 5Q0J; X-ray; 2.00 A; A/C=258-486.
PDB; 5Q0K; X-ray; 1.80 A; A=258-486.
PDB; 5Q0L; X-ray; 2.50 A; A/C=258-486.
PDB; 5Q0M; X-ray; 2.20 A; A=258-486.
PDB; 5Q0N; X-ray; 2.40 A; A/C=258-486.
PDB; 5Q0O; X-ray; 1.90 A; A/C=258-486.
PDB; 5Q0P; X-ray; 1.80 A; A/C=258-486.
PDB; 5Q0Q; X-ray; 2.60 A; A/C=258-486.
PDB; 5Q0R; X-ray; 1.91 A; A=258-486.
PDB; 5Q0S; X-ray; 2.50 A; A/C=258-486.
PDB; 5Q0T; X-ray; 2.14 A; A=258-486.
PDB; 5Q0U; X-ray; 1.90 A; A/C=258-486.
PDB; 5Q0V; X-ray; 1.87 A; A/C=258-486.
PDB; 5Q0W; X-ray; 1.90 A; A=258-486.
PDB; 5Q0X; X-ray; 2.26 A; A=258-486.
PDB; 5Q0Y; X-ray; 2.20 A; A/C=258-486.
PDB; 5Q0Z; X-ray; 2.26 A; A/C=258-486.
PDB; 5Q10; X-ray; 2.20 A; A=258-486.
PDB; 5Q11; X-ray; 2.20 A; A=258-486.
PDB; 5Q12; X-ray; 2.00 A; A=258-486.
PDB; 5Q13; X-ray; 1.90 A; A/C=258-486.
PDB; 5Q14; X-ray; 1.85 A; A/C=258-486.
PDB; 5Q15; X-ray; 1.90 A; A/C=258-486.
PDB; 5Q16; X-ray; 2.00 A; A/C=258-486.
PDB; 5Q17; X-ray; 2.10 A; A=258-486.
PDB; 5Q18; X-ray; 1.90 A; A/C=258-486.
PDB; 5Q19; X-ray; 1.98 A; A/C=258-486.
PDB; 5Q1A; X-ray; 2.00 A; A/C=258-486.
PDB; 5Q1B; X-ray; 2.30 A; A/C=258-486.
PDB; 5Q1C; X-ray; 2.30 A; A/C=258-486.
PDB; 5Q1D; X-ray; 1.89 A; A/C=258-486.
PDB; 5Q1E; X-ray; 1.85 A; A=258-486.
PDB; 5Q1F; X-ray; 2.30 A; A/C=258-486.
PDB; 5Q1G; X-ray; 2.00 A; A=258-486.
PDB; 5Q1H; X-ray; 2.20 A; A/C/E/G=258-486.
PDB; 5Q1I; X-ray; 1.95 A; A=258-486.
PDBsum; 1OSH; -.
PDBsum; 1OSK; -.
PDBsum; 3BEJ; -.
PDBsum; 3DCT; -.
PDBsum; 3DCU; -.
PDBsum; 3FLI; -.
PDBsum; 3FXV; -.
PDBsum; 3GD2; -.
PDBsum; 3HC5; -.
PDBsum; 3HC6; -.
PDBsum; 3L1B; -.
PDBsum; 3OKH; -.
PDBsum; 3OKI; -.
PDBsum; 3OLF; -.
PDBsum; 3OMK; -.
PDBsum; 3OMM; -.
PDBsum; 3OOF; -.
PDBsum; 3OOK; -.
PDBsum; 3P88; -.
PDBsum; 3P89; -.
PDBsum; 3RUT; -.
PDBsum; 3RUU; -.
PDBsum; 3RVF; -.
PDBsum; 4OIV; -.
PDBsum; 4QE6; -.
PDBsum; 4QE8; -.
PDBsum; 4WVD; -.
PDBsum; 5IAW; -.
PDBsum; 5ICK; -.
PDBsum; 5Q0I; -.
PDBsum; 5Q0J; -.
PDBsum; 5Q0K; -.
PDBsum; 5Q0L; -.
PDBsum; 5Q0M; -.
PDBsum; 5Q0N; -.
PDBsum; 5Q0O; -.
PDBsum; 5Q0P; -.
PDBsum; 5Q0Q; -.
PDBsum; 5Q0R; -.
PDBsum; 5Q0S; -.
PDBsum; 5Q0T; -.
PDBsum; 5Q0U; -.
PDBsum; 5Q0V; -.
PDBsum; 5Q0W; -.
PDBsum; 5Q0X; -.
PDBsum; 5Q0Y; -.
PDBsum; 5Q0Z; -.
PDBsum; 5Q10; -.
PDBsum; 5Q11; -.
PDBsum; 5Q12; -.
PDBsum; 5Q13; -.
PDBsum; 5Q14; -.
PDBsum; 5Q15; -.
PDBsum; 5Q16; -.
PDBsum; 5Q17; -.
PDBsum; 5Q18; -.
PDBsum; 5Q19; -.
PDBsum; 5Q1A; -.
PDBsum; 5Q1B; -.
PDBsum; 5Q1C; -.
PDBsum; 5Q1D; -.
PDBsum; 5Q1E; -.
PDBsum; 5Q1F; -.
PDBsum; 5Q1G; -.
PDBsum; 5Q1H; -.
PDBsum; 5Q1I; -.
ProteinModelPortal; Q96RI1; -.
SMR; Q96RI1; -.
BioGrid; 115296; 25.
DIP; DIP-39370N; -.
IntAct; Q96RI1; 14.
STRING; 9606.ENSP00000447149; -.
BindingDB; Q96RI1; -.
ChEMBL; CHEMBL2047; -.
DrugBank; DB06777; Chenodeoxycholic acid.
DrugBank; DB02545; Fexaramine.
DrugBank; DB05990; Obeticholic acid.
GuidetoPHARMACOLOGY; 603; -.
SwissLipids; SLP:000001581; -.
iPTMnet; Q96RI1; -.
PhosphoSitePlus; Q96RI1; -.
BioMuta; NR1H4; -.
DMDM; 46577705; -.
PaxDb; Q96RI1; -.
PeptideAtlas; Q96RI1; -.
PRIDE; Q96RI1; -.
DNASU; 9971; -.
Ensembl; ENST00000188403; ENSP00000188403; ENSG00000012504. [Q96RI1-4]
Ensembl; ENST00000392986; ENSP00000376712; ENSG00000012504. [Q96RI1-1]
Ensembl; ENST00000548884; ENSP00000448506; ENSG00000012504. [Q96RI1-2]
Ensembl; ENST00000549996; ENSP00000448978; ENSG00000012504. [Q96RI1-5]
Ensembl; ENST00000551379; ENSP00000447149; ENSG00000012504. [Q96RI1-3]
GeneID; 9971; -.
KEGG; hsa:9971; -.
UCSC; uc001thp.3; human. [Q96RI1-3]
CTD; 9971; -.
DisGeNET; 9971; -.
EuPathDB; HostDB:ENSG00000012504.13; -.
GeneCards; NR1H4; -.
HGNC; HGNC:7967; NR1H4.
HPA; HPA047699; -.
MalaCards; NR1H4; -.
MIM; 603826; gene.
MIM; 617049; phenotype.
neXtProt; NX_Q96RI1; -.
OpenTargets; ENSG00000012504; -.
Orphanet; 69665; Intrahepatic cholestasis of pregnancy.
PharmGKB; PA31752; -.
eggNOG; KOG3575; Eukaryota.
eggNOG; ENOG410XRZC; LUCA.
GeneTree; ENSGT00870000136372; -.
HOVERGEN; HBG108655; -.
InParanoid; Q96RI1; -.
KO; K08537; -.
OMA; MPQEITN; -.
OrthoDB; EOG091G0I4P; -.
PhylomeDB; Q96RI1; -.
TreeFam; TF316304; -.
Reactome; R-HSA-159418; Recycling of bile acids and salts.
Reactome; R-HSA-192105; Synthesis of bile acids and bile salts.
Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
Reactome; R-HSA-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
Reactome; R-HSA-1989781; PPARA activates gene expression.
Reactome; R-HSA-211976; Endogenous sterols.
Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
SignaLink; Q96RI1; -.
SIGNOR; Q96RI1; -.
EvolutionaryTrace; Q96RI1; -.
GeneWiki; Farnesoid_X_receptor; -.
GenomeRNAi; 9971; -.
PRO; PR:Q96RI1; -.
Proteomes; UP000005640; Chromosome 12.
Bgee; ENSG00000012504; -.
CleanEx; HS_NR1H4; -.
ExpressionAtlas; Q96RI1; baseline and differential.
Genevisible; Q96RI1; HS.
GO; GO:0005719; C:nuclear euchromatin; IDA:BHF-UCL.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0032052; F:bile acid binding; ISS:BHF-UCL.
GO; GO:0038181; F:bile acid receptor activity; IDA:UniProtKB.
GO; GO:1902122; F:chenodeoxycholic acid binding; IDA:UniProtKB.
GO; GO:0016922; F:ligand-dependent nuclear receptor binding; TAS:BHF-UCL.
GO; GO:0046965; F:retinoid X receptor binding; IEA:Ensembl.
GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:ParkinsonsUK-UCL.
GO; GO:0004879; F:RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding; IDA:ParkinsonsUK-UCL.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0003707; F:steroid hormone receptor activity; IEA:InterPro.
GO; GO:0004887; F:thyroid hormone receptor activity; IEA:InterPro.
GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:BHF-UCL.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc.
GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; IMP:UniProtKB.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:MGI.
GO; GO:0001190; F:transcriptional activator activity, RNA polymerase II transcription factor binding; IDA:BHF-UCL.
GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
GO; GO:0015721; P:bile acid and bile salt transport; TAS:Reactome.
GO; GO:0008206; P:bile acid metabolic process; IEA:Ensembl.
GO; GO:0038183; P:bile acid signaling pathway; ISS:BHF-UCL.
GO; GO:0007043; P:cell-cell junction assembly; IEA:Ensembl.
GO; GO:0071398; P:cellular response to fatty acid; IDA:UniProtKB.
GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
GO; GO:0071417; P:cellular response to organonitrogen compound; ISS:BHF-UCL.
GO; GO:0035356; P:cellular triglyceride homeostasis; IDA:UniProtKB.
GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl.
GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl.
GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
GO; GO:0034971; P:histone H3-R17 methylation; IDA:UniProtKB.
GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0072615; P:interleukin-17 secretion; IDA:UniProtKB.
GO; GO:0038185; P:intracellular bile acid receptor signaling pathway; IDA:UniProtKB.
GO; GO:0030522; P:intracellular receptor signaling pathway; ISS:BHF-UCL.
GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
GO; GO:0070858; P:negative regulation of bile acid biosynthetic process; IDA:UniProtKB.
GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
GO; GO:1902714; P:negative regulation of interferon-gamma secretion; IDA:UniProtKB.
GO; GO:0032692; P:negative regulation of interleukin-1 production; IEA:Ensembl.
GO; GO:0032703; P:negative regulation of interleukin-2 production; IEA:Ensembl.
GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
GO; GO:0071638; P:negative regulation of monocyte chemotactic protein-1 production; IEA:Ensembl.
GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
GO; GO:1904468; P:negative regulation of tumor necrosis factor secretion; IDA:UniProtKB.
GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
GO; GO:0001080; P:nitrogen catabolite activation of transcription from RNA polymerase II promoter; IC:BHF-UCL.
GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
GO; GO:1904179; P:positive regulation of adipose tissue development; IEA:Ensembl.
GO; GO:2001250; P:positive regulation of ammonia assimilation cycle; IEA:Ensembl.
GO; GO:2001275; P:positive regulation of glucose import in response to insulin stimulus; IEA:Ensembl.
GO; GO:2000213; P:positive regulation of glutamate metabolic process; ISS:BHF-UCL.
GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IEA:Ensembl.
GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
GO; GO:1905695; P:positive regulation of phosphatidic acid biosynthetic process; IDA:ParkinsonsUK-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:ParkinsonsUK-UCL.
GO; GO:0070857; P:regulation of bile acid biosynthetic process; TAS:BHF-UCL.
GO; GO:2000188; P:regulation of cholesterol homeostasis; IEA:Ensembl.
GO; GO:0090181; P:regulation of cholesterol metabolic process; TAS:BHF-UCL.
GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IDA:UniProtKB.
GO; GO:0010988; P:regulation of low-density lipoprotein particle clearance; IDA:UniProtKB.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
GO; GO:0034255; P:regulation of urea metabolic process; ISS:BHF-UCL.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:UniProtKB.
GO; GO:0034162; P:toll-like receptor 9 signaling pathway; IEA:Ensembl.
GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
Gene3D; 1.10.565.10; -; 1.
Gene3D; 3.30.50.10; -; 1.
InterPro; IPR035500; NHR_like_domain.
InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
InterPro; IPR001723; Nuclear_hrmn_rcpt.
InterPro; IPR001728; ThyrH_rcpt.
InterPro; IPR001628; Znf_hrmn_rcpt.
InterPro; IPR013088; Znf_NHR/GATA.
Pfam; PF00104; Hormone_recep; 1.
Pfam; PF00105; zf-C4; 1.
PRINTS; PR00398; STRDHORMONER.
PRINTS; PR00047; STROIDFINGER.
PRINTS; PR00546; THYROIDHORMR.
SMART; SM00430; HOLI; 1.
SMART; SM00399; ZnF_C4; 1.
SUPFAM; SSF48508; SSF48508; 1.
PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Activator; Alternative promoter usage;
Alternative splicing; Complete proteome; Disease mutation;
DNA-binding; Immunity; Inflammatory response; Innate immunity;
Intrahepatic cholestasis; Isopeptide bond; Metal-binding; Methylation;
Nucleus; Phosphoprotein; Receptor; Reference proteome; Repressor;
Transcription; Transcription regulation; Ubl conjugation; Zinc;
Zinc-finger.
CHAIN 1 486 Bile acid receptor.
/FTId=PRO_0000053538.
DNA_BIND 134 209 Nuclear receptor. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
ZN_FING 137 157 NR C4-type. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
ZN_FING 173 197 NR C4-type. {ECO:0000255|PROSITE-
ProRule:PRU00407}.
REGION 256 474 Ligand-binding.
REGION 342 350 Agonist binding.
{ECO:0000250|UniProtKB:Q62735}.
BINDING 375 375 Agonist. {ECO:0000250|UniProtKB:Q62735}.
BINDING 383 383 Agonist. {ECO:0000250|UniProtKB:Q62735}.
BINDING 461 461 Agonist. {ECO:0000250|UniProtKB:Q62735}.
BINDING 483 483 Agonist. {ECO:0000250|UniProtKB:Q62735}.
MOD_RES 145 145 Phosphoserine; by PKC/PRKCA.
{ECO:0000269|PubMed:18755856}.
MOD_RES 164 164 Phosphoserine; by PKC/PRKCA.
{ECO:0000269|PubMed:18755856}.
MOD_RES 167 167 N6-acetyllysine; by EP300.
MOD_RES 220 220 N6-methyllysine; by SETD7.
{ECO:0000269|PubMed:22345554}.
MOD_RES 227 227 N6-acetyllysine; by EP300.
MOD_RES 456 456 Phosphothreonine; by PKC/PRKCZ.
{ECO:0000305|PubMed:18668687}.
CROSSLNK 132 132 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO1).
{ECO:0000305|PubMed:23546875}.
CROSSLNK 289 289 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO1).
{ECO:0000305|PubMed:23546875}.
VAR_SEQ 1 36 MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK -> M
GSKMNLIEHSHLPTTDEFSFSENLF (in isoform 3,
isoform 4 and isoform 5).
