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FLASH GENE
Symbol STAT2 contributors: mct - updated : 21-08-2018
HGNC name signal transducer and activator of transcription 2, 113kDa
HGNC id 11363
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminus conserved domain, the coiled coil domain, (CCD) which encompasses amino acids 137–316, is known to bind IRF9
  • a conserved DNA-binding domain specific to the activity of ISGF3-independent STAT2-containing complexes
  • a SRC homology domain 2 (SH2)
  • a critical site of tyrosine phosphorylation
  • C-terminal transactivation domain
    • HOMOLOGY
    Homologene
    FAMILY STAT family of transcription factor
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • present in plasma membrane rafts, translocated to nucleus after activation
  • prior to phosphorylation, primarily resident in the cytoplasm, however, we found that it dynamically shuttles between nuclear and cytoplasmic compartments
    • basic FUNCTION
  • transcription activator in response to cytokine and growth factors
  • transcription factor critical to the signal transduction pathway of type I interferons
  • is a critical mediator in the activation of type I IFN-induced apoptosis
  • influences diverse cellular processes linked to RCAN1 by negatively affecting RCAN1 protein stability
  • is involved in the immunosuppressive function of human bone marrow-derived mesenchymal stem cells
  • is a positive modulator of the transcriptional response to type I interferons
  • in response to type I IFN, STAT2 is serine phosphorylated in the coiled-coil domain that when phosphorylated can negatively regulate the biological activities of type I IFNs
  • 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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • ISGF3 complex with STAT1 and STAT2
  • complex JAK2, STAT2, and STAT3 required for early myogenic differentiation (Wang 2008)
  • 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
  • specifically with CREBBP/EP300 (EBP/p300) in signaling induced by interferon alpha
  • nuclear transit of the intracellular domain of the interferon receptor subunit IFNAR2 requires STAT2 and IRF9
  • activated tyrosine-phosphorylated STAT2 associates with STAT1 and IRF9 to bind the ISRE elements in the promoters of a subset of IFN-inducible genes (ISGs)
  • RCAN1 interacts with the inflammation-linked transcription factor, signal transducer and activator of transcription 2 (STAT2)
  • interaction between STAT2 and IRF9
  • STAT2 and STAT4 are direct targets for POU2F1 protein
  • 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
    Phosphorylated by serine-phosphorylated in response to type I IFNs
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD44
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    leads to cytokine-independent, cell-mediated lethality in LPS-induced sepsis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS