ID XBP1_HUMAN Reviewed; 261 AA. AC P17861; Q8WYK6; Q969P1; Q96BD7; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2005, sequence version 2. DT 27-MAR-2024, entry version 221. DE RecName: Full=X-box-binding protein 1 {ECO:0000303|PubMed:2321018, ECO:0000312|HGNC:HGNC:12801}; DE Short=XBP-1 {ECO:0000303|PubMed:2321018}; DE AltName: Full=Tax-responsive element-binding protein 5 {ECO:0000303|PubMed:2196176}; DE Short=TREB-5 {ECO:0000303|PubMed:2196176}; DE Contains: DE RecName: Full=X-box-binding protein 1, cytoplasmic form {ECO:0000303|PubMed:25239945}; DE Contains: DE RecName: Full=X-box-binding protein 1, luminal form {ECO:0000303|PubMed:25239945}; GN Name=XBP1 {ECO:0000312|HGNC:HGNC:12801}; GN Synonyms=TREB5 {ECO:0000303|PubMed:2196176}, XBP2 GN {ECO:0000312|HGNC:HGNC:12801}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1), AND RP DNA-BINDING (ISOFORM 1). RC TISSUE=B-cell; RX PubMed=2321018; DOI=10.1126/science.2321018; RA Liou H.-C., Boothby M.R., Finn P.W., Davidon R., Nabavi N., RA Zeleznik-Le N.J., Ting J.P.-Y., Glimcher L.H.; RT "A new member of the leucine zipper class of proteins that binds to the HLA RT DR alpha promoter."; RL Science 247:1581-1584(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1), AND RP DNA-BINDING (ISOFORM 1). RX PubMed=2196176; DOI=10.1002/j.1460-2075.1990.tb07434.x; RA Yoshimura T., Fujisawa J., Yoshida M.; RT "Multiple cDNA clones encoding nuclear proteins that bind to the tax- RT dependent enhancer of HTLV-1: all contain a leucine zipper structure and RT basic amino acid domain."; RL EMBO J. 9:2537-2542(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DNA-BINDING. RX PubMed=8349596; DOI=10.1016/s0021-9258(19)85304-8; RA Ponath P.D., Fass D., Liou H.C., Glimcher L.H., Strominger J.L.; RT "The regulatory gene, hXBP-1, and its target, HLA-DRA, utilize both common RT and distinct regulatory elements and protein complexes."; RL J. Biol. Chem. 268:17074-17082(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION (ISOFORM 2), RP ALTERNATIVE SPLICING (ISOFORM 2), DNA-BINDING (ISOFORMS 1 AND 2), INDUCTION RP (ISOFORM 2), ER STRESS-MEDIATED DOWN-REGULATION (ISOFORM 1), AND DOMAIN RP (ISOFORMS 1 AND 2). RX PubMed=11779464; DOI=10.1016/s0092-8674(01)00611-0; RA Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K.; RT "XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress RT to produce a highly active transcription factor."; RL Cell 107:881-891(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Ovary, and Placenta; 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 [8] RP FUNCTION (ISOFORM 1), DNA-BINDING (ISOFORM 1), AND INTERACTION WITH FOS RP (ISOFORM 1). RX PubMed=1903538; DOI=10.1073/pnas.88.10.4309; RA Ono S.J., Liou H.C., Davidon R., Strominger J.L., Glimcher L.H.; RT "Human X-box-binding protein 1 is required for the transcription of a RT subset of human class II major histocompatibility genes and forms a RT heterodimer with c-fos."; RL Proc. Natl. Acad. Sci. U.S.A. 88:4309-4312(1991). RN [9] RP INDUCTION. RX PubMed=8627152; DOI=10.1084/jem.183.2.393; RA Reimold A.M., Ponath P.D., Li Y.S., Hardy R.R., David C.S., RA Strominger J.L., Glimcher L.H.; RT "Transcription factor B cell lineage-specific activator protein regulates RT the gene for human X-box binding protein 1."; RL J. Exp. Med. 183:393-401(1996). RN [10] RP FUNCTION (ISOFORM 1), DNA-BINDING (ISOFORM 1), AND DOMAIN (ISOFORMS 1 AND RP 2). RX PubMed=8657566; DOI=10.1093/nar/24.10.1855; RA Clauss I.M., Chu M., Zhao J.-L., Glimcher L.H.; RT "The basic domain/leucine zipper protein hXBP-1 preferentially binds to and RT transactivates CRE-like sequences containing an ACGT core."; RL Nucleic Acids Res. 24:1855-1864(1996). RN [11] RP INDUCTION. RX PubMed=10375612; DOI=10.3892/ijo.15.1.173; RA Wen X.Y., Stewart A.K., Sooknanan R.R., Henderson G., Hawley T.S., RA Reimold A.M., Glimcher L.H., Baumann H., Malek L.T., Hawley R.G.; RT "Identification of c-myc promoter-binding protein and X-box binding protein RT 1 as interleukin-6 target genes in human multiple myeloma cells."; RL Int. J. Oncol. 15:173-178(1999). RN [12] RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY. RX PubMed=11460154; DOI=10.1038/35085509; RA Reimold A.M., Iwakoshi N.N., Manis J., Vallabhajosyula P., RA Szomolanyi-Tsuda E., Gravallese E.M., Friend D., Grusby M.J., Alt F., RA Glimcher L.H.; RT "Plasma cell differentiation requires the transcription factor XBP-1."; RL Nature 412:300-307(2001). RN [13] RP INVOLVEMENT IN SUSCEPTIBILITY TO MAJOR AFFECTIVE DISORDER TYPE 7. RX PubMed=12949534; DOI=10.1038/ng1235; RA Kakiuchi C., Iwamoto K., Ishiwata M., Bundo M., Kasahara T., Kusumi I., RA Tsujita T., Okazaki Y., Nanko S., Kunugi H., Sasaki T., Kato T.; RT "Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar RT disorder."; RL Nat. Genet. 