XBP1 - X-box-binding protein 1 - human protein (Function)
 
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XBP1 »  X-box-binding protein 1  (XBP-1)
 
Protein also known as:  Tax-responsive element-binding protein 5 (TREB-5). Cleaved into:  X-box-binding protein 1, cytoplasmic form; X-box-binding protein 1, luminal form.
Gene name:  XBP1
Family name: bZIP
Entry whose protein(s) existence is based on evidence at protein level
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1 147 2
GENE REF ISO

Function

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Overview 
Functions as a transcription factor during endoplasmic reticulum (ER) 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 (By similarity). Involved in terminal differentiation of B lymphocytes to plasma cells and production of immunoglobulins (PubMed11460154). Modulates the cellular response to ER stress in a PIK3R-dependent manner (PubMed20348923). Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes (PubMed8349596). 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. 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 (By similarity).  
5
  • UniProtKB
Isoform  Iso 1   Plays a role in 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 (PubMed19394296, PubMed21233347). In endothelial cells (EC), associated with KDR, promotes IRE1-mediated XBP1 mRNA isoform 2 productions in a vascular endothelial growth factor (VEGF)-dependent manner, leading to EC proliferation and angiogenesis (PubMed23529610). 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 (PubMed16461360, PubMed25239945). Inhibits the transactivation activity of XBP1 isoform 2 in myeloma cells (By similarity). Acts as a weak transcriptional factor (PubMed8657566). Together with HDAC3, contributes to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to EC survival under disturbed flow/oxidative stress (PubMed25190803). Binds to the ER stress response element (ERSE) upon ER stress (PubMed11779464). Binds to the consensus 5'-GATGACGTG[TG]N(3)[AT]T-3' sequence related to cAMP responsive element (CRE)-like sequences (PubMed8657566). 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) (PubMed2321018, PubMed2196176, PubMed1903538, PubMed8657566). Associates preferentially to the HDAC3 gene promoter region in a static flow-dependent manner (PubMed25190803). Binds to the CDH5/VE-cadherin gene promoter region (PubMed19416856).  
14
  • UniProtKB
Isoform  Iso 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 (PubMed11779464, PubMed25239945). Plays a role in the production of immunoglobulins and interleukin-6 in the presence of stimuli required for plasma cell differentiation (By similarity). Induces phospholipid biosynthesis and ER expansion (PubMed15466483). 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 (PubMed23529610). 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 (PubMed19416856, PubMed23529610). Involved in the regulation of endostatin-induced autophagy in EC through BECN1 transcriptional activation (PubMed23184933). 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 (PubMed25280941). Involved in adipocyte differentiation by regulating lipogenic gene expression during lactation. 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. Increases insulin sensitivity in the liver as a response to a high carbohydrate diet, resulting in improved glucose tolerance. 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. 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 (By similarity). Associates preferentially to the HDAC3 gene promoter region in a disturbed flow-dependent manner (PubMed25190803). Binds to the BECN1 gene promoter region (PubMed23184933). Binds to the CDH5/VE-cadherin gene promoter region (PubMed19416856). Binds to the ER stress response element (ERSE) upon ER stress (PubMed11779464). Binds to the 5'-CCACG-3' motif in the PPARG promoter (By similarity).  
10
  • UniProtKB
GO molecular function 
Chromatin DNA bindingdefinition[GO:0031490]  
1
  • UniProtKB
Core promoter bindingdefinition[GO:0001047]  
1
  • Ortholog Curator
DNA bindingdefinition[GO:0003677]  
1
  • PINC
Enhancer sequence-specific DNA bindingdefinition[GO:0001158]  
1
  • UniProtKB
Isoform  Iso 2   Estrogen receptor bindingdefinition[GO:0030331]  
1
  • ParkinsonsUK-UCL
Histone deacetylase bindingdefinition[GO:0042826] silver  
1
  • Ortholog Compara
Phosphatidylinositol 3-kinase regulatory subunit bindingdefinition[GO:0036312] silver  
1
  • Ortholog Compara
