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 - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 homodimers** (historically **GAF**, gamma-interferon activation factor) bind **GAS** (gamma-activated sequence) DNA elements qualifier: enables - 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 - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1’s primary biochemical function is **sequence-specific transcriptional regulation** as part of IFN-activated transcription factor complexes (GAF and ISGF3), controlling expression of interferon-stimulated genes (ISGs). qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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 qualifier: enables - 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.' qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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.' qualifier: enables - 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). qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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). qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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 - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- receptor docking (via SH2), dimerization (via phosphotyrosine–SH2 interactions), DNA binding, and transcriptional activation qualifier: enables - 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 qualifier: enables - 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 qualifier: enables - 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 qualifier: enables - 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 qualifier: enables - 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 - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 is a signal transducer and transcription factor that is activated downstream of cytokine receptors (classically IFN receptors) via receptor-associated **Janus kinases (JAKs)**, leading to STAT phosphorylation, dimerization, nuclear translocation, and transcriptional regulation of IFN-responsive genes. qualifier: acts_upstream_of_or_within - 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 qualifier: enables - 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 qualifier: enables - 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 qualifier: enables - 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, reflecting STAT1's role in promoting JAK-STAT pathway signaling. This annotation is flagged retired:true in GOA. Per PR #831 review feedback, a retired annotation should not be ACCEPTed as-is; changed to MODIFY pointing at the current active form of the term (GO:0046427 was relabeled from "positive regulation of JAK-STAT cascade" to "positive regulation of receptor signaling pathway via JAK-STAT"). action: MODIFY proposed_replacement_terms: - id: GO:0046427 label: positive regulation of receptor signaling pathway via JAK-STAT 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 qualifier: enables - 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 qualifier: enables - 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. qualifier: enables - 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 qualifier: enables - 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 qualifier: enables - 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 qualifier: enables - 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 qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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 qualifier: is_active_in - 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 qualifier: enables - 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 qualifier: enables - term: id: GO:0042393 label: histone binding evidence_type: IPI original_reference_id: PMID:26479788 review: summary: | The IPI histone-binding annotation derives from PMID:26479788, which shows the PARP9-DTX3L ubiquitin ligase (not STAT1) directly targets histone H2BJ. STAT1 forms a complex with PARP9, so the histone co-recovery most likely reflects indirect association via the PARP9 complex rather than a direct STAT1-histone interaction. Per PR #831 review feedback, downgraded ACCEPT → MARK_AS_OVER_ANNOTATED to reflect the indirect nature. (The companion GO:0035035 histone acetyltransferase binding annotation, supported by STAT1 recruiting p300/CBP, remains ACCEPT.) action: MARK_AS_OVER_ANNOTATED reason: | Direct STAT1-histone binding is not demonstrated; PMID:26479788 shows PARP9-DTX3L targeting histone H2BJ, with STAT1 present in the complex. The histone-binding IPI most plausibly reflects indirect complex co-recovery, not a direct STAT1 molecular function. 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 qualifier: enables - 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 qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - 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 - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus** qualifier: enables - 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. qualifier: enables - 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' qualifier: enables - 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. qualifier: enables - 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 qualifier: involved_in - 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 qualifier: enables - 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 qualifier: enables - 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. qualifier: enables - 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 qualifier: enables - 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 qualifier: enables - 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. qualifier: enables - 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. qualifier: enables - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34521819 review: summary: | The generic protein binding annotation is supported by PMID:34521819, which could not be retrieved and verified. Per the schema convention ("ALWAYS USE UNDECIDED IF YOU ARE UNABLE TO ACCESS RELEVANT PUBLICATIONS") and PR #831 review feedback, the action is set to UNDECIDED rather than MARK_AS_OVER_ANNOTATED until the underlying publication can be accessed and the interaction assessed. action: UNDECIDED reason: | The supporting publication PMID:34521819 could not be retrieved or verified, so the annotation cannot be evaluated. Although generic GO:0005515 protein binding is uninformative in general, the schema requires UNDECIDED when the relevant publication is inaccessible. qualifier: enables - term: id: GO:0005634 label: nucleus evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: STAT1 translocates to the nucleus upon activation to act as a transcription factor at GAS/ISRE elements. Nuclear localization is a core, well-established site of STAT1 action. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 executes its transcriptional role in the **nucleus** at IFN-responsive promoters/enhancers. qualifier: is_active_in - term: id: GO:0006357 label: regulation of transcription by RNA polymerase II evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: STAT1 directly regulates RNA polymerase II-dependent transcription of interferon-stimulated genes. Core function. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1’s primary biochemical function is **sequence-specific transcriptional regulation** as part of IFN-activated transcription factor complexes (GAF and ISGF3), controlling expression of interferon-stimulated genes (ISGs). qualifier: involved_in - term: id: GO:0007259 label: cell surface receptor signaling pathway via JAK-STAT evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: STAT1 is the canonical signal transducer of the JAK-STAT cell surface receptor signaling pathway, activated by interferon and other cytokine receptors via receptor-associated Janus kinases. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 is a signal transducer and transcription factor that is activated downstream of cytokine receptors (classically IFN receptors) via receptor-associated **Janus kinases (JAKs)**, leading to STAT phosphorylation, dimerization, nuclear translocation, and transcriptional regulation of IFN-responsive genes. qualifier: involved_in - term: id: GO:0006952 label: defense response evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: STAT1 is essential for host defense, particularly via interferon-driven antiviral, antibacterial and antifungal gene expression. AR complete STAT1 deficiency abolishes IFN responses with severe infection susceptibility. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- A 2024 review summarizes **autosomal recessive complete STAT1 deficiency** as abolishing type I/II/III IFN and IL-27 signaling qualifier: involved_in - term: id: GO:0005737 label: cytoplasm evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: Latent STAT1 is cytoplasmic and acts in the cytoplasm to receive cytokine-receptor-driven JAK phosphorylation prior to nuclear translocation. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- In resting cells, STAT1 is largely cytoplasmic or shuttling in unphosphorylated/preassociated forms; after tyrosine phosphorylation it forms dimers that **translocate to the nucleus**. qualifier: is_active_in - term: id: GO:0042127 label: regulation of cell population proliferation evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: >- STAT1 generally exerts antiproliferative effects downstream of interferon signaling (e.g. induction of p21 and cell-cycle inhibitors), consistent with this phylogenetically inferred role in regulating cell population proliferation. action: KEEP_AS_NON_CORE reason: >- Regulation of cell proliferation is a downstream physiological consequence of STAT1-driven gene expression rather than its core molecular activity; the IBA term is biologically sound but represents a non-core pleiotropic output. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1's primary biochemical function is **sequence-specific transcriptional regulation** as part of IFN-activated transcription factor complexes (GAF and ISGF3), controlling expression of interferon-stimulated genes (ISGs). qualifier: involved_in - term: id: GO:0043434 label: response to peptide hormone evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: >- STAT1 can be activated downstream of peptide-hormone receptors (e.g. growth hormone, leptin, insulin-related signaling) that engage the JAK-STAT pathway, supporting a response to peptide hormone. action: KEEP_AS_NON_CORE reason: >- STAT1 participation in peptide-hormone responses reflects the broad use of the JAK-STAT module by many receptors; it is a peripheral, context-dependent role rather than STAT1's core interferon function. qualifier: involved_in - term: id: GO:0060337 label: type I interferon-mediated signaling pathway evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: STAT1, with STAT2 and IRF9, forms ISGF3 to mediate type I (IFN-alpha/beta) signaling and binds ISRE elements in target genes. Core function. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1–STAT2 heterodimers** plus **IRF9** form **ISGF3**, which binds **ISRE** (interferon-stimulated response element) DNA elements. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000044 review: summary: >- STAT1 translocates to the nucleus upon activation to act as a transcription factor; nuclear localization is well established. action: ACCEPT reason: >- Nuclear localization is a core, experimentally validated aspect of STAT1 biology; the IEA term is correct. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: >- Activated STAT1 dimers/ISGF3 act in the nucleoplasm at target-gene promoters. action: ACCEPT reason: >- Nucleoplasmic localization is consistent with STAT1's role as a nuclear transcription factor and is supported by experimental nuclear/nucleoplasm annotations. qualifier: located_in - term: id: GO:0006355 label: regulation of DNA-templated transcription evidence_type: IEA original_reference_id: GO_REF:0000002 review: summary: >- STAT1 regulates transcription of its target genes; this broad term is subsumed by the more specific RNA Pol II transcription-factor annotations. action: ACCEPT reason: >- A correct but general transcription-regulation term; acceptable as a broad parent of STAT1's specific transcriptional roles. qualifier: involved_in - term: id: GO:0007165 label: signal transduction evidence_type: IEA original_reference_id: GO_REF:0000002 review: summary: >- STAT1 is a signal transducer in the JAK-STAT pathway; the generic signal transduction term is correct but less informative than the specific JAK-STAT terms. action: ACCEPT reason: >- Generic signal transduction is a true parent of STAT1's JAK-STAT signaling role; acceptable though more specific terms are preferred. qualifier: involved_in - term: id: GO:0042981 label: regulation of apoptotic process evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: >- STAT1 regulates apoptosis, chiefly by inducing pro-apoptotic genes (caspases, Fas/TRAIL) downstream of interferon signaling. action: KEEP_AS_NON_CORE reason: >- Regulation of apoptosis is a downstream consequence of STAT1 transcriptional output rather than a core molecular function; biologically valid but non-core. qualifier: involved_in - term: id: GO:0051093 label: negative regulation of developmental process evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: >- STAT1 can negatively regulate certain developmental processes (e.g. angiogenesis, mesenchymal-to-epithelial transitions), consistent with this broad term. action: KEEP_AS_NON_CORE reason: >- Negative regulation of developmental processes reflects context-specific, pleiotropic outputs of STAT1, not its core interferon-signaling function. qualifier: involved_in - term: id: GO:0051607 label: defense response to virus evidence_type: IEA original_reference_id: GO_REF:0000120 review: summary: STAT1 drives interferon-induced antiviral gene programs (ISGs); STAT1 LOF abolishes IFN responses with severe viral disease. Core function. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- A 2024 review summarizes **autosomal recessive complete STAT1 deficiency** as abolishing type I/II/III IFN and IL-27 signaling and reports **24 patients** described "so far" in that review; it notes severe early-life infections qualifier: involved_in - term: id: GO:0060333 label: type II interferon-mediated signaling pathway evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: STAT1 homodimers form GAF and bind GAS DNA elements, mediating the type II (IFN-gamma) signaling pathway. Core function. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 homodimers** (historically **GAF**, gamma-interferon activation factor) bind **GAS** (gamma-activated sequence) DNA elements. qualifier: involved_in - term: id: GO:0060337 label: type I interferon-mediated signaling pathway evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: STAT1 (with STAT2 and IRF9) forms ISGF3 to mediate type I IFN signaling and binds ISRE elements; central, well-established function. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1–STAT2 heterodimers** plus **IRF9** form **ISGF3**, which binds **ISRE** (interferon-stimulated response element) DNA elements. qualifier: involved_in - term: id: GO:0007259 label: cell surface receptor signaling pathway via JAK-STAT evidence_type: NAS original_reference_id: PMID:24058793 review: summary: >- STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. action: ACCEPT reason: >- JAK-STAT signal transduction is a core STAT1 function directly supported here. supported_by: - reference_id: PMID:24058793 supporting_text: 'STAT heterodimers in immunity: A mixed message or a unique signal? Delgoffe GM(1), Vignali DA.' qualifier: involved_in - term: id: GO:0045944 label: positive regulation of transcription by RNA polymerase II evidence_type: NAS original_reference_id: PMID:24058793 review: summary: >- STAT1 directly drives positive transcription of interferon/cytokine target genes by RNA polymerase II (e.g. XAF1, IL12B, antiviral ISGs). action: ACCEPT reason: >- Positive regulation of RNA Pol II transcription is a core STAT1 function with strong direct and structural support. supported_by: - reference_id: PMID:24058793 supporting_text: 'STAT heterodimers in immunity: A mixed message or a unique signal? Delgoffe GM(1), Vignali DA.' qualifier: involved_in - term: id: GO:0045944 label: positive regulation of transcription by RNA polymerase II evidence_type: IDA original_reference_id: PMID:24065129 review: summary: STAT1 (as ISGF3 component) drives positive transcriptional regulation of antiviral genes by RNA polymerase II. Core function supported by direct experimental evidence. action: ACCEPT supported_by: - reference_id: PMID:24065129 supporting_text: IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1’s primary biochemical function is **sequence-specific transcriptional regulation** as part of IFN-activated transcription factor complexes (GAF and ISGF3), controlling expression of interferon-stimulated genes (ISGs). qualifier: involved_in - term: id: GO:0007259 label: cell surface receptor signaling pathway via JAK-STAT evidence_type: IEA original_reference_id: GO_REF:0000120 review: summary: >- STAT1 is the canonical signal transducer of the JAK-STAT cell surface receptor signaling pathway. action: ACCEPT reason: >- This is a core function of STAT1, well supported across the literature; the IEA term is correct. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 is a signal transducer and transcription factor that is activated downstream of cytokine receptors (classically IFN receptors) via receptor-associated **Janus kinases (JAKs)**, leading to STAT phosphorylation, dimerization, nuclear translocation, and transcriptional regulation of IFN-responsive genes. qualifier: involved_in - term: id: GO:0007584 label: response to nutrient evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'response to nutrient'. STAT1 can be engaged in this response in specific contexts via JAK-STAT signaling, but it is a peripheral, non- core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0008015 label: blood circulation evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'blood circulation'. STAT1 can be engaged in this response in specific contexts via JAK-STAT signaling, but it is a peripheral, non- core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0008284 label: positive regulation of cell population proliferation evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer of 'positive regulation of cell population proliferation'. STAT1 is predominantly antiproliferative downstream of interferon; a positive proliferation role is at best highly context-specific and not characteristic of STAT1. action: MARK_AS_OVER_ANNOTATED reason: >- This Ensembl-Compara orthology transfer conflicts with STAT1's well-documented antiproliferative/tumor-suppressive activity and lacks direct human evidence; likely an over-annotation. qualifier: involved_in - term: id: GO:0009410 label: response to xenobiotic stimulus evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'response to xenobiotic stimulus'. STAT1 can be engaged in this response in specific contexts via JAK-STAT signaling, but it is a peripheral, non-core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0009612 label: response to mechanical stimulus evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'response to mechanical stimulus'. STAT1 can be engaged in this response in specific contexts via JAK-STAT signaling, but it is a peripheral, non-core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0032869 label: cellular response to insulin stimulus evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'cellular response to insulin stimulus'. STAT1 can be engaged in this response in specific contexts via JAK-STAT signaling, but it is a peripheral, non-core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0034097 label: response to cytokine evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- STAT1 mediates cellular responses to numerous cytokines through the JAK-STAT pathway. action: ACCEPT reason: >- Response to cytokine is a core aspect of STAT1 function and is well supported. qualifier: involved_in - term: id: GO:0042542 label: response to hydrogen peroxide evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'response to hydrogen peroxide'. STAT1 can be engaged in this response in specific contexts via JAK-STAT signaling, but it is a peripheral, non-core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0043434 label: response to peptide hormone evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- STAT1 can be activated downstream of peptide-hormone receptors (e.g. growth hormone, leptin, insulin-related signaling) that