XBP1_HUMAN
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 03-AUG-2022, entry version 212.
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},
GN XBP2 {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}.
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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 SMR; P17861; -.
DR BioGRID; 113331; 43.
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; P17861; -.
DR PeptideAtlas; P17861; -.
DR PRIDE; P17861; -.
DR ProteomicsDB; 53522; -. [P17861-1]
DR ProteomicsDB; 53523; -. [P17861-2]
DR Antibodypedia; 10221; 714 antibodies from 43 providers.
DR DNASU; 7494; -.
DR Ensembl; ENST00000216037.10; ENSP00000216037.6; ENSG00000100219.17. [P17861-1]
DR Ensembl; ENST00000344347.5; ENSP00000343155.5; ENSG00000100219.17. [P17861-2]
DR GeneID; 7494; -.
DR KEGG; hsa:7494; -.
DR UCSC; uc062cvg.1; human. [P17861-1]
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 OMA; EQECPEP; -.
DR OrthoDB; 1269901at2759; -.
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; 13 hits in 1104 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 119 other 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; IEA:UniProtKB-SubCell.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0042803; F:protein homodimerization activity; TAS:ParkinsonsUK-UCL.
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; IC: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:0035356; P:cellular triglyceride homeostasis; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0036503; P:ERAD pathway; IC: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: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:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
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:0014065; P:phosphatidylinositol 3-kinase signaling; 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:1903071; P:positive regulation of ER-associated ubiquitin-dependent protein catabolic process; 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:0071073; P:positive regulation of phospholipid biosynthetic process; TAS:BHF-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:0051897; P:positive regulation of protein kinase B signaling; IDA:BHF-UCL.
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:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; TAS:ParkinsonsUK-UCL.
DR GO; GO:0006990; P:positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; IDA:UniProtKB.
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; IC: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 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 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
