NR1H4_MOUSE
ID NR1H4_MOUSE Reviewed; 488 AA.
AC Q60641; D3YTT2; E9QJW2; Q60642; Q60643;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Bile acid receptor;
DE AltName: Full=Farnesoid X-activated receptor;
DE AltName: Full=Farnesol receptor HRR-1;
DE AltName: Full=Nuclear receptor subfamily 1 group H member 4;
DE AltName: Full=Retinoid X receptor-interacting protein 14;
DE Short=RXR-interacting protein 14;
GN Name=Nr1h4; Synonyms=Bar, Fxr, Rip14;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND INTERACTION WITH RXRA.
RC TISSUE=Liver;
RX PubMed=7760852; DOI=10.1210/mend.9.1.7760852;
RA Seol W., Choi H.S., Moore D.D.;
RT "Isolation of proteins that interact specifically with the retinoid X
RT receptor: two novel orphan receptors.";
RL Mol. Endocrinol. 9:72-85(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11030617; DOI=10.1016/s0092-8674(00)00062-3;
RA Sinal C.J., Tohkin M., Miyata M., Ward J.M., Lambert G., Gonzalez F.J.;
RT "Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and
RT lipid homeostasis.";
RL Cell 102:731-744(2000).
RN [5]
RP FUNCTION IN LIPID HOMEOSTASIS.
RX PubMed=11579204; DOI=10.1210/mend.15.10.0712;
RA Kast H.R., Nguyen C.M., Sinal C.J., Jones S.A., Laffitte B.A., Reue K.,
RA Gonzalez F.J., Willson T.M., Edwards P.A.;
RT "Farnesoid X-activated receptor induces apolipoprotein C-II transcription:
RT a molecular mechanism linking plasma triglyceride levels to bile acids.";
RL Mol. Endocrinol. 15:1720-1728(2001).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF LYS-370 AND VAL-388.
RX PubMed=12004058; DOI=10.1074/jbc.m200824200;
RA Cui J., Heard T.S., Yu J., Lo J.L., Huang L., Li Y., Schaeffer J.M.,
RA Wright S.D.;
RT "The amino acid residues asparagine 354 and isoleucine 372 of human
RT farnesoid X receptor confer the receptor with high sensitivity to
RT chenodeoxycholate.";
RL J. Biol. Chem. 277:25963-25969(2002).
RN [7]
RP FUNCTION.
RX PubMed=11706036; DOI=10.1074/jbc.m109326200;
RA Kast H.R., Goodwin B., Tarr P.T., Jones S.A., Anisfeld A.M., Stoltz C.M.,
RA Tontonoz P., Kliewer S., Willson T.M., Edwards P.A.;
RT "Regulation of multidrug resistance-associated protein 2 (ABCC2) by the
RT nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and
RT constitutive androstane receptor.";
RL J. Biol. Chem. 277:2908-2915(2002).
RN [8]
RP FUNCTION IN LIPID HOMEOSTASIS.
RX PubMed=12891557; DOI=10.1016/s0016-5085(03)00896-5;
RA Claudel T., Inoue Y., Barbier O., Duran-Sandoval D., Kosykh V.,
RA Fruchart J., Fruchart J.C., Gonzalez F.J., Staels B.;
RT "Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII
RT expression.";
RL Gastroenterology 125:544-555(2003).
RN [9]
RP FUNCTION, AND ALTERNATIVE SPLICING.
RX PubMed=12393883; DOI=10.1074/jbc.m209505200;
RA Zhang Y., Kast-Woelbern H.R., Edwards P.A.;
RT "Natural structural variants of the nuclear receptor farnesoid X receptor
RT affect transcriptional activation.";
RL J. Biol. Chem. 278:104-110(2003).
RN [10]
RP FUNCTION IN LIPID HOMEOSTASIS.
RX PubMed=12421815; DOI=10.1074/jbc.m209525200;
RA Lambert G., Amar M.J., Guo G., Brewer H.B. Jr., Gonzalez F.J., Sinal C.J.;
RT "The farnesoid X-receptor is an essential regulator of cholesterol
RT homeostasis.";
RL J. Biol. Chem. 278:2563-2570(2003).
RN [11]
RP FUNCTION IN LIPID HOMEOSTASIS.
RX PubMed=12660231; DOI=10.1074/jbc.m302505200;
RA Anisfeld A.M., Kast-Woelbern H.R., Meyer M.E., Jones S.A., Zhang Y.,
RA Williams K.J., Willson T., Edwards P.A.;
RT "Syndecan-1 expression is regulated in an isoform-specific manner by the
RT farnesoid-X receptor.";
RL J. Biol. Chem. 278:20420-20428(2003).
RN [12]
RP INTERACTION WITH PPARGC1A.
