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Protein

X-box-binding protein 1

Gene

Xbp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as a transcription factor during endoplasmic reticulum stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development and the development of secretory tissues such as exocrine pancreas and salivary gland (PubMed:10425189, PubMed:10652269, PubMed:16362047, PubMed:17612490). Involved in differentiation of B lymphocytes to plasma cells and production of immunoglobulins. Modulates the cellular response to ER stress in a PIK3R-dependent manner. Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes (By similarity). Involved in VEGF-induced endothelial cell (EC) proliferation and retinal blood vessel formation during embryonic development but also for angiogenesis in adult tissues under ischemic conditions (PubMed:23529610). Functions also as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention (PubMed:15486293).By similarity6 Publications
Isoform 1: plays a role i n the unconventional cytoplasmic splicing processing of its own mRNA triggered by the endoplasmic reticulum (ER) transmembrane endoribonuclease ENR1: upon ER stress, the emerging XBP1 polypeptide chain, as part of a mRNA-ribosome-nascent chain (R-RNC) complex, cotranslationally recruits its own unprocessed mRNA through transient docking to the ER membrane and translational pausing, therefore facilitating efficient IRE1-mediated XBP1 mRNA isoform 2 production. In endothelial cells (EC), associated with KDR, promotes IRE1-mediated XBP1 mRNA isoform 2 production in a vascular endothelial growth factor (VEGF)-dependent manner, leading to EC proliferation and angiogenesis (By similarity). Functions as a negative feed-back regulator of the potent transcription factor XBP1 isoform 2 protein levels through proteasome-mediated degradation, thus preventing the constitutive activation of the ER stress response signaling pathway (PubMed:16332684). Inhibits the transactivation activity of XBP1 isoform 2 in myeloma cells (PubMed:12902539). Acts as a weak transcriptional factor. Together with HDAC3, contributes to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI3K/mTORC2/Akt-dependent signaling pathway leading to EC survival under disturbed flow/oxidative stress. Binds to the ER stress response element (ERSE) upon ER stress. Binds to the consensus 5'-GATGACGTG[TG]N3[AT]T-3' sequence related to cAMP responsive element (CRE)-like sequences. Binds the Tax-responsive element (TRE) present in the long terminal repeat (LTR) of T cell leukemia virus type 1 (HTLV-I) and to the TPA response elements (TRE). Associates preferentially to the HDAC3 gene promoter region in a static flow-dependent manner. Binds to the CDH5/VE-cadherin gene promoter region (By similarity).By similarity2 Publications
Isoform 2: functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components to enhance the capacity of productive folding and degradation mechanism, respectively, in order to maintain the homeostasis of the ER under ER stress (PubMed:11850408, PubMed:14559994). Plays a role in the production of immunoglobulins and interleukin-6 in the presence of stimuli required for plasma cell differentiation, and promotes as well membrane phospholipid biosynthesis necessary for ER expansion (PubMed:12612580, PubMed:17213183). Contributes to the VEGF-induced endothelial cell (EC) growth and proliferation in a Akt/GSK-dependent and/or -independent signaling pathway, respectively, leading to beta-catenin nuclear translocation and E2F2 gene expression. Promotes umbilical vein EC apoptosis and atherosclerotisis development in a caspase-dependent signaling pathway, and contributes to VEGF-induced EC proliferation and angiogenesis in adult tissues under ischemic conditions. Involved in the regulation of endostatin-induced autophagy in EC through BECN1 transcriptional activation. Plays a role as an oncogene by promoting tumor progression: stimulates zinc finger protein SNAI1 transcription to induce epithelial-to-mesenchymal (EMT) transition, cell migration and invasion of breast cancer cells (By similarity). Involved in adipocyte differentiation by regulating lipogenic gene expression during lactation (PubMed:23623498, PubMed:25223794). Plays a role in the survival of both dopaminergic neurons of the substantia nigra pars compacta (SNpc), by maintaining protein homeostasis and of myeloma cells (PubMed:12902539, PubMed:24753614). Increases insulin sensitivity in the liver as a response to a high carbohydrate diet, resulting in improved glucose tolerance (PubMed:20348926). Improves also glucose homeostasis in an ER stress- and/or insulin-independent manner through both binding and proteasome-induced degradation of the transcription factor FOXO1, hence resulting in suppression of gluconeogenic genes expression and in a reduction of blood glucose levels (PubMed:21317886). Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner (PubMed:18556558). Binds to the 5'-CCACG-3' motif in the PPARG promoter (PubMed:25223794). Associates preferentially to the HDAC3 gene promoter region in a disturbed flow-dependent manner. Binds to the BECN1 gene promoter region. Binds to the CDH5/VE-cadherin gene promoter region. Binds to the ER stress response element (ERSE) upon ER stress (By similarity).By similarity11 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei185 – 1862Cleavage; by HM13/SPPBy similarity

GO - Molecular functioni

GO - Biological processi

  • adipose tissue development Source: UniProtKB
  • angiogenesis Source: UniProtKB
  • autophagy Source: UniProtKB-KW
  • cell growth Source: UniProtKB
  • cellular response to amino acid stimulus Source: UniProtKB
  • cellular response to antibiotic Source: Ensembl
  • cellular response to fluid shear stress Source: UniProtKB
  • cellular response to fructose stimulus Source: UniProtKB
  • cellular response to glucose starvation Source: UniProtKB
  • cellular response to glucose stimulus Source: UniProtKB
  • cellular response to insulin stimulus Source: UniProtKB
  • cellular response to interleukin-4 Source: UniProtKB
  • cellular response to laminar fluid shear stress Source: UniProtKB
  • cellular response to lipopolysaccharide Source: UniProtKB
  • cellular response to nutrient Source: UniProtKB
  • cellular response to oxidative stress Source: UniProtKB
  • cellular response to peptide hormone stimulus Source: UniProtKB
  • cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
  • cellular triglyceride homeostasis Source: UniProtKB
  • cholesterol homeostasis Source: UniProtKB
  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • endothelial cell proliferation Source: UniProtKB
  • epithelial cell maturation Source: MGI
  • epithelial cell maturation involved in salivary gland development Source: MGI
  • exocrine pancreas development Source: MGI
  • fatty acid homeostasis Source: UniProtKB
  • glucose homeostasis Source: MGI
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • lipid metabolic process Source: UniProtKB-KW
  • liver development Source: UniProtKB
  • muscle organ development Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of endoplasmic reticulum unfolded protein response Source: UniProtKB
  • negative regulation of myotube differentiation Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • neuron development Source: UniProtKB
  • phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of B cell differentiation Source: UniProtKB
  • positive regulation of endoplasmic reticulum unfolded protein response Source: MGI
  • positive regulation of endothelial cell apoptotic process Source: UniProtKB
  • positive regulation of fat cell differentiation Source: UniProtKB
  • positive regulation of hepatocyte proliferation Source: UniProtKB
  • positive regulation of histone methylation Source: UniProtKB
  • positive regulation of immunoglobulin production Source: UniProtKB
  • positive regulation of immunoglobulin secretion Source: UniProtKB
  • positive regulation of interleukin-6 secretion Source: UniProtKB
  • positive regulation of lactation Source: UniProtKB
  • positive regulation of MHC class II biosynthetic process Source: UniProtKB
  • positive regulation of plasma cell differentiation Source: UniProtKB
  • positive regulation of proteasomal protein catabolic process Source: MGI
  • positive regulation of protein acetylation Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of T cell differentiation Source: UniProtKB
  • positive regulation of TOR signaling Source: UniProtKB
  • positive regulation of transcription factor import into nucleus Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: UniProtKB
  • protein destabilization Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of autophagy Source: UniProtKB
  • regulation of protein stability Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • response to drug Source: Ensembl
  • response to electrical stimulus Source: Ensembl
  • response to endoplasmic reticulum stress Source: UniProtKB
  • response to insulin-like growth factor stimulus Source: UniProtKB
  • serotonin secretion, neurotransmission Source: Ensembl
  • sterol homeostasis Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
  • vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Angiogenesis, Apoptosis, Autophagy, Differentiation, Lipid biosynthesis, Lipid metabolism, Myogenesis, Protein transport, Stress response, Transcription, Transcription regulation, Transport, Unfolded protein response

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
X-box-binding protein 1By similarityImported
Short name:
XBP-1By similarity
Alternative name(s):
Tax-responsive element-binding protein 51 Publication
Short name:
TREB-5Curated
Cleaved into the following 2 chains:
X-box-binding protein 1, cytoplasmic formBy similarity
X-box-binding protein 1, luminal formBy similarity
Gene namesi
Name:Xbp1By similarityImported
Synonyms:Treb51 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:98970. Xbp1.

Subcellular locationi

  • Endoplasmic reticulum By similarity

  • Note: Colocalizes with ERN1 and KDR in the endoplasmic reticulum in endothelial cells in a vascular endothelial growth factor (VEGF)-dependent manner (By similarity).By similarity
Isoform 1 :
  • Nucleus By similarity1 Publication
  • Cytoplasm By similarity1 Publication
  • Endoplasmic reticulum membrane By similarity; Single-pass type II membrane protein By similarity
  • Endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity
  • Membrane By similarity; Peripheral membrane protein By similarity

  • Note: Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Localizes predominantly at the endoplasmic reticulum membrane as a membrane-spanning protein; whereas may be only marginally localized on the cytosolic side of the ER membrane as a peripheral membrane (By similarity). Shows no preferential localization to either the nucleus or the cytoplasm (PubMed:16332684).By similarity1 Publication
Isoform 2 :
X-box-binding protein 1, cytoplasmic form :
  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Localizes in the cytoplasm and nucleus after HM13/SPP-mediated intramembranaire proteolytic cleavage of isoform 1 (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 180180CytoplasmicBy similarityAdd
BLAST
Transmembranei181 – 19818Helical; Signal-anchor for type II membrane proteinSequence AnalysisBy similarityAdd
BLAST
Topological domaini199 – 26769LumenalBy similarityAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice embryos die at 12.5-13.5 dpc and display less blood vessels (PubMed:23529610). Embryos display hypoplastic livers, cellular necrosis in the myocardium, hypoplasia of the heart and die in utero from severe anemia (PubMed:10425189, PubMed:10652269). Mice display severe abnormalities in the development and function of secretory cells, such as plasma B cells and pancreatic acinar cells (PubMed:16362047). Haploinsufficient mice fed a high-fat diet gain more weight, display enhanced ER stress in adipose tissue, reduced insulin receptor signaling and develop peripheral insulin resistance and type 2 diabetes (PubMed:15486293). Endothelial-specific knockout mice show delayed retinal vascular development and impaired postischemic angiogenesis (PubMed:23529610, PubMed:23184933). Dopaminergic neuron-specific knockout mice display ER dysfonction and accumulation of abnormal protein aggregates (PubMed:24753614). Liver-specific knockout mice leads to reduced lipogenic gene expression and diminished hepatic lipid synthesis (PubMed:18556558). Adipocyte-specific knockout female mice fed with a regular or high-fat diet, show no alteration in body weight, adipose tissue mass, blood glucose, serum insulin and lipid levels; however during lactation adipose tissue mass increases and milk production decreases but mammary gland structure and milk composition remains normal (PubMed:23623498). Intestinal epithelial cell-specific knockout mice born and developed normally but displayed small intestinal mucosal inflammation in association with increased ER stress, a diminution of Paneth and goblet cells with reduced secretory granules (PubMed:18775308).10 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi177 – 1782PP → LH: Reduces degradation (isoform 1); when associated with 238-L-H-239. 1 Publication
Mutagenesisi231 – 2311K → R: Enhances stability and accumulates in the cytoplasm; when associated with R-252 (isoform 1). 2 Publications
Mutagenesisi238 – 2392PP → LH: Reduces degradation (isoform 1); when associated with 177-L-H-178. 1 Publication
Mutagenesisi252 – 2521K → R: Enhances stability and accumulates in the cytoplasm; when associated with R-231 (isoform 1). 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 267267X-box-binding protein 1PRO_0000076544Add
BLAST
Chaini1 – 188188X-box-binding protein 1, cytoplasmic formBy similarityPRO_0000431893Add
BLAST
Chaini191 – 26777X-box-binding protein 1, luminal formBy similarityPRO_0000431894Add
BLAST