Isoform  Iso 1   Protease bindingdefinition[GO:0002020]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
3
  • UniProtKB
Protein heterodimerization activitydefinition[GO:0046982]  
2
  • ParkinsonsUK-UCL
  • UniProtKB
Isoform  Iso 2   Protein homodimerization activitydefinition[GO:0042803]  
1
  • ParkinsonsUK-UCL
Isoform  Iso 2   Protein kinase bindingdefinition[GO:0019901]  
1
  • UniProtKB
RNA polymerase II regulatory region sequence-specific DNA bindingdefinition[GO:0000977]  
1
  • UniProtKB
RNA polymerase II transcription factor activity, sequence-specific DNA bindingdefinition[GO:0000981] silver  
1
  • Ortholog Compara
RNA polymerase II transcription factor bindingdefinition[GO:0001085] silver  
1
  • Ortholog Compara
Transcription factor activity, sequence-specific DNA bindingdefinition[GO:0003700]  
2
  • ParkinsonsUK-UCL
  • UniProtKB
Transcription regulatory region DNA bindingdefinition[GO:0044212]  
2
  • UniProtKB
Isoform  Iso 1   Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • UniProtKB
GO biological process 
Adipose tissue developmentdefinition[GO:0060612]  
1
  • Ortholog Curator
Angiogenesisdefinition[GO:0001525]  
1
  • Ortholog Curator
Autophagydefinition[GO:0006914]  
1
  • UniProtKB KW
Isoform  Iso 2   Cell growthdefinition[GO:0016049]  
1
  • UniProtKB
Cellular response to amino acid stimulusdefinition[GO:0071230]  
1
  • Ortholog Curator
Cellular response to antibioticdefinition[GO:0071236] silver  
1
  • Ortholog Compara
Cellular response to fluid shear stressdefinition[GO:0071498]  
2
  • UniProtKB
Cellular response to fructose stimulusdefinition[GO:0071332]  
1
  • Ortholog Curator
Cellular response to glucose starvationdefinition[GO:0042149]  
1
  • Ortholog Curator
Cellular response to glucose stimulusdefinition[GO:0071333]  
1
  • Ortholog Curator
Cellular response to insulin stimulusdefinition[GO:0032869]  
1
  • Ortholog Curator
Cellular response to interleukin-4definition[GO:0071353]  
1
  • Ortholog Curator
Cellular response to laminar fluid shear stressdefinition[GO:0071499]  
1
  • UniProtKB
Cellular response to lipopolysaccharidedefinition[GO:0071222]  
1
  • UniProtKB
Cellular response to nutrientdefinition[GO:0031670]  
1
  • Ortholog Curator
Isoform  Iso 1   Cellular response to oxidative stressdefinition[GO:0034599]  
1
  • UniProtKB
Cellular response to peptide hormone stimulusdefinition[GO:0071375]  
1
  • Ortholog Curator
Cellular response to vascular endothelial growth factor stimulusdefinition[GO:0035924]  
1
  • UniProtKB
Cellular triglyceride homeostasisdefinition[GO:0035356]  
1
  • Ortholog Curator
Cholesterol homeostasisdefinition[GO:0042632]  
1
  • Ortholog Curator
Endoplasmic reticulum unfolded protein responsedefinition[GO:0030968]  
1
  • Ortholog Curator
Isoform  Iso 2   Endothelial cell proliferationdefinition[GO:0001935]  
1
  • UniProtKB
Epithelial cell maturation involved in salivary gland developmentdefinition[GO:0060691] silver  
1
  • Ortholog Compara
Exocrine pancreas developmentdefinition[GO:0031017] silver  
1
  • Ortholog Compara
Fatty acid biosynthetic processdefinition[GO:0006633]  
1
  • ParkinsonsUK-UCL
Fatty acid homeostasisdefinition[GO:0055089]  
1
  • Ortholog Curator
Immune responsedefinition[GO:0006955]  
1
  • ParkinsonsUK-UCL
Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stressdefinition[GO:0070059] silver  
1
  • Ortholog Compara
IRE1-mediated unfolded protein responsedefinition[GO:0036498]  
2
  • ParkinsonsUK-UCL
Liver developmentdefinition[GO:0001889]  
1
  • Ortholog Curator
Muscle organ developmentdefinition[GO:0007517]  
1
  • UniProtKB KW
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • Ortholog Curator
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwaydefinition[GO:1902236]  
1
  • ParkinsonsUK-UCL
Isoform  Iso 1   Negative regulation of endoplasmic reticulum unfolded protein responsedefinition[GO:1900102]  
1
  • UniProtKB
Negative regulation of myotube differentiationdefinition[GO:0010832]  
1
  • Ortholog Curator
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122]  
3
  • UniProtKB
Neuron developmentdefinition[GO:0048666]  
1
  • Ortholog Curator
Isoform  Iso 2   Organelle organizationdefinition[GO:0006996]  
1
  • ParkinsonsUK-UCL
Isoform  Iso 2   Phosphatidylinositol 3-kinase signalingdefinition[GO:0014065]  
1
  • UniProtKB
Isoform  Iso 2   Positive regulation of autophagydefinition[GO:0010508]  
1
  • UniProtKB
Positive regulation of B cell differentiationdefinition[GO:0045579]  
1
