XBP1_MOUSE
ID XBP1_MOUSE Reviewed; 267 AA.
AC O35426; Q8VHM0; Q922G5; Q9ESS3;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=X-box-binding protein 1 {ECO:0000250|UniProtKB:P17861, ECO:0000312|MGI:MGI:98970};
DE Short=XBP-1 {ECO:0000250|UniProtKB:P17861};
DE AltName: Full=Tax-responsive element-binding protein 5 {ECO:0000303|PubMed:10907849};
DE Short=TREB-5 {ECO:0000305};
DE Contains:
DE RecName: Full=X-box-binding protein 1, cytoplasmic form {ECO:0000250|UniProtKB:P17861};
DE Contains:
DE RecName: Full=X-box-binding protein 1, luminal form {ECO:0000250|UniProtKB:P17861};
GN Name=Xbp1 {ECO:0000250|UniProtKB:P17861, ECO:0000312|MGI:MGI:98970};
GN Synonyms=Treb5 {ECO:0000303|PubMed:10907849};
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 [GENOMIC DNA].
RX PubMed=10907849; DOI=10.1093/dnares/7.3.187;
RA Masaki T., Noguchi H., Kobayashi M., Yoshida M., Takamatsu K.;
RT "Isolation and characterization of the gene encoding mouse tax-responsive
RT element-binding protein (TREB) 5.";
RL DNA Res. 7:187-193(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 2),
RP INDUCTION (ISOFORM 2), AND ER STRESS-MEDIATED DOWN-REGULATION (ISOFORM 1).
RC STRAIN=129/SvEv;
RX PubMed=11780124; DOI=10.1038/415092a;
RA Calfon M., Zeng H., Urano F., Till J.H., Hubbard S.R., Harding H.P.,
RA Clark S.G., Ron D.;
RT "IRE1 couples endoplasmic reticulum load to secretory capacity by
RT processing the XBP-1 mRNA.";
RL Nature 415:92-96(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Lee C.M., Reddy E.P.;
RT "Sequence analysis of murine XBP-1.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=7693055; DOI=10.1002/aja.1001970207;
RA Clauss I.M., Gravallese E.M., Darling J.M., Shapiro F., Glimcher M.J.,
RA Glimcher L.H.;
RT "In situ hybridization studies suggest a role for the basic region-leucine
RT zipper protein hXBP-1 in exocrine gland and skeletal development during
RT mouse embryogenesis.";
RL Dev. Dyn. 197:146-156(1993).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10425189; DOI=10.1006/bbrc.1999.0972;
RA Masaki T., Yoshida M., Noguchi S.;
RT "Targeted disruption of CRE-binding factor TREB5 gene leads to cellular
RT necrosis in cardiac myocytes at the embryonic stage.";
RL Biochem. Biophys. Res. Commun. 261:350-356(1999).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10652269;
RA Reimold A.M., Etkin A., Clauss I., Perkins A., Friend D.S., Zhang J.,
RA Horton H.F., Scott A., Orkin S.H., Byrne M.C., Grusby M.J., Glimcher L.H.;
RT "An essential role in liver development for transcription factor XBP-1.";
RL Genes Dev. 14:152-157(2000).
RN [9]
RP FUNCTION (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 2), AND INDUCTION
RP (ISOFORM 2).
RX PubMed=11850408; DOI=10.1101/gad.964702;
RA Lee K., Tirasophon W., Shen X., Michalak M., Prywes R., Okada T.,
RA Yoshida H., Mori K., Kaufman R.J.;
RT "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage
RT merge to regulate XBP1 in signaling the unfolded protein response.";
RL Genes Dev. 16:452-466(2002).
RN [10]
RP FUNCTION (ISOFORM 2).
RX PubMed=14559994; DOI=10.1128/mcb.23.21.7448-7459.2003;
RA Lee A.H., Iwakoshi N.N., Glimcher L.H.;
RT "XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes
RT in the unfolded protein response.";
RL Mol. Cell. Biol. 23:7448-7459(2003).
RN [11]
RP FUNCTION (ISOFORM 2), AND INDUCTION (ISOFORMS 1 AND 2).
RX PubMed=12612580; DOI=10.1038/ni907;
RA Iwakoshi N.N., Lee A.-H., Vallabhajosyula P., Otipoby K.L., Rajewsky K.,
RA Glimcher L.H.;
RT "Plasma cell differentiation and the unfolded protein response intersect at
RT the transcription factor XBP-1.";
RL Nat. Immunol. 4:321-329(2003).
RN [12]
RP FUNCTION (ISOFORMS 1 AND 2), UBIQUITINATION (ISOFORM 1), AND MUTAGENESIS OF
RP LYS-231 AND LYS-252.
