X-box-binding protein 1

NameX-box-binding protein 1
SynonymsTax-responsive element-binding protein 5 TREB-5 TREB5 XBP-1 XBP2
Gene NameXBP1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009305|X-box-binding protein 1
MVVVAAAPNPADGTPKVLLLSGQPASAAGAPAGQALPLMVPAQRGASPEAASGGLPQARK
RQRLTHLSPEEKALRRKLKNRVAAQTARDRKKARMSELEQQVVDLEEENQKLLLENQLLR
EKTHGLVVENQELRQRLGMDALVAEEEAEAKGNEVRPVAGSAESAALRLRAPLQQVQAQL
SPLQNISPWILAVLTLQIQSLISCWAFWTTWTQSCSSNALPQSLPAWRSSQRSTQKDPVP
YQPPFLCQWGRHQPSWKPLMN
Number of residues261
Molecular Weight28694.66
Theoretical pINone
GO Classification
Functions
    transcription regulatory region DNA binding
protease binding
protein kinase binding
chromatin DNA binding
ubiquitin protein ligase binding
transcription factor activity, sequence-specific DNA binding
DNA binding
core promoter binding
protein homodimerization activity
enhancer sequence-specific DNA binding
protein heterodimerization activity
RNA polymerase II transcription factor activity, sequence-specific DNA binding
estrogen receptor binding
RNA polymerase II regulatory region sequence-specific DNA binding
Processes
    angiogenesis
cellular triglyceride homeostasis
positive regulation of proteasomal protein catabolic process
response to drug
positive regulation of protein phosphorylation
muscle organ development
negative regulation of myotube differentiation
cellular response to insulin stimulus
epithelial cell maturation involved in salivary gland development
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
positive regulation of protein acetylation
immune response
fatty acid biosynthetic process
regulation of autophagy
phosphatidylinositol 3-kinase signaling
positive regulation of hepatocyte proliferation
cellular response to lipopolysaccharide
exocrine pancreas development
protein destabilization
positive regulation of transcription factor import into nucleus
cellular response to interleukin-4
cellular response to amino acid stimulus
fatty acid homeostasis
neuron development
cholesterol homeostasis
positive regulation of endoplasmic reticulum unfolded protein response
endothelial cell proliferation
response to insulin-like growth factor stimulus
cell growth
response to endoplasmic reticulum stress
cellular protein metabolic process
cellular response to antibiotic
ubiquitin-dependent protein catabolic process
positive regulation of fat cell differentiation
cellular response to peptide hormone stimulus
positive regulation of endothelial cell apoptotic process
adipose tissue development
serotonin secretion, neurotransmission
transcription from RNA polymerase II promoter
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
positive regulation of autophagy
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
positive regulation of ER-associated ubiquitin-dependent protein catabolic process
cellular response to fluid shear stress
ATF6-mediated unfolded protein response
sterol homeostasis
negative regulation of apoptotic process
cellular response to glucose stimulus
cellular response to laminar fluid shear stress
positive regulation of histone methylation
regulation of protein stability
positive regulation of B cell differentiation
positive regulation of transcription from RNA polymerase II promoter
IRE1-mediated unfolded protein response
positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response
positive regulation of immunoglobulin production
organelle organization
positive regulation of interleukin-6 secretion
response to electrical stimulus
vascular endothelial growth factor receptor signaling pathway
positive regulation of lactation
cellular response to glucose starvation
positive regulation of MHC class II biosynthetic process
cellular response to vascular endothelial growth factor stimulus
positive regulation of T cell differentiation
cellular response to fructose stimulus
positive regulation of TOR signaling
positive regulation of phospholipid biosynthetic process by positive regulation of transcription from RNA polymerase II promoter
protein transport
endoplasmic reticulum unfolded protein response
positive regulation of immunoglobulin secretion
autophagy
negative regulation of transcription from RNA polymerase II promoter
