XBP1 [The Human Chemical-Genetic Interaction Map Project]

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======= XBP1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: XBP1
  * **<color #00a2e8>Official Name</color>**: X-box binding protein 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7494|7494]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P17861|P17861]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=XBP1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20XBP1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/194355|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a transcription factor that regulates MHC class II genes by binding to a promoter element referred to as an X box. This gene product is a bZIP protein, which was also identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. It may increase expression of viral proteins by acting as the DNA binding partner of a viral transactivator. It has been found that upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), the mRNA of this gene is processed to an active form by an unconventional splicing mechanism that is mediated by the endonuclease inositol-requiring enzyme 1 (IRE1). The resulting loss of 26 nt from the spliced mRNA causes a frame-shift and an isoform XBP1(S), which is the functionally active transcription factor. The isoform encoded by the unspliced mRNA, XBP1(U), is constitutively expressed, and thought to function as a negative feedback regulator of XBP1(S), which shuts off transcription of target genes during the recovery phase of ER stress. A pseudogene of XBP1 has been identified and localized to chromosome 5. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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 (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}. 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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|bZIP 1|
|bZIP 2|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|positive regulation of plasma cell differentiation|
|regulation of plasma cell differentiation|
|epithelial cell maturation involved in salivary gland development|
|epithelial cell differentiation involved in salivary gland development|
|positive regulation of lactation|
|cell differentiation involved in salivary gland development|
|response to insulin-like growth factor stimulus|
|positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response|
|positive regulation of vascular wound healing|
|regulation of lactation|
|cellular response to fructose stimulus|
|regulation of vascular wound healing|
|cellular triglyceride homeostasis|
|exocrine pancreas development|
|response to fructose|
|positive regulation of hepatocyte proliferation|
|ATF6-mediated unfolded protein response|
|positive regulation of MHC class II biosynthetic process|
|positive regulation of B cell differentiation|
|positive regulation of immunoglobulin secretion|
|positive regulation of endoplasmic reticulum unfolded protein response|
|fatty acid homeostasis|
|regulation of hepatocyte proliferation|
|regulation of MHC class II biosynthetic process|
|epithelial cell maturation|
|regulation of immunoglobulin secretion|
|negative regulation of myotube differentiation|
|negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway|
|positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus|
|endothelial cell proliferation|
|enhancer sequence-specific DNA binding|
|regulation of endoplasmic reticulum unfolded protein response|
|regulation of B cell differentiation|
|cellular response to interleukin-4|
|positive regulation of interleukin-6 secretion|
|response to interleukin-4|
|salivary gland development|
|regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway|
|intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress|
|triglyceride homeostasis|
|acylglycerol homeostasis|
|adipose tissue development|
|ER-nucleus signaling pathway|
|positive regulation of response to endoplasmic reticulum stress|
|negative regulation of striated muscle cell differentiation|
|cellular response to glucose starvation|
|positive regulation of immunoglobulin production|
|exocrine system development|
|negative regulation of response to endoplasmic reticulum stress|
|protein destabilization|
|positive regulation of wound healing|
|negative regulation of muscle cell differentiation|
|IRE1-mediated unfolded protein response|
|anion homeostasis|
|regulation of myotube differentiation|
|positive regulation of fat cell differentiation|
|regulation of immunoglobulin production|
|positive regulation of response to wounding|
|cellular response to nutrient|
|cellular response to glucose stimulus|
|cellular response to amino acid stimulus|
|cellular response to hexose stimulus|
|pancreas development|
|cellular response to monosaccharide stimulus|
|cholesterol homeostasis|
|cellular response to carbohydrate stimulus|
|sterol homeostasis|
|positive regulation of animal organ morphogenesis|
|positive regulation of T cell differentiation|
|regulation of response to endoplasmic reticulum stress|
|epithelial cell proliferation|
|cellular glucose homeostasis|
|positive regulation of lymphocyte differentiation|
|positive regulation of interleukin-6 production|
|negative regulation of intrinsic apoptotic signaling pathway|
|response to leukemia inhibitory factor|
|positive regulation of production of molecular mediator of immune response|
|cellular response to leukemia inhibitory factor|
|regulation of striated muscle cell differentiation|
|endoplasmic reticulum unfolded protein response|
|integral component of endoplasmic reticulum membrane|
|response to amino acid|
|fatty acid biosynthetic process|
|regulation of fat cell differentiation|
|liver development|
|cellular response to unfolded protein|
|hepaticobiliary system development|
|lipid homeostasis|
|anatomical structure maturation|
|regulation of wound healing|
|response to glucose|
|regulation of T cell differentiation|
|positive regulation of cytokine secretion|
|regulation of interleukin-6 production|
|regulation of production of molecular mediator of immune response|
|response to hexose|
|digestive system development|
|positive regulation of leukocyte differentiation|
|response to monosaccharide|
|cellular response to topologically incorrect protein|
|intrinsic apoptotic signaling pathway|
|cellular response to starvation|
|regulation of muscle cell differentiation|
|cell maturation|
|regulation of intrinsic apoptotic signaling pathway|
|cellular response to insulin stimulus|
|response to unfolded protein|
|positive regulation of angiogenesis|
|regulation of response to wounding|
|positive regulation of B cell activation|
|regulation of lymphocyte differentiation|
|response to carbohydrate|
|positive regulation of vasculature development|
|glucose homeostasis|
|cellular response to lipopolysaccharide|
|carbohydrate homeostasis|
|monocarboxylic acid biosynthetic process|
|response to topologically incorrect protein|
|positive regulation of hemopoiesis|
|positive regulation of epithelial cell proliferation|
|epithelial cell development|
|cellular response to molecule of bacterial origin|
