id: P42224
gene_symbol: STAT1
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: STAT1 is a latent cytoplasmic transcription factor that serves as a
  central mediator of cytokine signaling, particularly interferon responses. 
  Upon cytokine stimulation, STAT1 becomes phosphorylated on Y701 by JAK 
  kinases, forms homodimers or heterodimers (e.g., with STAT2), and translocates
  to the nucleus where it binds specific DNA elements to regulate gene 
  expression. STAT1 is essential for antiviral and antimicrobial immunity, 
  mediating both type I (IFN-α/β, forming ISGF3 complex) and type II (IFN-γ, 
  forming GAF complex) interferon responses. Knockout studies demonstrate 
  STAT1's non-redundant role in host defense against viruses, bacteria, and 
  fungi.
existing_annotations:
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: STAT1 binds to specific DNA regulatory elements including GAS 
      (gamma-activated sites) and ISRE sequences in gene promoters. This IBA 
      annotation accurately reflects STAT1's well-established function as a 
      sequence-specific transcription factor.
    action: ACCEPT
    reason: IBA annotations represent high-quality phylogenetically-inferred 
      annotations that have undergone extensive review. STAT1's 
      sequence-specific DNA binding to cis-regulatory regions is a core 
      molecular function well-supported by structural and biochemical evidence.
    supported_by:
    - reference_id: PMID:9630226
      supporting_text: The crystal structure of the DNA complex of a STAT-1 
        homodimer has been determined at 2.9 A resolution. STAT-1 utilizes a 
        DNA-binding domain with an immunoglobulin fold, similar to that of 
        NFkappaB and the p53 tumor suppressor protein
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: This is STAT1's core molecular function. STAT1 is a bona fide 
      transcription factor that activates RNA polymerase II-mediated 
      transcription of interferon-stimulated genes and other cytokine-responsive
      genes. IBA annotation is well-supported.
    action: ACCEPT
    reason: This represents STAT1's primary molecular function as established by
      decades of research. STAT1 directly regulates over 300 
      interferon-stimulated genes through RNA polymerase II-mediated 
      transcription. IBA evidence reflects phylogenetic conservation of this 
      core function.
    supported_by:
    - reference_id: file:human/STAT1/STAT1-deep-research.md
      supporting_text: STAT1 regulates a vast network of target genes, with over
        300 interferon-stimulated genes (ISGs) identified through experimental 
        validation
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: While STAT1 does bind DNA, this term is overly general. STAT1's DNA
      binding is sequence-specific and is better captured by more specific terms
      like GO:0000981 or GO:0043565.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic DNA binding (GO:0003677) provides insufficient functional 
      specificity for a well-characterized transcription factor like STAT1. The 
      more specific terms 'RNA polymerase II cis-regulatory region 
      sequence-specific DNA binding' and 'DNA-binding transcription factor 
      activity, RNA polymerase II-specific' better capture STAT1's functional 
      specificity.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: This is a core function of STAT1 as a transcription factor. 
      However, the more specific term GO:0000981 (DNA-binding transcription 
      factor activity, RNA polymerase II-specific) is more informative.
    action: ACCEPT
    reason: While GO:0000981 is more specific and preferred, this broader term 
      still accurately describes STAT1's transcriptional function. Both terms 
      can coexist as they represent different levels of annotation granularity, 
      with the specific term providing more mechanistic detail.
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Duplicate of the same term with IBA evidence. This IEA annotation 
      supports the same core function but is redundant with higher-quality IBA 
      annotation.
    action: ACCEPT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11238845
  review:
    summary: PMID:11238845 shows STAT1 interaction with vaccinia virus VH1 
      phosphatase. While STAT1 does bind proteins, this generic term provides 
      limited functional insight. STAT1's critical protein interactions 
      (homodimerization, JAK binding, coactivator binding) are better captured 
      by more specific terms.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:11238845
      supporting_text: 'Vaccinia virus blocks gamma interferon signal transduction:
        viral VH1 phosphatase reverses Stat1 activation.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12070153
  review:
    summary: Study shows STAT1 binding to EGFR domains. Generic protein binding 
      term lacks specificity about STAT1's functional protein interactions.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:12070153
      supporting_text: 2002 Jun 17. Identification of both positive and negative
        domains within the epidermal growth factor receptor COOH-terminal region
        for signal transducer and activator of transcription (STAT) activation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12788789
  review:
    summary: Study demonstrates STAT1 interaction with c-Fos in NOS2 gene 
      regulation. While this shows functional protein interaction, the generic 
      term is less informative than specific binding terms.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:12788789
      supporting_text: STAT-1 and c-Fos interaction in nitric oxide synthase-2 
        gene activation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15780933
  review:
    summary: Paper describes structural basis of STAT1 receptor binding 
      interactions. Generic protein binding term lacks functional specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:15780933
      supporting_text: Structural bases of unphosphorylated STAT1 association 
        and receptor binding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15825084
  review:
    summary: Shows HCV core protein degrading STAT1 to suppress interferon 
      signaling. Generic term doesn't capture the functional significance of 
      this pathogen-host interaction.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:15825084
      supporting_text: Hepatitis C virus expression suppresses interferon 
        signaling by degrading STAT1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  review:
    summary: Large-scale proteome interaction mapping study. While it may 
      identify STAT1 interactions, the generic protein binding term provides 
      minimal functional insight.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:16189514
      supporting_text: Towards a proteome-scale map of the human protein-protein
        interaction network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16273093
  review:
    summary: ErbB receptor protein microarray study. Mass interaction data lacks
      specific functional context for STAT1.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:16273093
      supporting_text: A quantitative protein interaction network for the ErbB 
        receptors using protein microarrays.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16940534
  review:
    summary: HCV core protein blocking STAT1 SH2 domain interactions. While 
      functionally relevant, generic protein binding doesn't capture the 
      mechanistic detail.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:16940534
      supporting_text: Hepatitis C virus core protein blocks interferon 
        signaling by interaction with the STAT1 SH2 domain.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17275127
  review:
    summary: HCV NS5A suppressing STAT1 phosphorylation. Generic protein binding
      term lacks functional specificity for this pathogen-mediated inhibition.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:17275127
      supporting_text: Dec 14. HCV NS5A inhibits interferon-alpha signaling 
        through suppression of STAT1 phosphorylation in hepatocyte-derived cell 
        lines.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17596301
  review:
    summary: SARS-CoV ORF6 antagonizing STAT1 nuclear import. While this 
      demonstrates pathogen-host protein interaction, the generic term lacks 
      functional context.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:17596301
      supporting_text: Severe acute respiratory syndrome coronavirus ORF6 
        antagonizes STAT1 function by sequestering nuclear import factors on the
        rough endoplasmic reticulum/Golgi membrane.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17923090
  review:
    summary: Study on acetylation-dependent interferon receptor signaling. 
      Generic protein binding term doesn't capture the regulatory complexity of 
      STAT1 interactions.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:17923090
      supporting_text: Acetylation-dependent signal transduction for type I 
        interferon receptor.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20195357
  review:
    summary: Comprehensive resource of transcription factor interaction 
      networks. Large-scale interaction data lacks specific functional context.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:20195357
      supporting_text: A comprehensive resource of interacting protein regions 
        for refining human transcription factor networks.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20576130
  review:
    summary: PAFR and FAK/STAT1 networking in BRCA1-mutant ovarian epithelium. 
      Context-specific interaction that is better described by more specific 
      terms.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:20576130
      supporting_text: Activated networking of platelet activating factor 
        receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant 
        at-risk ovarian epithelium.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21903422
  review:
    summary: Mapping innate immunity protein interaction networks regulating 
      type I interferon. While functionally relevant, generic term lacks 
      specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:21903422
      supporting_text: 2011 Sep 8. Mapping a dynamic innate immunity protein 
        interaction network regulating type I interferon production.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  review:
    summary: Human liver protein interaction network study. Large-scale 
      proteomic data without specific functional context for STAT1.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:21988832
      supporting_text: Toward an understanding of the protein interaction 
        network of the human liver.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24065129
  review:
    summary: IFN-β increases STAT1/STAT2/IRF9 complex formation for antiviral 
      resistance. While this shows functional protein interactions, generic term
      doesn't capture the specific complex formation.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:24065129
      supporting_text: IFNβ-dependent increases in STAT1, STAT2, and IRF9 
        mediate resistance to viruses and DNA damage.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24360797
  review:
    summary: RIG-I interaction with STAT1 in hepatocellular carcinoma interferon
      response. Generic protein binding lacks mechanistic specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:24360797
      supporting_text: 2013 Dec 19. Hepatic RIG-I predicts survival and 
        interferon-α therapeutic response in hepatocellular carcinoma.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24658140
  review:
    summary: Mammalian membrane two-hybrid assay for membrane protein 
      interactions. Technical methodology paper with limited functional insight.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:24658140
      supporting_text: The mammalian-membrane two-hybrid assay (MaMTH) for 
        probing membrane-protein interactions in human cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25241761
  review:
    summary: In situ proximity ligation assay for pathway protein interactions. 
      Methodological study without specific functional context for STAT1.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:25241761
      supporting_text: Oct 9. Using an in situ proximity ligation assay to 
        systematically profile endogenous protein-protein interactions in a 
        pathway network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: Large-scale proteome-scale human interactome network mapping. 
      Generic interaction data without specific functional context.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: A proteome-scale map of the human interactome network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25609649
  review:
    summary: Proteomic analysis of chromatin-associated vs. soluble 
      transcription factor complexes. While relevant to STAT1's transcriptional 
      function, generic protein binding lacks specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:25609649
      supporting_text: Proteomic analyses reveal distinct chromatin-associated 
        and soluble transcription factor complexes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26889034
  review:
    summary: Bovine herpesvirus VP8 protein interacting with STAT1 to inhibit 
      interferon signaling. Pathogen-host interaction better described by more 
      specific terms.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:26889034
      supporting_text: May 15. VP8, the Major Tegument Protein of Bovine 
        Herpesvirus 1, Interacts with Cellular STAT1 and Inhibits Interferon 
        Beta Signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26966684
  review:
    summary: PIPINO software for protein-protein interaction identification from
      mass spectrometry. Computational methodology paper with limited functional
      context.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:26966684
      supporting_text: 'PIPINO: A Software Package to Facilitate the Identification
        of Protein-Protein Interactions from Affinity Purification Mass Spectrometry
        Data.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31980649
  review:
    summary: EGFR network rewiring in KRAS-mutant colorectal cancer cells. 
      Cancer-specific context where generic protein binding lacks functional 
      detail.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:31980649
      supporting_text: Extensive rewiring of the EGFR network in colorectal 
        cancer cells expressing transforming levels of KRAS(G13D).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32953130
  review:
    summary: SARS-CoV-2 N protein antagonizing STAT1/STAT2 interferon signaling.
      While functionally relevant pathogen-host interaction, generic term lacks 
      mechanistic detail.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:32953130
      supporting_text: SARS-CoV-2 N protein antagonizes type I interferon 
        signaling by suppressing phosphorylation and nuclear translocation of 
        STAT1 and STAT2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: Cell-specific remodeling of human interactome networks. Large-scale
      proteomic data without specific functional context.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
        cell-specific remodeling of the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34950606
  review:
    summary: SARS-CoV-2 M and S proteins antagonizing interferon response. Viral
      interference with STAT1, but generic term lacks mechanistic detail.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:34950606
      supporting_text: Severe Acute Respiratory Syndrome Coronavirus 2 
        (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I 
        Interferon Response.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35140242
  review:
    summary: Human transcription factor protein interaction networks. 
      Large-scale interaction mapping without specific functional context.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:35140242
      supporting_text: Human transcription factor protein interaction networks.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8156998
  review:
    summary: IFN-γ receptor tyrosine phosphorylation coupling to STAT1 signal 
      transduction. While this demonstrates functional receptor-STAT1 
      interaction, generic term lacks specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:8156998
      supporting_text: Ligand-induced IFN gamma receptor tyrosine 
        phosphorylation couples the receptor to its signal transduction system 
        (p91).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8605877
  review:
    summary: STAT1/STAT2 SH2 domains mediating IFN-α signal transduction. While 
      this shows critical STAT1 protein interactions, the more specific 
      "identical protein binding" term for this paper better captures the 
      homodimerization function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:8605877
      supporting_text: The SH2 domains of Stat1 and Stat2 mediate multiple 
        interactions in the transduction of IFN-alpha signals.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8662591
  review:
    summary: Differential STAT3/STAT1 activation via gp130 cytoplasmic domain. 
      Shows STAT1 receptor interactions but generic term lacks functional 
      specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:8662591
      supporting_text: Differential activation of acute phase response 
        factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 
        signal transducer gp130.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9121453
  review:
    summary: STAT2 functional subdomains for IFN-α receptor interaction and 
      signaling. Shows STAT1-STAT2 heterodimerization but generic term lacks 
      specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:9121453
      supporting_text: Functional subdomains of STAT2 required for 
        preassociation with the alpha interferon receptor and for signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9881977
  review:
    summary: Adenoviral suppression of STAT1 function. Pathogen-host interaction
      where generic protein binding lacks mechanistic detail.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:9881977
      supporting_text: Direct suppression of Stat1 function during adenoviral 
        infection.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:8605877
  review:
    summary: PMID:8605877 demonstrates STAT1 SH2 domain-mediated 
      homodimerization essential for IFN-α signaling. This is a core molecular 
      function of STAT1 - formation of homodimers through reciprocal 
      SH2-phosphotyrosine interactions.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:8605877
      supporting_text: the SH2 domain of Stat1 and Stat2 can mediate homo- as 
        well as heterodimerization, suggest that a single SH2 
        domain-phosphotyrosyl interaction is sufficient for dimerization. 
        Moreover, they provide the first direct evidence that the target of the 
        SH2 domain is the STAT tyrosine activation site
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:9630226
  review:
    summary: Crystal structure paper showing STAT1 dimer bound to DNA. This 
      provides direct structural evidence for STAT1 homodimerization, which is 
      essential for its transcriptional function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9630226
      supporting_text: The STAT-1 dimer forms a contiguous C-shaped clamp around
        DNA that is stabilized by reciprocal and highly specific interactions 
        between the SH2 domain of one monomer and the C-terminal segment, 
        phosphorylated on tyrosine, of the other
- term:
    id: GO:0031730
    label: CCR5 chemokine receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This is a very specific interaction that is not part of STAT1's 
      core function. STAT1 primarily functions in interferon signaling, not 
      chemokine receptor binding. This appears to be an erroneous computational 
      annotation.
    action: REMOVE
    reason: STAT1 is a transcription factor that mediates interferon signaling 
      through JAK-STAT pathway activation. CCR5 chemokine receptor binding is 
      completely unrelated to STAT1's established molecular functions and 
      biological roles. This IEA annotation likely represents a computational 
      error or inappropriate sequence similarity inference.
    additional_reference_ids:
    - file:human/STAT1/STAT1-deep-research.md
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: STAT1 binds sequence-specifically to GAS elements and ISRE 
      sequences. This is a core molecular function, though the more specific RNA
      polymerase II terms are preferable.
    action: ACCEPT
    reason: STAT1 demonstrates sequence-specific DNA binding to GAS 
      (gamma-activated sites) elements as homodimers and to ISRE 
      (interferon-stimulated response elements) as part of ISGF3 complex. This 
      is a well-validated core molecular function.
    supported_by:
    - reference_id: PMID:9630226
      supporting_text: The STAT-1 dimer forms a contiguous C-shaped clamp around
        DNA that is stabilized by reciprocal and highly specific interactions 
        between the SH2 domain of one monomer and the C-terminal segment, 
        phosphorylated on tyrosine, of the other
- term:
    id: GO:0051721
    label: protein phosphatase 2A binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: While STAT1 may interact with phosphatases for dephosphorylation, 
      PP2A is not a well-established specific regulator of STAT1. This IEA 
      annotation lacks experimental support for a functionally relevant 
      interaction.
    action: REMOVE
    reason: STAT1 is primarily regulated by nuclear phosphatases such as 
      TC45/PTPN2 that dephosphorylate Y701, not PP2A. The literature does not 
      support PP2A as a major regulator of STAT1 function. This IEA annotation 
      lacks experimental validation and contradicts established regulatory 
      mechanisms.
    additional_reference_ids:
    - file:human/STAT1/STAT1-deep-research.md
- term:
    id: GO:0071345
    label: cellular response to cytokine stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This is a core biological process for STAT1. STAT1 mediates 
      cellular responses to multiple cytokines including interferons, IL-6, and 
      others. This is well-supported by extensive literature.
    action: ACCEPT
    reason: STAT1 is the master regulator of cytokine responses, particularly 
      interferon signaling. This biological process term accurately captures 
      STAT1's primary function in mediating cellular responses to IFN-α/β, 
      IFN-γ, and other cytokines through the JAK-STAT pathway.