RX PubMed=14729567; DOI=10.1101/gad.1138104;
RA Zhang Y., Castellani L.W., Sinal C.J., Gonzalez F.J., Edwards P.A.;
RT "Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-
RT 1alpha) regulates triglyceride metabolism by activation of the nuclear
RT receptor FXR.";
RL Genes Dev. 18:157-169(2004).
RN [13]
RP FUNCTION IN LIPID HOMEOSTASIS.
RX PubMed=15146238; DOI=10.1172/jci200421025;
RA Watanabe M., Houten S.M., Wang L., Moschetta A., Mangelsdorf D.J.,
RA Heyman R.A., Moore D.D., Auwerx J.;
RT "Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and
RT SREBP-1c.";
RL J. Clin. Invest. 113:1408-1418(2004).
RN [14]
RP FUNCTION IN BA HOMEOSTASIS.
RX PubMed=16213224; DOI=10.1016/j.cmet.2005.09.001;
RA Inagaki T., Choi M., Moschetta A., Peng L., Cummins C.L., McDonald J.G.,
RA Luo G., Jones S.A., Goodwin B., Richardson J.A., Gerard R.D., Repa J.J.,
RA Mangelsdorf D.J., Kliewer S.A.;
RT "Fibroblast growth factor 15 functions as an enterohepatic signal to
RT regulate bile acid homeostasis.";
RL Cell Metab. 2:217-225(2005).
RN [15]
RP FUNCTION IN GLUCOSE HOMEOSTASIS.
RX PubMed=15564327; DOI=10.1210/en.2004-0965;
RA Stayrook K.R., Bramlett K.S., Savkur R.S., Ficorilli J., Cook T.,
RA Christe M.E., Michael L.F., Burris T.P.;
RT "Regulation of carbohydrate metabolism by the farnesoid X receptor.";
RL Endocrinology 146:984-991(2005).
RN [16]
RP FUNCTION BA HOMEOSTASIS.
RX PubMed=16946559; DOI=10.2133/dmpk.21.315;
RA Miyata M., Matsuda Y., Tsuchiya H., Kitada H., Akase T., Shimada M.,
RA Nagata K., Gonzalez F.J., Yamazoe Y.;
RT "Chenodeoxycholic acid-mediated activation of the farnesoid X receptor
RT negatively regulates hydroxysteroid sulfotransferase.";
RL Drug Metab. Pharmacokinet. 21:315-323(2006).
RN [17]
RP FUNCTION IN GLUCOSE HOMEOSTASIS.
RX PubMed=16446356; DOI=10.1074/jbc.m510258200;
RA Cariou B., van Harmelen K., Duran-Sandoval D., van Dijk T.H., Grefhorst A.,
RA Abdelkarim M., Caron S., Torpier G., Fruchart J.C., Gonzalez F.J.,
RA Kuipers F., Staels B.;
RT "The farnesoid X receptor modulates adiposity and peripheral insulin
RT sensitivity in mice.";
RL J. Biol. Chem. 281:11039-11049(2006).
RN [18]
RP FUNCTION IN GLUCOSE HOMEOSTASIS.
RX PubMed=16557297; DOI=10.1172/jci25604;
RA Ma K., Saha P.K., Chan L., Moore D.D.;
RT "Farnesoid X receptor is essential for normal glucose homeostasis.";
RL J. Clin. Invest. 116:1102-1109(2006).
RN [19]
RP FUNCTION IN GLUCOSE HOMEOSTASIS.
RX PubMed=16410358; DOI=10.1073/pnas.0506982103;
RA Zhang Y., Lee F.Y., Barrera G., Lee H., Vales C., Gonzalez F.J.,
RA Willson T.M., Edwards P.A.;
RT "Activation of the nuclear receptor FXR improves hyperglycemia and
RT hyperlipidemia in diabetic mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:1006-1011(2006).
RN [20]
RP FUNCTION IN ANTIBACTERIAL DEFENSE, AND TISSUE SPECIFICITY.
RX PubMed=16473946; DOI=10.1073/pnas.0509592103;
RA Inagaki T., Moschetta A., Lee Y.K., Peng L., Zhao G., Downes M., Yu R.T.,
RA Shelton J.M., Richardson J.A., Repa J.J., Mangelsdorf D.J., Kliewer S.A.;
RT "Regulation of antibacterial defense in the small intestine by the nuclear
RT bile acid receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:3920-3925(2006).
RN [21]
RP POSSIBLE FUNCTION IN TUMOR SUPPRESSION.
RX PubMed=19047134; DOI=10.1158/0008-5472.can-08-1791;
RA Modica S., Murzilli S., Salvatore L., Schmidt D.R., Moschetta A.;
RT "Nuclear bile acid receptor FXR protects against intestinal
RT tumorigenesis.";
RL Cancer Res. 68:9589-9594(2008).
RN [22]
RP INTERACTION WITH EP300, AND ACETYLATION.