35:171-175(2003). RN [14] RP FUNCTION (ISOFORM 2). RX PubMed=15466483; DOI=10.1083/jcb.200406136; RA Sriburi R., Jackowski S., Mori K., Brewer J.W.; RT "XBP1: a link between the unfolded protein response, lipid biosynthesis, RT and biogenesis of the endoplasmic reticulum."; RL J. Cell Biol. 167:35-41(2004). RN [15] RP INDUCTION (ISOFORM 2). RX PubMed=17110785; DOI=10.1247/csf.06016; RA Yoshida H., Nadanaka S., Sato R., Mori K.; RT "XBP1 is critical to protect cells from endoplasmic reticulum stress: RT evidence from Site-2 protease-deficient Chinese hamster ovary cells."; RL Cell Struct. Funct. 31:117-125(2006). RN [16] RP FUNCTION (ISOFORMS 1 AND 2), INTERACTION WITH XBP1 ISOFORM 2 (ISOFORM 1), RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), INDUCTION (ISOFORMS 1 AND 2), RP STRESS-MEDIATED DOWN-REGULATION (ISOFORM 1), AND DOMAIN (ISOFORMS 1 AND 2). RX PubMed=16461360; DOI=10.1083/jcb.200508145; RA Yoshida H., Oku M., Suzuki M., Mori K.; RT "pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfolded protein RT response activator pXBP1(S) in mammalian ER stress response."; RL J. Cell Biol. 172:565-575(2006). RN [17] RP INTERACTION WITH ATF6 (ISOFORM 2). RX PubMed=17765680; DOI=10.1016/j.devcel.2007.07.018; RA Yamamoto K., Sato T., Matsui T., Sato M., Okada T., Yoshida H., Harada A., RA Mori K.; RT "Transcriptional induction of mammalian ER quality control proteins is RT mediated by single or combined action of ATF6alpha and XBP1."; RL Dev. Cell 13:365-376(2007). RN [18] RP UNCONVENTIONAL ALTERNATIVE SPLICING (ISOFORM 2). RX PubMed=19622636; DOI=10.1242/jcs.040584; RA Uemura A., Oku M., Mori K., Yoshida H.; RT "Unconventional splicing of XBP1 mRNA occurs in the cytoplasm during the RT mammalian unfolded protein response."; RL J. Cell Sci. 122:2877-2886(2009). RN [19] RP FUNCTION (ISOFORM 1), SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), TOPOLOGY RP (ISOFORM 1), DOMAIN (ISOFORM 1), AND MUTAGENESIS OF TRP-189; VAL-193; RP LEU-194; LEU-196; ILE-198 AND TRP-205. RX PubMed=19394296; DOI=10.1016/j.molcel.2009.02.033; RA Yanagitani K., Imagawa Y., Iwawaki T., Hosoda A., Saito M., Kimata Y., RA Kohno K.; RT "Cotranslational targeting of XBP1 protein to the membrane promotes RT cytoplasmic splicing of its own mRNA."; RL Mol. Cell 34:191-200(2009). RN [20] RP FUNCTION (ISOFORM 2), DNA-BINDING (ISOFORMS 1 AND 2), INDUCTION (ISOFORMS 1 RP AND 2), AND 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, INTERACTION WITH PIK3R1 (ISOFORM 2), AND SUBCELLULAR LOCATION RP (ISOFORMS 1 AND 2). RX PubMed=20348923; DOI=10.1038/nm.2121; RA Winnay J.N., Boucher J., Mori M.A., Ueki K., Kahn C.R.; RT "A regulatory subunit of phosphoinositide 3-kinase increases the nuclear RT accumulation of X-box-binding protein-1 to modulate the unfolded protein RT response."; RL Nat. Med. 16:438-445(2010). RN [22] RP ACETYLATION BY EP300 (ISOFORM 2), DEACETYLATION BY SIRT1 (ISOFORM 2), AND RP SUBCELLULAR LOCATION (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 1), DOMAIN (ISOFORM 1), AND MUTAGENESIS OF LEU-246; RP SER-255 AND TRP-256. RX PubMed=21233347; DOI=10.1126/science.1197142; RA Yanagitani K., Kimata Y., Kadokura H., Kohno K.; RT "Translational pausing ensures membrane targeting and cytoplasmic splicing RT of XBP1u mRNA."; RL Science 331:586-589(2011). RN [24] RP FUNCTION (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND INDUCTION (ISOFORM RP 2). 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 [25] RP FUNCTION (ISOFORM 2), DNA-BINDING (ISOFORM 2), AND INDUCTION (ISOFORM 2). 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 [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-68, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [27] RP FUNCTION (ISOFORM 2), AND TISSUE SPECIFICITY. RX PubMed=25280941; DOI=10.1016/j.cellsig.2014.09.018; RA Li H., Chen X., Gao Y., Wu J., Zeng F., Song F.; RT "XBP1 induces snail expression to promote epithelial-to-mesenchymal RT transition and invasion of breast cancer cells."; RL Cell. Signal. 27:82-89(2015). RN [28] RP FUNCTION (ISOFORMS 1 AND 2), INTERACTION WITH DERL1; HM13; RNF139 AND XBP1 RP ISOFORM 2 (ISOFORM 1), TOPOLOGY (ISOFORM 1), PROTEOLYTIC CLEAVAGE (ISOFORM RP 1), SUBCELLULAR LOCATION (ISOFORM 1 AND CYTOPLASMIC FORM), UBIQUITINATION RP (ISOFORM 1 AND LUMINAL FORM), STRESS-MEDIATED DOWN-REGULATION (ISOFORM 2), RP AND MUTAGENESIS OF GLN-197; GLN-199; SER-200; SER-203; THR-212; CYS-215 AND RP ARG-232. RX PubMed=25239945; DOI=10.15252/embj.201488208; RA Chen C.Y., Malchus N.S., Hehn B., Stelzer W., Avci D., Langosch D., RA Lemberg M.K.; RT "Signal peptide peptidase functions in ERAD to cleave the unfolded protein RT response regulator XBP1u."; RL EMBO J. 33:2492-2506(2014). RN [29] RP FUNCTION (ISOFORM 1), DNA-BINDING (ISOFORMS 1 AND 2), INTERACTION WITH RP HDAC3 AND AKT1 (ISOFORM 1), SUBCELLULAR LOCATION (ISOFORM 1), AND INDUCTION RP (ISOFORMS 1 AND 2). RX PubMed=25190803; DOI=10.1074/jbc.m114.571984; RA Martin D., Li Y., Yang J., Wang G., Margariti A., Jiang Z., Yu H., RA Zampetaki A., Hu Y., Xu Q., Zeng L.; RT "Unspliced X-box-binding protein 1 (XBP1) protects endothelial cells from RT oxidative stress through interaction with histone deacetylase 3."; RL J. Biol. Chem. 289:30625-30634(2014). RN [30] RP VARIANT [LARGE SCALE ANALYSIS] VAL-12. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [31] RP VARIANT LYS-232. RX PubMed=17224074; DOI=10.1186/bcr1637; RA Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., RA Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., RA Boerresen-Dale A.-L.; RT "Somatic sequence alterations in twenty-one genes selected by expression RT profile analysis of breast carcinomas."; RL Breast Cancer Res. 9:R5-R5(2007). CC -!- FUNCTION: Functions as a transcription factor during endoplasmic CC reticulum (ER) stress by regulating the unfolded protein response CC (UPR). Required for cardiac myogenesis and hepatogenesis during CC embryonic development, and the development of secretory tissues such as CC exocrine pancreas and salivary gland (By similarity). Involved in CC terminal differentiation of B lymphocytes to plasma cells and CC production of immunoglobulins (PubMed:11460154). Modulates the cellular CC response to ER stress in a PIK3R-dependent manner (PubMed:20348923). CC Binds to the cis-acting X box present in the promoter regions of major CC histocompatibility complex class II genes (PubMed:8349596). Involved in CC VEGF-induced endothelial cell (EC) proliferation and retinal blood CC vessel formation during embryonic development but also for angiogenesis CC in adult tissues under ischemic conditions. Functions also as a major CC regulator of the UPR in obesity-induced insulin resistance and type 2 CC diabetes for the management of obesity and diabetes prevention (By CC similarity). {ECO:0000250|UniProtKB:O35426, CC ECO:0000269|PubMed:11460154, ECO:0000269|PubMed:20348923, CC ECO:0000269|PubMed:8349596}. 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 (PubMed:19394296, PubMed:21233347). In endothelial CC cells (EC), associated with KDR, promotes IRE1-mediated XBP1 mRNA CC isoform 2 productions in a vascular endothelial growth factor (VEGF)- CC dependent manner, leading to EC proliferation and angiogenesis CC (PubMed:23529610). Functions as a negative feed-back regulator of the CC potent transcription factor XBP1 isoform 2 protein levels through CC proteasome-mediated degradation, thus preventing the constitutive CC activation of the ER stress response signaling pathway CC (PubMed:16461360, PubMed:25239945). Inhibits the transactivation CC activity of XBP1 isoform 2 in myeloma cells (By similarity). Acts as a CC weak transcriptional factor (PubMed:8657566). Together with HDAC3, CC contributes to the activation of NFE2L2-mediated HMOX1 transcription CC factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling CC pathway leading to EC survival under disturbed flow/oxidative stress CC (PubMed:25190803). Binds to the ER stress response element (ERSE) upon CC ER stress (PubMed:11779464). Binds to the consensus 5'- CC GATGACGTG[TG]N(3)[AT]T-3' sequence related to cAMP responsive element CC (CRE)-like sequences (PubMed:8657566). Binds the Tax-responsive element CC (TRE) present in the long terminal repeat (LTR) of T-cell leukemia CC virus type 1 (HTLV-I) and to the TPA response elements (TRE) CC (PubMed:2321018, PubMed:2196176, PubMed:1903538, PubMed:8657566). CC Associates preferentially to the HDAC3 gene promoter region in a static CC flow-dependent manner (PubMed:25190803). Binds to the CDH5/VE-cadherin CC gene promoter region (PubMed:19416856). {ECO:0000250|UniProtKB:O35426, CC ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:16461360, CC ECO:0000269|PubMed:1903538, ECO:0000269|PubMed:19394296, CC ECO:0000269|PubMed:19416856, ECO:0000269|PubMed:21233347, CC ECO:0000269|PubMed:2196176, ECO:0000269|PubMed:2321018, CC ECO:0000269|PubMed:23529610, ECO:0000269|PubMed:25190803, CC ECO:0000269|PubMed:25239945, ECO:0000269|PubMed:8657566}. 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:11779464, PubMed:25239945). Plays a role in the CC production of immunoglobulins and interleukin-6 in the presence of CC stimuli required for plasma cell differentiation (By similarity). CC Induces phospholipid biosynthesis and ER expansion (PubMed:15466483). CC Contributes to the VEGF-induced endothelial cell (EC) growth and CC proliferation in a Akt/GSK-dependent and/or -independent signaling CC pathway, respectively, leading to beta-catenin nuclear translocation CC and E2F2 gene expression (PubMed:23529610). Promotes umbilical vein EC CC apoptosis and atherosclerotisis development in a caspase-dependent CC signaling pathway, and contributes to VEGF-induced EC proliferation and CC angiogenesis in adult tissues under ischemic conditions CC (PubMed:19416856, PubMed:23529610). Involved in the regulation of CC endostatin-induced autophagy in EC through BECN1 transcriptional CC activation (PubMed:23184933). Plays a role as an oncogene by promoting CC tumor progression: stimulates zinc finger protein SNAI1 transcription CC to induce epithelial-to-mesenchymal (EMT) transition, cell migration CC and invasion of breast cancer cells (PubMed:25280941). Involved in CC adipocyte differentiation by regulating lipogenic gene expression CC during lactation. 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. Increases insulin sensitivity CC in the liver as a response to a high carbohydrate diet, resulting in CC improved glucose tolerance. 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. Controls the induction of de novo CC fatty acid synthesis in hepatocytes by regulating the expression of a CC subset of lipogenic genes in an ER stress- and UPR-independent manner CC (By similarity). Associates preferentially to the HDAC3 gene promoter CC region in a disturbed flow-dependent manner (PubMed:25190803). Binds to CC the BECN1 gene promoter region (PubMed:23184933). Binds to the CDH5/VE- CC cadherin gene promoter region (PubMed:19416856). Binds to the ER stress CC response element (ERSE) upon ER stress (PubMed:11779464). Binds to the CC 5'-CCACG-3' motif in the PPARG promoter (By similarity). CC {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:11779464, CC ECO:0000269|PubMed:15466483, ECO:0000269|PubMed:19416856, CC ECO:0000269|PubMed:23184933, ECO:0000269|PubMed:23529610, CC ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25239945, CC ECO:0000269|PubMed:25280941}. CC -!- SUBUNIT: Isoform 2 interacts with SIRT1. Isoform 2 interacts with CC PIK3R1 and PIK3R2; the interactions are direct and induce translocation CC of XBP1 isoform 2 into the nucleus and the unfolded protein response CC (UPR) XBP1-dependent target genes activation in a ER stress- and/or CC insulin-dependent but PI3K-independent manner. Isoform 2 interacts with CC FOXO1; the interaction is direct and leads to FOXO1 ubiquitination and CC degradation via the proteasome pathway in hepatocytes (By similarity). CC Isoform 1 interacts with HM13 (PubMed:25239945). Isoform 1 interacts CC with RNF139; the interaction induces ubiquitination and degradation of CC isoform 1 (PubMed:25239945). Isoform 1 interacts (via luminal domain) CC with DERL1; the interaction obviates the need for ectodomain shedding CC prior HM13/SPP-mediated XBP1 isoform 1 cleavage (PubMed:25239945). CC Isoform 1 interacts with isoform 2; the interaction sequesters isoform CC 2 from the nucleus and enhances isoform 2 degradation in the cytoplasm CC (PubMed:16461360, PubMed:25239945). Isoform 1 interacts with HDAC3 and CC AKT1; the interactions occur in endothelial cell (EC) under disturbed CC flow (PubMed:25190803). Isoform 1 interacts with the oncoprotein FOS CC (PubMed:1903538). Isoform 2 interacts with ATF6; the interaction occurs CC in a ER stress-dependent manner and is required for DNA binding to the CC unfolded protein response element (UPRE) (PubMed:17765680). Isoform 2 CC interacts with PIK3R1; the interaction is direct and induces CC translocation of XBP1 isoform 2 into the nucleus and the unfolded CC protein response (UPR) XBP1-dependent target genes activation in a ER CC stress- and/or insulin-dependent but PI3K-independent manner CC (PubMed:20348923). {ECO:0000250|UniProtKB:O35426, CC ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:17765680, CC ECO:0000269|PubMed:1903538, ECO:0000269|PubMed:20348923, CC ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25239945}. CC -!- INTERACTION: CC P17861; P18850: ATF6; NbExp=4; IntAct=EBI-6942961, EBI-852157; CC P17861; Q99941: ATF6B; NbExp=2; IntAct=EBI-6942961, EBI-2841031; CC P17861; Q9NS37: CREBZF; NbExp=4; IntAct=EBI-6942961, EBI-632965; CC P17861; Q16665: HIF1A; NbExp=3; IntAct=EBI-6942961, EBI-447269; CC P17861; Q13404: UBE2V1; NbExp=3; IntAct=EBI-6942961, EBI-1050671; CC P17861; P17861: XBP1; NbExp=2; IntAct=EBI-6942961, EBI-6942961; CC P17861-1; Q8TCT9: HM13; NbExp=2; IntAct=EBI-7631279, EBI-347472; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:23529610}. Note=Colocalizes with ERN1 and KDR in CC the endoplasmic reticulum in endothelial cells in a vascular CC endothelial growth factor (VEGF)-dependent manner (PubMed:23529610). CC {ECO:0000269|PubMed:23529610}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus CC {ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296}. Cytoplasm CC {ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296, CC ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:25190803}. Endoplasmic CC reticulum membrane {ECO:0000269|PubMed:25239945}; Single-pass type II CC membrane protein {ECO:0000269|PubMed:25239945}. Endoplasmic reticulum CC membrane {ECO:0000303|PubMed:25239945}; Peripheral membrane protein CC {ECO:0000303|PubMed:25239945}. Membrane {ECO:0000269|PubMed:19394296}; CC Peripheral membrane protein {ECO:0000303|PubMed:19394296}. Note=Shows CC no preferential localization to either the nucleus or the