Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003329
UniProt IDP17861
Primary gene name(s)XBP1
Synonym gene name(s)TREB5, XBP2
Protein nameX-box-binding protein 1
Protein 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. {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:11460154, ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:8349596}.; FUNCTION: 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(3K/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. {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:1903538, ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:19416856, ECO:0000269|PubMed:21233347, ECO:0000269|PubMed:2196176, ECO:0000269|PubMed:2321018, ECO:0000269|PubMed:23529610, ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25239945, ECO:0000269|PubMed:8657566}.; FUNCTION: 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. {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:15466483, ECO:0000269|PubMed:19416856, ECO:0000269|PubMed:23184933, ECO:0000269|PubMed:23529610, ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25239945, ECO:0000269|PubMed:25280941}.
Subcellular locationEndoplasmic reticulum {ECO:0000269|PubMed:23529610}. Note=Colocalizes with ERN1 and KDR in the endoplasmic reticulum in endothelial cells in a vascular endothelial growth factor, VEGF-dependent manner, PubMed:23529610. {ECO:0000269|PubMed:23529610}.;
SUBCELLULAR LOCATION: Isoform 1: Nucleus {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296}. Cytoplasm {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:25190803}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:25239945};
Single-pass type II membrane protein {ECO:0000269|PubMed:25239945}. Endoplasmic reticulum membrane {ECO:0000303|PubMed:25239945};
Peripheral membrane protein {ECO:0000303|PubMed:25239945}. Membrane {ECO:0000269|PubMed:19394296};
Peripheral membrane protein {ECO:0000303|PubMed:19394296}. Note=Shows no preferential localization to either the nucleus or the cytoplasm, By similarity. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner, PubMed:16461360. 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, PubMed:19394296, PubMed:25190803. {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:25190803}.;
SUBCELLULAR LOCATION: Isoform 2: Nucleus {ECO:0000250|UniProtKB:O35426, ECO:0000269|PubMed:16461360, ECO:0000269|PubMed:19394296, ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:20955178}. Cytoplasm {ECO:0000250|UniProtKB:O35426}. Note=Localizes predominantly in the nucleus. Colocalizes in the nucleus with SIRT1. Translocates into the nucleus in a PIK3R-, ER stress-induced- and/or insulin-dependent manner, By similarity. {ECO:0000250|UniProtKB:O35426}.;
SUBCELLULAR LOCATION: X-box-binding protein 1, cytoplasmic form: Cytoplasm {ECO:0000269|PubMed:25239945}. Nucleus {ECO:0000269|PubMed:25239945}. Note=Localizes in the cytoplasm and nucleus after HM13/SPP-mediated intramembranaire proteolytic cleavage of isoform 1, PubMed:25239945. {ECO:0000269|PubMed:25239945}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P17861
Gene Ontology
(Biological Process)
Complete annatation
adipose tissue development [GO:0060612];
angiogenesis [GO:0001525];
ATF6-mediated unfolded protein response [GO:0036500];
autophagy [GO:0006914];
cell growth [GO:0016049];
cellular response to amino acid stimulus [GO:0071230];
cellular response to fluid shear stress [GO:0071498];
cellular response to fructose stimulus [GO:0071332];
cellular response to glucose starvation [GO:0042149];
cellular response to glucose stimulus [GO:0071333];
cellular response to insulin stimulus [GO:0032869];
cellular response to interleukin-4 [GO:0071353];
cellular response to laminar fluid shear stress [GO:0071499];
cellular response to lipopolysaccharide [GO:0071222];
cellular response to nutrient [GO:0031670];
cellular response to oxidative stress [GO:0034599];
cellular response to peptide hormone stimulus [GO:0071375];
cellular response to vascular endothelial growth factor stimulus [GO:0035924];
cellular triglyceride homeostasis [GO:0035356];
cholesterol homeostasis [GO:0042632];
endoplasmic reticulum unfolded protein response [GO:0030968];
endothelial cell proliferation [GO:0001935];
epithelial cell maturation involved in salivary gland development [GO:0060691];
exocrine pancreas development [GO:0031017];
fatty acid biosynthetic process [GO:0006633];
fatty acid homeostasis [GO:0055089];
immune response [GO:0006955];
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059];
IRE1-mediated unfolded protein response [GO:0036498];
liver development [GO:0001889];
muscle organ development [GO:0007517];
negative regulation of apoptotic process [GO:0043066];
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway [GO:1902236];
negative regulation of endoplasmic reticulum unfolded protein response [GO:1900102];
negative regulation of ERK1 and ERK2 cascade [GO:0070373];
negative regulation of myotube differentiation [GO:0010832];
negative regulation of pathway-restricted SMAD protein phosphorylation [GO:0060394];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512];