RX PubMed=18842595; DOI=10.1074/jbc.m803531200;
RA Fang S., Tsang S., Jones R., Ponugoti B., Yoon H., Wu S.Y., Chiang C.M.,
RA Willson T.M., Kemper J.K.;
RT "The p300 acetylase is critical for ligand-activated farnesoid X receptor
RT (FXR) induction of SHP.";
RL J. Biol. Chem. 283:35086-35095(2008).
RN [23]
RP FUNCTION IN INFLAMMATORY RESPONSE.
RX PubMed=18972444; DOI=10.1002/hep.22519;
RA Wang Y.D., Chen W.D., Wang M., Yu D., Forman B.M., Huang W.;
RT "Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic
RT inflammatory response.";
RL Hepatology 48:1632-1643(2008).
RN [24]
RP TISSUE SPECIFICITY.
RX PubMed=19393742; DOI=10.1016/j.bbadis.2009.04.004;
RA Renga B., Migliorati M., Mencarelli A., Fiorucci S.;
RT "Reciprocal regulation of the bile acid-activated receptor FXR and the
RT interferon-gamma-STAT-1 pathway in macrophages.";
RL Biochim. Biophys. Acta 1792:564-573(2009).
RN [25]
RP ACETYLATION.
RX PubMed=19883617; DOI=10.1016/j.cmet.2009.09.009;
RA Kemper J.K., Xiao Z., Ponugoti B., Miao J., Fang S., Kanamaluru D.,
RA Tsang S., Wu S.Y., Chiang C.M., Veenstra T.D.;
RT "FXR acetylation is normally dynamically regulated by p300 and SIRT1 but
RT constitutively elevated in metabolic disease states.";
RL Cell Metab. 10:392-404(2009).
RN [26]
RP FUNCTION IN INTESTINAL INNATE IMMUNITY, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19864602; DOI=10.4049/jimmunol.0803978;
RA Vavassori P., Mencarelli A., Renga B., Distrutti E., Fiorucci S.;
RT "The bile acid receptor FXR is a modulator of intestinal innate immunity.";
RL J. Immunol. 183:6251-6261(2009).
RN [27]
RP INTERACTION WITH SMARCA4.
RX PubMed=19805516; DOI=10.1128/mcb.00825-09;
RA Miao J., Fang S., Lee J., Comstock C., Knudsen K.E., Kemper J.K.;
RT "Functional specificities of Brm and Brg-1 Swi/Snf ATPases in the feedback
RT regulation of hepatic bile acid biosynthesis.";
RL Mol. Cell. Biol. 29:6170-6181(2009).
RN [28]
RP FUNCTION IN GLUCOSE HOMEOSTASIS, AND TISSUE SPECIFICITY.
RX PubMed=20447400; DOI=10.1016/j.febslet.2010.04.068;
RA Popescu I.R., Helleboid-Chapman A., Lucas A., Vandewalle B., Dumont J.,
RA Bouchaert E., Derudas B., Kerr-Conte J., Caron S., Pattou F., Staels B.;
RT "The nuclear receptor FXR is expressed in pancreatic beta-cells and
RT protects human islets from lipotoxicity.";
RL FEBS Lett. 584:2845-2851(2010).
RN [29]
RP DNA-BINDING.
RX PubMed=20091679; DOI=10.1002/hep.23450;
RA Thomas A.M., Hart S.N., Kong B., Fang J., Zhong X.B., Guo G.L.;
RT "Genome-wide tissue-specific farnesoid X receptor binding in mouse liver
RT and intestine.";
RL Hepatology 51:1410-1419(2010).
RN [30]
RP DNA-BINDING, AND INTERACTION WITH NR5A2.
RX PubMed=20483916; DOI=10.1093/nar/gkq397;
RA Chong H.K., Infante A.M., Seo Y.K., Jeon T.I., Zhang Y., Edwards P.A.,
RA Xie X., Osborne T.F.;
RT "Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif
RT and synergy with LRH-1.";
RL Nucleic Acids Res. 38:6007-6017(2010).
RN [31]
RP REVIEW.
RX PubMed=21383957; DOI=10.1621/nrs.08005;
RA Modica S., Gadaleta R.M., Moschetta A.;
RT "Deciphering the nuclear bile acid receptor FXR paradigm.";
RL Nucl. Recept. Signal. 8:E005-E005(2010).
RN [32]
RP FUNCTION IN INTESTINAL INFLAMMATION.
RX PubMed=21242261; DOI=10.1136/gut.2010.212159;
RA Gadaleta R.M., van Erpecum K.J., Oldenburg B., Willemsen E.C., Renooij W.,
RA Murzilli S., Klomp L.W., Siersema P.D., Schipper M.E., Danese S., Penna G.,
RA Laverny G., Adorini L., Moschetta A., van Mil S.W.;
RT "Farnesoid X receptor activation inhibits inflammation and preserves the
RT intestinal barrier in inflammatory bowel disease.";
RL Gut 60:463-472(2011).