RX PubMed=12902539; DOI=10.1073/pnas.1334037100;
RA Lee A.H., Iwakoshi N.N., Anderson K.C., Glimcher L.H.;
RT "Proteasome inhibitors disrupt the unfolded protein response in myeloma
RT cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:9946-9951(2003).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15486293; DOI=10.1126/science.1103160;
RA Ozcan U., Cao Q., Yilmaz E., Lee A.H., Iwakoshi N.N., Ozdelen E.,
RA Tuncman G., Gorgun C., Glimcher L.H., Hotamisligil G.S.;
RT "Endoplasmic reticulum stress links obesity, insulin action, and type 2
RT diabetes.";
RL Science 306:457-461(2004).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16362047; DOI=10.1038/sj.emboj.7600903;
RA Lee A.H., Chu G.C., Iwakoshi N.N., Glimcher L.H.;
RT "XBP-1 is required for biogenesis of cellular secretory machinery of
RT exocrine glands.";
RL EMBO J. 24:4368-4380(2005).
RN [15]
RP FUNCTION (ISOFORM 1), UBIQUITINATION (ISOFORM 1), SUBCELLULAR LOCATION
RP (ISOFORMS 1 AND 2), DOMAIN (ISOFORMS 1 AND 2), AND MUTAGENESIS OF
RP 177-PRO-PRO-178; LYS-231; 238-PRO-PRO-239 AND LYS-252.
RX PubMed=16332684; DOI=10.1074/jbc.m509061200;
RA Tirosh B., Iwakoshi N.N., Glimcher L.H., Ploegh H.L.;
RT "Rapid turnover of unspliced Xbp-1 as a factor that modulates the unfolded
RT protein response.";
RL J. Biol. Chem. 281:5852-5860(2006).
RN [16]
RP FUNCTION (ISOFORM 2).
RX PubMed=17213183; DOI=10.1074/jbc.m609490200;
RA Sriburi R., Bommiasamy H., Buldak G.L., Robbins G.R., Frank M.,
RA Jackowski S., Brewer J.W.;
RT "Coordinate regulation of phospholipid biosynthesis and secretory pathway
RT gene expression in XBP-1(S)-induced endoplasmic reticulum biogenesis.";
RL J. Biol. Chem. 282:7024-7034(2007).
RN [17]
RP FUNCTION, DNA-BINDING, INDUCTION (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=17612490; DOI=10.1016/j.molcel.2007.06.011;
RA Acosta-Alvear D., Zhou Y., Blais A., Tsikitis M., Lents N.H., Arias C.,
RA Lennon C.J., Kluger Y., Dynlacht B.D.;
RT "XBP1 controls diverse cell type- and condition-specific transcriptional
RT regulatory networks.";
RL Mol. Cell 27:53-66(2007).
RN [18]
RP DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUTS.
RX PubMed=18775308; DOI=10.1016/j.cell.2008.07.021;
RA Kaser A., Lee A.H., Franke A., Glickman J.N., Zeissig S., Tilg H.,
RA Nieuwenhuis E.E., Higgins D.E., Schreiber S., Glimcher L.H., Blumberg R.S.;
RT "XBP1 links ER stress to intestinal inflammation and confers genetic risk
RT for human inflammatory bowel disease.";
RL Cell 134:743-756(2008).
RN [19]
RP FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), INDUCTION (ISOFORM
RP 2), DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUT.
RX PubMed=18556558; DOI=10.1126/science.1158042;
RA Lee A.H., Scapa E.F., Cohen D.E., Glimcher L.H.;
RT "Regulation of hepatic lipogenesis by the transcription factor XBP1.";
RL Science 320:1492-1496(2008).
RN [20]
RP TISSUE SPECIFICITY (ISOFORMS 1 AND 2).
RX PubMed=19416856; DOI=10.1073/pnas.0903197106;
RA Zeng L., Zampetaki A., Margariti A., Pepe A.E., Alam S., Martin D.,
RA Xiao Q., Wang W., Jin Z.G., Cockerill G., Mori K., Li Y.S., Hu Y.,
RA Chien S., Xu Q.;
RT "Sustained activation of XBP1 splicing leads to endothelial apoptosis and
RT atherosclerosis development in response to disturbed flow.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:8326-8331(2009).
RN [21]
RP FUNCTION (ISOFORM 2), INTERACTION WITH PIK3R1 AND PIK3R2 (ISOFORM 2),
RP SUBCELLULAR LOCATION (ISOFORM 2), AND INDUCTION (ISOFORM 2).
RX PubMed=20348926; DOI=10.1038/nm.2099;
RA Park S.W., Zhou Y., Lee J., Lu A., Sun C., Chung J., Ueki K., Ozcan U.;
RT "The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1
RT and increase its nuclear translocation.";
RL Nat. Med. 16:429-437(2010).
RN [22]
RP ACETYLATION BY EP300 (ISOFORM 2), DEACETYLATION BY SIRT1 (ISOFORM 2),
RP SUBCELLULAR LOCATION (ISOFORM 2), AND INTERACTION WITH SIRT1 (ISOFORM 2).
RX PubMed=20955178; DOI=10.1042/bj20101293;
RA Wang F.M., Chen Y.J., Ouyang H.J.;
RT "Regulation of unfolded protein response modulator XBP1s by acetylation and
RT deacetylation.";
RL Biochem. J. 433:245-252(2011).
RN [23]
RP FUNCTION (ISOFORM 2), AND INTERACTION WITH FOXO1 (ISOFORM 2).