cytoplasm (By CC similarity). Shuttles between the nucleus and the cytoplasm in a CRM1- CC dependent manner (PubMed:16461360). Localizes predominantly at the CC endoplasmic reticulum membrane as a membrane-spanning protein; whereas CC may be only marginally localized on the cytosolic side of the ER CC membrane as a peripheral membrane (PubMed:19394296, PubMed:25190803). CC {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:16461360, CC ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:25190803}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus CC {ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296, CC ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:20955178}. Cytoplasm CC {ECO:0000250|UniProtKB:O35426}. Note=Localizes predominantly in the CC nucleus. Colocalizes in the nucleus with SIRT1. Translocates into the CC nucleus in a PIK3R-, ER stress-induced- and/or insulin-dependent manner CC (By similarity). {ECO:0000250|UniProtKB:O35426}. CC -!- SUBCELLULAR LOCATION: [X-box-binding protein 1, cytoplasmic form]: CC Cytoplasm {ECO:0000269|PubMed:25239945}. Nucleus CC {ECO:0000269|PubMed:25239945}. Note=Localizes in the cytoplasm and CC nucleus after HM13/SPP-mediated intramembranaire proteolytic cleavage CC of isoform 1 (PubMed:25239945). {ECO:0000269|PubMed:25239945}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Unprocessed XBP-1 {ECO:0000305}, XBP-1U CC {ECO:0000303|PubMed:11779464}, XBP1u {ECO:0000303|PubMed:19394296}; CC IsoId=P17861-1; Sequence=Displayed; CC Name=2; Synonyms=Processed XBP-1 {ECO:0000305}, XBP-1S CC {ECO:0000303|PubMed:11779464}, XBP1s {ECO:0000303|PubMed:19394296}; CC IsoId=P17861-2; Sequence=VSP_012936; CC -!- TISSUE SPECIFICITY: Expressed in plasma cells in rheumatoid synovium CC (PubMed:11460154). Over-expressed in primary breast cancer and CC metastatic breast cancer cells (PubMed:25280941). Isoform 1 and isoform CC 2 are expressed at higher level in proliferating as compared to CC confluent quiescent endothelial cells (PubMed:19416856). CC {ECO:0000269|PubMed:11460154, ECO:0000269|PubMed:19416856, CC ECO:0000269|PubMed:25280941}. CC -!- INDUCTION: Isoform 1 is up-regulated at the recovery phase of the CC endoplasmic reticulum (ER) stress response and isoform 2 is up- CC regulated early during the ER stress response and gradually decreased CC at later phase of ER stress (PubMed:16461360). Isoform 1 and isoform 2 CC are down-regulated by laminar flow but up-regulated by disturbed flow CC in umbilical vein endothelial cells in vitro (at protein level) CC (PubMed:19416856). Down-regulated by the B-cell-specific transcription CC factor PAX5 (PubMed:8627152). Up-regulated by interleukin IL-6 in CC myeloma cells (PubMed:10375612). Up-regulated during plasma-cell CC differentiation, either through the CD40 receptor signaling pathway or CC mitogens such as lipopolysaccharide (LPS) (PubMed:11460154). Isoform 1 CC and isoform 2 are down-regulated by laminar flow but up-regulated by CC disturbed flow in umbilical vein endothelial cells in vitro CC (PubMed:25190803). Isoform 2 is up-regulated early during the ER stress CC response in a ATF6-dependent manner (PubMed:11779464, PubMed:17110785, CC PubMed:16461360). Isoform 2 is up-regulated by endostatin in a ERN1- CC dependent manner (PubMed:23184933). Isoform 2 is transiently up- CC regulated by the mitogenic vascular endothelial growth factor (VEGF) in CC endothelial cells (PubMed:23529610). {ECO:0000269|PubMed:10375612, CC ECO:0000269|PubMed:11460154, ECO:0000269|PubMed:11779464, CC ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:17110785, CC ECO:0000269|PubMed:19416856, ECO:0000269|PubMed:23184933, CC ECO:0000269|PubMed:23529610, ECO:0000269|PubMed:25190803, CC ECO:0000269|PubMed:8627152}. CC -!- DOMAIN: Isoform 1 and isoform 2 N-terminus domains are necessary for CC nuclear localization targeting. Isoform 1 C-terminus domain confers CC localization to the cytoplasm and is sufficient to impose rapid CC degradation (By similarity). Isoform 1 transmembrane signal-anchor CC domain is necessary for its own mRNA to be recruited to the endoplasmic CC reticulum (ER) which will undergo unconventional ERN1-dependent CC splicing in response to ER stress (PubMed:19394296, PubMed:21233347). CC Isoform 1 N-terminus and C-terminus regions are necessary for DNA- CC binding and weak transcriptional activity, respectively. Isoform 2 N- CC terminus and C-terminus regions are necessary for DNA-binding and CC strong transcriptional activity upon ER stress, respectively CC (PubMed:11779464, PubMed:8657566). Isoform 2 C-terminus region contains CC a nuclear exclusion signal (NES) at positions 186 through 208. Isoform CC 2 C-terminus region contains a degradation domain at positions 209 CC through 261 (PubMed:16461360). {ECO:0000250|UniProtKB:O35426, CC ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:16461360, CC ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:21233347, CC ECO:0000269|PubMed:8657566}. 