RN [33]
RP FUNCTION IN LIPID HOMEOSTASIS.
RX PubMed=21804189; DOI=10.1172/jci45277;
RA Chennamsetty I., Claudel T., Kostner K.M., Baghdasaryan A., Kratky D.,
RA Levak-Frank S., Frank S., Gonzalez F.J., Trauner M., Kostner G.M.;
RT "Farnesoid X receptor represses hepatic human APOA gene expression.";
RL J. Clin. Invest. 121:3724-3734(2011).
RN [34]
RP REVIEW.
RX PubMed=22820415; DOI=10.1016/j.bbalip.2012.07.004;
RA Hollman D.A., Milona A., van Erpecum K.J., van Mil S.W.;
RT "Anti-inflammatory and metabolic actions of FXR: insights into molecular
RT mechanisms.";
RL Biochim. Biophys. Acta 1821:1443-1452(2012).
RN [35]
RP POSSIBLE FUNCTION IN PROTECTION AGAINST CHOLESTASIS.
RX PubMed=22057115; DOI=10.1053/j.gastro.2011.10.028;
RA Modica S., Petruzzelli M., Bellafante E., Murzilli S., Salvatore L.,
RA Celli N., Di Tullio G., Palasciano G., Moustafa T., Halilbasic E.,
RA Trauner M., Moschetta A.;
RT "Selective activation of nuclear bile acid receptor FXR in the intestine
RT protects mice against cholestasis.";
RL Gastroenterology 142:355-365(2012).
RN [36]
RP FUNCTION IN INFLAMMATORY RESPONSE.
RX PubMed=23372731; DOI=10.1371/journal.pone.0054472;
RA Renga B., Mencarelli A., Cipriani S., D'Amore C., Carino A., Bruno A.,
RA Francisci D., Zampella A., Distrutti E., Fiorucci S.;
RT "The bile acid sensor FXR is required for immune-regulatory activities of
RT TLR-9 in intestinal inflammation.";
RL PLoS ONE 8:E54472-E54472(2013).
RN [37]
RP FUNCTION IN BA HOMEOSTASIS.
RX PubMed=25651182; DOI=10.1016/j.cmet.2015.01.007;
RA de Aguiar Vallim T.Q., Tarling E.J., Ahn H., Hagey L.R., Romanoski C.E.,
RA Lee R.G., Graham M.J., Motohashi H., Yamamoto M., Edwards P.A.;
RT "MAFG is a transcriptional repressor of bile acid synthesis and
RT metabolism.";
RL Cell Metab. 21:298-310(2015).
RN [38]
RP FUNCTION IN BA HOMEOSTASIS.
RX PubMed=25545350; DOI=10.1002/hep.27677;
RA Kim Y.C., Fang S., Byun S., Seok S., Kemper B., Kemper J.K.;
RT "Farnesoid X receptor-induced lysine-specific histone demethylase reduces
RT hepatic bile acid levels and protects the liver against bile acid
RT toxicity.";
RL Hepatology 62:220-231(2015).
RN [39]
RP FUNCTION IN BA HOMEOSTASIS.
RX PubMed=26505219; DOI=10.1210/me.2015-1226;
RA Fu T., Kim Y.C., Byun S., Kim D.H., Seok S., Suino-Powell K., Xu H.E.,
RA Kemper B., Kemper J.K.;
RT "FXR primes the liver for intestinal FGF15 signaling by transient induction
RT of beta-Klotho.";
RL Mol. Endocrinol. 30:92-103(2016).
CC -!- FUNCTION: Ligand-activated transcription factor. Receptor for bile
CC acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid,
CC deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential
CC role in BA homeostasis through the regulation of genes involved in BA
CC synthesis, conjugation and enterohepatic circulation. Also regulates
CC lipid and glucose homeostasis and is involved in innate immune response
CC (PubMed:11030617, PubMed:21383957, PubMed:22820415). The FXR-RXR
CC heterodimer binds predominantly to farnesoid X receptor response
CC elements (FXREs) containing two inverted repeats of the consensus
CC sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide
CC (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can
CC be activated by either FXR or RXR-specific ligands. It is proposed that
CC monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory
CC nuclear responsive element (NRE) halfsites located in close proximity
CC to FXREs modulate transcriptional activity (PubMed:20091679,
CC PubMed:20483916). In the liver activates transcription of the
CC corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1
CC (involved in BA synthesis) implicating at least in part histone
CC demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP
CC (involved in hepatic uptake of conjugated BAs). Activates transcription
CC of the repressor MAFG (involved in regulation of BA synthesis)
CC (PubMed:21383957, PubMed:25651182, PubMed:25545350). Activates
CC transcription of SLC27A5/BACS and BAAT (involved in BA conjugation),
CC ABCB11/BSEP (involved in bile salt export) by directly recruiting
CC histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion
CC of conjugated BAs) and ABCB4 (involved in secretion of
CC phosphatidylcholine in the small intestine) (PubMed:21383957). In ileal
CC enterocytes activates FABP6/IBABP (involved in cytosolic transport),
CC SLC51A/OSTA and SLC51B/OSTB (involved in secretion of conjugated BAs to
CC the portal blood), and repressor NR0B2/SHP thereby indirectly
CC inhibiting SLC10A2/ASBT (involved in BA uptake) (By similarity). In the
CC intestine activates FGF15 expression and secretion leading to hepatic
CC CYP7A1 repression; the function also involves the coordinated induction
CC of hepatic KLB/beta-klotho expression (PubMed:16213224,
CC PubMed:26505219). Transcriptional activation of FABP6/IBAP and SCD1 but
CC not of ABCB11 is isoform-specific (PubMed:12393883). Regulates
CC transcription of liver UGT2B4 and SULT2A1 involved in BA
CC detoxification; binding to the UGT2B4 promoter seems to imply a
CC monomeric transactivation independent of RXRA (By similarity).