RX PubMed=21317886; DOI=10.1038/nm.2293;
RA Zhou Y., Lee J., Reno C.M., Sun C., Park S.W., Chung J., Lee J.,
RA Fisher S.J., White M.F., Biddinger S.B., Ozcan U.;
RT "Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction.";
RL Nat. Med. 17:356-365(2011).
RN [24]
RP FUNCTION (ISOFORM 2), DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT, TISSUE
RP SPECIFICITY (ISOFORMS 1 AND 2), AND INDUCTION (ISOFORMS 1 AND 2).
RX PubMed=23623498; DOI=10.1016/j.celrep.2013.03.042;
RA Gregor M.F., Misch E.S., Yang L., Hummasti S., Inouye K.E., Lee A.H.,
RA Bierie B., Hotamisligil G.S.;
RT "The role of adipocyte XBP1 in metabolic regulation during lactation.";
RL Cell Rep. 3:1430-1439(2013).
RN [25]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUT.
RX PubMed=23529610; DOI=10.1161/circulationaha.112.001337;
RA Zeng L., Xiao Q., Chen M., Margariti A., Martin D., Ivetic A., Xu H.,
RA Mason J., Wang W., Cockerill G., Mori K., Li J.Y., Chien S., Hu Y., Xu Q.;
RT "Vascular endothelial cell growth-activated XBP1 splicing in endothelial
RT cells is crucial for angiogenesis.";
RL Circulation 127:1712-1722(2013).
RN [26]
RP DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUT.
RX PubMed=23184933; DOI=10.1074/jbc.m112.412783;
RA Margariti A., Li H., Chen T., Martin D., Vizcay-Barrena G., Alam S.,
RA Karamariti E., Xiao Q., Zampetaki A., Zhang Z., Wang W., Jiang Z., Gao C.,
RA Ma B., Chen Y.G., Cockerill G., Hu Y., Xu Q., Zeng L.;
RT "XBP1 mRNA splicing triggers an autophagic response in endothelial cells
RT through BECLIN-1 transcriptional activation.";
RL J. Biol. Chem. 288:859-872(2013).
RN [27]
RP FUNCTION (ISOFORM 2), DNA-BINDING (ISOFORM 2), AND INDUCTION (ISOFORM 2).
RX PubMed=25223794; DOI=10.1111/febs.13052;
RA Cho Y.M., Kwak S.N., Joo N.S., Kim D.H., Lee A.H., Kim K.S., Seo J.B.,
RA Jeong S.W., Kwon O.J.;
RT "X-box binding protein 1 is a novel key regulator of peroxisome
RT proliferator-activated receptor gamma2.";
RL FEBS J. 281:5132-5146(2014).
RN [28]
RP FUNCTION (ISOFORM 2), DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUT.
RX PubMed=24753614; DOI=10.1073/pnas.1321845111;
RA Valdes P., Mercado G., Vidal R.L., Molina C., Parsons G., Court F.A.,
RA Martinez A., Galleguillos D., Armentano D., Schneider B.L., Hetz C.;
RT "Control of dopaminergic neuron survival by the unfolded protein response
RT transcription factor XBP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:6804-6809(2014).
CC -!- FUNCTION: Functions as a transcription factor during endoplasmic
CC reticulum stress by regulating the unfolded protein response (UPR).
CC Required for cardiac myogenesis and hepatogenesis during embryonic
CC development and the development of secretory tissues such as exocrine
CC pancreas and salivary gland (PubMed:10425189, PubMed:10652269,
CC PubMed:16362047, PubMed:17612490). Involved in differentiation of B
CC lymphocytes to plasma cells and production of immunoglobulins.
CC Modulates the cellular response to ER stress in a PIK3R-dependent
CC manner. Binds to the cis-acting X box present in the promoter regions
CC of major histocompatibility complex class II genes (By similarity).
CC Involved in VEGF-induced endothelial cell (EC) proliferation and
CC retinal blood vessel formation during embryonic development but also
CC for angiogenesis in adult tissues under ischemic conditions
CC (PubMed:23529610). Functions also as a major regulator of the UPR in
CC obesity-induced insulin resistance and type 2 diabetes for the
CC management of obesity and diabetes prevention (PubMed:15486293).
CC {ECO:0000250|UniProtKB:P17861, ECO:0000269|PubMed:10425189,
CC ECO:0000269|PubMed:10652269, ECO:0000269|PubMed:15486293,
CC ECO:0000269|PubMed:16362047, ECO:0000269|PubMed:17612490,
CC ECO:0000269|PubMed:23529610}.
