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
  - 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