CC Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated
CC repression of SREBF1 isoform SREBP-1C (involved in de novo
CC lipogenesis), expression of PLTP (involved in HDL formation), SCARB1
CC (involved in HDL hepatic uptake), APOE, APOC1, APOC4, VLDLR and SDC1
CC (involved in the hepatic uptake of LDL and IDL remnants), and
CC inhibiting expression of MTTP (involved in VLDL assembly)
CC (PubMed:12421815, PubMed:15146238). Increases expression of APOC2
CC (promoting lipoprotein lipase activity implicated in triglyceride
CC clearance) (PubMed:11579204). Transrepresses APOA1 probably involving a
CC monomeric competition with NR2A1 for binding to a DR1 element
CC (PubMed:21804189). Also reduces triglyceride clearance by inhibiting
CC expression of ANGPTL3 and APOC3 (both involved in inhibition of
CC lipoprotein lipase) (PubMed:12891557, PubMed:15146238). Involved in
CC glucose homeostasis by modulating hepatic gluconeogenesis through
CC activation of NR0B2/SHP-mediated repression of respective genes.
CC Modulates glycogen synthesis (inducing phosphorylation of glycogen
CC synthase kinase-3). Modulates glucose-stimulated insulin secretion and
CC is involved in insulin resistance (PubMed:15564327, PubMed:16446356,
CC PubMed:16557297, PubMed:16410358, PubMed:20447400). Involved in
CC intestinal innate immunity. Plays a role in protecting the distal small
CC intestine against bacterial overgrowth and preservation of the
CC epithelial barrier (PubMed:16473946, PubMed:21242261). Down-regulates
CC inflammatory cytokine expression in several types of immune cells
CC including macrophages and mononuclear cells (PubMed:19864602). Mediates
CC transrepression of TLR4-induced cytokine expression; the function seems
CC to require its sumoylation and prevents N-CoR nuclear receptor
CC corepressor clearance from target genes such as IL1B and NOS2 (By
CC similarity). Involved in the TLR9-mediated protective mechanism in
CC intestinal inflammation (PubMed:23372731). Plays a anti-inflammatory
CC role in liver inflammation; proposed to inhibit pro-inflammatory (but
CC not antiapoptotic) NF-kappa-B signaling (PubMed:18972444).
CC {ECO:0000250|UniProtKB:Q62735, ECO:0000250|UniProtKB:Q96RI1,
CC ECO:0000269|PubMed:11030617, ECO:0000269|PubMed:11579204,
CC ECO:0000269|PubMed:11706036, ECO:0000269|PubMed:12004058,
CC ECO:0000269|PubMed:12393883, ECO:0000269|PubMed:12421815,
CC ECO:0000269|PubMed:12660231, ECO:0000269|PubMed:12891557,
CC ECO:0000269|PubMed:15146238, ECO:0000269|PubMed:15564327,
CC ECO:0000269|PubMed:16213224, ECO:0000269|PubMed:16410358,
CC ECO:0000269|PubMed:16446356, ECO:0000269|PubMed:16473946,
CC ECO:0000269|PubMed:16557297, ECO:0000269|PubMed:16946559,
CC ECO:0000269|PubMed:18972444, ECO:0000269|PubMed:19864602,
CC ECO:0000269|PubMed:20091679, ECO:0000269|PubMed:20447400,
CC ECO:0000269|PubMed:20483916, ECO:0000269|PubMed:21242261,
CC ECO:0000269|PubMed:21804189, ECO:0000269|PubMed:23372731,
CC ECO:0000269|PubMed:25545350, ECO:0000269|PubMed:25651182,
CC ECO:0000269|PubMed:26505219, ECO:0000305|PubMed:21383957,
CC ECO:0000305|PubMed:22820415}.
