STAT3 [The Human Chemical-Genetic Interaction Map Project]

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======= STAT3 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: STAT3
  * **<color #00a2e8>Official Name</color>**: signal transducer and activator of transcription 3
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6774|6774]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P40763|P40763]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=STAT3&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20STAT3|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/102582|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2015]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:17344214, PubMed:18242580, PubMed:23084476). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:17344214). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity (PubMed:28065600). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity). {ECO:0000250|UniProtKB:P42227, ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:12359225, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:17344214, ECO:0000269|PubMed:18242580, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:28065600}.

<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'>
|SH2|
|STAT bind|
|STAT int|
|STAT alpha|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|positive regulation of skeletal muscle satellite cell proliferation|
|positive regulation of growth factor dependent skeletal muscle satellite cell proliferation|
|positive regulation of metalloendopeptidase activity|
|positive regulation of skeletal muscle cell proliferation|
|negative regulation of hydrogen peroxide biosynthetic process|
|regulation of metalloendopeptidase activity|
|T-helper 17 cell lineage commitment|
|positive regulation of metallopeptidase activity|
|CCR5 chemokine receptor binding|
|response to interleukin-21|
|T-helper 17 cell differentiation|
|negative regulation of hydrogen peroxide metabolic process|
|regulation of hydrogen peroxide biosynthetic process|
|T-helper 17 type immune response|
|interleukin-21-mediated signaling pathway|
|negative regulation of cofactor metabolic process|
|cellular response to interleukin-21|
|interleukin-23-mediated signaling pathway|
|postsynapse to nucleus signaling pathway|
|cellular response to interleukin-9|
|interleukin-9-mediated signaling pathway|
|T-helper cell lineage commitment|
|leptin-mediated signaling pathway|
|response to interleukin-9|
|interleukin-35-mediated signaling pathway|
|interleukin-27-mediated signaling pathway|
|CD4-positive, alpha-beta T cell lineage commitment|
|radial glial cell differentiation|
|positive regulation of ATP biosynthetic process|
|negative regulation of neuron migration|
|negative regulation of glycolytic process|
|miRNA mediated inhibition of translation|
|regulation of translation, ncRNA-mediated|
|interleukin-15-mediated signaling pathway|
|regulation of skeletal muscle satellite cell proliferation|
|cellular response to interleukin-15|
|regulation of metallopeptidase activity|
|negative regulation of translation, ncRNA-mediated|
|alpha-beta T cell lineage commitment|
|CD4-positive or CD8-positive, alpha-beta T cell lineage commitment|
|growth hormone receptor signaling pathway via JAK-STAT|
|regulation of skeletal muscle cell proliferation|
|response to interleukin-15|
|positive regulation of vascular endothelial cell proliferation|
|positive regulation of interleukin-6 biosynthetic process|
|glucocorticoid receptor binding|
|interleukin-6-mediated signaling pathway|
|negative regulation of purine nucleotide metabolic process|
|regulation of ATP biosynthetic process|
|cellular response to leptin stimulus|
|mRNA transcription by RNA polymerase II|
|regulation of vascular endothelial cell proliferation|
|interleukin-7-mediated signaling pathway|
|negative regulation of nucleotide metabolic process|
|regulation of hydrogen peroxide metabolic process|
|growth hormone receptor signaling pathway|
|T cell lineage commitment|
|negative regulation of stem cell differentiation|
|cellular response to growth hormone stimulus|
|positive regulation of purine nucleotide biosynthetic process|
|response to leptin|
|positive regulation of nucleotide biosynthetic process|
|positive regulation of gene silencing by miRNA|
|regulation of interleukin-6 biosynthetic process|
|positive regulation of posttranscriptional gene silencing|
|negative regulation of ATP metabolic process|
|mRNA transcription|
|positive T cell selection|
|CD4-positive, alpha-beta T cell differentiation involved in immune response|
|negative regulation of reactive oxygen species biosynthetic process|
|T-helper cell differentiation|
|regulation of feeding behavior|
|alpha-beta T cell activation involved in immune response|
|alpha-beta T cell differentiation involved in immune response|
|response to interleukin-7|
|cellular response to interleukin-7|
|eating behavior|
|temperature homeostasis|
|positive regulation of erythrocyte differentiation|
|positive regulation of pri-miRNA transcription by RNA polymerase II|
|T cell differentiation involved in immune response|
|cellular response to interleukin-6|
|energy homeostasis|
|CD4-positive, alpha-beta T cell differentiation|
|response to growth hormone|
|RNA polymerase II repressing transcription factor binding|