cellular response to nutrient
positive regulation of plasma cell differentiation
liver development
cellular response to oxidative stress
negative regulation of endoplasmic reticulum unfolded protein response
Components
    endoplasmic reticulum membrane
integral component of endoplasmic reticulum membrane
integral component of membrane
cytoplasm
cytosol
nucleus
nucleoplasm
endoplasmic reticulum
General FunctionUbiquitin protein ligase binding
Specific FunctionFunctions 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 (PubMed:11460154). Modulates the cellular response to ER stress in a PIK3R-dependent manner (PubMed:20348923). Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes (PubMed:8349596). 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).Isoform 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 (PubMed:19394296, PubMed:21233347). 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 (PubMed:23529610). 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:16461360, PubMed:25239945). Inhibits the transactivation activity of XBP1 isoform 2 in myeloma cells (By similarity). Acts as a weak transcriptional factor (PubMed:8657566). 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 (PubMed:25190803). Binds to the ER stress response element (ERSE) upon ER stress (PubMed:11779464). Binds to the consensus 5'-GATGACGTG[TG]N(3)[AT]T-3' sequence related to cAMP responsive element (CRE)-like sequences (PubMed:8657566). 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) (PubMed:2321018, PubMed:2196176, PubMed:1903538, PubMed:8657566). Associates preferentially to the HDAC3 gene promoter region in a static flow-dependent manner (PubMed:25190803). Binds to the CDH5/VE-cadherin gene promoter region (PubMed:19416856).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:11779464, PubMed:25239945). 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 (PubMed:15466483). 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 (PubMed:23529610). 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 (PubMed:19416856, PubMed:23529610). Involved in the regulation of endostatin-induced autophagy in EC through BECN1 transcriptional activation (PubMed:23184933). 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 (PubMed:25280941). 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 (PubMed:25190803). Binds to the BECN1 gene promoter region (PubMed:23184933). Binds to the CDH5/VE-cadherin gene promoter region (PubMed:19416856). Binds to the ER stress response element (ERSE) upon ER stress (PubMed:11779464). Binds to the 5'-CCACG-3' motif in the PPARG promoter (By similarity).
Transmembrane Regions186-203
GenBank Protein ID
UniProtKB IDP17861
UniProtKB Entry NameXBP1_HUMAN
Cellular LocationEndoplasmic reticulum
Gene sequence
>lcl|BSEQ0013730|X-box-binding protein 1 (XBP1)
ATGGTGGTGGTGGCAGCCGCGCCGAACCCGGCCGACGGGACCCCTAAAGTTCTGCTTCTG
TCGGGGCAGCCCGCCTCCGCCGCCGGAGCCCCGGCCGGCCAGGCCCTGCCGCTCATGGTG
CCAGCCCAGAGAGGGGCCAGCCCGGAGGCAGCGAGCGGGGGGCTGCCCCAGGCGCGCAAG
CGACAGCGCCTCACGCACCTGAGCCCCGAGGAGAAGGCGCTGAGGAGGAAACTGAAAAAC
AGAGTAGCAGCTCAGACTGCCAGAGATCGAAAGAAGGCTCGAATGAGTGAGCTGGAACAG
CAAGTGGTAGATTTAGAAGAAGAGAACCAAAAACTTTTGCTAGAAAATCAGCTTTTACGA
GAGAAAACTCATGGCCTTGTAGTTGAGAACCAGGAGTTAAGACAGCGCTTGGGGATGGAT
GCCCTGGTTGCTGAAGAGGAGGCGGAAGCCAAGGGGAATGAAGTGAGGCCAGTGGCCGGG
TCTGCTGAGTCCGCAGCAGGTGCAGGCCCAGTTGTCACCCCTCCAGAACATCTCCCCATG
GATTCTGGCGGTATTGACTCTTCAGATTCAGAGTCTGATATCCTGTTGGGCATTCTGGAC
AACTTGGACCCAGTCATGTTCTTCAAATGCCCTTCCCCAGAGCCTGCCAGCCTGGAGGAG
CTCCCAGAGGTCTACCCAGAAGGACCCAGTTCCTTACCAGCCTCCCTTTCTCTGTCAGTG
GGGACGTCATCAGCCAAGCTGGAAGCCATTAATGAACTAATTCGTTTTGACCACATATAT
ACCAAGCCCCTAGTCTTAGAGATACCCTCTGAGACAGAGAGCCAAGCTAATGTGGTAGTG
AAAATCGAGGAAGCACCTCTCAGCCCCTCAGAGAATGATCACCCTGAATTCATTGTCTCA
GTGAAGGAAGAACCTGTAGAAGATGACCTCGTTCCGGAGCTGGGTATCTCAAATCTGCTT
TCATCCAGCCACTGCCCAAAGCCATCTTCCTGCCTACTGGATGCTTACAGTGACTGTGGA
TACGGGGGTTCCCTTTCCCCATTCAGTGACATGTCCTCTCTGCTTGGTGTAAACCATTCT
TGGGAGGACACTTTTGCCAATGAACTCTTTCCCCAGCTGATTAGTGTCTAA
GenBank Gene ID
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:12801
Chromosome Location22
LocusNone
References
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