engage the JAK-STAT pathway, supporting a response to peptide hormone. action: KEEP_AS_NON_CORE reason: >- STAT1 participation in peptide-hormone responses reflects the broad use of the JAK-STAT module by many receptors; it is a peripheral, context-dependent role rather than STAT1's core interferon function. qualifier: involved_in - term: id: GO:0045429 label: positive regulation of nitric oxide biosynthetic process evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'positive regulation of nitric oxide biosynthetic process'. STAT1 can be engaged in this response in specific contexts via JAK- STAT signaling, but it is a peripheral, non-core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0048661 label: positive regulation of smooth muscle cell proliferation evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'positive regulation of smooth muscle cell proliferation'. STAT1 can be engaged in this response in specific contexts via JAK-STAT signaling, but it is a peripheral, non-core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0051591 label: response to cAMP evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: >- IEA orthology transfer (Ensembl Compara) of 'response to cAMP'. STAT1 can be engaged in this response in specific contexts via JAK-STAT signaling, but it is a peripheral, non- core role transferred computationally without direct human evidence. action: KEEP_AS_NON_CORE reason: >- Context-specific physiological-stimulus response transferred by orthology; biologically plausible as a downstream/secondary STAT1 role but not part of its core interferon function and lacking direct human experimental support. qualifier: involved_in - term: id: GO:0097696 label: cell surface receptor signaling pathway via STAT evidence_type: IDA original_reference_id: PMID:18035482 review: summary: >- STAT1 mediates cell surface receptor signaling via STAT, activating XAF1 expression downstream of IFN-beta in colon cancer cells. action: ACCEPT reason: >- STAT-mediated receptor signaling is core to STAT1; directly supported. 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.' qualifier: involved_in - term: id: GO:0007259 label: cell surface receptor signaling pathway via JAK-STAT evidence_type: NAS original_reference_id: PMID:9630226 review: summary: >- STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. action: ACCEPT reason: >- JAK-STAT signal transduction is a core STAT1 function directly supported here. supported_by: - reference_id: PMID:9630226 supporting_text: Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. qualifier: involved_in - term: id: GO:0045944 label: positive regulation of transcription by RNA polymerase II evidence_type: NAS original_reference_id: PMID:9630226 review: summary: >- STAT1 directly drives positive transcription of interferon/cytokine target genes by RNA polymerase II (e.g. XAF1, IL12B, antiviral ISGs). action: ACCEPT reason: >- Positive regulation of RNA Pol II transcription is a core STAT1 function with strong direct and structural support. supported_by: - reference_id: PMID:9630226 supporting_text: Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. qualifier: involved_in - term: id: GO:0005654 label: nucleoplasm evidence_type: IDA original_reference_id: GO_REF:0000052 review: summary: >- Immunofluorescence localizes STAT1 to the nucleoplasm, consistent with its active nuclear form. action: ACCEPT reason: >- Nucleoplasmic localization is consistent with STAT1's core nuclear transcription-factor function. qualifier: located_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:32209697 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. 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. qualifier: located_in - term: id: GO:0045944 label: positive regulation of transcription by RNA polymerase II evidence_type: IDA original_reference_id: PMID:32209697 review: summary: >- STAT1 directly drives positive transcription of interferon/cytokine target genes by RNA polymerase II (e.g. XAF1, IL12B, antiviral ISGs). action: ACCEPT reason: >- Positive regulation of RNA Pol II transcription is a core STAT1 function with strong direct and structural support. 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. qualifier: involved_in - term: id: GO:0038111 label: interleukin-7-mediated signaling pathway evidence_type: IDA original_reference_id: PMID:29202461 review: summary: >- Under lymphopenic conditions, IL-7 induces STAT1 activation that limits homeostatic CD4+ T cell expansion, placing STAT1 in the IL-7-mediated signaling pathway. action: KEEP_AS_NON_CORE reason: >- IL-7-mediated STAT1 signaling is a context-specific (lymphopenia) role; biologically supported but peripheral to STAT1's core interferon function. supported_by: - reference_id: PMID:29202461 supporting_text: >- under lymphopenic conditions, there is a modulation of STAT1 expression resulting in an IL-7-dependent STAT1 and STAT5 activation qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IC original_reference_id: PMID:28753426 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. supported_by: - reference_id: PMID:28753426 supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. qualifier: is_active_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:18035482 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. 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.' qualifier: is_active_in - term: id: GO:0060337 label: type I interferon-mediated signaling pathway evidence_type: IDA original_reference_id: PMID:23386060 review: summary: >- STAT1 directly mediates 'type I interferon-mediated signaling pathway', a core interferon- response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. supported_by: - reference_id: PMID:23386060 supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting STAT1. qualifier: involved_in - term: id: GO:0007259 label: cell surface receptor signaling pathway via JAK-STAT evidence_type: IDA original_reference_id: PMID:11972023 review: summary: >- STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. action: ACCEPT reason: >- JAK-STAT signal transduction is a core STAT1 function directly supported here. supported_by: - reference_id: PMID:11972023 supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma. qualifier: involved_in - term: id: GO:0034341 label: response to type II interferon evidence_type: IDA original_reference_id: PMID:11972023 review: summary: >- STAT1 directly mediates 'response to type II interferon', a core interferon-response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. supported_by: - reference_id: PMID:11972023 supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:28753426 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. supported_by: - reference_id: PMID:28753426 supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. qualifier: is_active_in - term: id: GO:0007259 label: cell surface receptor signaling pathway via JAK-STAT evidence_type: IDA original_reference_id: PMID:28753426 review: summary: >- STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. action: ACCEPT reason: >- JAK-STAT signal transduction is a core STAT1 function directly supported here. supported_by: - reference_id: PMID:28753426 supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. qualifier: involved_in - term: id: GO:0035458 label: cellular response to interferon-beta evidence_type: IDA original_reference_id: PMID:28753426 review: summary: >- STAT1 directly mediates 'cellular response to interferon-beta', a core interferon-response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. supported_by: - reference_id: PMID:28753426 supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. qualifier: involved_in - term: id: GO:0071346 label: cellular response to type II interferon evidence_type: IDA original_reference_id: PMID:11972023 review: summary: >- STAT1 directly mediates 'cellular response to type II interferon', a core interferon- response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. supported_by: - reference_id: PMID:11972023 supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma. qualifier: involved_in - term: id: GO:0006357 label: regulation of transcription by RNA polymerase II evidence_type: IDA original_reference_id: PMID:28753426 review: summary: >- SETD2-mediated methylation of STAT1 modulates STAT1-dependent transcription of ISGs by RNA Pol II. action: ACCEPT reason: >- Regulation of RNA Pol II transcription is core to STAT1; directly supported. supported_by: - reference_id: PMID:28753426 supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:15322115 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. supported_by: - reference_id: PMID:15322115 supporting_text: 2004 Aug 20. Protein kinase Cdelta regulates apoptosis via activation of STAT1. qualifier: is_active_in - term: id: GO:0007259 label: cell surface receptor signaling pathway via JAK-STAT evidence_type: IDA original_reference_id: PMID:22002246 review: summary: >- STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. action: ACCEPT reason: >- JAK-STAT signal transduction is a core STAT1 function directly supported here. 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. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IC original_reference_id: PMID:9535918 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. 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. qualifier: is_active_in - term: id: GO:0038113 label: interleukin-9-mediated signaling pathway evidence_type: IDA original_reference_id: PMID:9535918 review: summary: >- STAT1 is activated downstream of the IL-9 receptor (gammac/IL-9Ralpha), participating in IL-9-mediated signaling and apoptosis prevention. action: KEEP_AS_NON_CORE reason: >- IL-9-mediated STAT1 signaling is a specific cytokine-context role, peripheral to STAT1's core interferon function. 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 qualifier: involved_in - term: id: GO:0070106 label: interleukin-27-mediated signaling pathway evidence_type: IDA original_reference_id: PMID:32270034 review: summary: >- IL-27 activates STAT1 in skin cells to induce innate antiviral proteins, placing STAT1 in the IL-27-mediated signaling pathway. action: KEEP_AS_NON_CORE reason: >- IL-27-mediated STAT1 signaling is a specific cytokine-context antiviral role; supported but non-core relative to interferon signaling. supported_by: - reference_id: PMID:32270034 supporting_text: >- IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection. qualifier: involved_in - term: id: GO:1990841 label: promoter-specific chromatin binding evidence_type: IDA original_reference_id: PMID:26479788 review: summary: >- STAT1 binds specific gene promoters (promoter-specific chromatin binding) to activate ISGs, consistent with its sequence-specific transcription-factor function. action: ACCEPT reason: >- Promoter-specific chromatin binding is a core molecular feature of STAT1 as a DNA-binding transcription factor. 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. qualifier: enables - term: id: GO:0000785 label: chromatin evidence_type: ISA original_reference_id: GO_REF:0000113 review: summary: >- As a DNA-binding transcription factor, STAT1 localizes to chromatin at target-gene promoters. action: ACCEPT reason: >- Chromatin localization is consistent with STAT1's core transcription-factor function and is additionally supported by promoter-occupancy/ChIP data. qualifier: located_in - term: id: GO:0002230 label: positive regulation of defense response to virus by host evidence_type: IMP original_reference_id: PMID:26479788 review: summary: >- STAT1, via PARP9-DTX3L-enhanced interferon signaling, positively regulates the host antiviral defense response. action: ACCEPT reason: >- Positive regulation of host antiviral defense is central to STAT1 function and is directly supported. 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. qualifier: involved_in - term: id: GO:0002230 label: positive regulation of defense response to virus by host evidence_type: IGI original_reference_id: PMID:26479788 review: summary: >- STAT1, via PARP9-DTX3L-enhanced interferon signaling, positively regulates the host antiviral defense response. action: ACCEPT reason: >- Positive regulation of host antiviral defense is central to STAT1 function and is directly supported. 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. qualifier: involved_in - term: id: GO:0045893 label: positive regulation of DNA-templated transcription evidence_type: IMP original_reference_id: PMID:26479788 review: summary: >- STAT1 positively regulates transcription of its target genes; directly supported (e.g. PARP9-DTX3L/STAT1 enhancing ISG expression; Stat1 export-signal mutants altering target- gene activation). action: ACCEPT reason: >- Positive regulation of DNA-templated transcription is a core STAT1 activity; the broad term is correct and complementary to the RNA Pol II-specific terms. 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. qualifier: involved_in - term: id: GO:0045893 label: positive regulation of DNA-templated transcription evidence_type: IGI original_reference_id: PMID:26479788 review: summary: >- STAT1 positively regulates transcription of its target genes; directly supported (e.g. PARP9-DTX3L/STAT1 enhancing ISG expression; Stat1 export-signal mutants altering target- gene activation). action: ACCEPT reason: >- Positive regulation of DNA-templated transcription is a core STAT1 activity; the broad term is correct and complementary to the RNA Pol II-specific terms. 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. qualifier: involved_in - term: id: GO:0060333 label: type II interferon-mediated signaling pathway evidence_type: IMP original_reference_id: PMID:26479788 review: summary: >- STAT1 directly mediates 'type II interferon-mediated signaling pathway', a core interferon-response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. 