CC -!- FUNCTION: [Isoform 2]: Activates transcription of IBAP and SDC1.
CC {ECO:0000269|PubMed:12393883}.
CC -!- FUNCTION: [Isoform 4]: Activates transcription of IBAP and SDC1.
CC {ECO:0000269|PubMed:12393883}.
CC -!- SUBUNIT: Heterodimer with RXRA; the heterodimerization enhances the
CC binding affinity for LXXLL motifs from coactivators (By similarity).
CC Binds DNA predominantly as a heterodimer with RXRA (PubMed:7760852).
CC After activation by agonist binding interacts with coactivators.
CC Interacts with PPARGC1A, SMARCA4 and EP300 (PubMed:14729567,
CC PubMed:18842595, PubMed:19805516). Interacts with NCOA1, NCOA2, CARM1,
CC SETD7, PRMT1, GPS2, SMARCA4 and MED1. Interacts with XRCC5 and XRCC6;
CC decreasing NR1H4/FXR transactivation activity towards ABCB11/BSEP.
CC Interacts with PAGR1 AND NCOA6; indicative for an association with an
CC MLL2/MLL3 complex (ASCOM) (By similarity). Interacts with NR5A2
CC (PubMed:20483916). {ECO:0000250|UniProtKB:Q62735,
CC ECO:0000250|UniProtKB:Q96RI1, ECO:0000269|PubMed:14729567,
CC ECO:0000269|PubMed:18842595, ECO:0000269|PubMed:19805516,
CC ECO:0000269|PubMed:20483916, ECO:0000269|PubMed:7760852}.
CC -!- INTERACTION:
CC Q60641-1; O70343-1: Ppargc1a; NbExp=3; IntAct=EBI-11659377, EBI-11359934;
CC Q60641-2; O70343-1: Ppargc1a; NbExp=2; IntAct=EBI-11659386, EBI-11359934;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19864602}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=FXRbeta1, FXRalpha3, FXRalpha2(+);
CC IsoId=Q60641-1; Sequence=Displayed;
CC Name=2; Synonyms=FXRbeta2, FXFRalpha4, FXRalpha2(-);
CC IsoId=Q60641-2; Sequence=VSP_003666;
CC Name=3; Synonyms=FXRalpha1, FXRalpha1(+);
CC IsoId=Q60641-3; Sequence=VSP_058157;
CC Name=4; Synonyms=FXRalpha2, FXRalpha1(-);
CC IsoId=Q60641-4; Sequence=VSP_058157, VSP_003666;
CC -!- TISSUE SPECIFICITY: Expressed in liver and kidney. Expressed in
CC pancreatic beta cells and macrophages. Expressed in the villus
CC epithelium in adult ileum, with highest expression in the intervillus
CC regions. Expression in colon is reduced by inflammation.
CC {ECO:0000269|PubMed:16473946, ECO:0000269|PubMed:19393742,
CC ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:20447400}.
CC -!- PTM: Acetylated by EP300 (PubMed:18842595). Lys-228 as is the major
CC acetylation site for EP300; the dynamicly regulated acetylation
CC inhibits heterodimerization with RXRA and transactivation activity.
CC Deacetylated by SIRT1 (By similarity). Elevated acetylation levels are
CC found in metabolic disease states (mouse models of obesity and type II
CC diabetes) (PubMed:19883617). {ECO:0000250|UniProtKB:Q96RI1,
CC ECO:0000269|PubMed:18842595, ECO:0000269|PubMed:19883617}.
CC -!- PTM: Methylation may increase transactivation of target genes.
CC {ECO:0000250|UniProtKB:Q96RI1}.
CC -!- PTM: Phosphorylation by PKC/PRKCA increases transactivation activity by
CC promoting association with PPARGC1A. {ECO:0000250|UniProtKB:Q96RI1}.
CC -!- PTM: Sumoylated upon ligand binding. {ECO:0000250|UniProtKB:Q96RI1}.
CC -!- DISEASE: Note=Activation protects mice against cholestasis, development
CC of chronical intestinal inflammation and fibrosis. May suppress
CC intestinal tumorigenesis. {ECO:0000269|PubMed:19047134,
CC ECO:0000269|PubMed:19864602, ECO:0000269|PubMed:22057115}.
CC -!- DISRUPTION PHENOTYPE: Elevated serum bile acid, cholesterol, and
CC triglycerides, increased hepatic cholesterol and triglycerides, and a
CC proatherogenic serum lipoprotein profile. Reduced bile acid pools and
CC reduced fecal bile acid excretion. {ECO:0000269|PubMed:11030617}.
CC -!- MISCELLANEOUS: Mouse Nr1h4/FXR is less responsive to CDCA and more
CC responsive to cholic acid (CA) than human FXR.
CC {ECO:0000305|PubMed:12004058, ECO:0000305|PubMed:21383957}.