    supported_by:
    - reference_id: file:human/STAT1/STAT1-deep-research.md
      supporting_text: STAT1 functions as a latent cytosolic transcription 
        factor that becomes activated upon extracellular stimulation. The 
        protein undergoes a well-characterized activation cycle through cytokine
        binding to membrane receptors
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IDA
  original_reference_id: PMID:32209697
  review:
    summary: Study shows noncanonical STAT1 phosphorylation expanding 
      transcriptional activity to include LPS-induced IL-6 and IL-12p40 
      production. Strong experimental evidence (IDA) for STAT1's core 
      transcriptional function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:32209697
      supporting_text: STAT1 phosphorylated at Thr749 directly enhanced 
        transcription of the gene encoding IL-12p40 (IL12B). Instead of 
        affecting STAT1 nuclear translocation, phosphorylation of Thr749 
        facilitated the binding of STAT1 to a noncanonical DNA motif 
        (5'-TTTGANNC-3') in the promoter regions of ARID5A and IL12B
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: Requirement of Ca2+ and CaMKII for STAT1 Ser-727 phosphorylation in
      IFN-γ response. Demonstrates STAT1's transcriptional activation function 
      with experimental evidence.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: In response to IFN-γ, the latent cytoplasmic protein 
        signal transducers and activators of transcription 1 (Stat1) becomes 
        phosphorylated on Y701, dimerizes, and accumulates in the nucleus to 
        activate transcription of IFN-γ-responsive genes
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: SETD2-mediated methylation of STAT1 critical for interferon 
      antiviral activity. Strong experimental evidence for STAT1's transcription
      factor function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: SETD2 directly mediates STAT1 methylation on lysine 525 
        via its methyltransferase activity, which reinforces IFN-activated STAT1
        phosphorylation and antiviral cellular response. In addition, SETD2 
        selectively catalyzes the tri-methylation of H3K36 on promoters of some 
        ISGs such as ISG15, leading to gene activation
- term:
    id: GO:0046427
    label: positive regulation of receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:16257975
  retired: true
  review:
    summary: Study shows conserved Leu-724 required for STAT1 serine 
      phosphorylation and coactivator recruitment for IFN-γ mediated 
      transcription. This accurately reflects STAT1's role in promoting JAK-STAT
      pathway signaling.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:16257975
      supporting_text: the conserved Leu-724 residue is also essential for gene 
        activation mediated by Stat1.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:9535918
  review:
    summary: IL-9 receptor leads to STAT activation and apoptosis prevention. 
      While this shows STAT1's transcriptional activity, the more specific RNA 
      polymerase II term is preferable for precision.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9535918
      supporting_text: Heteromerization of the gammac chain with the 
        interleukin-9 receptor alpha subunit leads to STAT activation and 
        prevention of apoptosis
- term:
    id: GO:0000977
    label: RNA polymerase II transcription regulatory region sequence-specific 
      DNA binding
  evidence_type: IDA
  original_reference_id: PMID:22002246
  review:
    summary: DOT1L interaction required for STAT1-activated gene expression. 
      This demonstrates STAT1's sequence-specific binding to regulatory regions,
      which is a core molecular function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:22002246
      supporting_text: STAT1 binding to its DNA recognition element near the 
        IRF1 promoter is diminished 2-fold in the DOT1L-depleted cell line. In 
        vivo and in vitro protein interaction assays reveal a DOT1L-STAT1 
        interaction
- term:
    id: GO:0001223
    label: transcription coactivator binding
  evidence_type: IPI
  original_reference_id: PMID:22002246
  review:
    summary: STAT1 interaction with DOT1L coactivator for gene expression. This 
      reflects STAT1's ability to recruit transcriptional machinery, which is 
      essential for its transcriptional activation function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:22002246
      supporting_text: Domain mapping identifies the middle region of DOT1L 
        (amino acids 580–1183) as the STAT1 interaction domain.
- term:
    id: GO:0001222
    label: transcription corepressor binding
  evidence_type: IPI
  original_reference_id: PMID:23386060
  review:
    summary: hCAF1/CNOT7 regulates interferon signaling by targeting STAT1. 
      While STAT1 may interact with corepressors as part of regulatory 
      mechanisms, this is not a core function and may represent context-specific
      regulation.
    action: KEEP_AS_NON_CORE
    reason: Transcription corepressor binding represents a regulatory mechanism 
      for fine-tuning STAT1 activity rather than a core molecular function. 
      While functionally relevant for STAT1 regulation, this interaction is 
      context-dependent and not part of STAT1's primary interferon signaling 
      functions.
    supported_by:
    - reference_id: PMID:23386060
      supporting_text: hcaf1/cnot7 regulates interferon signalling by targeting 
        stat1
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: ISA
  original_reference_id: GO_REF:0000113
  review:
    summary: Annotation based on sequence similarity to known transcription 
      factors. While ISA evidence is less strong than experimental evidence, 
      this accurately reflects STAT1's core function.
    action: ACCEPT
    reason: ISA (Inferred from Sequence Alignment) annotation is supported by 
      STAT1's well-characterized DNA-binding domain structure and sequence 
      similarity to other transcription factors. The annotation accurately 
      reflects STAT1's core transcriptional function despite being 
      computationally inferred.
    additional_reference_ids:
    - GO_REF:0000113
- term:
    id: GO:0000979
    label: RNA polymerase II core promoter sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:23386060
  review:
    summary: hCAF1/CNOT7 regulation of STAT1 interferon signaling. While STAT1 
      can bind core promoter regions, it more commonly binds to enhancer regions
      (GAS elements). This may be context-specific.
    action: KEEP_AS_NON_CORE
    reason: STAT1 primarily binds to enhancer elements (GAS sites) and distal 
      regulatory regions rather than core promoters. While it may occasionally 
      bind core promoter sequences in specific contexts, this represents a 
      minority of STAT1's DNA binding activity and is not a core molecular 
      function.
    supported_by:
    - reference_id: PMID:23386060
      supporting_text: Consistently, hCAF1 silencing enhances STAT1 basal 
        promoter occupancy associated with increased expression of a subset of 
        STAT1-regulated genes
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: HDA
  original_reference_id: PMID:25468996
  review:
    summary: E-cadherin interactome study using high-throughput methods. 
      Cadherin binding is not a known or relevant function of STAT1, which is a 
      cytokine-responsive transcription factor. This appears to be a false 
      positive from proteomic screening.
    action: REMOVE
    reason: STAT1 functions as a cytosolic/nuclear transcription factor in 
      interferon signaling pathways. Cadherin binding is completely unrelated to
      STAT1's established molecular functions and likely represents a false 
      positive from high-throughput proteomics screening (HDA evidence). No 
      mechanistic rationale exists for STAT1-cadherin interactions.
    supported_by:
    - reference_id: PMID:25468996
      supporting_text: E-cadherin interactome complexity and robustness resolved
        by quantitative proteomics
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:21268089
  review:
    summary: STAT1-mediated gene transcription inhibition by simvastatin and 
      PPAR/LXR agonists. This demonstrates STAT1's binding to cis-regulatory 
      elements, which is a core function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:21268089
      supporting_text: Simvastatin and PPAR agonists had no effect on the 
        IFN-γ-induced, phosphorylation-mediated activation of STAT1 and its DNA 
        binding but attenuated its ability to activate gene transcription.
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IDA
  original_reference_id: PMID:21268089
  review:
    summary: Another duplicate of STAT1's core transcription factor function 
      with strong experimental evidence. Consistent with previous assessments.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:21268089
      supporting_text: Simvastatin and PPAR agonists had no effect on the 
        IFN-γ-induced, phosphorylation-mediated activation of STAT1 and its DNA 
        binding but attenuated its ability to activate gene transcription.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26479788
  review:
    summary: PARP9-DTX3L targeting histone H2BJ and viral protease to enhance 
      interferon signaling. While this shows STAT1 in regulatory complexes, 
      generic protein binding lacks functional specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:26479788
  review:
    summary: STAT1 translocates to the nucleus upon activation where it 
      functions as a transcription factor. Nuclear localization is a key aspect 
      of STAT1's function cycle.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:26479788
  review:
    summary: STAT1 interactions with various enzymes (kinases, phosphatases, 
      methyltransferases) are critical for its regulation. This is more 
      informative than generic protein binding but still quite broad.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection
- term:
    id: GO:0035035
    label: histone acetyltransferase binding
  evidence_type: IPI
  original_reference_id: PMID:26479788
  review:
    summary: STAT1 interacts with histone-modifying enzymes as part of 
      transcriptional activation complexes. This reflects STAT1's role in 
      chromatin regulation during gene activation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection
- term:
    id: GO:0042393
    label: histone binding
  evidence_type: IPI
  original_reference_id: PMID:26479788
  review:
    summary: STAT1's interaction with histones is part of its transcriptional 
      regulatory function, involving chromatin remodeling at target genes. This 
      is a relevant molecular function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection
- term:
    id: GO:0044389
    label: ubiquitin-like protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:26479788
  review:
    summary: STAT1 regulation involves ubiquitin-like modifications and 
      interactions with ligases for protein stability and localization control. 
      This is a relevant regulatory mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection
- term:
    id: GO:0000979
    label: RNA polymerase II core promoter sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: SETD2 methylation study showing STAT1 binding to core promoter 
      regions. While STAT1 primarily binds enhancer regions, it can also bind 
      promoter regions depending on gene context.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28753426
  review:
    summary: SETD2 methyltransferase interaction with STAT1. While this is a 
      functionally important interaction for STAT1 regulation, the generic 
      protein binding term lacks specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: Demonstrates STAT1 homodimerization essential for transcriptional 
      function. This is a more specific and accurate term than "identical 
      protein binding" for describing STAT1's dimerization.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: SETD2 directly mediates STAT1 methylation on lysine 525 
        via its methyltransferase activity, which reinforces IFN-activated STAT1
        phosphorylation and antiviral cellular response
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:23386060
  review:
    summary: hCAF1/CNOT7 regulation of STAT1. Strong experimental evidence for 
      STAT1's transcriptional function, though RNA polymerase II-specific terms 
      are more precise.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:23386060
      supporting_text: Consistently, hCAF1 silencing enhances STAT1 basal 
        promoter occupancy associated with increased expression of a subset of 
        STAT1-regulated genes.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:18035482
  review:
    summary: STAT1 regulation of XAF1 expression in colon cancer cells by IFN-β.