CC -!- FUNCTION: [Isoform 1]: Plays a role in the unconventional cytoplasmic
CC splicing processing of its own mRNA triggered by the endoplasmic
CC reticulum (ER) transmembrane endoribonuclease ERN1: upon ER stress, the
CC emerging XBP1 polypeptide chain, as part of a mRNA-ribosome-nascent
CC chain (R-RNC) complex, cotranslationally recruits its own unprocessed
CC mRNA through transient docking to the ER membrane and translational
CC pausing, therefore facilitating efficient IRE1-mediated XBP1 mRNA
CC isoform 2 production. In endothelial cells (EC), associated with KDR,
CC promotes IRE1-mediated XBP1 mRNA isoform 2 production in a vascular
CC endothelial growth factor (VEGF)-dependent manner, leading to EC
CC proliferation and angiogenesis (By similarity). Functions as a negative
CC feed-back regulator of the potent transcription factor XBP1 isoform 2
CC protein levels through proteasome-mediated degradation, thus preventing
CC the constitutive activation of the ER stress response signaling pathway
CC (PubMed:16332684). Inhibits the transactivation activity of XBP1
CC isoform 2 in myeloma cells (PubMed:12902539). Acts as a weak
CC transcriptional factor. Together with HDAC3, contributes to the
CC activation of NFE2L2-mediated HMOX1 transcription factor gene
CC expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading
CC to EC survival under disturbed flow/oxidative stress. Binds to the ER
CC stress response element (ERSE) upon ER stress. Binds to the consensus
CC 5'-GATGACGTG[TG]N(3)[AT]T-3' sequence related to cAMP responsive
CC element (CRE)-like sequences. Binds the Tax-responsive element (TRE)
CC present in the long terminal repeat (LTR) of T-cell leukemia virus type
CC 1 (HTLV-I) and to the TPA response elements (TRE). Associates
CC preferentially to the HDAC3 gene promoter region in a static flow-
CC dependent manner. Binds to the CDH5/VE-cadherin gene promoter region
CC (By similarity). {ECO:0000250|UniProtKB:P17861,
CC ECO:0000269|PubMed:12902539, ECO:0000269|PubMed:16332684}.
CC -!- FUNCTION: [Isoform 2]: Functions as a stress-inducible potent
CC transcriptional activator during endoplasmic reticulum (ER) stress by
CC inducing unfolded protein response (UPR) target genes via binding to
CC the UPR element (UPRE). Up-regulates target genes encoding ER
CC chaperones and ER-associated degradation (ERAD) components to enhance
CC the capacity of productive folding and degradation mechanism,
CC respectively, in order to maintain the homeostasis of the ER under ER
CC stress (PubMed:11850408, PubMed:14559994). Plays a role in the
CC production of immunoglobulins and interleukin-6 in the presence of
CC stimuli required for plasma cell differentiation, and promotes as well
CC membrane phospholipid biosynthesis necessary for ER expansion
CC (PubMed:12612580, PubMed:17213183). Contributes to the VEGF-induced
CC endothelial cell (EC) growth and proliferation in a Akt/GSK-dependent
CC and/or -independent signaling pathway, respectively, leading to beta-
CC catenin nuclear translocation and E2F2 gene expression. Promotes
CC umbilical vein EC apoptosis and atherosclerotisis development in a
CC caspase-dependent signaling pathway, and contributes to VEGF-induced EC
CC proliferation and angiogenesis in adult tissues under ischemic
CC conditions. Involved in the regulation of endostatin-induced autophagy
CC in EC through BECN1 transcriptional activation. Plays a role as an
CC oncogene by promoting tumor progression: stimulates zinc finger protein
CC SNAI1 transcription to induce epithelial-to-mesenchymal (EMT)
CC transition, cell migration and invasion of breast cancer cells (By
CC similarity). Involved in adipocyte differentiation by regulating
CC lipogenic gene expression during lactation (PubMed:23623498,
CC PubMed:25223794). Plays a role in the survival of both dopaminergic
CC neurons of the substantia nigra pars compacta (SNpc), by maintaining
CC protein homeostasis and of myeloma cells (PubMed:12902539,
CC PubMed:24753614). Increases insulin sensitivity in the liver as a
CC response to a high carbohydrate diet, resulting in improved glucose
CC tolerance (PubMed:20348926). Improves also glucose homeostasis in an ER
CC stress- and/or insulin-independent manner through both binding and
CC proteasome-induced degradation of the transcription factor FOXO1, hence
CC resulting in suppression of gluconeogenic genes expression and in a
CC reduction of blood glucose levels (PubMed:21317886). Controls the
CC induction of de novo fatty acid synthesis in hepatocytes by regulating
CC the expression of a subset of lipogenic genes in an ER stress- and UPR-
CC independent manner (PubMed:18556558). Binds to the 5'-CCACG-3' motif in
CC the PPARG promoter (PubMed:25223794). Associates preferentially to the
CC HDAC3 gene promoter region in a disturbed flow-dependent manner. Binds
CC to the BECN1 gene promoter region. Binds to the CDH5/VE-cadherin gene
CC promoter region. Binds to the ER stress response element (ERSE) upon ER
CC stress (By similarity). {ECO:0000250|UniProtKB:P17861,
CC ECO:0000269|PubMed:11850408, ECO:0000269|PubMed:12612580,
CC ECO:0000269|PubMed:12902539, ECO:0000269|PubMed:14559994,
CC ECO:0000269|PubMed:17213183, ECO:0000269|PubMed:18556558,
CC ECO:0000269|PubMed:20348926, ECO:0000269|PubMed:21317886,
CC ECO:0000269|PubMed:23623498, ECO:0000269|PubMed:24753614,
CC ECO:0000269|PubMed:25223794}.