Post-translational modificationi

Isoform 2 is acetylated by EP300; acetylation positively regulates the transcriptional activity of XBP1 isoform 2 (PubMed:20955178). Isoform 2 is deacetylated by SIRT1; deacetylation negatively regulates the transcriptional activity of XBP1 isoform 2 (PubMed:20955178).1 Publication1 Publication
Isoform 1 is ubiquitinated, leading to proteasomal degradation in response to ER stress (PubMed:11780124, PubMed:12902539, PubMed:16332684).By similarity3 Publications
X-box-binding protein 1, cytoplasmic form and luminal form are produced by intramembrane proteolytic cleavage of ER membrane-anchored isoform 1 triggered by HM13/SPP in a DERL1-RNF139-dependent and VCP/p97-independent manner. X-box-binding protein 1, luminal form is ubiquitinated leading to proteasomal degradation (By similarity).By similarity

Keywords - PTMi

Acetylation, Cleavage on pair of basic residues, Ubl conjugation

Proteomic databases

PRIDEiO35426.

PTM databases

PhosphoSiteiO35426.

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are expressed at higher level in branch curves of vessel walls and in atherosclerotic plaques relative to healthy segments of the same aortas (at protein level) (PubMed:19416856). Expressed in skeletal muscles, plasma cells and pancreatic beta cells (PubMed:17612490). Isoform 1 and isoform 2 are expressed in gonadal adipose tissue. Isoform 1 is expressed in inguinal adipose tissue (PubMed:23623498).3 Publications

Developmental stagei

Expressed mainly in exocrine glands and bone precursors in the embryonic mouse (PubMed:7693055).1 Publication

Inductioni

Isoform 2 is up-regulated during adipocyte differentiation (PubMed:25223794). Isoform 2 is up-regulated upon refeeding after a fasting period in liver and in ob/ob mice (obese) (at protein level) (PubMed:20348926). Induced by chemical activators of the unfolded protein response (UPR) such as tunicamycin, DTT and thapsigargin (PubMed:17612490). Up-regulated after partial hepatectomy during the acute phase response (PubMed:10652269). Isoform 1 and isoform 2 are up-regulated by interleukin-4 in B cells in a STAT6-dependent manner (PubMed:12612580). Isoform 1 and isoform 2 are up-regulated during lactation and by the lactogenic hormone prolactin (PubMed:23623498). Isoform 2 is up-regulated by prolonged feeding of high-carbohydrate diets in hepatocytes in absence of ER-stress (PubMed:18556558). Isoform 2 is up-regulated by insulin-like growth factor and glucose starvation (PubMed:17612490). Isoform 2 is up-regulated during plasma-cell differentiation in response to endoplasmic reticulum (ER) stress, such as lipopolysaccharide (LPS) (PubMed:11780124, PubMed:11850408, PubMed:12612580).9 Publications

Gene expression databases

BgeeiO35426.
CleanExiMM_XBP1.
ExpressionAtlasiO35426. baseline and differential.
GenevisibleiO35426. MM.

Interactioni

Subunit structurei

Isoform 1 interacts with HM13. Isoform 1 interacts with RNF139; the interaction induces ubiquitination and degradation of isoform 1. Isoform 1 interacts (via luminal domain) with DERL1; the interaction obviates the need for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage. Isoform 1 interacts with isoform 2; the interaction sequesters isoform 2 from the nucleus and enhances isoform 2 degradation in the cytoplasm. Isoform 1 interacts with HDAC3 and AKT1; the interactions occur in endothelial cell (EC) under disturbed flow. Isoform 1 interacts with the oncoprotein FOS. Isoform 2 interacts with ATF6; the interaction occurs in a ER stress-dependent manner and is required for DNA binding to the unfolded protein response element (UPRE). Isoform 2 interacts with PIK3R1; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus and the unfolded protein response (UPR) XBP1-dependent target genes activation in a ER stress- and/or insulin-dependent but PI3K-independent manner (By similarity). Isoform 2 interacts with SIRT1 (PubMed:20955178). Isoform 2 interacts with PIK3R1 and PIK3R2; the interactions are direct and induce translocation of XBP1 isoform 2 into the nucleus and the unfolded protein response (UPR) XBP1-dependent target genes activation in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348926). Isoform 2 interacts with FOXO1; the interaction is direct and leads to FOXO1 ubiquitination and degradation via the proteasome pathway in hepatocytes (PubMed:21317886).By similarity3 Publications