      Demonstrates STAT1's sequence-specific binding to regulatory regions, 
      which is a core function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:18035482
      supporting_text: 'Regulation of XAF1 expression in human colon cancer cell by
        interferon beta: activation by the transcription regulator STAT1'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12867595
  review:
    summary: GRIM-19 as inhibitor of STAT3, may also interact with STAT1. 
      Generic protein binding term lacks functional specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:12867595
      supporting_text: The cell death regulator GRIM-19 is an inhibitor of 
        signal transducer and activator of transcription 3.
- term:
    id: GO:0043542
    label: endothelial cell migration
  evidence_type: IMP
  original_reference_id: PMID:16585190
  negated: true
  review:
    summary: PMID:16585190 reports STAT1 activation inhibits angiogenesis and 
      tube formation; GOA captures this PMID as NOT involved in endothelial cell
      migration.
    action: ACCEPT
    reason: GOA marks this PMID as NOT involved_in endothelial cell migration. 
      The study shows STAT1-driven inhibition of angiogenic responses in 
      endothelial cells rather than promoting migration, so the negated 
      annotation is appropriate.
    supported_by:
    - reference_id: PMID:16585190
      supporting_text: Signal transducer and activator of transcription 1 
        activation in endothelial cells is a negative regulator of angiogenesis
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:10973496
  review:
    summary: Nucleocytoplasmic translocation of STAT1 regulated by leucine-rich 
      export signal. Strong experimental evidence for STAT1's transcriptional 
      function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10973496
      supporting_text: Signal transducer and activator of transcription (Stat) 
        proteins are latent transcription factors that reside in the cytoplasm 
        before activation. On cytokine-induced tyrosine phosphorylation, these 
        molecules dimerize and accumulate transiently in the nucleus
- term:
    id: GO:0005164
    label: tumor necrosis factor receptor binding
  evidence_type: IPI
  original_reference_id: PMID:10848577
  review:
    summary: STAT1 as component of TNFR1-TRADD signaling complex to inhibit 
      NF-κB. While this shows STAT1 in TNF signaling context, this is not a core
      function compared to interferon signaling.
    action: KEEP_AS_NON_CORE
    reason: While STAT1 can participate in TNF receptor signaling complexes, 
      this represents cross-pathway interactions rather than STAT1's core 
      function. STAT1's primary role is as an interferon-responsive 
      transcription factor in JAK-STAT signaling, not TNF receptor binding. This
      interaction may be functionally relevant in specific contexts but is not a
      central molecular function.
    supported_by:
    - reference_id: PMID:10848577
      supporting_text: Stat1 as a component of tumor necrosis factor alpha 
        receptor 1-TRADD signaling complex to inhibit NF-kappaB activation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10848577
  review:
    summary: STAT1-TNFR interaction. Generic protein binding lacks functional 
      specificity for this cross-pathway interaction.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:10848577
      supporting_text: Stat1 as a component of tumor necrosis factor alpha 
        receptor 1-TRADD signaling complex to inhibit NF-kappaB activation.
- term:
    id: GO:0003690
    label: double-stranded DNA binding
  evidence_type: IDA
  original_reference_id: PMID:9630226
  review:
    summary: Crystal structure of STAT1 dimer bound to DNA shows double-stranded
      DNA binding. While accurate, the sequence-specific DNA binding terms are 
      more informative for STAT1's function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9630226
      supporting_text: The crystal structure of the DNA complex of a STAT-1 
        homodimer has been determined at 2.9 A resolution. STAT-1 utilizes a 
        DNA-binding domain with an immunoglobulin fold, similar to that of 
        NFkappaB and the p53 tumor suppressor protein
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:9630226
  review:
    summary: Crystal structure provides definitive evidence for STAT1 
      homodimerization through reciprocal SH2-phosphotyrosine interactions. This
      is a core molecular function.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9630226
      supporting_text: The STAT-1 dimer forms a contiguous C-shaped clamp around
        DNA that is stabilized by reciprocal and highly specific interactions 
        between the SH2 domain of one monomer and the C-terminal segment, 
        phosphorylated on tyrosine, of the other
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16531398
  review:
    summary: Tid1 isoforms as mitochondrial DnaJ-like chaperones interacting 
      with STAT1. Generic protein binding lacks functional context for this 
      chaperone interaction.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:16531398
      supporting_text: Epub 2006 Mar 10. Tid1 isoforms are mitochondrial 
        DnaJ-like chaperones with unique carboxyl termini that determine 
        cytosolic fate.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16306601
  review:
    summary: RSV-inducible BCL-3 antagonizing STAT/IRF and NF-κB signaling. 
      Pathogen-mediated interference with STAT1 signaling, but generic term 
      lacks specificity.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:16306601
      supporting_text: Respiratory syncytial virus-inducible BCL-3 expression 
        antagonizes the STAT/IRF and NF-kappaB signaling pathways by inducing 
        histone deacetylase 1 recruitment to the interleukin-8 promoter.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34521819
  review:
    summary: The generic protein binding term does not provide informative 
      functional annotation. STAT1 binds many specific proteins as part of its 
      transcription factor function, but this represents over-annotation. 
      Additionally, the referenced PMID:34521819 could not be retrieved and 
      verified.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0005515 (protein binding) is too general and uninformative for a 
      well-characterized transcription factor like STAT1. While STAT1 does 
      interact with many proteins (JAKs, co-activators, other STATs), this 
      generic term provides no functional insight. More specific binding terms 
      like "identical protein binding" or "enzyme binding" are more informative.
      Consistent with other protein binding annotations that are marked as 
      over-annotated rather than completely removed.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006952
    label: defense response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043434
    label: response to peptide hormone
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0051093
    label: negative regulation of developmental process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0051607
    label: defense response to virus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060333
    label: type II interferon-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: NAS
  original_reference_id: PMID:24058793
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:24058793
      supporting_text: 'STAT heterodimers in immunity: A mixed message or a unique
        signal? Delgoffe GM(1), Vignali DA.'
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: NAS
  original_reference_id: PMID:24058793
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:24058793
      supporting_text: 'STAT heterodimers in immunity: A mixed message or a unique
        signal? Delgoffe GM(1), Vignali DA.'
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:24065129
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:24065129
      supporting_text: IFNβ-dependent increases in STAT1, STAT2, and IRF9 
        mediate resistance to viruses and DNA damage.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007584
    label: response to nutrient
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008015
    label: blood circulation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0009612
    label: response to mechanical stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0032869
    label: cellular response to insulin stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0034097
    label: response to cytokine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042542
    label: response to hydrogen peroxide
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043434
    label: response to peptide hormone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045429
    label: positive regulation of nitric oxide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048661
    label: positive regulation of smooth muscle cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0051591
    label: response to cAMP
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0097696
    label: cell surface receptor signaling pathway via STAT
  evidence_type: IDA
  original_reference_id: PMID:18035482
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:18035482
      supporting_text: 'Epub 2007 Nov 26. Regulation of XAF1 expression in human colon
        cancer cell by interferon beta: activation by the transcription regulator
        STAT1.'
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: NAS
  original_reference_id: PMID:9630226
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:9630226
      supporting_text: Crystal structure of a tyrosine phosphorylated STAT-1 
        dimer bound to DNA.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: NAS
  original_reference_id: PMID:9630226
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:9630226
      supporting_text: Crystal structure of a tyrosine phosphorylated STAT-1 
        dimer bound to DNA.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:32209697
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:32209697
      supporting_text: Noncanonical STAT1 phosphorylation expands its 
        transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 
        production.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:32209697
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:32209697
      supporting_text: Noncanonical STAT1 phosphorylation expands its 
        transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 
        production.
- term:
    id: GO:0038111
    label: interleukin-7-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:29202461
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:29202461
      supporting_text: eCollection 2017 Nov 16.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IC
  original_reference_id: PMID:28753426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18035482
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:18035482
      supporting_text: 'Epub 2007 Nov 26. Regulation of XAF1 expression in human colon
        cancer cell by interferon beta: activation by the transcription regulator
        STAT1.'
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:23386060
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:23386060
      supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting 
        STAT1.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 
        phosphorylation in response to IFN-gamma.
- term:
    id: GO:0034341
    label: response to type II interferon
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 
        phosphorylation in response to IFN-gamma.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0035458
    label: cellular response to interferon-beta
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0071346
    label: cellular response to type II interferon
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 
        phosphorylation in response to IFN-gamma.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15322115
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:15322115
      supporting_text: 2004 Aug 20. Protein kinase Cdelta regulates apoptosis 
        via activation of STAT1.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:22002246
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:22002246
      supporting_text: Epub 2011 Oct 15. A novel disrupter of telomere silencing
        1-like (DOT1L) interaction is required for signal transducer and 
        activator of transcription 1 (STAT1)-activated gene expression.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IC
  original_reference_id: PMID:9535918
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:9535918
      supporting_text: Heteromerization of the gammac chain with the 
        interleukin-9 receptor alpha subunit leads to STAT activation and 
        prevention of apoptosis.
- term:
    id: GO:0038113
    label: interleukin-9-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:9535918
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:9535918
      supporting_text: Heteromerization of the gammac chain with the 
        interleukin-9 receptor alpha subunit leads to STAT activation and 
        prevention of apoptosis.
- term:
    id: GO:0070106
    label: interleukin-27-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:32270034
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:32270034
      supporting_text: 2020 Apr. IL-27 signaling activates skin cells to induce 
        innate antiviral proteins and protects against Zika virus infection.
- term:
    id: GO:1990841
    label: promoter-specific chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:26479788
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: ISA
  original_reference_id: GO_REF:0000113
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002230
    label: positive regulation of defense response to virus by host
  evidence_type: IMP
  original_reference_id: PMID:26479788
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0002230
    label: positive regulation of defense response to virus by host
  evidence_type: IGI
  original_reference_id: PMID:26479788
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:26479788
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IGI
  original_reference_id: PMID:26479788
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0060333
    label: type II interferon-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:26479788
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0032727
    label: positive regulation of interferon-alpha production
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0051607
    label: defense response to virus
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23386060
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:23386060
      supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting 
        STAT1.
- term:
    id: GO:0071346
    label: cellular response to type II interferon
  evidence_type: IDA
  original_reference_id: PMID:23386060
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:23386060
      supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting 
        STAT1.
- term:
    id: GO:0045648
    label: positive regulation of erythrocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:28283061
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28283061
      supporting_text: Functional Selectivity in Cytokine Signaling Revealed 
        Through a Pathogenic EPO Mutation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15825084
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:15825084
      supporting_text: Hepatitis C virus expression suppresses interferon 
        signaling by degrading STAT1.
- term:
    id: GO:0035456
    label: response to interferon-beta
  evidence_type: IMP
  original_reference_id: PMID:24882218
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:24882218
      supporting_text: 2014 May 29. Unanchored K48-linked polyubiquitin 
        synthesized by the E3-ubiquitin ligase TRIM6 stimulates the 
        interferon-IKKε kinase-mediated antiviral response.
- term:
    id: GO:0046725
    label: negative regulation by virus of viral protein levels in host cell
  evidence_type: IMP
  original_reference_id: PMID:15825084
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:15825084
      supporting_text: Hepatitis C virus expression suppresses interferon 
        signaling by degrading STAT1.
- term:
    id: GO:0035458
    label: cellular response to interferon-beta
  evidence_type: IMP
  original_reference_id: PMID:18035482
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:18035482
      supporting_text: 'Epub 2007 Nov 26. Regulation of XAF1 expression in human colon
        cancer cell by interferon beta: activation by the transcription regulator
        STAT1.'
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:18035482
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:18035482
      supporting_text: 'Epub 2007 Nov 26. Regulation of XAF1 expression in human colon
        cancer cell by interferon beta: activation by the transcription regulator
        STAT1.'
- term:
    id: GO:0060333
    label: type II interferon-mediated signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:18035482
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:18035482
      supporting_text: 'Epub 2007 Nov 26. Regulation of XAF1 expression in human colon
        cancer cell by interferon beta: activation by the transcription regulator
        STAT1.'
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001937
    label: negative regulation of endothelial cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:16585190
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:16585190
      supporting_text: Signal transducer and activator of transcription 1 
        activation in endothelial cells is a negative regulator of angiogenesis.
- term:
    id: GO:0002053
    label: positive regulation of mesenchymal cell proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003340
    label: negative regulation of mesenchymal to epithelial transition involved 
      in metanephros morphogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0016525
    label: negative regulation of angiogenesis
  evidence_type: IMP
  original_reference_id: PMID:16585190
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:16585190
      supporting_text: Signal transducer and activator of transcription 1 
        activation in endothelial cells is a negative regulator of angiogenesis.
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: TAS
  original_reference_id: PMID:12108949
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:12108949
      supporting_text: The role of STATs in apoptosis.
- term:
    id: GO:0061326
    label: renal tubule development
  evidence_type: IMP
  original_reference_id: PMID:20861313
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:20861313
      supporting_text: 2010 Sep 22. STAT1 is required for redifferentiation 
        during Madin-Darby canine kidney tubulogenesis.
- term:
    id: GO:0072136
    label: metanephric mesenchymal cell proliferation involved in metanephros 
      development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0072162
    label: metanephric mesenchymal cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0072308
    label: negative regulation of metanephric nephron tubule epithelial cell 
      differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:10692450
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:10692450
      supporting_text: Thrombin inhibits tumor cell growth in association with 
        up-regulation of p21(waf/cip1) and caspases via a p53-independent, 
        STAT-1-dependent pathway.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:10973496
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:10973496
      supporting_text: Nucleocytoplasmic translocation of Stat1 is regulated by 
        a leucine-rich export signal in the coiled-coil domain.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:10973496
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:10973496
      supporting_text: Nucleocytoplasmic translocation of Stat1 is regulated by 
        a leucine-rich export signal in the coiled-coil domain.
- term:
    id: GO:0033209
    label: tumor necrosis factor-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:10848577
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:10848577
      supporting_text: Stat1 as a component of tumor necrosis factor alpha 
        receptor 1-TRADD signaling complex to inhibit NF-kappaB activation.
- term:
    id: GO:0043124
    label: negative regulation of canonical NF-kappaB signal transduction
  evidence_type: IMP
  original_reference_id: PMID:10848577
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:10848577
      supporting_text: Stat1 as a component of tumor necrosis factor alpha 
        receptor 1-TRADD signaling complex to inhibit NF-kappaB activation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:21268089
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:21268089
      supporting_text: Molecular mechanisms underlying the inhibition of 
        IFN-γ-induced, STAT1-mediated gene transcription in human macrophages by
        simvastatin and agonists of PPARs and LXRs.
- term:
    id: GO:0060333
    label: type II interferon-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:21268089
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:21268089
      supporting_text: Molecular mechanisms underlying the inhibition of 
        IFN-γ-induced, STAT1-mediated gene transcription in human macrophages by
        simvastatin and agonists of PPARs and LXRs.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16306601
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:16306601
      supporting_text: Respiratory syncytial virus-inducible BCL-3 expression 
        antagonizes the STAT/IRF and NF-kappaB signaling pathways by inducing 
        histone deacetylase 1 recruitment to the interleukin-8 promoter.
- term:
    id: GO:0070721
    label: ISGF3 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0090575
    label: RNA polymerase II transcription regulator complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0090575
    label: RNA polymerase II transcription regulator complex
  evidence_type: IPI
  original_reference_id: PMID:8662591
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:8662591
      supporting_text: Differential activation of acute phase response 
        factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 
        signal transducer gp130.
- term:
    id: GO:0070721
    label: ISGF3 complex
  evidence_type: IPI
  original_reference_id: PMID:24065129
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:24065129
      supporting_text: IFNβ-dependent increases in STAT1, STAT2, and IRF9 
        mediate resistance to viruses and DNA damage.
- term:
    id: GO:0090575
    label: RNA polymerase II transcription regulator complex
  evidence_type: NAS
  original_reference_id: PMID:24058793
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:24058793
      supporting_text: 'STAT heterodimers in immunity: A mixed message or a unique
        signal? Delgoffe GM(1), Vignali DA.'
- term:
    id: GO:0030424
    label: axon
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0090575
    label: RNA polymerase II transcription regulator complex
  evidence_type: IPI
  original_reference_id: PMID:9630226
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:9630226
      supporting_text: Crystal structure of a tyrosine phosphorylated STAT-1 
        dimer bound to DNA.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:32209697
  review:
    summary: STAT1 resides in the cytoplasm in its inactive state and becomes 
      activated upon phosphorylation by JAK kinases. It must be present in the 
      cytoplasm to receive signals from cytokine receptors and before 
      translocating to the nucleus.
    action: ACCEPT
    reason: Cytoplasmic localization is essential for STAT1's signaling 
      mechanism, as it must be available in the cytoplasm to be phosphorylated 
      by activated JAK kinases and to form dimers before nuclear translocation 
      for transcriptional regulation.
    supported_by:
    - reference_id: PMID:32209697
      supporting_text: Noncanonical STAT1 phosphorylation expands its 
        transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 
        production.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9851142
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985981
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985983
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9865524
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985900
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985943
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985966
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985981
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985983
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985988
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9865511
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:26479788
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:27796300
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:27796300
      supporting_text: PARP9 and PARP14 cross-regulate macrophage activation via
        STAT1 ADP-ribosylation.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:26479788
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:26479788
      supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ 
        and viral 3C protease to enhance interferon signaling and control viral 
        infection.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:28753426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:28753426
      supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is 
        Critical for Interferon Antiviral Activity.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:23386060
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:23386060
      supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting 
        STAT1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987218
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1112565
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1112602
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1169406
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1433456
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1470009
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1678841
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1888198
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380782
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788571
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788582
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6790041
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950441
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950453
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950485
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950518
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950522
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8983835
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8983841
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8983845
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8983983
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8983996
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8984014
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8984021
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8984023
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8985929
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8986985
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987007
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987080
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987097
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987150
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987218
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987230
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987255
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987266
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8987270
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9006870
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9006873
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9670412
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9670416
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9672159
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9672176
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9729454
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9835443
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1112587
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788623
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950522
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950733
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9021334
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17275127
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:17275127
      supporting_text: Dec 14. HCV NS5A inhibits interferon-alpha signaling 
        through suppression of STAT1 phosphorylation in hepatocyte-derived cell 
        lines.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17275127
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:17275127
      supporting_text: Dec 14. HCV NS5A inhibits interferon-alpha signaling 
        through suppression of STAT1 phosphorylation in hepatocyte-derived cell 
        lines.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15825084
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:15825084
      supporting_text: Hepatitis C virus expression suppresses interferon 
        signaling by degrading STAT1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1015699
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1031713
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1470012
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-873917
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-877281
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-909721
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-913529
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9670426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-997326
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1112727
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1470010
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1470012
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-873917
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-873921
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-873922
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-873927
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-909552
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-909718
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-909721
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-909722
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-909725
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-909726
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-913529
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9670417
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9670426
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9710959
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9710963
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-997309
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1112538
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1112587
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1112604
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788622
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788623
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6788628
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950733
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8950782
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:10692450
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:10692450
      supporting_text: Thrombin inhibits tumor cell growth in association with 
        up-regulation of p21(waf/cip1) and caspases via a p53-independent, 
        STAT-1-dependent pathway.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:10973496
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
    supported_by:
    - reference_id: PMID:10973496
      supporting_text: Nucleocytoplasmic translocation of Stat1 is regulated by 
        a leucine-rich export signal in the coiled-coil domain.
- term:
    id: GO:0045087
    label: innate immune response
  evidence_type: IEA
  review:
    summary: Essential mediator of innate immune responses through interferon 
      signaling pathway activation and antimicrobial gene expression
    action: NEW
    reason: STAT1 is a central component of the innate immune response, serving 
      as the key transcriptional mediator for both type I (IFN-α/β) and type II 
      (IFN-γ) interferon signaling pathways. Upon pathogen recognition, STAT1 is
      activated by JAK kinases and translocates to the nucleus to induce 
      expression of interferon-stimulated genes (ISGs) that establish antiviral 
      and antimicrobial states. STAT1 knockout studies demonstrate its 
      non-redundant role in host defense against viruses, bacteria, and fungi, 
      making it essential for innate immunity.
    supported_by:
    - reference_id: PMID:21903422
      supporting_text: Mapping a dynamic innate immunity protein interaction 
        network regulating type I interferon production.
    - reference_id: PMID:23386060
      supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting 
        STAT1.
core_functions:
- description: Master transcriptional regulator of interferon responses and 
    cytokine signaling
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0071345
    label: cellular response to cytokine stimulus
  - id: GO:0060337
    label: type I interferon-mediated signaling pathway
  - id: GO:0060333
    label: type II interferon-mediated signaling pathway
  - id: GO:0045087
    label: innate immune response
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/STAT1/STAT1-deep-research.md
    supporting_text: STAT1 regulates a vast network of target genes, with over 
      300 interferon-stimulated genes (ISGs) identified through experimental 
      validation including IRF1, ISG15, MX1, OAS1, and CXCL10
  - reference_id: PMID:32209697
    supporting_text: STAT1 phosphorylated at Thr749 directly enhanced 
      transcription of the gene encoding IL-12p40 (IL12B) and facilitated the 
      binding of STAT1 to a noncanonical DNA motif in promoter regions
    full_text_unavailable: true
- description: SH2 domain-mediated homodimerization and heterodimerization 
    essential for transcriptional activation
  molecular_function:
    id: GO:0042803
    label: protein homodimerization activity
  directly_involved_in:
  - id: GO:0046427
    label: positive regulation of receptor signaling pathway via JAK-STAT
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:9630226
    supporting_text: The STAT-1 dimer forms a contiguous C-shaped clamp around 
      DNA that is stabilized by reciprocal and highly specific interactions 
      between the SH2 domain of one monomer and the C-terminal segment, 
      phosphorylated on tyrosine, of the other
  - reference_id: PMID:8605877
    supporting_text: the SH2 domain of Stat1 and Stat2 can mediate homo- as well
      as heterodimerization, suggest that a single SH2 domain-phosphotyrosyl 
      interaction is sufficient for dimerization
- description: Sequence-specific DNA binding to interferon-responsive regulatory
    elements (GAS and ISRE)
  molecular_function:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  directly_involved_in:
  - id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:9630226
    supporting_text: STAT-1 utilizes a DNA-binding domain with an immunoglobulin
      fold, similar to that of NFkappaB and the p53 tumor suppressor protein
  - reference_id: file:human/STAT1/STAT1-deep-research.md
    supporting_text: STAT1 demonstrates remarkable functional versatility 
      through its ability to form different transcriptional complexes - STAT1 
      homodimers (GAF) respond to IFN-γ and bind GAS elements, while STAT1:STAT2
      heterodimers combine with IRF9 to form ISGF3 complex responding to type I 
      interferons and binding ISRE sequences
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms.
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara.
  findings: []
- id: GO_REF:0000113
  title: Gene Ontology annotation of human sequence-specific DNA binding 
    transcription factors (DbTFs) based on the TFClass database
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning 
    models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods.
  findings: []
- id: PMID:10848577
  title: Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD 
    signaling complex to inhibit NF-kappaB activation.
  findings: []
- id: PMID:10973496
  title: Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich
    export signal in the coiled-coil domain.
  findings: []
- id: PMID:11238845
  title: 'Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase
    reverses Stat1 activation.'
  findings: []
- id: PMID:11972023
  title: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in 
    response to IFN-gamma.
  findings: []
- id: PMID:12070153
  title: Identification of both positive and negative domains within the 
    epidermal growth factor receptor COOH-terminal region for signal transducer 
    and activator of transcription (STAT) activation.
  findings: []
- id: PMID:12788789
  title: STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene 
    activation.
  findings: []
- id: PMID:12867595
  title: The cell death regulator GRIM-19 is an inhibitor of signal transducer 
    and activator of transcription 3.
  findings: []
- id: PMID:15780933
  title: Structural bases of unphosphorylated STAT1 association and receptor 
    binding.
  findings: []
- id: PMID:15825084
  title: Hepatitis C virus expression suppresses interferon signaling by 
    degrading STAT1.
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction 
    network.
  findings: []
- id: PMID:16257975
  title: The conserved Leu-724 residue is required for both serine 
    phosphorylation and co-activator recruitment for Stat1-mediated 
    transcription activation in response to interferon-gamma.
  findings: []
- id: PMID:16273093
  title: A quantitative protein interaction network for the ErbB receptors using
    protein microarrays.
  findings: []
- id: PMID:16306601
  title: Respiratory syncytial virus-inducible BCL-3 expression antagonizes the 
    STAT/IRF and NF-kappaB signaling pathways by inducing histone deacetylase 1 
    recruitment to the interleukin-8 promoter.
  findings: []
- id: PMID:16531398
  title: Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique 
    carboxyl termini that determine cytosolic fate.
  findings: []
- id: PMID:16585190
  title: Signal transducer and activator of transcription 1 activation in 
    endothelial cells is a negative regulator of angiogenesis.
  findings: []
- id: PMID:16940534
  title: Hepatitis C virus core protein blocks interferon signaling by 
    interaction with the STAT1 SH2 domain.
  findings: []
- id: PMID:17275127
  title: HCV NS5A inhibits interferon-alpha signaling through suppression of 
    STAT1 phosphorylation in hepatocyte-derived cell lines.
  findings: []
- id: PMID:17596301
  title: Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 
    function by sequestering nuclear import factors on the rough endoplasmic 
    reticulum/Golgi membrane.
  findings: []
- id: PMID:17923090
  title: Acetylation-dependent signal transduction for type I interferon 
    receptor.
  findings: []
- id: PMID:18035482
  title: 'Regulation of XAF1 expression in human colon cancer cell by interferon beta:
    activation by the transcription regulator STAT1.'
  findings: []
- id: PMID:20195357
  title: A comprehensive resource of interacting protein regions for refining 
    human transcription factor networks.
  findings: []
- id: PMID:20576130
  title: Activated networking of platelet activating factor receptor and 
    FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian 
    epithelium.
