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FLASH GENE
Symbol STAT1 contributors: mct/pgu - updated : 27-10-2018
HGNC name signal transducer and activator of transcription 1, 91kDa
HGNC id 11362
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunespleen   highly
Reproductivefemale systemuterus  highly
Respiratoryrespiratory tracttrachea  highly
Urinarybladder   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminus conserved domain
  • the coiled coil domain
  • the DNA binding domain
  • a linker region
  • a SRC homology domain 2 (SH2)
  • a critical site of tyrosine phosphorylation
  • the carboxy-terminal transactivation domain
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Stat1 (93.7pc)
    homolog to murine Stat1 (93.6pc)
    Homologene
    FAMILY
  • STAT protein family of transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    text translocated to cholesterol-enriched microdomains (lipid rafts) after tyrosylation
    basic FUNCTION
  • activated during monocyte to macrophage differentiation as an early transcription factor initially activated by adherence and then able to modulate the expression of functional genes such as ICAM1 and FCGR1
  • playing a dual role with JAK1 and STAT3 in myogenic differentiation, participating in myoblast proliferation and actively repressing differentiation
  • in response to type II IFN, STAT1 is phosphorylated and forms homodimer that migrates to the nucleus and drives the expression of target genes, inducing a cellular antiviral state
  • functioning as a negative regulator of HIF-1-dependent transcription in tumor cells
  • is involved in maintaining the latency III viral program observed in transformed B cells and regulating immunorecognition by EBV-specific T cells
  • master regulator of ras-mediated transformation
  • unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes
  • is associated with an apoptosis pathway and required to promote the tumor killing effect of STAT3 inhibtion in head and neck squamous cell carcinoma
  • may be a novel risk genes for the differentiation of peak bone mass at the monocyte stage
  • early cellular responses to human interferons are critically dependent on the amount of STAT1 and are essential for the appropriate control of mycobacterial and viral infections
  • required for the cell death induced by IFNA1
  • STAT6-STAT1 axis regulates osteoclast stimulatory transmembrane protein and dendritic cell-specific transmembrane protein expression and governs fusogenic mechanisms in foreign body giant cells
  • activated STAT1 and STAT3 regulate VEGFA expression indirectly, by modulating HIF1A activity
  • control of HIF1A by STAT1 and STAT3 is an important mechanism by which VEGFA expression is regulated in smooth muscle cells (SMC)
  • STAT1 and STAT2 proteins are key mediators of type I and type III interferon (IFN) signaling, and are essential components of the cellular antiviral response and adaptive immunity
  • CELLULAR PROCESS nucleotide, transcription, regulation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    JAK-STAT1 pathway activated by IFNG enhancing the recruitment of coactivators
    a component
  • ISGF3 complex with STAT1 (STAT1b) and STAT2 (113kD)
  • STAT1, STAT2 associate with IFN regulatory factor 9 (IRF9) to form a heterotrimeric transcription factor complex known as ISGF3
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • recruiting a minichromosome maintenance complex MCM5/MCM3 through direct interaction with MCM5 in the process of IFNG-induced gene activation
  • KPNA2 for translocation into the nucleus
  • IFNA1 (protection against IFNA1-mediated injury in the CNS )
  • associating with SPI1 and coactivating Fcgamma receptor 1 promoter
  • dimerizing with phosphorylated STAT2 and associating with ISGF3G in ISGF3 transcription factor complex
  • STAT1-DOT1L interaction is required for the regulation JAK-STAT-inducible gene expression
  • interacting with NMI
  • SMURF1 interacted with STAT1 through the WW domains of SMURF1 and the PY motif in STAT1 and catalyzed K48-linked polyubiquitination of STAT1
  • STAT1 inhibited VEGFA expression, while STAT3 promoted the expression of VEGFA
  • STAT1 and STAT3 have opposing roles in modulating HIF1A activity and subsequently, VEGFA expression
  • TYK2 controls STAT1 and STAT6 activation in response to IL13 stimulation
  • physically interacts with both STAT1A and STAT1B through its macrodomains in an ADP-ribosylation-dependent manner, and directly inhibits, together with STAT1B, the expression of tumor suppressor and interferon response factor IRF1
  • RELA and STAT1 cooperate to control NOS2 gene transcription in response to proinflammatory cytokines by a coactivator exchange mechanism
  • IFNG directly controls IL33 protein level through a STAT1- and PSMB9-dependent mechanism
  • NDN bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML
  • endogenous STAT1 and IFNGR1 in target cells are indispensable to sustain the activation of STAT1 signaling by extracellular vesicles (EVs)-associated IFNG/IFNGR1 complexes
  • IFIT3 showed binding to MAPK8 and STAT1, the latter being an important inducer of IFIT3 expression
  • STAT1 and STAT3 have at least partially opposing roles in IL21 signaling in CD4(+) T cells
  • positive feedback loop between phosphorylated STAT1 and IFIT1, IFIT2, IFIT3
  • IRF1 could induce STAT1 phosphorylation and in turn STAT1 activation
  • HDAC3 interacts with FOXK1, co-localizes with FOXK1 at the promoter of STAT1 and STAT2, and is required for protecting FOXK1 from lysosomal system-mediated degradation
  • cell & other
    REGULATION
    activated by cytokines IFNA, IFNG stimulating tyrosine phosphorylation, dimerization, transport to the nucleus and regulating gene expression
    IGFBP3 in chondrogenesis
    EGF, PDGF and IL6
    inhibited by PIAS1 and prevented of binding to DNA
    Other covalently modified by SUMO-1 in cytokine signaling
    regulated by a phosphorylation-acetylation switch
    ASSOCIATED DISORDERS
    corresponding disease(s) STAT1D , CANDF7
    related resource STAT1base: Mutation registry for STAT1 deficiency
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    impairing the response to interferon alpha/beta increases the susceptibility to lethal viral disease
    Susceptibility susceptibility to lethal viral disease
    Variant & Polymorphism
    Candidate gene
  • might play an important role in sarcoidosis
  • significant association of STAT1 with bone mineral density, important in circulating monocytes in the etiology of osteoporosis
  • Marker
    Therapy target
    ANIMAL & CELL MODELS