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. qualifier: involved_in - term: id: GO:0032727 label: positive regulation of interferon-alpha production evidence_type: IDA original_reference_id: PMID:28753426 review: summary: >- SETD2-methylated STAT1 reinforces interferon antiviral responses including IFN-alpha production in a positive feedback loop. action: KEEP_AS_NON_CORE reason: >- Positive regulation of IFN-alpha production reflects STAT1's feed-forward amplification of the interferon system; a genuine but secondary output relative to its core transcription- factor role. supported_by: - reference_id: PMID:28753426 supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. qualifier: involved_in - term: id: GO:0051607 label: defense response to virus evidence_type: IDA original_reference_id: PMID:28753426 review: summary: >- STAT1 directly mediates 'defense response to virus', a core interferon-response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. supported_by: - reference_id: PMID:28753426 supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:23386060 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. supported_by: - reference_id: PMID:23386060 supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting STAT1. qualifier: located_in - term: id: GO:0071346 label: cellular response to type II interferon evidence_type: IDA original_reference_id: PMID:23386060 review: summary: >- STAT1 directly mediates 'cellular response to type II interferon', a core interferon- response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. supported_by: - reference_id: PMID:23386060 supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting STAT1. qualifier: involved_in - term: id: GO:0045648 label: positive regulation of erythrocyte differentiation evidence_type: IMP original_reference_id: PMID:28283061 review: summary: >- A pathogenic EPO mutation study implicates STAT1 (alongside STAT5) in cytokine signaling affecting erythroid differentiation. action: KEEP_AS_NON_CORE reason: >- Erythrocyte differentiation is a specialized, context-dependent role downstream of cytokine receptor signaling, peripheral to STAT1's core interferon function. supported_by: - reference_id: PMID:28283061 supporting_text: Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:15825084 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. supported_by: - reference_id: PMID:15825084 supporting_text: Hepatitis C virus expression suppresses interferon signaling by degrading STAT1. qualifier: located_in - term: id: GO:0035456 label: response to interferon-beta evidence_type: IMP original_reference_id: PMID:24882218 review: summary: >- STAT1 directly mediates 'response to interferon-beta', a core interferon-response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. 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. qualifier: involved_in - 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: >- In the HCV system, STAT1-driven interferon signaling restricts viral protein levels; HCV core counteracts this by degrading STAT1. action: KEEP_AS_NON_CORE reason: >- This term captures STAT1's antiviral restriction of viral protein accumulation in a specific host-pathogen context; biologically valid but non-core and somewhat contorted. supported_by: - reference_id: PMID:15825084 supporting_text: >- Hepatitis C virus expression suppresses interferon signaling by degrading STAT1. qualifier: involved_in - term: id: GO:0035458 label: cellular response to interferon-beta evidence_type: IMP original_reference_id: PMID:18035482 review: summary: >- STAT1 directly mediates 'cellular response to interferon-beta', a core interferon-response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. 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.' qualifier: involved_in - term: id: GO:0045944 label: positive regulation of transcription by RNA polymerase II evidence_type: IMP original_reference_id: PMID:18035482 review: summary: >- STAT1 directly drives positive transcription of interferon/cytokine target genes by RNA polymerase II (e.g. XAF1, IL12B, antiviral ISGs). action: ACCEPT reason: >- Positive regulation of RNA Pol II transcription is a core STAT1 function with strong direct and structural support. 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.' qualifier: involved_in - term: id: GO:0060333 label: type II interferon-mediated signaling pathway evidence_type: ISS original_reference_id: GO_REF:0000024 review: summary: >- STAT1 homodimers (GAF) mediate the type II (IFN-gamma) signaling pathway. action: ACCEPT reason: >- Core STAT1 function; the ISS annotation duplicates the well-supported type II IFN signaling role. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- * **STAT1 homodimers** (historically **GAF**, gamma-interferon activation factor) bind **GAS** (gamma-activated sequence) DNA elements. qualifier: involved_in - term: id: GO:0060337 label: type I interferon-mediated signaling pathway evidence_type: ISS original_reference_id: GO_REF:0000024 review: summary: >- STAT1 (with STAT2/IRF9 as ISGF3) mediates the type I IFN signaling pathway. action: ACCEPT reason: >- Core STAT1 function; ISS annotation duplicates the well-supported type I IFN signaling role. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- **STAT1–STAT2 heterodimers** plus **IRF9** form **ISGF3**, which binds **ISRE** (interferon-stimulated response element) DNA elements. qualifier: involved_in - term: id: GO:0000785 label: chromatin evidence_type: IDA original_reference_id: PMID:18035482 review: summary: >- STAT1 binds chromatin at the ISRE of the XAF1 promoter (quantitative ChIP), directly demonstrating chromatin localization. action: ACCEPT reason: >- Direct ChIP evidence supports STAT1 chromatin localization, consistent with its core DNA- binding transcription-factor function. 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.' qualifier: located_in - term: id: GO:0000122 label: negative regulation of transcription by RNA polymerase II evidence_type: ISS original_reference_id: GO_REF:0000024 review: summary: >- STAT1 can act as a transcriptional repressor at specific targets (e.g. repressing ULK1 and certain pro-angiogenic/proliferative genes), supporting negative regulation of RNA Pol II transcription. action: KEEP_AS_NON_CORE reason: >- While STAT1 is primarily a transcriptional activator, context-specific repression is documented; this ISS term captures a real but non-core, gene-specific repressive activity. qualifier: involved_in - term: id: GO:0001937 label: negative regulation of endothelial cell proliferation evidence_type: IMP original_reference_id: PMID:16585190 review: summary: >- IFN-gamma-activated STAT1 in endothelial cells inhibits proliferation and tube formation, negatively regulating endothelial cell proliferation. action: KEEP_AS_NON_CORE reason: >- Endothelial antiproliferative/antiangiogenic activity is a context-specific downstream output of STAT1 signaling, peripheral to its