{ECO:0000303|PubMed:15489334,
ECO:0000303|Ref.1, ECO:0000303|Ref.2}.
/FTId=VSP_010135.
VAR_SEQ 159 209 Missing (in isoform 5).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_044547.
VAR_SEQ 207 210 Missing (in isoform 2 and isoform 4).
{ECO:0000303|PubMed:12062799,
ECO:0000303|Ref.2}.
/FTId=VSP_003665.
VARIANT 149 149 Y -> YK (in PFIC5; loss of isoform 4
transcription regulatory region sequence-
specific DNA binding activity; loss of
isoform 4 function in regulation of
transcription DNA-templated).
{ECO:0000269|PubMed:26888176}.
/FTId=VAR_077017.
MUTAGEN 132 132 K->R: Abrogates SUMO1-medieated
inhibition of ligand-induced
transcactivation at ABCB11/BSEP and
NR0B2/SHP promoters; when associated with
R-289 and A-291.
{ECO:0000269|PubMed:23546875}.
MUTAGEN 132 132 K->R: Decreases transcriptional
activation SLC51A/OSTA, SLC51B/OSTB and
ABCB11/BSEP, no effect on interaction
with RXRA and SETD7.
{ECO:0000269|PubMed:23462506}.
MUTAGEN 145 145 S->A: Impairs ligand-dependent
transactivation activity, impairs
interaction with PPARGC1A; when
associated with A-164.
{ECO:0000269|PubMed:18755856}.
MUTAGEN 164 164 S->A: Impairs ligand-dependent
transactivation activity, impairs
interaction with PPARGC1A; when
associated with A-145.
{ECO:0000269|PubMed:18755856}.
MUTAGEN 167 167 K->R: Decreases transcriptional
activation of SLC51B/OSTB, no effect on
SLC51A/OSTA and ABCB11/BSEP, no effect on
interaction with RXRA and SETD7.
{ECO:0000269|PubMed:23462506}.
MUTAGEN 220 220 K->R: Decreases transcriptional
activation of SLC51B/OSTB, no effect on
SLC51A/OSTA and ABCB11/BSEP, impairs
interaction with RXRA and SETD7.
{ECO:0000269|PubMed:23462506}.
MUTAGEN 227 227 K->R: Decreases transcriptional
activation SC51A/OSTA, SLC51B/OSTB and
ABCB11/BSEP, impairs interaction with
RXRA and enhances interaction with SETD7,
decreases association with ABCB11/BSEP
promoter. {ECO:0000269|PubMed:23462506}.
MUTAGEN 289 289 K->R: Abrogates SUMO1-mediated inhibition
of ligand-induced transcactivation at
ABCB11/BSEP and NR0B2/SHP promoters; when
associated with R-132 and A-291.
{ECO:0000269|PubMed:23546875}.
MUTAGEN 291 291 E->A: Abrogates SUMO1-mediated inhibition
of ligand-induced transcactivation at
ABCB11/BSEP and NR0B2/SHP promoters; when
associated with R-132 and R-289.
{ECO:0000269|PubMed:23546875}.
MUTAGEN 353 353 K->R: Decreases transcriptional
activation SLC51A/OSTA, SLC51B/OSTB and
ABCB11/BSEP, no effect on interaction
with RXRA and SETD7, decreases
association with ABCB11/BSEP promoter.
{ECO:0000269|PubMed:23462506}.
MUTAGEN 456 456 T->A: Impairs transcriptional activation
of ABCB11/BSEP.
{ECO:0000269|PubMed:18668687}.
MUTAGEN 474 474 K->R: Decreases transcriptional
activation SLC51A/OSTA, SLC51B/OSTB and
ABCB11/BSEP, no effect on interaction
with RXRA and impairs interaction with
SETD7. {ECO:0000269|PubMed:23462506}.
CONFLICT 198 198 K -> R (in Ref. 7; AAI44185).
{ECO:0000305}.
CONFLICT 217 217 C -> V (in Ref. 7; BC144183).
{ECO:0000305}.