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 proteasome-mediated CC degradation in response to ER stress (PubMed:11779464, PubMed:16461360, CC PubMed:25239945). {ECO:0000250|UniProtKB:O35426, CC ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:16461360, CC ECO:0000269|PubMed:25239945}. 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 (PubMed:25239945). CC {ECO:0000269|PubMed:25239945}. CC -!- DISEASE: Major affective disorder 7 (MAFD7) [MIM:612371]: A major CC psychiatric disorder that is characterized by severe mood swings, with CC fluctuation between two abnormal mood states (manic or major depressive CC episode). Mania is accompanied by symptoms of euphoria, irritability, CC or excitation, whereas depression is associated with low mood and CC decreased motivation and energy. Note=Disease susceptibility may be CC associated with variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: Potent transcriptional activator. Induced CC by unconventional ERN1-dependent splicing in response to endoplasmic CC reticulum stress (PubMed:11779464, PubMed:19622636, PubMed:19394296). CC ERN1 cleaves a 26-bp fragment causing a frameshift of the mRNA CC transcript (PubMed:11779464). {ECO:0000269|PubMed:11779464, CC ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:19622636}. CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M31627; AAA36031.1; -; mRNA. DR EMBL; X55543; CAA39149.1; -; Genomic_DNA. DR EMBL; L13850; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB076383; BAB82981.1; -; mRNA. DR EMBL; AB076384; BAB82982.1; -; mRNA. DR EMBL; CR456611; CAG30497.1; -; mRNA. DR EMBL; Z93930; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000938; AAH00938.1; -; mRNA. DR EMBL; BC012841; AAH12841.1; -; mRNA. DR EMBL; BC015709; AAH15709.1; -; mRNA. DR CCDS; CCDS13847.1; -. [P17861-1] DR PIR; A36299; A36299. DR RefSeq; NP_001073007.1; NM_001079539.1. [P17861-2] DR RefSeq; NP_005071.2; NM_005080.3. [P17861-1] DR PDB; 6R5Q; EM; 3.00 A; 1=237-260. DR PDB; 6R6G; EM; 3.70 A; 1=237-260. DR PDB; 6R6P; EM; 3.10 A; 1=237-260. DR PDB; 6R7Q; EM; 3.90 A; 1=237-260. DR PDBsum; 6R5Q; -. DR PDBsum; 6R6G; -. DR PDBsum; 6R6P; -. DR PDBsum; 6R7Q; -. DR AlphaFoldDB; P17861; -. DR EMDB; EMD-4729; -. DR EMDB; EMD-4735; -. DR EMDB; EMD-4737; -. DR EMDB; EMD-4745; -. DR SMR; P17861; -. DR BioGRID; 113331; 47. DR ComplexPortal; CPX-6597; bZIP transcription factor complex, ATF6-XBP1. DR ComplexPortal; CPX-6600; bZIP transcription factor complex, ATF6B-XBP1. DR DIP; DIP-41692N; -. DR IntAct; P17861; 30. DR MINT; P17861; -. DR STRING; 9606.ENSP00000216037; -. DR BindingDB; P17861; -. DR ChEMBL; CHEMBL1741176; -. DR iPTMnet; P17861; -. DR PhosphoSitePlus; P17861; -. DR SwissPalm; P17861; -. DR BioMuta; XBP1; -. DR DMDM; 60416406; -. DR EPD; P17861; -. DR jPOST; P17861; -. DR MassIVE; P17861; -. DR MaxQB; P17861; -. DR PaxDb; 9606-ENSP00000216037; -. DR PeptideAtlas; P17861; -. DR ProteomicsDB; 53522; -. [P17861-1] DR ProteomicsDB; 53523; -. [P17861-2] DR Antibodypedia; 10221; 799 antibodies from 43 providers. DR DNASU; 7494; -. DR Ensembl; ENST00000216037.10; ENSP00000216037.6; ENSG00000100219.17. [P17861-1] DR Ensembl; ENST00000344347.6; ENSP00000343155.5; ENSG00000100219.17. [P17861-2] DR GeneID; 7494; -. DR KEGG; hsa:7494; -. DR MANE-Select; ENST00000344347.6; ENSP00000343155.5; NM_001079539.2; NP_001073007.1. [P17861-2] DR UCSC; uc062cvg.1; human. [P17861-1] DR AGR; HGNC:12801; -. DR CTD; 7494; -. DR DisGeNET; 7494; -. DR GeneCards; XBP1; -. DR HGNC; HGNC:12801; XBP1. DR HPA; ENSG00000100219; Tissue enhanced (pancreas). DR MalaCards; XBP1; -. DR MIM; 194355; gene. DR MIM; 612371; phenotype. DR neXtProt; NX_P17861; -. DR OpenTargets; ENSG00000100219; -. DR PharmGKB; PA37400; -. DR VEuPathDB; HostDB:ENSG00000100219; -. DR eggNOG; KOG4005; Eukaryota. DR GeneTree; ENSGT00390000017751; -. DR HOGENOM; CLU_069050_0_0_1; -. DR InParanoid; P17861; -. DR OrthoDB; 5406889at2759; -. DR PhylomeDB; P17861; -. DR TreeFam; TF319837; -. DR PathwayCommons; P17861; -. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. [P17861-2] DR Reactome; R-HSA-381070; IRE1alpha activates chaperones. [P17861-2] DR Reactome; R-HSA-381183; ATF6 (ATF6-alpha) activates chaperone genes. [P17861-2] DR SignaLink; P17861; -. DR SIGNOR; P17861; -. DR BioGRID-ORCS; 7494; 16 hits in 1182 CRISPR screens. DR ChiTaRS; XBP1; human. DR GeneWiki; XBP1; -. DR GenomeRNAi; 7494; -. DR Pharos; P17861; Tchem. DR PRO; PR:P17861; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P17861; Protein. DR Bgee; ENSG00000100219; Expressed in body of pancreas and 120 other cell types or tissues. DR ExpressionAtlas; P17861; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:LIFEdb. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal. DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0030331; F:nuclear estrogen receptor binding; TAS:ParkinsonsUK-UCL. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0036500; P:ATF6-mediated unfolded protein response; NAS:ComplexPortal. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB. DR GO; GO:0071498; P:cellular response to fluid shear stress; IDA:UniProtKB. DR GO; GO:0071332; P:cellular response to fructose stimulus; ISS:UniProtKB. DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB. DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB. DR GO; GO:0071353; P:cellular response to interleukin-4; ISS:UniProtKB. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; IDA:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB. DR GO; GO:0031670; P:cellular response to nutrient; ISS:UniProtKB. DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB. DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; ISS:UniProtKB. DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB. DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB. DR GO; GO:0001935; P:endothelial cell proliferation; IDA:UniProtKB. DR GO; GO:0036503; P:ERAD pathway; NAS:ComplexPortal. DR GO; GO:0006633; P:fatty acid biosynthetic process; TAS:ParkinsonsUK-UCL. DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB. DR GO; GO:0006955; P:immune response; TAS:ParkinsonsUK-UCL. DR GO; GO:0035356; P:intracellular triglyceride homeostasis; ISS:UniProtKB. DR GO; GO:0036498; P:IRE1-mediated unfolded protein response; TAS:ParkinsonsUK-UCL. DR GO; GO:0001889; P:liver development; ISS:UniProtKB. DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:1900102; P:negative regulation of endoplasmic reticulum unfolded protein response; IDA:UniProtKB. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL. DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0048666; P:neuron development; ISS:UniProtKB. DR GO; GO:0006996; P:organelle organization; TAS:ParkinsonsUK-UCL. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB. DR GO; GO:0045579; P:positive regulation of B cell differentiation; IDA:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; IMP:UniProtKB. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IDA:UniProtKB. DR GO; GO:1904294; P:positive regulation of ERAD pathway; TAS:ParkinsonsUK-UCL. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB. DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISS:UniProtKB. DR GO; GO:0031062; P:positive regulation of histone methylation; IDA:UniProtKB. DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IDA:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB. DR GO; GO:1903489; P:positive regulation of lactation; ISS:UniProtKB. DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IMP:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. DR GO; GO:0071073; P:positive regulation of phospholipid biosynthetic process; TAS:ParkinsonsUK-UCL. DR GO; GO:1900100; P:positive regulation of plasma cell differentiation; IDA:UniProtKB. DR GO; GO:1901985; P:positive regulation of protein acetylation; IDA:UniProtKB. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL. DR GO; GO:0045582; P:positive regulation of T cell differentiation; IDA:UniProtKB. DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL. DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IDA:BHF-UCL. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:0035470; P:positive regulation of vascular wound healing; IDA:BHF-UCL. DR GO; GO:0031648; P:protein destabilization; IDA:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0001558; P:regulation of cell growth; IDA:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB. DR GO; GO:1990418; P:response to insulin-like growth factor stimulus; ISS:UniProtKB. DR GO; GO:0055092; P:sterol homeostasis; ISS:UniProtKB. DR GO; GO:0006366; P:transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB. DR CDD; cd14691; bZIP_XBP1; 1. DR Gene3D; 1.20.5.170; -; 1. DR InterPro; IPR004827; bZIP. DR InterPro; IPR046347; bZIP_sf. DR PANTHER; PTHR46542; X-BOX BINDING PROTEIN 1; 1. DR PANTHER; PTHR46542:SF3; X-BOX-BINDING PROTEIN 1; 1. DR Pfam; PF07716; bZIP_2; 1. DR SMART; SM00338; BRLZ; 1. DR SUPFAM; SSF57959; Leucine zipper domain; 1. DR PROSITE; PS50217; BZIP; 1. DR PROSITE; PS00036; BZIP_BASIC; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; Angiogenesis; KW Apoptosis; 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 Oncogene; Phosphoprotein; Protein transport; Reference proteome; KW Signal-anchor; Stress response; Transcription; Transcription regulation; KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation; KW Unfolded protein response. FT CHAIN 1..261 FT /note="X-box-binding protein 1" FT /id="PRO_0000076543" FT CHAIN 1..193 FT /note="X-box-binding protein 1, cytoplasmic form" FT /evidence="ECO:0000303|PubMed:25239945" FT /id="PRO_0000431891" FT CHAIN 196..261 FT /note="X-box-binding protein 1, luminal form" FT /evidence="ECO:0000303|PubMed:25239945" FT /id="PRO_0000431892" FT TOPO_DOM 1..185 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:25239945" FT