CC -!- SUBUNIT: Isoform 1 interacts with HM13. Isoform 1 interacts with
CC RNF139; the interaction induces ubiquitination and degradation of
CC isoform 1. Isoform 1 interacts (via luminal domain) with DERL1; the
CC interaction obviates the need for ectodomain shedding prior HM13/SPP-
CC mediated XBP1 isoform 1 cleavage. Isoform 1 interacts with isoform 2;
CC the interaction sequesters isoform 2 from the nucleus and enhances
CC isoform 2 degradation in the cytoplasm. Isoform 1 interacts with HDAC3
CC and AKT1; the interactions occur in endothelial cell (EC) under
CC disturbed flow. Isoform 1 interacts with the oncoprotein FOS. Isoform 2
CC interacts with ATF6; the interaction occurs in a ER stress-dependent
CC manner and is required for DNA binding to the unfolded protein response
CC element (UPRE). Isoform 2 interacts with PIK3R1; the interaction is
CC direct and induces translocation of XBP1 isoform 2 into the nucleus and
CC the unfolded protein response (UPR) XBP1-dependent target genes
CC activation in a ER stress- and/or insulin-dependent but PI3K-
CC independent manner (By similarity). Isoform 2 interacts with SIRT1
CC (PubMed:20955178). Isoform 2 interacts with PIK3R1 and PIK3R2; the
CC interactions are direct and induce translocation of XBP1 isoform 2 into
CC the nucleus and the unfolded protein response (UPR) XBP1-dependent
CC target genes activation in a ER stress- and/or insulin-dependent but
CC PI3K-independent manner (PubMed:20348926). Isoform 2 interacts with
CC FOXO1; the interaction is direct and leads to FOXO1 ubiquitination and
CC degradation via the proteasome pathway in hepatocytes
CC (PubMed:21317886). {ECO:0000250|UniProtKB:P17861,
CC ECO:0000269|PubMed:20348926, ECO:0000269|PubMed:20955178,
CC ECO:0000269|PubMed:21317886}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P17861}. Note=Colocalizes with ERN1 and KDR in
CC the endoplasmic reticulum in endothelial cells in a vascular
CC endothelial growth factor (VEGF)-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:P17861}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:16332684}. Cytoplasm {ECO:0000269|PubMed:16332684}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17861}; Single-
CC pass type II membrane protein {ECO:0000250|UniProtKB:P17861}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17861};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P17861}. Membrane
CC {ECO:0000250|UniProtKB:P17861}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17861}. Note=Shuttles between the nucleus and
CC the cytoplasm in a CRM1-dependent manner. Localizes predominantly at
CC the endoplasmic reticulum membrane as a membrane-spanning protein;
CC whereas may be only marginally localized on the cytosolic side of the
CC ER membrane as a peripheral membrane (By similarity). Shows no
CC preferential localization to either the nucleus or the cytoplasm
CC (PubMed:16332684). {ECO:0000250|UniProtKB:P17861,
CC ECO:0000269|PubMed:16332684}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:16332684, ECO:0000269|PubMed:18556558,
CC ECO:0000269|PubMed:20348926, ECO:0000269|PubMed:20955178}. Cytoplasm
CC {ECO:0000269|PubMed:16332684}. Note=Localizes predominantly in the
CC nucleus (PubMed:16332684). Colocalizes in the nucleus with SIRT1
CC (PubMed:20955178). Translocates into the nucleus in a PIK3R-, ER
CC stress-induced- and/or insulin-dependent manner (PubMed:20348926).
CC {ECO:0000269|PubMed:16332684, ECO:0000269|PubMed:18556558,
CC ECO:0000269|PubMed:20348926, ECO:0000269|PubMed:20955178}.
CC -!- SUBCELLULAR LOCATION: [X-box-binding protein 1, cytoplasmic form]:
CC Cytoplasm {ECO:0000250|UniProtKB:P17861}. Nucleus
CC {ECO:0000250|UniProtKB:P17861}. Note=Localizes in the cytoplasm and
CC nucleus after HM13/SPP-mediated intramembranaire proteolytic cleavage
CC of isoform 1 (By similarity). {ECO:0000250|UniProtKB:P17861}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Unprocessed XBP-1, XBP-1U
CC {ECO:0000303|PubMed:11780124};
CC IsoId=O35426-1; Sequence=Displayed;
CC Name=2; Synonyms=Processed XBP-1, XBP-1S {ECO:0000303|PubMed:11780124};
CC IsoId=O35426-2; Sequence=VSP_012937;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed at higher
CC level in branch curves of vessel walls and in atherosclerotic plaques
CC relative to healthy segments of the same aortas (at protein level)
CC (PubMed:19416856). Expressed in skeletal muscles, plasma cells and
CC pancreatic beta cells (PubMed:17612490). Isoform 1 and isoform 2 are
CC expressed in gonadal adipose tissue. Isoform 1 is expressed in inguinal
CC adipose tissue (PubMed:23623498). {ECO:0000269|PubMed:17612490,
CC ECO:0000269|PubMed:19416856, ECO:0000269|PubMed:23623498}.