HELIX 261 274 {ECO:0000244|PDB:4QE6}.
HELIX 281 289 {ECO:0000244|PDB:4QE6}.
HELIX 294 317 {ECO:0000244|PDB:4QE6}.
HELIX 322 324 {ECO:0000244|PDB:4QE6}.
HELIX 327 349 {ECO:0000244|PDB:4QE6}.
TURN 354 356 {ECO:0000244|PDB:4OIV}.
HELIX 360 367 {ECO:0000244|PDB:4QE6}.
TURN 368 370 {ECO:0000244|PDB:3OKH}.
HELIX 373 387 {ECO:0000244|PDB:4QE6}.
TURN 388 390 {ECO:0000244|PDB:4OIV}.
HELIX 393 404 {ECO:0000244|PDB:4QE6}.
STRAND 407 411 {ECO:0000244|PDB:3OMM}.
HELIX 415 436 {ECO:0000244|PDB:4QE6}.
HELIX 443 465 {ECO:0000244|PDB:4QE6}.
STRAND 468 472 {ECO:0000244|PDB:4OIV}.
HELIX 477 482 {ECO:0000244|PDB:4QE6}.
SEQUENCE 486 AA; 55914 MW; C23283576A8CF76B CRC64;
MVMQFQGLEN PIQISPHCSC TPSGFFMEMM SMKPAKGVLT EQVAGPLGQN LEVEPYSQYS
NVQFPQVQPQ ISSSSYYSNL GFYPQQPEEW YSPGIYELRR MPAETLYQGE TEVAEMPVTK
KPRMGASAGR IKGDELCVVC GDRASGYHYN ALTCEGCKGF FRRSITKNAV YKCKNGGNCV
MDMYMRRKCQ ECRLRKCKEM GMLAECMYTG LLTEIQCKSK RLRKNVKQHA DQTVNEDSEG
RDLRQVTSTT KSCREKTELT PDQQTLLHFI MDSYNKQRMP QEITNKILKE EFSAEENFLI
LTEMATNHVQ VLVEFTKKLP GFQTLDHEDQ IALLKGSAVE AMFLRSAEIF NKKLPSGHSD
LLEERIRNSG ISDEYITPMF SFYKSIGELK MTQEEYALLT AIVILSPDRQ YIKDREAVEK
LQEPLLDVLQ KLCKIHQPEN PQHFACLLGR LTELRTFNHH HAEMLMSWRV NDHKFTPLLC
EIWDVQ


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Catalog number Product name Quantity
E2042m ELISA Bar,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,Fxr,Mouse,Mus musculus,Nr1h4,Nuclear receptor subfamily 1 group H member 4,Retinoid X receptor-interacting protein 1 96T
U2042m CLIA Bar,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,Fxr,Mouse,Mus musculus,Nr1h4,Nuclear receptor subfamily 1 group H member 4,Retinoid X receptor-interacting protein 14 96T
U2042r CLIA Bar,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,Fxr,Nr1h4,Nuclear receptor subfamily 1 group H member 4,Rat,Rattus norvegicus,Retinoid X receptor-interacting protein 96T
E2042r ELISA kit Bar,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,Fxr,Nr1h4,Nuclear receptor subfamily 1 group H member 4,Rat,Rattus norvegicus,Retinoid X receptor-interacting p 96T
U2042r CLIA kit Bar,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,Fxr,Nr1h4,Nuclear receptor subfamily 1 group H member 4,Rat,Rattus norvegicus,Retinoid X receptor-interacting pr 96T
E2042m ELISA kit Bar,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,Fxr,Mouse,Mus musculus,Nr1h4,Nuclear receptor subfamily 1 group H member 4,Retinoid X receptor-interacting prot 96T
U2042m CLIA kit Bar,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,Fxr,Mouse,Mus musculus,Nr1h4,Nuclear receptor subfamily 1 group H member 4,Retinoid X receptor-interacting prote 96T
E2042r ELISA Bar,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,Fxr,Nr1h4,Nuclear receptor subfamily 1 group H member 4,Rat,Rattus norvegicus,Retinoid X receptor-interacting protei 96T
E2042h ELISA kit BAR,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,FXR,Homo sapiens,HRR1,Human,NR1H4,Nuclear receptor subfamily 1 group H member 4,Retinoid X receptor-interacting 96T
U2042h CLIA kit BAR,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,FXR,Homo sapiens,HRR1,Human,NR1H4,Nuclear receptor subfamily 1 group H member 4,Retinoid X receptor-interacting 96T
E2042h ELISA BAR,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,FXR,Homo sapiens,HRR1,Human,NR1H4,Nuclear receptor subfamily 1 group H member 4,Retinoid X receptor-interacting prot 96T
U2042h CLIA BAR,Bile acid receptor,Farnesoid X-activated receptor,Farnesol receptor HRR-1,FXR,Homo sapiens,HRR1,Human,NR1H4,Nuclear receptor subfamily 1 group H member 4,Retinoid X receptor-interacting prote 96T
E2042b ELISA kit Bile acid receptor,Bos taurus,Bovine,Farnesoid X-activated receptor,Farnesol receptor HRR-1,NR1H4,Nuclear receptor subfamily 1 group H member 4 96T
U2042b CLIA kit Bile acid receptor,Bos taurus,Bovine,Farnesoid X-activated receptor,Farnesol receptor HRR-1,NR1H4,Nuclear receptor subfamily 1 group H member 4 96T
E2042b ELISA Bile acid receptor,Bos taurus,Bovine,Farnesoid X-activated receptor,Farnesol receptor HRR-1,NR1H4,Nuclear receptor subfamily 1 group H member 4 96T
U2042b CLIA Bile acid receptor,Bos taurus,Bovine,Farnesoid X-activated receptor,Farnesol receptor HRR-1,NR1H4,Nuclear receptor subfamily 1 group H member 4 96T
EIAAB27780 Liver X receptor beta,Lxrb,Mouse,Mus musculus,Nr1h2,Nuclear receptor subfamily 1 group H member 2,Oxysterols receptor LXR-beta,Retinoid X receptor-interacting protein No.15,Rip15,Ubiquitously-expresse
EIAAB36502 Nr2b2,Nuclear receptor coregulator 1,Nuclear receptor subfamily 2 group B member 2,Rat,Rattus norvegicus,Rcor-1,Retinoic acid receptor RXR-beta,Retinoid X receptor beta,Rxrb
EIAAB36503 MHC class I regulatory element-binding protein H-2RIIBP,Mouse,Mus musculus,Nr2b2,Nuclear receptor subfamily 2 group B member 2,Retinoic acid receptor RXR-beta,Retinoid X receptor beta,Rxrb
EIAAB36506 NR2B3,Nuclear receptor subfamily 2 group B member 3,Pig,Retinoic acid receptor RXR-gamma,Retinoid X receptor gamma,RXRG,Sus scrofa
EIAAB36510 Mouse,Mus musculus,Nr2b3,Nuclear receptor subfamily 2 group B member 3,Retinoic acid receptor RXR-gamma,Retinoid X receptor gamma,Rxrg
EIAAB36509 Bos taurus,Bovine,NR2B3,Nuclear receptor subfamily 2 group B member 3,Retinoic acid receptor RXR-gamma,Retinoid X receptor gamma,RXRG
EIAAB36508 Nr2b3,Nuclear receptor subfamily 2 group B member 3,Rat,Rattus norvegicus,Retinoic acid receptor RXR-gamma,Retinoid X receptor gamma,Rxrg
E2043r ELISA Nr2b1,Nuclear receptor subfamily 2 group B member 1,Rat,Rattus norvegicus,Retinoic acid receptor RXR-alpha,Retinoid X receptor alpha,Rxra 96T
E2043r ELISA kit Nr2b1,Nuclear receptor subfamily 2 group B member 1,Rat,Rattus norvegicus,Retinoic acid receptor RXR-alpha,Retinoid X receptor alpha,Rxra 96T


 

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