STAT1

STAT1 ;
Signal transducer and activator of transcription 1-alpha/beta ;
Transcription factor ISGF-3 components p91/p84

disease:Defects in STAT1 are a cause of mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950]; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species , such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria , and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections , with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood , whereas others develop , later in life , disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive , autosomal dominant or X-linked inheritance. ,disease:Defects in STAT1 are the cause of STAT1 deficiency [MIM:600555]. Patients generally suffer from mycobacterial or viral diseases. In the case of complete deficiency , patients can die of viral disease. ,function:Signal transducer and activator of transcription that mediates signaling by interferons (IFNs) . Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors , Jak kinases (TYK2 and JAK1) are activated , leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize , associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor , that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes , which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma) , STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF) , migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes , inducing a cellular antiviral state. ,online information:STAT1 entry ,online information:STAT1 mutation db ,PTM:Phosphorylated on tyrosine and serine residues in response to IFN-alpha , IFN-gamma , PDGF and EGF. Phosphorylation on Tyr-701 (lacking in beta form) by JAK promotes dimerization and subsequent translocation to the nucleus. Phosphorylation on Ser-727 by several kinases including MAPK14 , ERK1/2 and CAMKII on IFN-gamma stimulation , regulates STAT1 transcriptional activity. Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS. Phosphorylation on Ser-727 by PKCdelta induces apoptosis in response to DNA-damaging agents. ,PTM:Sumoylated by SUMO1 , SUMO2 and SUMO3. Sumoylation is enhanced by IFN-gamma-induced phosphorylation on Ser-727 , and by interaction with PIAS proteins. Enhances the transactivation activity. ,similarity:Belongs to the transcription factor STAT family. ,similarity:Contains 1 SH2 domain. ,subcellular location:Translocated into the nucleus in response to IFN-gamma-induced tyrosine phosphorylation and dimerization. ,subunit:Isoform alpha homodimerizes upon IFN-gamma induced phosphorylation. Heterodimer with STAT2 upon IFN-alpha/beta induced phosphorylation. Interacts with NMI. Interacts with Sendai virus C' , C , Y1 and Y2 proteins , Nipah virus P , V and W proteins , and rabies virus phosphoprotein preventing activation of ISRE and GAS promoter (By similarity) . Interacts with HCV core protein; the interaction results in STAT1 degradation. Interacts with PIAS1; the interaction requires phosphorylation on Ser-727 and inhibits STAT1 activation. ,

response to reactive oxygen species , response to molecule of bacterial origin , circulatory system process ,transcription , transcription , DNA-dependent , regulation of transcription , DNA-dependent , transcription from RNA polymerase II promoter , protein amino acid phosphorylation , phosphorus metabolic process , phosphate metabolic process , apoptosis , induction of apoptosis , activation of caspase activity , response to oxidative stress , cell surface receptor linked signal transduction , intracellular signaling cascade , protein kinase cascade , I-kappaB kinase/NF-kappaB cascade , JAK-STAT cascade , tyrosine phosphorylation of STAT protein , response to nutrient , blood circulation ,cell death , positive regulation of cell proliferation , response to mechanical stimulus , response to virus , response to bacterium , response to abiotic stimulus , response to endogenous stimulus , response to hormone stimulus , response to extracellular stimulus , response to organic substance , response to inorganic substance , regulation of cell death ,positive regulation of cell death , positive regulation of peptidase activity , programmed cell death , induction of programmed cell death , response to organic cyclic substance , death , phosphorylation , peptidyl-tyrosine phosphorylation , peptidyl-tyrosine modification , cytokine-mediated signaling pathway , lipopolysaccharide-mediated signaling pathway , response to nutrient levels , response to lipopolysaccharide , RNA biosynthetic process , response to insulin stimulus , cellular response to insulin stimulus , cellular response to hormone stimulus , response to cytokine stimulus , regulation of cell proliferation , response to drug , response to hydrogen peroxide , regulation of apoptosis ,positive regulation of apoptosis , regulation of programmed cell death , positive regulation of programmed cell death ,positive regulation of catalytic activity , positive regulation of caspase activity , regulation of caspase activity , response to exogenous dsRNA , response to dsRNA , response to peptide hormone stimulus , positive regulation of molecular function , regulation of transcription , regulation of smooth muscle cell proliferation , positive regulation of smooth muscle cell proliferation , regulation of RNA metabolic process , regulation of hydrolase activity , positive regulation of hydrolase activity , response to cAMP , regulation of peptidase activity , regulation of endopeptidase activity ,

Cytoplasm . Nucleus . Translocated into the nucleus upon tyrosine phosphorylation and dimerization , in response to IFN-gamma and signaling by activated FGFR1 , FGFR2 , FGFR3 or FGFR4 (PubMed:15322115) . Monomethylation at Lys-525 is required for phosphorylation at Tyr-701 and translocation into the nucleus (PubMed:28753426) . Translocates into the nucleus in response to interferon-beta stimulation (PubMed:26479788) . .