CC -!- DEVELOPMENTAL STAGE: Expressed mainly in exocrine glands and bone
CC precursors in the embryonic mouse (PubMed:7693055).
CC {ECO:0000269|PubMed:7693055}.
CC -!- INDUCTION: Isoform 2 is up-regulated during adipocyte differentiation
CC (PubMed:25223794). Isoform 2 is up-regulated upon refeeding after a
CC fasting period in liver and in ob/ob mice (obese) (at protein level)
CC (PubMed:20348926). Induced by chemical activators of the unfolded
CC protein response (UPR) such as tunicamycin, DTT and thapsigargin
CC (PubMed:17612490). Up-regulated after partial hepatectomy during the
CC acute phase response (PubMed:10652269). Isoform 1 and isoform 2 are up-
CC regulated by interleukin-4 in B cells in a STAT6-dependent manner
CC (PubMed:12612580). Isoform 1 and isoform 2 are up-regulated during
CC lactation and by the lactogenic hormone prolactin (PubMed:23623498).
CC Isoform 2 is up-regulated by prolonged feeding of high-carbohydrate
CC diets in hepatocytes in absence of ER-stress (PubMed:18556558). Isoform
CC 2 is up-regulated by insulin-like growth factor and glucose starvation
CC (PubMed:17612490). Isoform 2 is up-regulated during plasma-cell
CC differentiation in response to endoplasmic reticulum (ER) stress, such
CC as lipopolysaccharide (LPS) (PubMed:11780124, PubMed:11850408,
CC PubMed:12612580). {ECO:0000269|PubMed:10652269,
CC ECO:0000269|PubMed:11780124, ECO:0000269|PubMed:11850408,
CC ECO:0000269|PubMed:12612580, ECO:0000269|PubMed:17612490,
CC ECO:0000269|PubMed:18556558, ECO:0000269|PubMed:20348926,
CC ECO:0000269|PubMed:23623498, ECO:0000269|PubMed:25223794}.
CC -!- DOMAIN: Isoform 1 transmembrane signal-anchor domain is necessary for
CC its own mRNA to be recruited to the endoplasmic reticulum (ER) which
CC will undergo unconventional ERN1-dependent splicing in response to ER
CC stress. Isoform 1 N-terminus and C-terminus regions are necessary for
CC DNA-binding and weak transcriptional activity, respectively. Isoform 2
CC N-terminus and C-terminus regions are necessary for DNA-binding and
CC strong transcriptional activity upon ER stress, respectively. Isoform 2
CC C-terminus region contains a nuclear exclusion signal (NES) at
CC positions 182 through 204. Isoform 2 C-terminus region contains a
CC degradation domain at positions 204 through 256 (By similarity).
CC Isoform 1 and isoform 2 N-terminus domains are necessary for nuclear
CC localization targeting. Isoform 1 C-terminus domain confers
CC localization to the cytoplasm and is sufficient to impose rapid
CC degradation (PubMed:16332684). {ECO:0000250|UniProtKB:P17861,
CC ECO:0000269|PubMed:16332684}.
CC -!- PTM: [Isoform 2]: Acetylated by EP300; acetylation positively regulates
CC the transcriptional activity of XBP1 isoform 2 (PubMed:20955178).
CC Isoform 2 is deacetylated by SIRT1; deacetylation negatively regulates
CC the transcriptional activity of XBP1 isoform 2 (PubMed:20955178).
CC {ECO:0000269|PubMed:20955178, ECO:0000305|PubMed:20955178}.
CC -!- PTM: [Isoform 1]: Ubiquitinated, leading to proteasomal degradation in
CC response to ER stress (PubMed:11780124, PubMed:12902539,
CC PubMed:16332684). {ECO:0000250|UniProtKB:P17861,
CC ECO:0000269|PubMed:11780124, ECO:0000269|PubMed:12902539,
CC ECO:0000269|PubMed:16332684}.
CC -!- PTM: X-box-binding protein 1, cytoplasmic form and luminal form are
CC produced by intramembrane proteolytic cleavage of ER membrane-anchored
CC isoform 1 triggered by HM13/SPP in a DERL1-RNF139-dependent and
CC VCP/p97-independent manner. X-box-binding protein 1, luminal form is
CC ubiquitinated leading to proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:P17861}.
CC -!- DISRUPTION PHENOTYPE: Mice embryos die at 12.5-13.5 dpc and display
CC less blood vessels (PubMed:23529610). Embryos display hypoplastic
CC livers, cellular necrosis in the myocardium, hypoplasia of the heart
CC and die in utero from severe anemia (PubMed:10425189, PubMed:10652269).
