STAT3

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. This gene also plays a role in regulating host response to viral and bacterial infections. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome.

signal transducer and activator of transcription 3

Acute phase response factor, APRF, FLJ20882, HIES, STAT3

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:22306293, 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).
Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-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).

Astrocyte differentiationISS:UniProtKB
Cell population proliferationIEA:Ensembl
Cellular response to hormone stimulusManual Assertion Based On ExperimentIDA:BHF-UCL
Cellular response to leptin stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Defense responseManual Assertion Based On ExperimentIBA:GO_Central
Eating behaviorISS:UniProtKB
Energy homeostasisISS:UniProtKB
Eye photoreceptor cell differentiationISS:UniProtKB
Glucose homeostasisISS:UniProtKB
Growth hormone receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Growth hormone receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIDA:BHF-UCL
Inflammatory responseISS:UniProtKB
Interleukin-6-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Intracellular receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Leptin-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
mRNA transcription by RNA polymerase IIIEA:Ensembl
Negative regulation of autophagyManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cell population proliferationIEA:Ensembl
Negative regulation of glycolytic processIEA:Ensembl
Negative regulation of neuron migrationIEA:Ensembl
Negative regulation of primary miRNA processingManual Assertion Based On ExperimentIMP:ARUK-UCL
Negative regulation of stem cell differentiationIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentTAS:ProtInc
Nervous system developmentManual Assertion Based On ExperimentTAS:ProtInc
PhosphorylationISS:UniProtKB
Positive regulation of angiogenesisIEA:Ensembl
Positive regulation of cell migrationManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of cytokine production involved in inflammatory responseManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of erythrocyte differentiationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of gene expressionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of gene silencing by miRNAManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of interleukin-1 beta productionManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of interleukin-10 productionManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of interleukin-6 productionISS:ARUK-UCL
Positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of metalloendopeptidase activityManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of miRNA transcriptionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of miRNA-mediated gene silencing by inhibition of translationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of NF-kappaB transcription factor activityISS:ARUK-UCL
Positive regulation of Notch signaling pathwayISS:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of vascular endothelial cell proliferationIEA:Ensembl
Protein import into nucleusManual Assertion Based On ExperimentIDA:UniProtKB
Radial glial cell differentiationISS:UniProtKB
Receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIBA:GO_Central
Regulation of cell cycleManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cell population proliferationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of feeding behaviorISS:UniProtKB
Regulation of multicellular organism growthIEA:Ensembl
Regulation of transcription by RNA polymerase IIISS:UniProtKB
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Response to estradiolManual Assertion Based On ExperimentIDA:BHF-UCL
Response to leptinManual Assertion Based On ExperimentIDA:UniProtKB
Response to peptide hormoneManual Assertion Based On ExperimentIBA:GO_Central
Sexual reproductionISS:UniProtKB
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Stem cell population maintenanceIEA:Ensembl
T-helper 17 cell lineage commitmentISS:UniProtKB
T-helper 17 type immune responseManual Assertion Based On ExperimentIDA:UniProtKB
Temperature homeostasisISS:UniProtKB
Transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIGI:ARUK-UCL

Cytoplasm
Nucleus
Shuttles between the nucleus and the cytoplasm. Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3. Identified in a complex with LYN and PAG1.

Hyper-IgE recurrent infection syndrome 1, autosomal dominant (HIES1):
A rare disorder of immunity and connective tissue characterized by immunodeficiency, chronic eosinophilia, distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures.
Autoimmune disease, multisystem, infantile-onset, 1 (ADMIO1):
A disorder characterized by early childhood onset of a spectrum of autoimmune manifestations affecting multiple organs, including insulin-dependent diabetes mellitus and autoimmune enteropathy or celiac disease. Other features include short stature, non-specific dermatitis, hypothyroidism, autoimmune arthritis, and delayed puberty.

Tyrosine phosphorylated upon stimulation with EGF. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity).
Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, LIF, CNTF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha, LEP and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity. ARL2BP may participate in keeping the phosphorylated state of STAT3 within the nucleus. Upon LPS challenge, phosphorylated within the nucleus by IRAK1. Upon erythropoietin treatment, phosphorylated on Ser-727 by RPS6KA5. Phosphorylation at Tyr-705 by PTK6, isoform M2 of PKM (PKM2) or FER leads to an increase of its transcriptional activity (PubMed:12763138, PubMed:16568091, PubMed:21135090, PubMed:22306293).
Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling.
Acetylated on lysine residues by CREBBP. Deacetylation by LOXL3 leads to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600).
Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600)..
Some lysine residues are oxidized to allysine by LOXL3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600).
Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600)..
(Microbial infection) Phosphorylated on Tyr-705 in the presence of S.typhimurium SarA.