|response to starvation|
|positive regulation of T cell activation|
|regulation of cytokine secretion|
|regulation of B cell activation|
|cellular response to acid chemical|
|cellular response to biotic stimulus|
|response to nutrient|
|positive regulation of leukocyte cell-cell adhesion|
|positive regulation of immune effector process|
|connective tissue development|
|negative regulation of apoptotic signaling pathway|
|response to insulin|
|cellular response to nutrient levels|
|developmental maturation|
|positive regulation of cell-cell adhesion|
|regulation of animal organ morphogenesis|
|response to endoplasmic reticulum stress|
|autophagy|
|process utilizing autophagic mechanism|
|cellular response to extracellular stimulus|
|cellular response to peptide hormone stimulus|
|positive regulation of protein secretion|
|regulation of leukocyte differentiation|
|apoptotic signaling pathway|
|regulation of angiogenesis|
|regulation of protein stability|
|positive regulation of peptide secretion|
|muscle organ development|
|regulation of leukocyte cell-cell adhesion|
|carboxylic acid biosynthetic process|
|organic acid biosynthetic process|
|RNA polymerase II regulatory region sequence-specific DNA binding|
|response to lipopolysaccharide|
|angiogenesis|
|regulation of T cell activation|
|regulation of vasculature development|
|fatty acid metabolic process|
|cellular response to peptide|
|response to molecule of bacterial origin|
|regulation of autophagy|
|regulation of epithelial cell proliferation|
|cellular response to external stimulus|
|response to acid chemical|
|positive regulation of lymphocyte activation|
|response to peptide hormone|
|regulation of apoptotic signaling pathway|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of secretion by cell|
|positive regulation of leukocyte activation|
|blood vessel morphogenesis|
|gland development|
|positive regulation of cell activation|
|positive regulation of protein transport|
|positive regulation of secretion|
|positive regulation of cytokine production|
|regulation of hemopoiesis|
|positive regulation of establishment of protein localization|
|regulation of protein secretion|
|regulation of immune effector process|
|response to peptide|
|muscle structure development|
|transcription by RNA polymerase II|
|blood vessel development|
|protein heterodimerization activity|
|regulation of peptide secretion|
|regulation of body fluid levels|
|response to nutrient levels|
|positive regulation of cell migration|
|RNA polymerase II proximal promoter sequence-specific DNA binding|
|negative regulation of intracellular signal transduction|
|vasculature development|
|regulation of lymphocyte activation|
|cardiovascular system development|
|cellular response to lipid|
|positive regulation of cell motility|
|ubiquitin-dependent protein catabolic process|
|monocarboxylic acid metabolic process|
|response to extracellular stimulus|
|modification-dependent protein catabolic process|
|positive regulation of cellular component movement|
|modification-dependent macromolecule catabolic process|
|positive regulation of locomotion|
|cell population proliferation|
|lipid biosynthetic process|
|proteolysis involved in cellular protein catabolic process|
|small molecule biosynthetic process|
|cellular response to organonitrogen compound|
|regulation of leukocyte activation|
|cellular response to hormone stimulus|
|cellular protein catabolic process|
|transcription, DNA-templated|
|regulation of cell activation|
|nucleic acid-templated transcription|
|RNA biosynthetic process|
|tube morphogenesis|
|cellular response to nitrogen compound|
|DNA-binding transcription factor activity|
|epithelial cell differentiation|
|regulation of cell adhesion|
|protein catabolic process|
|response to bacterium|
|regulation of cytokine production|
|regulation of protein transport|
|negative regulation of cell differentiation|
|regulation of cellular response to stress|
|regulation of peptide transport|
|cellular chemical homeostasis|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|ion homeostasis|
|regulation of secretion|
|neuron development|
|regulation of cellular catabolic process|
|tube development|
|regulation of cell migration|
|response to lipid|
|positive regulation of immune response|
|circulatory system development|
|negative regulation of apoptotic process|
|anatomical structure formation involved in morphogenesis|
|cellular homeostasis|
|negative regulation of programmed cell death|
|cellular macromolecule catabolic process|
|carboxylic acid metabolic process|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|apoptotic process|
|negative regulation of developmental process|
|cellular lipid metabolic process|
|positive regulation of cell differentiation|
|regulation of locomotion|
|positive regulation of transport|
|regulation of catabolic process|
|negative regulation of cell death|
|regulation of cellular component movement|
|response to organonitrogen compound|
|oxoacid metabolic process|
|cellular response to cytokine stimulus|
|endoplasmic reticulum|
|neuron differentiation|
|organic acid metabolic process|
|regulation of protein localization|
|macromolecule catabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|regulation of anatomical structure morphogenesis|
|organonitrogen compound catabolic process|
|response to nitrogen compound|
|cell death|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|chemical homeostasis|
|epithelium development|
|positive regulation of immune system process|
|regulation of immune response|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|lipid metabolic process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|negative regulation of signal transduction|
|proteolysis|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|DNA binding|
|response to endogenous stimulus|
|regulation of response to stress|
|protein transport|
|generation of neurons|
|peptide transport|
|regulation of apoptotic process|
|positive regulation of transcription, DNA-templated|
|response to oxygen-containing compound|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|regulation of programmed cell death|
|amide transport|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|cell development|
|regulation of immune system process|
|positive regulation of signal transduction|
|RNA metabolic process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|small molecule metabolic process|
|tissue development|
|macromolecule biosynthetic process|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|nitrogen compound transport|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp40|2-Methoxyestradiol 0.2μM R01 exp40]]|1.79|
|[[:results:exp73|LJH685 5μM R02 exp73]]|1.81|
|[[:results:exp122|Golgicide-A 4μM R03 exp122]]|2.35|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 2/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|2/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 7284
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 9.88 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='XBP1 Expression in NALM6 Cells: 9.88'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>