CC Mice display severe abnormalities in the development and function of
CC secretory cells, such as plasma B cells and pancreatic acinar cells
CC (PubMed:16362047). Haploinsufficient mice fed a high-fat diet gain more
CC weight, display enhanced ER stress in adipose tissue, reduced insulin
CC receptor signaling and develop peripheral insulin resistance and type 2
CC diabetes (PubMed:15486293). Endothelial-specific knockout mice show
CC delayed retinal vascular development and impaired postischemic
CC angiogenesis (PubMed:23529610, PubMed:23184933). Dopaminergic neuron-
CC specific knockout mice display ER dysfonction and accumulation of
CC abnormal protein aggregates (PubMed:24753614). Liver-specific knockout
CC mice leads to reduced lipogenic gene expression and diminished hepatic
CC lipid synthesis (PubMed:18556558). Adipocyte-specific knockout female
CC mice fed with a regular or high-fat diet, show no alteration in body
CC weight, adipose tissue mass, blood glucose, serum insulin and lipid
CC levels; however during lactation adipose tissue mass increases and milk
CC production decreases but mammary gland structure and milk composition
CC remains normal (PubMed:23623498). Intestinal epithelial cell-specific
CC knockout mice born and developed normally but displayed small
CC intestinal mucosal inflammation in association with increased ER
CC stress, a diminution of Paneth and goblet cells with reduced secretory
CC granules (PubMed:18775308). {ECO:0000269|PubMed:10425189,
CC ECO:0000269|PubMed:10652269, ECO:0000269|PubMed:15486293,
CC ECO:0000269|PubMed:16362047, ECO:0000269|PubMed:18556558,
CC ECO:0000269|PubMed:18775308, ECO:0000269|PubMed:23184933,
CC ECO:0000269|PubMed:23529610, ECO:0000269|PubMed:23623498,
CC ECO:0000269|PubMed:24753614}.
CC -!- MISCELLANEOUS: [Isoform 2]: Potent transcriptional activator. Induced
CC by unconventional ERN1-dependent splicing in response to endoplasmic
CC reticulum stress. ERN1 cleaves a 26-bp fragment causing a frameshift of
CC the mRNA transcript (PubMed:11780124, PubMed:11850408).
CC {ECO:0000269|PubMed:11780124, ECO:0000269|PubMed:11850408}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; AB036745; BAB13793.1; -; Genomic_DNA.
DR EMBL; AF443192; AAL60202.1; -; mRNA.
DR EMBL; AF027963; AAB81862.2; -; mRNA.
DR EMBL; AL662876; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008153; AAH08153.1; -; mRNA.
DR EMBL; BC029197; AAH29197.1; -; mRNA.
DR CCDS; CCDS24400.1; -. [O35426-1]
DR PIR; JC7300; JC7300.
DR RefSeq; NP_001258659.1; NM_001271730.1. [O35426-2]
DR RefSeq; NP_038870.2; NM_013842.3. [O35426-1]
DR AlphaFoldDB; O35426; -.
DR SMR; O35426; -.
DR BioGRID; 204589; 11.
DR IntAct; O35426; 1.
DR STRING; 10090.ENSMUSP00000054852; -.
DR iPTMnet; O35426; -.
DR PhosphoSitePlus; O35426; -.
DR PaxDb; O35426; -.
DR PRIDE; O35426; -.
DR ProteomicsDB; 297567; -. [O35426-1]
DR ProteomicsDB; 297568; -. [O35426-2]
DR Antibodypedia; 10221; 714 antibodies from 43 providers.
DR DNASU; 22433; -.
DR Ensembl; ENSMUST00000063084; ENSMUSP00000054852; ENSMUSG00000020484. [O35426-1]
DR GeneID; 22433; -.
DR KEGG; mmu:22433; -.
DR UCSC; uc007hwm.2; mouse. [O35426-2]
DR UCSC; uc007hwn.2; mouse. [O35426-1]
DR CTD; 7494; -.
DR MGI; MGI:98970; Xbp1.
DR VEuPathDB; HostDB:ENSMUSG00000020484; -.
DR eggNOG; KOG4005; Eukaryota.
DR GeneTree; ENSGT00390000017751; -.
DR HOGENOM; CLU_093516_0_0_1; -.
DR InParanoid; O35426; -.
DR OMA; QTMSLIC; -.
DR OrthoDB; 1269901at2759; -.
DR PhylomeDB; O35426; -.
DR TreeFam; TF319837; -.
DR BioGRID-ORCS; 22433; 7 hits in 80 CRISPR screens.
DR ChiTaRS; Xbp1; mouse.
DR PRO; PR:O35426; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O35426; protein.
DR Bgee; ENSMUSG00000020484; Expressed in lacrimal gland and 298 other tissues.
DR ExpressionAtlas; O35426; baseline and differential.
DR Genevisible; O35426; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; IPI:UniProtKB.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0060612; P:adipose tissue development; IMP:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:UniProtKB.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
DR GO; GO:0071332; P:cellular response to fructose stimulus; IDA:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IDA:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0071353; P:cellular response to interleukin-4; IDA:UniProtKB.
DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; ISS:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0031670; P:cellular response to nutrient; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IDA:UniProtKB.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0035356; P:cellular triglyceride homeostasis; IMP:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0060691; P:epithelial cell maturation involved in salivary gland development; IMP:MGI.
DR GO; GO:0031017; P:exocrine pancreas development; IMP:MGI.