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative promoter usage.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing of isoform
CC 3. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; U09416; AAC53066.1; -; mRNA.
DR EMBL; U09417; AAC53065.1; -; mRNA.
DR EMBL; U09418; AAC52978.1; -; mRNA.
DR EMBL; AC152417; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015261; AAH15261.1; -; mRNA.
DR CCDS; CCDS24116.1; -. [Q60641-2]
DR CCDS; CCDS48668.1; -. [Q60641-1]
DR CCDS; CCDS48669.1; -. [Q60641-3]
DR PIR; I49018; I49018.
DR PIR; I49019; I49019.
DR PIR; I49020; I49020.
DR RefSeq; NP_001156976.1; NM_001163504.1. [Q60641-3]
DR RefSeq; NP_001157172.1; NM_001163700.1. [Q60641-1]
DR RefSeq; XP_006513454.1; XM_006513391.3. [Q60641-3]
DR RefSeq; XP_006513456.1; XM_006513393.3. [Q60641-4]
DR AlphaFoldDB; Q60641; -.
DR SMR; Q60641; -.
DR BioGRID; 203043; 8.
DR CORUM; Q60641; -.
DR DIP; DIP-443N; -.
DR IntAct; Q60641; 1.
DR STRING; 10090.ENSMUSP00000053092; -.
DR BindingDB; Q60641; -.
DR ChEMBL; CHEMBL5343; -.
DR iPTMnet; Q60641; -.
DR PhosphoSitePlus; Q60641; -.
DR MaxQB; Q60641; -.
DR PaxDb; Q60641; -.
DR PRIDE; Q60641; -.
DR ProteomicsDB; 295519; -. [Q60641-1]
DR ProteomicsDB; 295520; -. [Q60641-2]
DR ProteomicsDB; 295521; -. [Q60641-3]
DR ProteomicsDB; 295522; -. [Q60641-4]
DR Antibodypedia; 17868; 447 antibodies from 37 providers.
DR DNASU; 20186; -.
DR Ensembl; ENSMUST00000058126; ENSMUSP00000053092; ENSMUSG00000047638. [Q60641-2]
DR Ensembl; ENSMUST00000105296; ENSMUSP00000100933; ENSMUSG00000047638. [Q60641-1]
DR Ensembl; ENSMUST00000105297; ENSMUSP00000100934; ENSMUSG00000047638. [Q60641-3]
DR GeneID; 20186; -.
DR KEGG; mmu:20186; -.
DR UCSC; uc007gsg.2; mouse. [Q60641-1]
DR UCSC; uc007gsh.2; mouse.
DR CTD; 9971; -.
DR MGI; MGI:1352464; Nr1h4.
DR VEuPathDB; HostDB:ENSMUSG00000047638; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000158037; -.
DR HOGENOM; CLU_007368_12_3_1; -.
DR InParanoid; Q60641; -.
DR OMA; IPSETFF; -.
DR OrthoDB; 1137281at2759; -.
DR PhylomeDB; Q60641; -.
DR TreeFam; TF316304; -.
DR Reactome; R-MMU-159418; Recycling of bile acids and salts.
DR Reactome; R-MMU-192105; Synthesis of bile acids and bile salts.
DR Reactome; R-MMU-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-MMU-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR BioGRID-ORCS; 20186; 3 hits in 75 CRISPR screens.
DR PRO; PR:Q60641; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q60641; protein.
DR Bgee; ENSMUSG00000047638; Expressed in right kidney and 81 other tissues.
DR ExpressionAtlas; Q60641; baseline and differential.
DR Genevisible; Q60641; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0000791; C:euchromatin; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0032052; F:bile acid binding; IMP:BHF-UCL.
DR GO; GO:0038181; F:bile acid receptor activity; ISO:MGI.
DR GO; GO:1902122; F:chenodeoxycholic acid binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IGI:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:MGI.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IDA:MGI.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0015721; P:bile acid and bile salt transport; ISO:MGI.
DR GO; GO:0008206; P:bile acid metabolic process; IMP:MGI.
DR GO; GO:0038183; P:bile acid signaling pathway; IMP:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007043; P:cell-cell junction assembly; IMP:UniProtKB.
DR GO; GO:0001678; P:cellular glucose homeostasis; IDA:UniProtKB.
DR GO; GO:1903413; P:cellular response to bile acid; ISO:MGI.
DR GO; GO:0071398; P:cellular response to fatty acid; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0071417; P:cellular response to organonitrogen compound; IMP:BHF-UCL.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0035356; P:cellular triglyceride homeostasis; ISO:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; IMP:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IDA:UniProtKB.
DR GO; GO:0034971; P:histone H3-R17 methylation; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0038185; P:intracellular bile acid receptor signaling pathway; ISO:MGI.