neuron development [GO:0048666];
organelle organization [GO:0006996];
phosphatidylinositol 3-kinase signaling [GO:0014065];
positive regulation of angiogenesis [GO:0045766];
positive regulation of autophagy [GO:0010508];
positive regulation of B cell differentiation [GO:0045579];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of endoplasmic reticulum unfolded protein response [GO:1900103];
positive regulation of endothelial cell apoptotic process [GO:2000353];
positive regulation of ER-associated ubiquitin-dependent protein catabolic process [GO:1903071];
positive regulation of fat cell differentiation [GO:0045600];
positive regulation of hepatocyte proliferation [GO:2000347];
positive regulation of histone methylation [GO:0031062];
positive regulation of immunoglobulin production [GO:0002639];
positive regulation of immunoglobulin secretion [GO:0051024];
positive regulation of interleukin-6 secretion [GO:2000778];
positive regulation of lactation [GO:1903489];
positive regulation of MHC class II biosynthetic process [GO:0045348];
positive regulation of phospholipid biosynthetic process by positive regulation of transcription from RNA polymerase II promoter [GO:1900413];
positive regulation of plasma cell differentiation [GO:1900100];
positive regulation of proteasomal protein catabolic process [GO:1901800];
positive regulation of protein acetylation [GO:1901985];
positive regulation of protein kinase B signaling [GO:0051897];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of T cell differentiation [GO:0045582];
positive regulation of TOR signaling [GO:0032008];
positive regulation of transcription factor import into nucleus [GO:0042993];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress [GO:1990440];
positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response [GO:0006990];
positive regulation of vascular associated smooth muscle cell migration [GO:1904754];
positive regulation of vascular smooth muscle cell proliferation [GO:1904707];
positive regulation of vascular wound healing [GO:0035470];
protein destabilization [GO:0031648];
protein transport [GO:0015031];
regulation of autophagy [GO:0010506];
regulation of protein stability [GO:0031647];
response to endoplasmic reticulum stress [GO:0034976];
response to insulin-like growth factor stimulus [GO:1990418];
sterol homeostasis [GO:0055092];
transcription from RNA polymerase II promoter [GO:0006366];
ubiquitin-dependent protein catabolic process [GO:0006511];
vascular endothelial growth factor receptor signaling pathway [GO:0048010]
Gene Ontology
(Molecular Function)
Complete annatation
chromatin DNA binding [GO:0031490];
core promoter binding [GO:0001047];
DNA binding [GO:0003677];
enhancer sequence-specific DNA binding [GO:0001158];
estrogen receptor binding [GO:0030331];
protease binding [GO:0002020];
protein heterodimerization activity [GO:0046982];
protein homodimerization activity [GO:0042803];
protein kinase binding [GO:0019901];
RNA polymerase II regulatory region sequence-specific DNA binding [GO:0000977];
RNA polymerase II transcription factor activity, sequence-specific DNA binding [GO:0000981];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
transcription regulatory region DNA binding [GO:0044212];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum membrane [GO:0005789];
integral component of endoplasmic reticulum membrane [GO:0030176];
integral component of membrane [GO:0016021];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction113331
Phylogenetic treeP17861
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-0.4488537243810890.1720616589049080.271409034329123
AZA vs. DISU-0.3687452483829220.1447380517171730.718797155225174
AZA vs. IL70.02227554904809780.9074912930071660.999311006273513
AZA vs. SAHA-0.3227350002413770.1856981774004190.550557437423883
DISU vs. CD30.06831149549850010.8512527014921270.89965527745161
DISU vs. IL70.3822794256856040.1291848261259440.47071701121675
DISU vs. SAHA0.04696904326375950.8717225583686840.966103245960785
DMSO vs. AZA-0.04981474785433560.7653750221973471
DMSO vs. CD30.3846052312237030.2306879729125460.334357736379402
DMSO vs. DISU0.316300710102910.1945063314797130.713270904924328
DMSO vs. IL70.07979033383335290.6562841875463060.928690053236322
DMSO vs. SAHA-0.2788480681242150.2365782058563630.583784200844332
HIV vs. Mock in Activation-0.1828609248519250.7686098584603850.999983755607037
HIV vs. Mock in Latency-0.2507296943822550.1279431049303090.999834320637052
IL7 vs. CD30.4796708872628570.1367488901546220.241151103843226
SAHA vs. CD30.1012110854550320.7758967683925360.839756126089882
SAHA vs. IL7-0.3486491161145310.1523138459149820.370075834385372
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
1.2 0.262151215 1.8 0.025144845 1.9 0.005130976
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.471591 0.00241278
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
200670_at 1.38 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Tat induces phosphorylation of 19009018

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
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