Protein-protein interaction databases

BioGridi204589. 2 interactions.
STRINGi10090.ENSMUSP00000054852.

Structurei

3D structure databases

ProteinModelPortaliO35426.
SMRiO35426. Positions 56-119.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini63 – 12664bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni65 – 8723Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni69 – 8517Nuclear localization signal (NLS); in isoforms 1 and isoform 2By similarityAdd
BLAST
Regioni91 – 12636Leucine-zipperPROSITE-ProRule annotationAdd
BLAST
Regioni230 – 25627Necessary for the translational pausing of its own mRNABy similarityAdd
BLAST

Domaini

Isoform 1 transmembrane signal-anchor domain is necessary for its own mRNA to be recruited to the endoplasmic reticulum (ER) which will undergo unconventional ERN1-dependent splicing in response to ER stress. Isoform 1 N-terminus and C-terminus regions are necessary for DNA-binding and weak transcriptional activity, respectively. Isoform 2 N-terminus and C-terminus regions are necessary for DNA-binding and strong transcriptional activity upon ER stress, respectively. Isoform 2 C-terminus region contains a nuclear exclusion signal (NES) at positions 182 through 204. Isoform 2 C-terminus region contains a degradation domain at positions 204 through 256 (By similarity). Isoform 1 and isoform 2 N-terminus domains are necessary for nuclear localization targeting. Isoform 1 C-terminus domain confers localization to the cytoplasm and is sufficient to impose rapid degradation (PubMed:16332684).By similarity1 Publication

Sequence similaritiesi

Belongs to the bZIP family.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG285368.
GeneTreeiENSGT00390000017751.
HOGENOMiHOG000007671.
HOVERGENiHBG061457.
InParanoidiO35426.
KOiK09027.
OMAiNQELRCR.
OrthoDBiEOG74BJVQ.
TreeFamiTF319837.

Family and domain databases

InterProiIPR004827. bZIP.
[Graphical view]
PfamiPF07716. bZIP_2. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O35426-1) [UniParc]FASTAAdd to basket

Also known as: Unprocessed XBP-1, XBP-1U1 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVVVAAAPSA ATAAPKVLLL SGQPASGGRA LPLMVPGPRA AGSEASGTPQ
60 70 80 90 100
ARKRQRLTHL SPEEKALRRK LKNRVAAQTA RDRKKARMSE LEQQVVDLEE
110 120 130 140 150
ENHKLQLENQ LLREKTHGLV VENQELRTRL GMDTLDPDEV PEVEAKGSGV
160 170 180 190 200
RLVAGSAESA ALRLCAPLQQ VQAQLSPPQN IFPWTLTLLP LQILSLISFW
210 220 230 240 250
AFWTSWTLSC FSNVLPQSLL VWRNSQRSTQ KDLVPYQPPF LCQWGPHQPS
260
WKPLMNSFVL TMYTPSL
Length:267
Mass (Da):29,619
Last modified:June 1, 2001 - v2
Checksum:i15009E684F6D426F
GO
Isoform 2 (identifier: O35426-2) [UniParc]FASTAAdd to basket

Also known as: Processed XBP-1, XBP-1S1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     162-267: LRLCAPLQQV...FVLTMYTPSL → GAGPVVTSPE...NELFPQLISV