DR GO; GO:0030522; P:intracellular receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:UniProtKB.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; IMP:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0071638; P:negative regulation of monocyte chemotactic protein-1 production; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0010868; P:negative regulation of triglyceride biosynthetic process; ISO:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0010903; P:negative regulation of very-low-density lipoprotein particle remodeling; IDA:MGI.
DR GO; GO:0001080; P:nitrogen catabolite activation of transcription from RNA polymerase II promoter; IC:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; IMP:UniProtKB.
DR GO; GO:2001250; P:positive regulation of ammonia assimilation cycle; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:2000213; P:positive regulation of glutamate metabolic process; IMP:BHF-UCL.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
DR GO; GO:1905695; P:positive regulation of phosphatidic acid biosynthetic process; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0006109; P:regulation of carbohydrate metabolic process; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0010988; P:regulation of low-density lipoprotein particle clearance; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0034255; P:regulation of urea metabolic process; IMP:BHF-UCL.
DR GO; GO:0071873; P:response to norepinephrine; ISO:MGI.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; ISO:MGI.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0070328; P:triglyceride homeostasis; IDA:UniProtKB.
DR CDD; cd06936; NR_LBD_Fxr; 1.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR044114; NR_LBD_NR1H4.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001728; ThyrH_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR PRINTS; PR00546; THYROIDHORMR.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative promoter usage; Alternative splicing;
KW DNA-binding; Immunity; Inflammatory response; Innate immunity;
KW Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein;
KW Receptor; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..488
FT /note="Bile acid receptor"
FT /id="PRO_0000053539"
FT DOMAIN 264..488
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 135..210
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 138..158
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 174..198
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT BINDING 347
FT /ligand="chenodeoxycholate"
FT /ligand_id="ChEBI:CHEBI:36234"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT BINDING 377
FT /ligand="chenodeoxycholate"
FT /ligand_id="ChEBI:CHEBI:36234"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT BINDING 385
FT /ligand="chenodeoxycholate"
FT /ligand_id="ChEBI:CHEBI:36234"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT BINDING 463
FT /ligand="chenodeoxycholate"
FT /ligand_id="ChEBI:CHEBI:36234"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT MOD_RES 146
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT MOD_RES 165
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT MOD_RES 168
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT MOD_RES 221
FT /note="N6-methyllysine; by SETD7"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT MOD_RES 228
FT /note="N6-acetyllysine; by EP300"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT MOD_RES 458
FT /note="Phosphothreonine; by PKC/PRKCZ"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT CROSSLNK 133
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT CROSSLNK 291
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q96RI1"
FT VAR_SEQ 1..36
FT /note="MVMQFQGLENPIQISLHHSHRLSGFVPEGMSVKPAK -> MNLIGHSHLQAT
FT DEFSLSESLF (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12393883"
FT /id="VSP_058157"
FT VAR_SEQ 208..211
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:12393883,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7760852"
FT /id="VSP_003666"
FT MUTAGEN 370
FT /note="K->N: Increases affinity to CDCA and transcriptional
FT activity in response to CDCA; when associated with I-388."
FT /evidence="ECO:0000269|PubMed:12004058"
FT MUTAGEN 388
FT /note="V->I: Increases affinity to CDCA and transcriptional
FT activity in response to CDCA; when associated with N-370."
FT /evidence="ECO:0000269|PubMed:12004058"
FT CONFLICT 28
FT /note="E -> D (in Ref. 1; AAC53066 and 3; AAH15261)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="K -> R (in Ref. 1; AAC53065/AAC53066/AAC52978 and 3;
FT AAH15261)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="A -> V (in Ref. 1; AAC53065/AAC53066/AAC52978 and 3;
FT AAH15261)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 488 AA; 55994 MW; 3E59B7146F8ECC86 CRC64;
MVMQFQGLEN PIQISLHHSH RLSGFVPEGM SVKPAKGMLT EHAAGPLGQN LDLESYSPYN
NVPFPQVQPQ ISSSSYYSNL GFYPQQPEDW YSPGIYELRR MPAETGYQGE TEVSEMPVTK
KPRMAAASAG RIKGDELCVV CGDRASGYHY NALTCEGCKG FFRRSITKNA VYKCKNGGNC
VMDMYMRRKC QECRLRKCKE MGMLAECMYT GLLTEIQCKS KRLRKNVKQH ADQTANEDDS
EGRDLRQVTS TTKFCREKTE LTADQQTLLD YIMDSYNKQR MPQEITNKIL KEEFSAEENF
LILTEMATSH VQILVEFTKK LPGFQTLDHE DQIALLKGSA VEAMFLRSAE IFNKKLPAGH
ADLLEERIRK SGISDEYITP MFSFYKSVGE LKMTQEEYAL LTAIVILSPD RQYIKDREAV
EKLQEPLLDV LQKLCKMYQP ENPQHFACLL GRLTELRTFN HHHAEMLMSW RVNDHKFTPL
LCEIWDVQ