  • UniProtKB
Positive regulation of endoplasmic reticulum unfolded protein responsedefinition[GO:1900103]  
1
  • UniProtKB
Isoform  Iso 2   Positive regulation of endothelial cell apoptotic processdefinition[GO:2000353]  
1
  • UniProtKB
Isoform  Iso 2   Positive regulation of ER-associated ubiquitin-dependent protein catabolic processdefinition[GO:1903071]  
1
  • ParkinsonsUK-UCL
Positive regulation of fat cell differentiationdefinition[GO:0045600]  
1
  • Ortholog Curator
Positive regulation of hepatocyte proliferationdefinition[GO:2000347]  
1
  • Ortholog Curator
Isoform  Iso 2   Positive regulation of histone methylationdefinition[GO:0031062]  
1
  • UniProtKB
Positive regulation of immunoglobulin productiondefinition[GO:0002639]  
1
  • UniProtKB
Positive regulation of immunoglobulin secretiondefinition[GO:0051024]  
1
  • Ortholog Curator
Positive regulation of interleukin-6 secretiondefinition[GO:2000778]  
1
  • Ortholog Curator
Positive regulation of lactationdefinition[GO:1903489]  
1
  • Ortholog Curator
Positive regulation of MHC class II biosynthetic processdefinition[GO:0045348]  
1
  • UniProtKB
Isoform  Iso 2   Positive regulation of phospholipid biosynthetic process by positive regulation of transcription from RNA polymerase II promoterdefinition[GO:1900413]  
1
  • ParkinsonsUK-UCL
Positive regulation of plasma cell differentiationdefinition[GO:1900100]  
1
  • UniProtKB
Positive regulation of proteasomal protein catabolic processdefinition[GO:1901800] silver  
1
  • Ortholog Compara
Isoform  Iso 2   Positive regulation of protein acetylationdefinition[GO:1901985]  
1
  • UniProtKB
Isoform  Iso 1   Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • UniProtKB
Positive regulation of T cell differentiationdefinition[GO:0045582]  
1
  • UniProtKB
Isoform  Iso 1   Positive regulation of TOR signalingdefinition[GO:0032008]  
1
  • UniProtKB
Isoform  Iso 1   Positive regulation of transcription factor import into nucleusdefinition[GO:0042993]  
1
  • UniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
7
  • UniProtKB
  • ParkinsonsUK-UCL
  • Ortholog Curator
Isoform  Iso 2   Positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stressdefinition[GO:1990440]  
1
  • ParkinsonsUK-UCL
Positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein responsedefinition[GO:0006990]  
2
  • UniProtKB
  • Ortholog Curator
Protein destabilizationdefinition[GO:0031648]  
3
  • UniProtKB
Protein transportdefinition[GO:0015031]  
1
  • UniProtKB KW
Regulation of autophagydefinition[GO:0010506] silver  
1
  • Ortholog Compara
Isoform  Iso 1   Regulation of protein stabilitydefinition[GO:0031647]  
1
  • UniProtKB
Response to drugdefinition[GO:0042493] silver  
1
  • Ortholog Compara
Response to electrical stimulusdefinition[GO:0051602] silver  
1
  • Ortholog Compara
Response to endoplasmic reticulum stressdefinition[GO:0034976]  
4
  • UniProtKB
Response to insulin-like growth factor stimulusdefinition[GO:1990418]  
1
  • Ortholog Curator
Serotonin secretion, neurotransmissiondefinition[GO:0060096] silver  
1
  • Ortholog Compara
Sterol homeostasisdefinition[GO:0055092]  
1
  • Ortholog Curator
Transcription from RNA polymerase II promoterdefinition[GO:0006366]  
1
  • Ortholog Curator
Ubiquitin-dependent protein catabolic processdefinition[GO:0006511]  
1
  • Ortholog Curator
Isoform  Iso 2   Vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0048010]  
1
  • UniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
HTLV-I infection  hsa05166+7494  
Protein processing in endoplasmic reticulum  hsa04141+7494  
According to Reactome, this protein belongs to the following pathways:
ATF6-alpha activates chaperone genes  R-HSA-381183  
IRE1alpha activates chaperones  R-HSA-381070  
XBP1(S) activates chaperone genes  R-HSA-381038  
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Apoptosis  definition   [KW-0053]
Autophagy  definition   [KW-0072]
Differentiation  definition   [KW-0221]
Lipid biosynthesis  definition   [KW-0444]
Lipid metabolism  definition   [KW-0443]
Myogenesis  definition   [KW-0517]
Protein transport  definition   [KW-0653]
Stress response  definition   [KW-0346]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Transport  definition   [KW-0813]
Unfolded protein response  definition   [KW-0834]
Molecular function 
Activator  definition   [KW-0010]
Developmental protein  definition   [KW-0217]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: XBP1
GenomeRNAi: 7494
PRO: PR:P17861