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FLASH GENE
Symbol XBP1 contributors: mct - updated : 06-09-2011
HGNC name X-box binding protein 1
HGNC id 12801
Location 22q12.1      Physical location : 29.190.548 - 29.196.560
Synonym name Tax-responsive element-binding protein 5
Synonym symbol(s) TREB5, XBP2, XBP-1
DNA
TYPE functioning gene
STRUCTURE 6.01 kb     4 Exon(s)
10 Kb 5' upstream gene genomic sequence study
text structure a cis-acting element in the MDG1/ERdj4 promoter region
MAPPING cloned Y linked N status confirmed
Physical map
MN1 22q12.1 meningioma (disrupted in balanced translocation) 1 PITPNB 22q12.1 phosphotidylinositol transfer protein, beta KIAA1043 22q12.1 KIAA1043 protein LOC284901 22q12.2 similar to bA436C9.2 (PUTATIVE novel protein similar to part of HSP70/HSP90 organizing protein and transformation sensitive protein) CHEK2 22q12.1 CHK2 checkpoint homolog (S. pombe) HSC20 22q12.2 J-type co-chaperone HSC20 FLJ33814 22q12.2 hypothetical protein FLJ33814 XBP1 22q12.2 X-box binding protein 1 LOC388890 22 LOC388890 FLJ12747 22q12.1 novel C3HC4 type Zinc finger (ring finger) HS747E2A 22q12.1 hypothetical protein HS747E2A KREMEN1 22q12.1 kringle containing transmembrane protein 1 EMU1 22q12.2 emilin and multimerin-domain containing protein 1 C22orf3 22q12.1-q12.2 chromosome 22 open reading frame 3 EWSR1 22q12.2 Ewing sarcoma breakpoint region 1 GAS2L1 22q12.2 growth arrest-specific 2 like 1 RRP22 22q12.2 growth arrest-specific 2 like 1 AP1B1 22q12.2 adaptor-related protein complex 1, beta 1 subunit RFPL1 22q12.2 ret finger protein-like 1 NEFH 22q12.2 neurofilament, heavy polypeptide 200kDa C22orf19 22q12 chromosome 22 open reading frame 19 NIPSNAP1 22q12.2 nipsnap homolog 1 (C. elegans) NF2 22q12.2 neurofibromin 2 (bilateral acoustic neuroma) CABP7 22q12.2 calcium binding protein 7 LOC55954 22cen-q12.3 hypothetical protein LOC55954 HSPC051 22cen-q12.3 ubiquinol-cytochrome c reductase complex (7.2 kD) ASC1p100 22q12.1 ASC-1 complex subunit P100 MTMR3 22q12.2 myotubularin related protein 3 LOC391326 22 similar to h2-calponin
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 1820 - 261 - 2011 21398633
  • also called XBP1(U), having a hydrophobic region 2 (HR2), which is a membrane-targeting signal, and present only on the XBP1U protein, and a C-terminus responsible for the translational pausing and required for the efficient targeting and splicing of the XBP1u mRNA
  • spliced form acting as a transcription factor and inducing the expression of ER-resident molecular chaperones
  • in the cytosol is an unspliced precursor form of XBP1s, under unstressed conditions
  • upon ER stress, cleaved to initiate the unconventional splicing of XBP1u mRNA on the ER membrane
    • 6 splicing 1810 - 376 - 2011 21398633
  • also called XBP1(S)
  • key factor in ER stress, through transcriptionnal regulation of an array of genes, including molecular chaperones
  • upon endoplasmic reticulum (ER) stress, mammalian cells induce the synthesis of a transcriptional activator XBP1s to alleviate the stress
  • phosphate was incorporated into XBP1s mRNA in the cytosol to ligate the two exons
  • active/spliced form of XBP1 protein, that directly binds to the AABS (A-activator-binding site) in the iNOS promoter
    		•
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Endocrineplacenta   highly
    Reproductivefemale systembreastmammary gland highly
     female systemuterus  highly
     female systemplacenta  highly
    cell lineage
    cell lines highly in hepatocellular carcinomas
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • basic leucine zipper (bZIP) motif
    • HOMOLOGY
    interspecies homolog to murine Xbp1
    Homologene
    FAMILY
  • CREB/ATF family
  • bZIP family
    • CATEGORY immunity/defense , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus
    basic FUNCTION
  • acting as an essential survival factor for hypoxic stress and tumor growth
  • key transcription factor in the endoplasmic reticulum (ER) stress response pathway
  • plays an important role in membrane lipid synthesis in the ER
  • transcription factor governing hepatic lipogenesis
  • key regulator of the unfolded protein response, required for the unrelated function of normal fatty acid synthesis in the liver