|response to interleukin-6|
|regulation of cofactor metabolic process|
|receptor signaling pathway via JAK-STAT|
|regulation of purine nucleotide biosynthetic process|
|T cell selection|
|receptor signaling pathway via STAT|
|postsynaptic signal transduction|
|CD4-positive, alpha-beta T cell activation|
|regulation of nucleotide biosynthetic process|
|acute-phase response|
|regulation of neuron migration|
|negative regulation of cellular carbohydrate metabolic process|
|regulation of pri-miRNA transcription by RNA polymerase II|
|eye photoreceptor cell differentiation|
|positive regulation of purine nucleotide metabolic process|
|positive regulation of nucleotide metabolic process|
|positive regulation of ATP metabolic process|
|regulation of erythrocyte differentiation|
|nuclear receptor activity|
|gene silencing by miRNA|
|negative regulation of carbohydrate metabolic process|
|alpha-beta T cell differentiation|
|positive regulation of Notch signaling pathway|
|astrocyte differentiation|
|negative regulation of reactive oxygen species metabolic process|
|posttranscriptional gene silencing by RNA|
|photoreceptor cell differentiation|
|posttranscriptional gene silencing|
|alpha-beta T cell activation|
|T cell activation involved in immune response|
|somatic stem cell population maintenance|
|regulation of multicellular organism growth|
|positive regulation of cytokine biosynthetic process|
|positive regulation of tyrosine phosphorylation of STAT protein|
|acute inflammatory response|
|RNA polymerase II transcription factor complex|
|chromatin DNA binding|
|regulation of mitochondrial membrane permeability|
|regulation of behavior|
|regulation of glycolytic process|
|regulation of tyrosine phosphorylation of STAT protein|
|regulation of membrane permeability|
|Schaffer collateral - CA1 synapse|
|negative regulation of autophagy|
|positive regulation of receptor signaling pathway via JAK-STAT|
|regulation of reactive oxygen species biosynthetic process|
|feeding behavior|
|protein phosphatase binding|
|regulation of gene silencing by miRNA|
|gene silencing by RNA|
|positive regulation of receptor signaling pathway via STAT|
|regulation of carbohydrate catabolic process|
|regulation of gene silencing by RNA|
|regulation of posttranscriptional gene silencing|
|negative regulation of small molecule metabolic process|
|positive regulation of myeloid cell differentiation|
|positive regulation of endothelial cell proliferation|
|positive regulation of interleukin-6 production|
|protein import into nucleus|
|regulation of Notch signaling pathway|
|regulation of cytokine biosynthetic process|
|lymphocyte activation involved in immune response|
|import into nucleus|
|regulation of purine nucleotide metabolic process|
|regulation of stem cell differentiation|
|regulation of nucleotide metabolic process|
|regulation of ATP metabolic process|
|response to ethanol|
|mitochondrial membrane organization|
|regulation of gene silencing|
|regulation of endothelial cell proliferation|
|negative regulation of translation|
|regulation of receptor signaling pathway via JAK-STAT|
|regulation of receptor signaling pathway via STAT|
|stem cell population maintenance|
|T cell differentiation|
|response to estradiol|
|maintenance of cell number|
|positive regulation of small molecule metabolic process|
|regulation of cellular carbohydrate metabolic process|
|regulation of interleukin-6 production|
|protein import|
|eye morphogenesis|
|negative regulation of cellular amide metabolic process|
|gene silencing|
|positive regulation of NF-kappaB transcription factor activity|
|protein dimerization activity|
|regulation of generation of precursor metabolites and energy|
|protein localization to nucleus|
|intracellular receptor signaling pathway|
|positive regulation of angiogenesis|
|glial cell differentiation|
|positive regulation of endopeptidase activity|
|regulation of reactive oxygen species metabolic process|
|positive regulation of vasculature development|
|glucose homeostasis|
|carbohydrate homeostasis|
|positive regulation of hemopoiesis|
|positive regulation of epithelial cell proliferation|
|positive regulation of peptidyl-tyrosine phosphorylation|
|positive regulation of peptidase activity|
|regulation of carbohydrate metabolic process|
|transcription factor complex|
|negative regulation of neuron death|
|gliogenesis|
|mitochondrial transport|
|transcription regulatory region DNA binding|
|regulation of myeloid cell differentiation|
|response to alcohol|
|T cell activation|
|regulation of gene expression, epigenetic|
|lymphocyte differentiation|
|nuclear chromatin|
|cell fate commitment|
|regulation of peptidyl-tyrosine phosphorylation|
|postsynaptic density|
|negative regulation of cellular catabolic process|
|sensory organ morphogenesis|
|negative regulation of cell migration|
|positive regulation of DNA-binding transcription factor activity|
|nucleocytoplasmic transport|
|cellular response to peptide hormone stimulus|
|nuclear transport|
|negative regulation of cell motility|
|aging|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|regulation of angiogenesis|
|negative regulation of neurogenesis|
|response to antibiotic|
|negative regulation of cellular component movement|
|negative regulation of catabolic process|
|regulation of neuron death|
|negative regulation of nervous system development|
|regulation of vasculature development|
|negative regulation of locomotion|
|multicellular organismal homeostasis|
|cellular response to peptide|
|regulation of developmental growth|
|leukocyte differentiation|
|regulation of autophagy|
|transcription factor binding|
|negative regulation of cell development|
|regulation of epithelial cell proliferation|
|glutamatergic synapse|
|regulation of translation|
|positive regulation of proteolysis|
|eye development|
|visual system development|
|sensory system development|
|lymphocyte activation|
|response to peptide hormone|
|mitochondrial inner membrane|
|regulation of cellular amide metabolic process|
|regulation of endopeptidase activity|
|regulation of small molecule metabolic process|
|regulation of DNA-binding transcription factor activity|
|establishment of protein localization to organelle|
|mitochondrion organization|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|regulation of peptidase activity|
|negative regulation of phosphorylation|
|DNA-binding transcription activator activity, RNA polymerase II-specific|
|positive regulation of cytokine production|
|regulation of hemopoiesis|
|synaptic signaling|
|protein kinase binding|
|response to peptide|
|transcription by RNA polymerase II|
|inflammatory response|
|positive regulation of cell migration|
|RNA polymerase II proximal promoter sequence-specific DNA binding|
|response to toxic substance|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|positive regulation of cell motility|
|posttranscriptional regulation of gene expression|
|positive regulation of cellular component movement|
|cellular response to organic cyclic compound|
|sensory organ development|
|positive regulation of locomotion|
|cell population proliferation|
|hemopoiesis|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|behavior|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|immune system development|
|RNA biosynthetic process|
|cellular response to nitrogen compound|
|regulation of growth|
|cytokine-mediated signaling pathway|
|negative regulation of cell population proliferation|
|DNA-binding transcription factor activity|
|mRNA metabolic process|
|regulation of cytokine production|
|viral process|
|negative regulation of cell differentiation|
|enzyme linked receptor protein signaling pathway|
|regulation of proteolysis|
|protein localization to organelle|
|positive regulation of hydrolase activity|
|symbiotic process|
|regulation of neurogenesis|
|interspecies interaction between organisms|
|sexual reproduction|
|regulation of cellular catabolic process|
|regulation of cell migration|
|membrane organization|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|protein homodimerization activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|response to organic cyclic compound|
|regulation of nervous system development|
|leukocyte activation|
|regulation of cell development|
|negative regulation of developmental process|
|animal organ morphogenesis|
|positive regulation of cell differentiation|
|central nervous system development|
|regulation of locomotion|
|intracellular protein transport|
|regulation of cellular component movement|
|negative regulation of cell death|
|multi-organism reproductive process|
|regulation of catabolic process|
|response to organonitrogen compound|
|cellular response to cytokine stimulus|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|response to drug|
|negative regulation of cellular protein metabolic process|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|identical protein binding|
|cell activation|
|response to nitrogen compound|
|immune effector process|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|negative regulation of protein metabolic process|
|chemical homeostasis|
|cell-cell signaling|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|positive regulation of immune system process|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|regulation of hydrolase activity|
|phosphorylation|
|organic cyclic compound biosynthetic process|
|negative regulation of RNA metabolic process|
|defense response|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|protein transport|
|negative regulation of cellular biosynthetic process|
|intracellular transport|
|generation of neurons|
|peptide transport|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|regulation of programmed cell death|
|amide transport|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|RNA metabolic process|
|regulation of cell death|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|establishment of localization in cell|
|regulation of protein modification process|
|nitrogen compound 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:exp484|GSK-J5 1.5μM R08 exp484]]|-2.42|
|[[:results:exp510|Nicotine 3000μM R08 exp510]]|1.72|
|[[:results:exp155|UNC1999 2μM R03 exp155]]|1.82|
|[[:results:exp212|Phenformin 20μM R05 exp212]]|2.09|
</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|2/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|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>**: 17006
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.06 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='STAT3 Expression in NALM6 Cells: 6.06'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>