Note: Potent transcriptional activator. Induced by unconventional ERN1-dependent splicing in response to endoplasmic reticulum stress. ENR1 cleaves a 26-bp fragment causing a frameshift of the mRNA transcript (Ref.2, Ref.9).2 Publications
Show »
Length:371
Mass (Da):39,888
Checksum:i6F67EC346DBF3AC8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti27 – 271Missing in BAB13793 (PubMed:10907849).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei162 – 267106LRLCA…YTPSL → GAGPVVTSPEHLPMDSDTVA SSDSESDILLGILDKLDPVM FFKCPSPESASLEELPEVYP EGPSSLPASLSLSVGTSSAK LEAINELIRFDHVYTKPLVL EIPSETESQTNVVVKIEEAP LSSSEEDHPEFIVSVKKEPL EDDFIPELGISNLLSSSHCL RPPSCLLDAHSDCGYEGSPS PFSDMSSPLGTDHSWEDTFA NELFPQLISV in isoform 2. 1 PublicationVSP_012937Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB036745 Genomic DNA. Translation: BAB13793.1.
AF443192 mRNA. Translation: AAL60202.1.
AF027963 mRNA. Translation: AAB81862.2.
AL662876 Genomic DNA. Translation: CAI24935.1.
BC008153 mRNA. Translation: AAH08153.1.
BC029197 mRNA. Translation: AAH29197.1.
CCDSiCCDS24400.1. [O35426-1]
PIRiJC7300.
RefSeqiNP_001258659.1. NM_001271730.1. [O35426-2]
NP_038870.2. NM_013842.3. [O35426-1]
UniGeneiMm.469937.

Genome annotation databases

EnsembliENSMUST00000063084; ENSMUSP00000054852; ENSMUSG00000020484. [O35426-1]
GeneIDi22433.
KEGGimmu:22433.
UCSCiuc007hwm.2. mouse. [O35426-2]
uc007hwn.2. mouse. [O35426-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB036745 Genomic DNA. Translation: BAB13793.1.
AF443192 mRNA. Translation: AAL60202.1.
AF027963 mRNA. Translation: AAB81862.2.
AL662876 Genomic DNA. Translation: CAI24935.1.
BC008153 mRNA. Translation: AAH08153.1.
BC029197 mRNA. Translation: AAH29197.1.
CCDSiCCDS24400.1. [O35426-1]
PIRiJC7300.
RefSeqiNP_001258659.1. NM_001271730.1. [O35426-2]
NP_038870.2. NM_013842.3. [O35426-1]
UniGeneiMm.469937.

3D structure databases

ProteinModelPortaliO35426.
SMRiO35426. Positions 56-119.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204589. 2 interactions.
STRINGi10090.ENSMUSP00000054852.

PTM databases

PhosphoSiteiO35426.

Proteomic databases

PRIDEiO35426.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000063084; ENSMUSP00000054852; ENSMUSG00000020484. [O35426-1]
GeneIDi22433.
KEGGimmu:22433.
UCSCiuc007hwm.2. mouse. [O35426-2]
uc007hwn.2. mouse. [O35426-1]

Organism-specific databases

CTDi7494.
MGIiMGI:98970. Xbp1.

Phylogenomic databases

eggNOGiNOG285368.
GeneTreeiENSGT00390000017751.
HOGENOMiHOG000007671.
HOVERGENiHBG061457.
InParanoidiO35426.
KOiK09027.
OMAiNQELRCR.
OrthoDBiEOG74BJVQ.
TreeFamiTF319837.

Miscellaneous databases

ChiTaRSiXbp1. mouse.
NextBioi302881.
PROiO35426.
SOURCEiSearch...

Gene expression databases

BgeeiO35426.
CleanExiMM_XBP1.
ExpressionAtlasiO35426. baseline and differential.
GenevisibleiO35426. MM.