  • under endoplasmic reticulum (ER) stress conditions, is processed by unconventional splicing and translated into a functional transcription factor
  • required for development and maintenance of secretory cells and linked to JNK activation
  • transcription factor essential for hepatocyte growth, as well as for plasma cell differentiation
  • key effector of the unfolded protein response (UPR), in skeletal muscle and secretory cells
  • regulates functionally distinct targets through different sequence motifs
  • may regulate signal transduction, transcription factors and bone marrow colonization in B cells
  • major endoplasmic reticulum stress-linked transcriptional factor, contributing to cellular resistance to oxidative stress
  • having a protective role against oxidative stress, and its positive regulation of catalase expression may at least in part account for this function
  • essential for survival under hypoxic conditions, and positively regulates tumor growth
  • key UPR transcription factor that regulates genes involved in protein folding and quality control
  • having a function in the control of autophagy and indicate critical cross-talk between these two signaling pathways that can provide protection against neurodegeneration
  • key modulator of the UPR (unfolded protein response), which is involved in a wide range of pathological and physiological processes
  • involved in the regulation of NOS2 induction by the interaction between its spliced and unspliced forms in response to ER stress
  • first identified as a key regulator of major histocompatibility complex (MHC) class II gene expression in B cells
  • critical for cell fate determination in response to ER stress
  • role for XBP1 in an antiviral response
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    ERN1-XBP1 pathway is involved in osteoblast differentiation through promoting SP7 transcription
    a component
  • key component of the endoplasmic reticulum (ER) stress response
    • INTERACTION
    DNA binding to HLA-DRA, HLA-DRB promoter
    RNA
    small molecule
    protein
  • regulating DNAJB9, a member of the DnaJ family (target sequence for the IRE1-XBP1 pathway under ER stress conditions)
  • interacting with BHLHA15, a critical regulator of differentiation (important target of XBP1, providing an explanation for developmental defects associated with XBP1 loss of function)
  • SUMOylated, mainly by PIAS2 at two lysine residues located in the C-terminal transactivation domain
  • target of acetylation and deacetylation mediated by EP300 and SIRT1 (sirtuin 1) respectively (
  • interacts with the Forkhead box O1 (FOXO1A) transcription factor and directs it toward proteasome-mediated degradation (through its interaction with FoxO1, can bypass hepatic insulin resistance independent of its effects on ER folding capacity)
  • IL3 interacting with XBP1 (the proper transcriptional and splicing regulation of XBP1 by IL3 signaling is important in homeostasis of hematopoietic cells)
  • ERN1 target XBP1, and are essential for bone morphogenic protein 2-induced osteoblast differentiation
    • cell & other
    REGULATION
    activated by IRE1
    induced by ATF6
    Other regulated by alpha FP
    activated in B cells when they differentiate to plasma cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in prostate cancer in progression
    tumoral     --over  
    in primary colorectal carcinomas and in colorectal adenomas
    constitutional     --over  
    increased XBP1 expression may contribute to a reduction of oxidative stress and prevention of aging
    Susceptibility
  • to bipolar disorder
  • to inflammatory bowel disease
    • Variant & Polymorphism other
  • C116G increases the risk of bipolar disorder
  • variants increasing the risk of inflammatory bowel disease
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    potential of XBP1 as targets for Alzheimer disease therapeutics
    diabetetype 2 
    potential new therapeutic approach for the treatment of type 2 diabetes
    ANIMAL & CELL MODELS
  • mutant SOD1 transgenic mice with specific deletion of XBP-1 in the nervous system were more resistant to developing disease, correlating with increased levels of autophagy in motoneurons and reduced accumulation of mutant SOD1 aggregates in the spinal cord