TRANSMEM 186..203 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255, ECO:0000269|PubMed:25239945, FT ECO:0000303|PubMed:25239945" FT TOPO_DOM 204..261 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:25239945" FT DOMAIN 70..133 FT /note="bZIP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT REGION 44..93 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 72..94 FT /note="Basic motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT REGION 75..92 FT /note="Nuclear localization signal (NLS); in isoforms 1 and FT isoform 2" FT /evidence="ECO:0000269|PubMed:16461360" FT REGION 98..133 FT /note="Leucine-zipper" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978" FT REGION 235..261 FT /note="Necessary for the translational pausing of its own FT mRNA" FT /evidence="ECO:0000269|PubMed:21233347" FT COMPBIAS 63..93 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 194..195 FT /note="Cleavage; by HM13/SPP" FT /evidence="ECO:0000303|PubMed:25239945" FT MOD_RES 47 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 68 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 167..261 FT /note="LRLRAPLQQVQAQLSPLQNISPWILAVLTLQIQSLISCWAFWTTWTQSCSSN FT ALPQSLPAWRSSQRSTQKDPVPYQPPFLCQWGRHQPSWKPLMN -> GAGPVVTPPEHL FT PMDSGGIDSSDSESDILLGILDNLDPVMFFKCPSPEPASLEELPEVYPEGPSSLPASLS FT LSVGTSSAKLEAINELIRFDHIYTKPLVLEIPSETESQANVVVKIEEAPLSPSENDHPE FT FIVSVKEEPVEDDLVPELGISNLLSSSHCPKPSSCLLDAYSDCGYGGSLSPFSDMSSLL FT GVNHSWEDTFANELFPQLISV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11779464" FT /id="VSP_012936" FT VARIANT 12 FT /note="D -> V (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035998" FT VARIANT 232 FT /note="R -> K (in a breast cancer sample; somatic mutation; FT dbSNP:rs1379560430)" FT /evidence="ECO:0000269|PubMed:17224074" FT /id="VAR_033023" FT MUTAGEN 189 FT /note="W->E: Reduces endoplasmic reticulum localization of FT its own mRNA; when associated with E-193 and D-196." FT /evidence="ECO:0000269|PubMed:19394296" FT MUTAGEN 193 FT /note="V->E: Reduces endoplasmic reticulum localization of FT its own mRNA; when associated with E-189 and D-196." FT /evidence="ECO:0000269|PubMed:19394296" FT MUTAGEN 194 FT /note="L->E: Reduces endoplasmic reticulum localization of FT its own mRNA; when associated with D-198 and E-205." FT /evidence="ECO:0000269|PubMed:19394296" FT MUTAGEN 196 FT /note="L->D: Reduces endoplasmic reticulum localization of FT its own mRNA; when associated with E-189 and E-193." FT /evidence="ECO:0000269|PubMed:19394296" FT MUTAGEN 197 FT /note="Q->L: Inhibits HM13/SPP-mediated degradation of FT XBP1; when associated with L-199; L-200 and L-203." FT /evidence="ECO:0000269|PubMed:25239945" FT MUTAGEN 198 FT /note="I->D: Reduces endoplasmic reticulum localization of FT its own mRNA; when associated with E-194 and E-205." FT /evidence="ECO:0000269|PubMed:19394296" FT MUTAGEN 199 FT /note="Q->L: Inhibits HM13/SPP-mediated degradation of FT XBP1; when associated with L-197; L-200 and L-203." FT /evidence="ECO:0000269|PubMed:25239945" FT MUTAGEN 200 FT /note="S->L: Inhibits HM13/SPP-mediated degradation of FT XBP1; when associated with L-197; L-199 and L-203." FT /evidence="ECO:0000269|PubMed:25239945" FT MUTAGEN 203 FT /note="S->L: Inhibits HM13/SPP-mediated degradation of FT XBP1; when associated with L-197; L-199 and L-200." FT /evidence="ECO:0000269|PubMed:25239945" FT MUTAGEN 205 FT /note="W->E: Reduces endoplasmic reticulum localization of FT its own mRNA; when associated with E-194 and D-198." FT /evidence="ECO:0000269|PubMed:19394296" FT MUTAGEN 212 FT /note="T->N: Does not induce glycosylation." FT /evidence="ECO:0000269|PubMed:25239945" FT MUTAGEN 215 FT /note="C->N: Induces glycosylation." FT /evidence="ECO:0000269|PubMed:25239945" FT MUTAGEN 232 FT /note="R->N: Induces glycosylation." FT /evidence="ECO:0000269|PubMed:25239945" FT MUTAGEN 246 FT /note="L->A: Reduces translational pausing, membrane FT targeting and cytoplasmic splicing of its own mRNA." FT /evidence="ECO:0000269|PubMed:21233347" FT MUTAGEN 255 FT /note="S->A: Increases translational pausing of its own FT mRNA." FT /evidence="ECO:0000269|PubMed:21233347" FT MUTAGEN 256 FT /note="W->A: Reduces translational pausing, membrane FT targeting and cytoplasmic splicing of its own mRNA." FT /evidence="ECO:0000269|PubMed:21233347" FT CONFLICT 33..35 FT /note="GQA -> AR (in Ref. 1; AAA36031)" FT /evidence="ECO:0000305" FT CONFLICT 130 FT /note="N -> T (in Ref. 3; L13850)" FT /evidence="ECO:0000305" FT CONFLICT 196 FT /note="L -> F (in Ref. 3; L13850)" FT /evidence="ECO:0000305" SQ SEQUENCE 261 AA; 28695 MW; A4EF69EEE0D344A6 CRC64; MVVVAAAPNP ADGTPKVLLL SGQPASAAGA PAGQALPLMV PAQRGASPEA ASGGLPQARK RQRLTHLSPE EKALRRKLKN RVAAQTARDR KKARMSELEQ QVVDLEEENQ KLLLENQLLR EKTHGLVVEN QELRQRLGMD ALVAEEEAEA KGNEVRPVAG SAESAALRLR APLQQVQAQL SPLQNISPWI LAVLTLQIQS LISCWAFWTT WTQSCSSNAL PQSLPAWRSS QRSTQKDPVP YQPPFLCQWG RHQPSWKPLM N //