DR GO; GO:0055089; P:fatty acid homeostasis; IMP:UniProtKB.
DR GO; GO:0002071; P:glandular epithelial cell maturation; IMP:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0001889; P:liver development; IMP:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:1900102; P:negative regulation of endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IDA:UniProtKB.
DR GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0048666; P:neuron development; IDA:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; ISO:MGI.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:UniProtKB.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IMP:UniProtKB.
DR GO; GO:0031062; P:positive regulation of histone methylation; ISS:UniProtKB.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IDA:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:1903489; P:positive regulation of lactation; IMP:UniProtKB.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISS:UniProtKB.
DR GO; GO:1900100; P:positive regulation of plasma cell differentiation; ISS:UniProtKB.
DR GO; GO:1901985; P:positive regulation of protein acetylation; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006990; P:positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; IDA:UniProtKB.
DR GO; GO:0035470; P:positive regulation of vascular wound healing; ISO:MGI.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0051602; P:response to electrical stimulus; ISO:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:1990418; P:response to insulin-like growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0060096; P:serotonin secretion, neurotransmission; ISO:MGI.
DR GO; GO:0055092; P:sterol homeostasis; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR Pfam; PF07716; bZIP_2; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Angiogenesis; Apoptosis;
KW Autophagy; Cleavage on pair of basic residues; Cytoplasm;
KW Developmental protein; Differentiation; DNA-binding; Endoplasmic reticulum;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Myogenesis; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome; Signal-anchor;
KW Stress response; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation; Unfolded protein response.
FT CHAIN 1..267
FT /note="X-box-binding protein 1"
FT /id="PRO_0000076544"
FT CHAIN 1..188
FT /note="X-box-binding protein 1, cytoplasmic form"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT /id="PRO_0000431893"
FT CHAIN 191..267
FT /note="X-box-binding protein 1, luminal form"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT /id="PRO_0000431894"
FT TOPO_DOM 1..180
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT TRANSMEM 181..198
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000250|UniProtKB:P17861, ECO:0000255"
FT TOPO_DOM 199..267
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT DOMAIN 63..126
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 35..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..87
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 69..85
FT /note="Nuclear localization signal (NLS); in isoforms 1 and
FT isoform 2"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT REGION 91..126
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 230..256
FT /note="Necessary for the translational pausing of its own
FT mRNA"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT SITE 185..186
FT /note="Cleavage; by HM13/SPP"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17861"
FT VAR_SEQ 162..267
FT /note="LRLCAPLQQVQAQLSPPQNIFPWTLTLLPLQILSLISFWAFWTSWTLSCFSN
FT VLPQSLLVWRNSQRSTQKDLVPYQPPFLCQWGPHQPSWKPLMNSFVLTMYTPSL -> G
FT AGPVVTSPEHLPMDSDTVASSDSESDILLGILDKLDPVMFFKCPSPESASLEELPEVYP
FT EGPSSLPASLSLSVGTSSAKLEAINELIRFDHVYTKPLVLEIPSETESQTNVVVKIEEA
FT PLSSSEEDHPEFIVSVKKEPLEDDFIPELGISNLLSSSHCLRPPSCLLDAHSDCGYEGS
FT PSPFSDMSSPLGTDHSWEDTFANELFPQLISV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11780124"
FT /id="VSP_012937"
FT MUTAGEN 177..178
FT /note="PP->LH: Reduces degradation (isoform 1); when
FT associated with 238-L-H-239."
FT /evidence="ECO:0000269|PubMed:16332684"
FT MUTAGEN 231
FT /note="K->R: Enhances stability and accumulates in the
FT cytoplasm; when associated with R-252 (isoform 1)."
FT /evidence="ECO:0000269|PubMed:12902539,
FT ECO:0000269|PubMed:16332684"
FT MUTAGEN 238..239
FT /note="PP->LH: Reduces degradation (isoform 1); when
FT associated with 177-L-H-178."
FT /evidence="ECO:0000269|PubMed:16332684"
FT MUTAGEN 252
FT /note="K->R: Enhances stability and accumulates in the
FT cytoplasm; when associated with R-231 (isoform 1)."
FT /evidence="ECO:0000269|PubMed:12902539,
FT ECO:0000269|PubMed:16332684"
FT CONFLICT 27
FT /note="Missing (in Ref. 1; BAB13793)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 267 AA; 29619 MW; 15009E684F6D426F CRC64;
MVVVAAAPSA ATAAPKVLLL SGQPASGGRA LPLMVPGPRA AGSEASGTPQ ARKRQRLTHL
SPEEKALRRK LKNRVAAQTA RDRKKARMSE LEQQVVDLEE ENHKLQLENQ LLREKTHGLV
VENQELRTRL GMDTLDPDEV PEVEAKGSGV RLVAGSAESA ALRLCAPLQQ VQAQLSPPQN
IFPWTLTLLP LQILSLISFW AFWTSWTLSC FSNVLPQSLL VWRNSQRSTQ KDLVPYQPPF
LCQWGPHQPS WKPLMNSFVL TMYTPSL