  findings: []
- id: PMID:21268089
  title: Molecular mechanisms underlying the inhibition of IFN-γ-induced, 
    STAT1-mediated gene transcription in human macrophages by simvastatin and 
    agonists of PPARs and LXRs.
  findings: []
- id: PMID:21903422
  title: Mapping a dynamic innate immunity protein interaction network 
    regulating type I interferon production.
  findings: []
- id: PMID:21988832
  title: Toward an understanding of the protein interaction network of the human
    liver.
  findings: []
- id: PMID:22002246
  title: A novel disrupter of telomere silencing 1-like (DOT1L) interaction is 
    required for signal transducer and activator of transcription 1 
    (STAT1)-activated gene expression.
  findings: []
- id: PMID:23386060
  title: hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.
  findings: []
- id: PMID:24065129
  title: IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance 
    to viruses and DNA damage.
  findings: []
- id: PMID:24360797
  title: Hepatic RIG-I predicts survival and interferon-α therapeutic response 
    in hepatocellular carcinoma.
  findings: []
- id: PMID:24658140
  title: The mammalian-membrane two-hybrid assay (MaMTH) for probing 
    membrane-protein interactions in human cells.
  findings: []
- id: PMID:25241761
  title: Using an in situ proximity ligation assay to systematically profile 
    endogenous protein-protein interactions in a pathway network.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25468996
  title: E-cadherin interactome complexity and robustness resolved by 
    quantitative proteomics.
  findings: []
- id: PMID:25609649
  title: Proteomic analyses reveal distinct chromatin-associated and soluble 
    transcription factor complexes.
  findings: []
- id: PMID:26479788
  title: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C 
    protease to enhance interferon signaling and control viral infection.
  findings: []
- id: PMID:26889034
  title: VP8, the Major Tegument Protein of Bovine Herpesvirus 1, Interacts with
    Cellular STAT1 and Inhibits Interferon Beta Signaling.
  findings: []
- id: PMID:26966684
  title: 'PIPINO: A Software Package to Facilitate the Identification of Protein-Protein
    Interactions from Affinity Purification Mass Spectrometry Data.'
  findings: []
- id: PMID:28753426
  title: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for 
    Interferon Antiviral Activity.
  findings: []
- id: PMID:31980649
  title: Extensive rewiring of the EGFR network in colorectal cancer cells 
    expressing transforming levels of KRAS(G13D).
  findings: []
- id: PMID:32209697
  title: Noncanonical STAT1 phosphorylation expands its transcriptional activity
    into promoting LPS-induced IL-6 and IL-12p40 production.
  findings: []
- id: PMID:32953130
  title: SARS-CoV-2 N protein antagonizes type I interferon signaling by 
    suppressing phosphorylation and nuclear translocation of STAT1 and STAT2.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the 
    human interactome.
  findings: []
- id: PMID:34950606
  title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane 
    (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response.
  findings: []
- id: PMID:35140242
  title: Human transcription factor protein interaction networks.
  findings: []
- id: PMID:8156998
  title: Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the 
    receptor to its signal transduction system (p91).
  findings: []
- id: PMID:8605877
  title: The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the
    transduction of IFN-alpha signals.
  findings: []
- id: PMID:8662591
  title: Differential activation of acute phase response factor/STAT3 and STAT1 
    via the cytoplasmic domain of the interleukin 6 signal transducer gp130. I. 
    Definition of a novel phosphotyrosine motif mediating STAT1 activation.
  findings: []
- id: PMID:9121453
  title: Functional subdomains of STAT2 required for preassociation with the 
    alpha interferon receptor and for signaling.
  findings: []
- id: PMID:9535918
  title: Heteromerization of the gammac chain with the interleukin-9 receptor 
    alpha subunit leads to STAT activation and prevention of apoptosis.
  findings: []
- id: PMID:9630226
  title: Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to 
    DNA.
  findings: []
- id: PMID:34521819
  title: Could not retrieve title - publication not available
  findings: []
- id: PMID:9881977
  title: Direct suppression of Stat1 function during adenoviral infection.
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity.
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
    Location vocabulary mapping, accompanied by conservative changes to GO terms
    applied by UniProt.
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: PMID:10692450
  title: Thrombin inhibits tumor cell growth in association with up-regulation 
    of p21(waf/cip1) and caspases via a p53-independent, STAT-1-dependent 
    pathway.
  findings: []
- id: PMID:12108949
  title: The role of STATs in apoptosis.
  findings: []
- id: PMID:15322115
  title: Protein kinase Cdelta regulates apoptosis via activation of STAT1.
  findings: []
- id: PMID:20861313
  title: STAT1 is required for redifferentiation during Madin-Darby canine 
    kidney tubulogenesis.
  findings: []
- id: PMID:24058793
  title: 'STAT heterodimers in immunity: A mixed message or a unique signal?'
  findings: []
- id: PMID:24882218
  title: Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin 
    ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral 
    response.
  findings: []
- id: PMID:28283061
  title: Functional Selectivity in Cytokine Signaling Revealed Through a 
    Pathogenic EPO Mutation.
  findings: []
- id: PMID:29202461
  title: IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell 
    expansion.
  findings: []
- id: PMID:32270034
  title: IL-27 signaling activates skin cells to induce innate antiviral 
    proteins and protects against Zika virus infection.
  findings: []
- id: PMID:27796300
  title: PARP9 and PARP14 cross-regulate macrophage activation via STAT1 
    ADP-ribosylation.
  findings: []
- id: Reactome:R-HSA-1015699
  title: ISGF3 binds the ISRE promoter elements in IFN-stimulated genes
  findings: []
- id: Reactome:R-HSA-1031713
  title: GAF binds the GAS promoter elements in the IFNG-regulated genes
  findings: []
- id: Reactome:R-HSA-1112538
  title: Phosphorylated STAT1, STAT3 form dimers
  findings: []
- id: Reactome:R-HSA-1112565
  title: Tyrosine phosphorylated IL6ST binds STAT1,STAT3
  findings: []
- id: Reactome:R-HSA-1112587
  title: STAT1 and STAT3 dimers translocate to the nucleus
  findings: []
- id: Reactome:R-HSA-1112602
  title: Tyrosine phosphorylation of STAT1, STAT3 by IL6 receptor
  findings: []
- id: Reactome:R-HSA-1112604
  title: Phosphorylated STATs are released
  findings: []
- id: Reactome:R-HSA-1112727
  title: Serine phosphorylation of STATs
  findings: []
- id: Reactome:R-HSA-1169406
  title: ISGylation of host proteins
  findings: []
- id: Reactome:R-HSA-1433456
  title: Recruitment of STATs
  findings: []
- id: Reactome:R-HSA-1470009
  title: Phosphorylation of STATs
  findings: []
- id: Reactome:R-HSA-1470010
  title: Dimerization of STATs
  findings: []
- id: Reactome:R-HSA-1470012
  title: Disassociation and translocation of STATs to the nucleus
  findings: []
- id: Reactome:R-HSA-1678841
  title: Regulation of protein ISGylation by ISG15 deconjugating enzyme USP18
  findings: []
- id: Reactome:R-HSA-1888198
  title: FGFR1OP-FGFR1 phosphorylates STAT1 and STAT3
  findings: []
- id: Reactome:R-HSA-380782
  title: STAT binds to the active receptor
  findings: []
- id: Reactome:R-HSA-6788571
  title: STAT1,STAT3,STAT6 bind IL13:IL13R type II
  findings: []
- id: Reactome:R-HSA-6788582
  title: STAT1,STAT3,STAT6 phosphorylation
  findings: []
- id: Reactome:R-HSA-6788622
  title: p-Y-STATs dimerize
  findings: []
- id: Reactome:R-HSA-6788623
  title: p-Y-STATs translocate to nucleus
  findings: []
- id: Reactome:R-HSA-6788628
  title: p-Y-STATs dissociate