Family and domain databases

InterProiIPR004827. bZIP.
[Graphical view]
PfamiPF07716. bZIP_2. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of the gene encoding mouse tax-responsive element-binding protein (TREB) 5."
    Masaki T., Noguchi H., Kobayashi M., Yoshida M., Takamatsu K.
    DNA Res. 7:187-193(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA."
    Calfon M., Zeng H., Urano F., Till J.H., Hubbard S.R., Harding H.P., Clark S.G., Ron D.
    Nature 415:92-96(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 2), INDUCTION (ISOFORM 2), ER STRESS-MEDIATED DOWN-REGULATION (ISOFORM 1).
    Strain: 129/SvEv.
  3. "Sequence analysis of murine XBP-1."
    Lee C.M., Reddy E.P.
    Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Mammary tumor.
  6. "In situ hybridization studies suggest a role for the basic region-leucine zipper protein hXBP-1 in exocrine gland and skeletal development during mouse embryogenesis."
    Clauss I.M., Gravallese E.M., Darling J.M., Shapiro F., Glimcher M.J., Glimcher L.H.
    Dev. Dyn. 197:146-156(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  7. "Targeted disruption of CRE-binding factor TREB5 gene leads to cellular necrosis in cardiac myocytes at the embryonic stage."
    Masaki T., Yoshida M., Noguchi S.
    Biochem. Biophys. Res. Commun. 261:350-356(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  8. "An essential role in liver development for transcription factor XBP-1."
    Reimold A.M., Etkin A., Clauss I., Perkins A., Friend D.S., Zhang J., Horton H.F., Scott A., Orkin S.H., Byrne M.C., Grusby M.J., Glimcher L.H.
    Genes Dev. 14:152-157(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  9. "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response."
    Lee K., Tirasophon W., Shen X., Michalak M., Prywes R., Okada T., Yoshida H., Mori K., Kaufman R.J.
    Genes Dev. 16:452-466(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 2), INDUCTION (ISOFORM 2).
  10. "XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response."
    Lee A.H., Iwakoshi N.N., Glimcher L.H.
    Mol. Cell. Biol. 23:7448-7459(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2).
  11. "Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1."
    Iwakoshi N.N., Lee A.-H., Vallabhajosyula P., Otipoby K.L., Rajewsky K., Glimcher L.H.
    Nat. Immunol. 4:321-329(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2), INDUCTION (ISOFORMS 1 AND 2).
  12. "Proteasome inhibitors disrupt the unfolded protein response in myeloma cells."
    Lee A.H., Iwakoshi N.N., Anderson K.C., Glimcher L.H.
    Proc. Natl. Acad. Sci. U.S.A. 100:9946-9951(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORMS 1 AND 2), UBIQUITINATION (ISOFORM 1), MUTAGENESIS OF LYS-231 AND LYS-252.
  13. "Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes."
    Ozcan U., Cao Q., Yilmaz E., Lee A.H., Iwakoshi N.N., Ozdelen E., Tuncman G., Gorgun C., Glimcher L.H., Hotamisligil G.S.
    Science 306:457-461(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  14. "XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands."
    Lee A.H., Chu G.C., Iwakoshi N.N., Glimcher L.H.
    EMBO J. 24:4368-4380(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  15. "Rapid turnover of unspliced Xbp-1 as a factor that modulates the unfolded protein response."
    Tirosh B., Iwakoshi N.N., Glimcher L.H., Ploegh H.L.
    J. Biol. Chem. 281:5852-5860(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 1), UBIQUITINATION (ISOFORM 1), SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), DOMAIN (ISOFORMS 1 AND 2), MUTAGENESIS OF 177-PRO-PRO-178; LYS-231; 238-PRO-PRO-239 AND LYS-252.
  16. "Coordinate regulation of phospholipid biosynthesis and secretory pathway gene expression in XBP-1(S)-induced endoplasmic reticulum biogenesis."
    Sriburi R., Bommiasamy H., Buldak G.L., Robbins G.R., Frank M., Jackowski S., Brewer J.W.
    J. Biol. Chem. 282:7024-7034(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2).
  17. "XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks."
    Acosta-Alvear D., Zhou Y., Blais A., Tsikitis M., Lents N.H., Arias C., Lennon C.J., Kluger Y., Dynlacht B.D.
    Mol. Cell 27:53-66(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DNA-BINDING, INDUCTION (ISOFORM 2), TISSUE SPECIFICITY.
  18. "XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease."
    Kaser A., Lee A.H., Franke A., Glickman J.N., Zeissig S., Tilg H., Nieuwenhuis E.E., Higgins D.E., Schreiber S., Glimcher L.H., Blumberg R.S.
    Cell 134:743-756(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUTS.
  19. "Regulation of hepatic lipogenesis by the transcription factor XBP1."
    Lee A.H., Scapa E.F., Cohen D.E., Glimcher L.H.
    Science 320:1492-1496(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), INDUCTION (ISOFORM 2), DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT.
  20. "Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow."
    Zeng L., Zampetaki A., Margariti A., Pepe A.E., Alam S., Martin D., Xiao Q., Wang W., Jin Z.G., Cockerill G., Mori K., Li Y.S., Hu Y., Chien S., Xu Q.
    Proc. Natl. Acad. Sci. U.S.A. 106:8326-8331(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY (ISOFORMS 1 AND 2).
  21. "The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation."
    Park S.W., Zhou Y., Lee J., Lu A., Sun C., Chung J., Ueki K., Ozcan U.
    Nat. Med. 16:429-437(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2), INTERACTION WITH PIK3R1 AND PIK3R2 (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), INDUCTION (ISOFORM 2).
  22. "Regulation of unfolded protein response modulator XBP1s by acetylation and deacetylation."
    Wang F.M., Chen Y.J., Ouyang H.J.
    Biochem. J. 433:245-252(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION BY EP300 (ISOFORM 2), DEACETYLATION BY SIRT1 (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), INTERACTION WITH SIRT1 (ISOFORM 2).
  23. "Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction."
    Zhou Y., Lee J., Reno C.M., Sun C., Park S.W., Chung J., Lee J., Fisher S.J., White M.F., Biddinger S.B., Ozcan U.
    Nat. Med. 17:356-365(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2), INTERACTION WITH FOXO1 (ISOFORM 2).
  24. "The role of adipocyte XBP1 in metabolic regulation during lactation."
    Gregor M.F., Misch E.S., Yang L., Hummasti S., Inouye K.E., Lee A.H., Bierie B., Hotamisligil G.S.
    Cell Rep. 3:1430-1439(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2), DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT, TISSUE SPECIFICITY (ISOFORMS 1 AND 2), INDUCTION (ISOFORMS 1 AND 2).
  25. "Vascular endothelial cell growth-activated XBP1 splicing in endothelial cells is crucial for angiogenesis."
    Zeng L., Xiao Q., Chen M., Margariti A., Martin D., Ivetic A., Xu H., Mason J., Wang W., Cockerill G., Mori K., Li J.Y., Chien S., Hu Y., Xu Q.
    Circulation 127:1712-1722(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT.
  26. "XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation."
    Margariti A., Li H., Chen T., Martin D., Vizcay-Barrena G., Alam S., Karamariti E., Xiao Q., Zampetaki A., Zhang Z., Wang W., Jiang Z., Gao C., Ma B., Chen Y.G., Cockerill G., Hu Y., Xu Q., Zeng L.
    J. Biol. Chem. 288:859-872(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT.
  27. "X-box binding protein 1 is a novel key regulator of peroxisome proliferator-activated receptor gamma2."
    Cho Y.M., Kwak S.N., Joo N.S., Kim D.H., Lee A.H., Kim K.S., Seo J.B., Jeong S.W., Kwon O.J.
    FEBS J. 281:5132-5146(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2), DNA-BINDING (ISOFORM 2), INDUCTION (ISOFORM 2).
  28. "Control of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1."
    Valdes P., Mercado G., Vidal R.L., Molina C., Parsons G., Court F.A., Martinez A., Galleguillos D., Armentano D., Schneider B.L., Hetz C.
    Proc. Natl. Acad. Sci. U.S.A. 111:6804-6809(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 2), DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT.

Entry informationi

Entry nameiXBP1_MOUSE
AccessioniPrimary (citable) accession number: O35426
Secondary accession number(s): Q8VHM0, Q922G5, Q9ESS3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: June 1, 2001
Last modified: July 22, 2015
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.