  findings: []
- id: Reactome:R-HSA-6790041
  title: Expression of STAT3-upregulated cytosolic proteins
  findings: []
- id: Reactome:R-HSA-873917
  title: Translocation of STAT1 dimer to nucleus
  findings: []
- id: Reactome:R-HSA-873921
  title: Binding of STAT1 to p-IFNGR1
  findings: []
- id: Reactome:R-HSA-873922
  title: Phosphorylation of STAT1 by JAK kinases
  findings: []
- id: Reactome:R-HSA-873927
  title: Release of STAT1 dimer from active receptor unit
  findings: []
- id: Reactome:R-HSA-877281
  title: PIAS1 binds p-STAT1 dimer
  findings: []
- id: Reactome:R-HSA-8950441
  title: p-Y701-STAT1 and p-Y705-STAT3 dissociate from IL27:IL27 receptor
  findings: []
- id: Reactome:R-HSA-8950453
  title: JAK1/JAK2 bound to IL12RB2:IL6ST receptor phosphorylates STAT1 and 
    STAT4
  findings: []
- id: Reactome:R-HSA-8950485
  title: STAT3 and STAT1 are phosphorylated by JAKs after IL27:IL27R interaction
  findings: []
- id: Reactome:R-HSA-8950518
  title: STAT1, STAT3 bind p-Y611-IL27RA from Interleukin-27:Interleukin-27 
    receptor complex
  findings: []
- id: Reactome:R-HSA-8950522
  title: p-STAT1:p-STAT4 translocates to the nucleus
  findings: []
- id: Reactome:R-HSA-8950733
  title: p-Y701-STAT1:p-Y705-STAT3 translocates to the nucleus
  findings: []
- id: Reactome:R-HSA-8950782
  title: p-STAT1 binds p-STAT3
  findings: []
- id: Reactome:R-HSA-8983835
  title: JAK1/JAK2/TYK2 bound to IL6ST:IL6ST phosphorylate STAT1
  findings: []
- id: Reactome:R-HSA-8983841
  title: STAT1 associates with IL6ST:IL6ST
  findings: []
- id: Reactome:R-HSA-8983845
  title: p-STAT1 dissociates from IL6ST:IL6ST
  findings: []
- id: Reactome:R-HSA-8983983
  title: p-STAT1 and p-STAT4 dissociate from IL12RB2:IL6ST receptor
  findings: []
- id: Reactome:R-HSA-8983996
  title: STAT1 and STAT4 associate with IL12RB2:IL6ST receptor
  findings: []
- id: Reactome:R-HSA-8984014
  title: JAK1,JAK2 bound to IL27RA:IL12RB2 receptor phosphorylate STAT1,STAT3
  findings: []
- id: Reactome:R-HSA-8984021
  title: STAT1,STAT3 associate with IL27RA:IL12RB2 receptor
  findings: []
- id: Reactome:R-HSA-8984023
  title: p-STAT1, p-STAT3 dissociate from IL27RA:IL12RB2 receptor
  findings: []
- id: Reactome:R-HSA-8985900
  title: p-Y701-STAT1, p-Y705-STAT3, p-Y649-STAT5 dissociates from 
    IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3:p-Y705-STAT3
  findings: []
- id: Reactome:R-HSA-8985929
  title: IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3 binds STAT1, STAT3, STAT5A or
    STAT5B
  findings: []
- id: Reactome:R-HSA-8985943
  title: p-Y701-STAT1 dimerizes
  findings: []
- id: Reactome:R-HSA-8985966
  title: p-Y701-STAT1 binds p-Y705-STAT3
  findings: []
- id: Reactome:R-HSA-8985981
  title: p-Y701-STAT1:p-Y705-STAT3 translocates from the cytosol to the nucleus
  findings: []
- id: Reactome:R-HSA-8985983
  title: p-Y701-STAT1 dimer translocates from the cytosol to the nucleus
  findings: []
- id: Reactome:R-HSA-8985988
  title: IL9:p-Y116-IL9R:JAK1:IL2RG:p-904,939-JAK3:STAT3 phosphorylates STAT1, 
    STAT3 or STAT5
  findings: []
- id: Reactome:R-HSA-8986985
  title: IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:STAT1 phosphorylates 
    STAT1, STAT2, STAT3, STAT4 and STAT5
  findings: []
- id: Reactome:R-HSA-8987007
  title: p-STAT1 dimerizes
  findings: []
- id: Reactome:R-HSA-8987033
  title: p-STAT1, p-Y-STAT2, p-STAT3, p-STAT4, p-STAT5 dissociates from 
    IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:p-STAT1,p-STAT2,p-STAT3,p-STAT4,p-STAT5
  findings: []
- id: Reactome:R-HSA-8987080
  title: IL26:IL10RB:p-TYK2:IL20RA:p-JAK1 binds STAT1, STAT3
  findings: []
- id: Reactome:R-HSA-8987097
  title: IL24:p-IL20RA:p-JAK1:IL20RB binds STAT1,STAT3
  findings: []
- id: Reactome:R-HSA-8987150
  title: IL24:IL20RA:p-JAK1:IL20RB:STAT1,STAT3 phosphorylates STAT1 or STAT3
  findings: []
- id: Reactome:R-HSA-8987218
  title: p-STAT1 dimer translocates from the cytosol to the nucleoplasm
  findings: []
- id: Reactome:R-HSA-8987230
  title: p-STAT1 and p-STAT3 dissociates from IL26:IL10RB:p-TYK2:IL20RA:p-JAK1
  findings: []
- id: Reactome:R-HSA-8987255
  title: IL26:IL10RB:p-TYK2:IL20RA:p-JAK1:STAT1,STAT3  phosphorylates 
    STAT1,STAT3
  findings: []
- id: Reactome:R-HSA-8987266
  title: IFNL1:p-Y434,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2 binds STAT1, STAT2, 
    STAT3, STAT4, STAT5
  findings: []
- id: Reactome:R-HSA-8987270
  title: p-STAT1,p-STAT3 dissociate from 
    IL24:IL20RA:p-Y1022,Y1023-JAK1:IL20RB:p-STAT1, p-STAT3
  findings: []
- id: Reactome:R-HSA-9006870
  title: IL21 receptor STAT phosphorylation
  findings: []
- id: Reactome:R-HSA-9006873
  title: IL21 receptor STAT binding
  findings: []
- id: Reactome:R-HSA-9021334
  title: STAT1 binds HEY1 gene promoter
  findings: []
- id: Reactome:R-HSA-909552
  title: Phosphorylation of STAT1 at Ser727
  findings: []
- id: Reactome:R-HSA-909718
  title: Formation of p-STAT1 homodimer
  findings: []
- id: Reactome:R-HSA-909721
  title: Translocation of ISGF3 complex to nucleus
  findings: []
- id: Reactome:R-HSA-909722
  title: Release of p-STAT2:p-STAT1 dimer
  findings: []
- id: Reactome:R-HSA-909725
  title: Interaction of IRF9 with p-STAT2:p-STAT1
  findings: []
- id: Reactome:R-HSA-909726
  title: Phosphorylation of STAT1
  findings: []
- id: Reactome:R-HSA-913529
  title: Translocation of p-STAT1:p-STAT1 dimer to nucleus
  findings: []
- id: Reactome:R-HSA-9670412
  title: Phosphorylation of STATs downstream of KIT mutants
  findings: []
- id: Reactome:R-HSA-9670416
  title: Recruitment of STATs by KIT mutants
  findings: []
- id: Reactome:R-HSA-9670417
  title: Dimerization of STATs downstream of KIT mutants
  findings: []
- id: Reactome:R-HSA-9670426
  title: Disassociation and translocation of STATs to the nucleus downstream of 
    KIT mutants
  findings: []
- id: Reactome:R-HSA-9672159
  title: 'STAT binds to p-11Y PDGFRA extracellular domain dimers '
  findings: []
- id: Reactome:R-HSA-9672176
  title: STAT binds to the mutant PDGFRA receptor
  findings: []
- id: Reactome:R-HSA-9710959
  title: p-STAT1 dimer binds KPNA1
  findings: []
- id: Reactome:R-HSA-9710963
  title: p-STAT1dimer:KPNA1 binds KPNB1
  findings: []
- id: Reactome:R-HSA-9729454
  title: SARS-CoV-2 N protein binds STAT1, STAT2
  findings: []
- id: Reactome:R-HSA-9835443
  title: STAT1,STAT3 binds PKR
  findings: []
- id: Reactome:R-HSA-9851142
  title: TYK2-dependent STAT1 and STAT3 phosphorylation
  findings: []
- id: Reactome:R-HSA-9865511
  title: Phosphorylation of STAT1 on tyrosine-701 is enhanced by p-S172-IKBKE
  findings: []
- id: Reactome:R-HSA-9865524
  title: p-Y701-STAT1 binds the NLRP3 gene
  findings: []
- id: Reactome:R-HSA-997309
  title: Dephosphorylation of STAT1 by SHP2
  findings: []
- id: Reactome:R-HSA-997326
  title: Dephosphorylation of p-STAT1 dimer by nuclear isoform of TCPTP
  findings: []
suggested_questions:
- question: How does STAT1 achieve gene-specific transcriptional regulation and 
    what determines its chromatin binding specificity?
- question: What are the molecular mechanisms that distinguish STAT1 homodimer 
    from STAT1-STAT2 heterodimer function?
- question: How do post-translational modifications of STAT1 regulate its 
    nuclear translocation, DNA binding, and transcriptional activity?
- question: What role does STAT1 play in balancing immune activation versus 
    immunosuppression in different disease contexts?
suggested_experiments:
- description: ChIP-seq combined with RNA-seq to map genome-wide STAT1 binding 
    sites and correlate with transcriptional outcomes in different immune 
    contexts
- description: Single-molecule imaging of STAT1 nuclear translocation and 
    chromatin binding dynamics in response to interferon stimulation
- description: Cryo-EM structural determination of STAT1 dimers bound to DNA and
    associated transcriptional co-regulators
- description: Mass spectrometry-based analysis of STAT1 post-translational 
    modifications and their effects on protein stability and activity
status: COMPLETE