core interferon transcription-factor role. supported_by: - reference_id: PMID:16585190 supporting_text: >- IFN-gamma inhibited cell growth and tube formation of HUVECs qualifier: involved_in - term: id: GO:0002053 label: positive regulation of mesenchymal cell proliferation evidence_type: ISS original_reference_id: GO_REF:0000024 review: summary: >- Sequence-similarity-based transfer of a kidney/metanephros developmental role ('positive regulation of mesenchymal cell proliferation'). STAT1 has a documented role in renal tubule (re)differentiation, so a developmental kidney role is plausible, but these specific metanephric terms are non-core developmental annotations. action: KEEP_AS_NON_CORE reason: >- These curator-judgment ISS transfers describe specialized kidney-developmental roles that are peripheral to STAT1's core interferon/transcription-factor function; retained as non- core. supported_by: - reference_id: PMID:20861313 supporting_text: >- STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis. qualifier: involved_in - 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: >- Sequence-similarity-based transfer of a kidney/metanephros developmental role ('negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis'). STAT1 has a documented role in renal tubule (re)differentiation, so a developmental kidney role is plausible, but these specific metanephric terms are non-core developmental annotations. action: KEEP_AS_NON_CORE reason: >- These curator-judgment ISS transfers describe specialized kidney-developmental roles that are peripheral to STAT1's core interferon/transcription-factor function; retained as non- core. supported_by: - reference_id: PMID:20861313 supporting_text: >- STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis. qualifier: involved_in - term: id: GO:0016525 label: negative regulation of angiogenesis evidence_type: IMP original_reference_id: PMID:16585190 review: summary: >- STAT1 activation in endothelial cells is a negative regulator of angiogenesis, suppressing VEGF-driven growth and tube formation. action: KEEP_AS_NON_CORE reason: >- Negative regulation of angiogenesis is a documented but context-specific downstream effect of STAT1; retained as non-core. 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. qualifier: involved_in - term: id: GO:0042981 label: regulation of apoptotic process evidence_type: TAS original_reference_id: PMID:12108949 review: summary: >- STAT1 regulates apoptosis, predominantly transducing pro-apoptotic signals by inducing genes such as caspases, Fas and TRAIL. action: KEEP_AS_NON_CORE reason: >- Regulation of apoptosis is a downstream transcriptional output of STAT1 rather than a core molecular function; supported as a non-core role. supported_by: - reference_id: PMID:12108949 supporting_text: >- STAT1 and, under some circums-tances. STAT3 are important for transducing pro-apoptotic signals qualifier: involved_in - term: id: GO:0061326 label: renal tubule development evidence_type: IMP original_reference_id: PMID:20861313 review: summary: >- STAT1 is required for epithelial redifferentiation during MDCK kidney tubulogenesis, supporting a role in renal tubule development. action: KEEP_AS_NON_CORE reason: >- Renal tubule development is a specialized morphogenetic role, peripheral to STAT1's core interferon function; supported but non-core. supported_by: - reference_id: PMID:20861313 supporting_text: >- STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis. qualifier: involved_in - term: id: GO:0072136 label: metanephric mesenchymal cell proliferation involved in metanephros development evidence_type: ISS original_reference_id: GO_REF:0000024 review: summary: >- Sequence-similarity-based transfer of a kidney/metanephros developmental role ('metanephric mesenchymal cell proliferation involved in metanephros development'). STAT1 has a documented role in renal tubule (re)differentiation, so a developmental kidney role is plausible, but these specific metanephric terms are non-core developmental annotations. action: KEEP_AS_NON_CORE reason: >- These curator-judgment ISS transfers describe specialized kidney-developmental roles that are peripheral to STAT1's core interferon/transcription-factor function; retained as non- core. supported_by: - reference_id: PMID:20861313 supporting_text: >- STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis. qualifier: involved_in - term: id: GO:0072162 label: metanephric mesenchymal cell differentiation evidence_type: ISS original_reference_id: GO_REF:0000024 review: summary: >- Sequence-similarity-based transfer of a kidney/metanephros developmental role ('metanephric mesenchymal cell differentiation'). STAT1 has a documented role in renal tubule (re)differentiation, so a developmental kidney role is plausible, but these specific metanephric terms are non-core developmental annotations. action: KEEP_AS_NON_CORE reason: >- These curator-judgment ISS transfers describe specialized kidney-developmental roles that are peripheral to STAT1's core interferon/transcription-factor function; retained as non- core. supported_by: - reference_id: PMID:20861313 supporting_text: >- STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis. qualifier: involved_in - 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: >- Sequence-similarity-based transfer of a kidney/metanephros developmental role ('negative regulation of metanephric nephron tubule epithelial cell differentiation'). STAT1 has a documented role in renal tubule (re)differentiation, so a developmental kidney role is plausible, but these specific metanephric terms are non-core developmental annotations. action: KEEP_AS_NON_CORE reason: >- These curator-judgment ISS transfers describe specialized kidney-developmental roles that are peripheral to STAT1's core interferon/transcription-factor function; retained as non- core. supported_by: - reference_id: PMID:20861313 supporting_text: >- STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:10692450 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. 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. qualifier: located_in - term: id: GO:0045893 label: positive regulation of DNA-templated transcription evidence_type: IDA original_reference_id: PMID:10973496 review: summary: >- STAT1 positively regulates transcription of its target genes; directly supported (e.g. PARP9-DTX3L/STAT1 enhancing ISG expression; Stat1 export-signal mutants altering target- gene activation). action: ACCEPT reason: >- Positive regulation of DNA-templated transcription is a core STAT1 activity; the broad term is correct and complementary to the RNA Pol II-specific terms. 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. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:10973496 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. 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. qualifier: located_in - term: id: GO:0033209 label: tumor necrosis factor-mediated signaling pathway evidence_type: IDA original_reference_id: PMID:10848577 review: summary: >- STAT1 is a component of the TNFR1-TRADD signaling complex, participating in TNF-alpha- mediated signaling. action: KEEP_AS_NON_CORE reason: >- STAT1's role in TNF signaling (inhibiting NF-kappaB) is a specific, non-canonical function distinct from its core interferon-driven transcription; retained as non-core. 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. qualifier: involved_in - term: id: GO:0043124 label: negative regulation of canonical NF-kappaB signal transduction evidence_type: IMP original_reference_id: PMID:10848577 review: summary: >- STAT1 negatively regulates canonical NF-kappaB signaling as part of the TNFR1-TRADD complex. action: KEEP_AS_NON_CORE reason: >- Negative regulation of NF-kappaB is a specific, non-canonical STAT1 activity in TNF signaling; biologically supported but peripheral to STAT1's core 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. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:21268089 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. 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. qualifier: located_in - term: id: GO:0060333 label: type II interferon-mediated signaling pathway evidence_type: IDA original_reference_id: PMID:21268089 review: summary: >- STAT1 directly mediates 'type II interferon-mediated signaling pathway', a core interferon-response function demonstrated experimentally in this study. action: ACCEPT reason: >- Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. 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. qualifier: involved_in - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:16306601 review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. 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. qualifier: located_in - term: id: GO:0070721 label: ISGF3 complex evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: STAT1 is a defining component of the ISGF3 transcription factor complex, together with STAT2 and IRF9, that drives type I/III IFN responses by binding ISRE elements. Core complex assignment. action: ACCEPT supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1–STAT2 heterodimers** plus **IRF9** form **ISGF3**, which binds **ISRE** (interferon-stimulated response element) DNA elements. qualifier: part_of - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 review: summary: >- Latent STAT1 resides in the cytoplasm prior to cytokine-induced phosphorylation and nuclear import. action: ACCEPT reason: >- Cytoplasmic localization of the latent pool is a core, well-established feature of STAT1 signaling. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: >- STAT1's latent pool is cytosolic; this cytosol localization is consistent with established biology. action: ACCEPT reason: >- Cytosolic localization of latent STAT1 is well supported; the IEA term is appropriate. qualifier: located_in - term: id: GO:0090575 label: RNA polymerase II transcription regulator complex evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: >- As a sequence-specific RNA Pol II transcription factor, STAT1 is part of RNA polymerase II transcription regulator complexes (e.g. GAF/ISGF3 assembled on promoters). action: ACCEPT reason: >- Membership in an RNA Pol II transcription regulator complex is consistent with STAT1's core transcription-factor function. qualifier: part_of - term: id: GO:0090575 label: RNA polymerase II transcription regulator complex evidence_type: IPI original_reference_id: PMID:8662591 review: summary: >- STAT1 assembles into RNA polymerase II transcription regulator complexes (e.g. STAT dimers and ISGF3) on target promoters. action: ACCEPT reason: >- Membership in an RNA Pol II transcription regulator complex is consistent with STAT1's core transcription-factor function. 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. qualifier: part_of - term: id: GO:0070721 label: ISGF3 complex evidence_type: IPI original_reference_id: PMID:24065129 review: summary: Direct IPI evidence for STAT1's role in the ISGF3 complex (with STAT2 and IRF9). Core complex assignment. action: ACCEPT supported_by: - reference_id: PMID:24065129 supporting_text: IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1–STAT2 heterodimers** plus **IRF9** form **ISGF3**, which binds **ISRE** (interferon-stimulated response element) DNA elements. qualifier: part_of - term: id: GO:0090575 label: RNA polymerase II transcription regulator complex evidence_type: NAS original_reference_id: PMID:24058793 review: summary: >- STAT1 assembles into RNA polymerase II transcription regulator complexes (e.g. STAT dimers and ISGF3) on target promoters. action: ACCEPT reason: >- Membership in an RNA Pol II transcription regulator complex is consistent with STAT1's core transcription-factor function. supported_by: - reference_id: PMID:24058793 supporting_text: 'STAT heterodimers in immunity: A mixed message or a unique signal? Delgoffe GM(1), Vignali DA.' qualifier: part_of - term: id: GO:0030424 label: axon evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: | STAT1 is a cytoplasmic/nuclear transcription factor that translocates to the nucleus upon IFN-driven phosphorylation. Axonal localization is not a documented STAT1 compartment; this IEA annotation (Ensembl Compara ortholog transfer, GO_REF:0000107) is most likely an erroneous transfer. Per PR #831 review feedback, resolved PENDING → REMOVE. action: REMOVE reason: | Axon localization is inconsistent with STAT1's well-established cytoplasmic-to-nuclear transcription-factor biology and is not supported by direct evidence; the IEA orthology transfer is an over-prediction. qualifier: located_in - term: id: GO:0030425 label: dendrite evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: | As with the axon annotation, dendritic localization is not a documented STAT1 compartment. STAT1 is a cytoplasmic/nuclear transcription factor; this IEA orthology transfer (GO_REF:0000107) is most likely erroneous. Per PR #831 review feedback, resolved PENDING → REMOVE. action: REMOVE reason: | Dendrite localization is inconsistent with STAT1's cytoplasmic-to- nuclear transcription-factor biology and lacks direct supporting evidence; the IEA orthology transfer is an over-prediction. qualifier: located_in - term: id: GO:0090575 label: RNA polymerase II transcription regulator complex evidence_type: IPI original_reference_id: PMID:9630226 review: summary: >- STAT1 assembles into RNA polymerase II transcription regulator complexes (e.g. STAT dimers and ISGF3) on target promoters. action: ACCEPT reason: >- Membership in an RNA Pol II transcription regulator complex is consistent with STAT1's core transcription-factor function. supported_by: - reference_id: PMID:9630226 supporting_text: Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. qualifier: part_of - term: id: GO:0005730 label: nucleolus evidence_type: IDA original_reference_id: GO_REF:0000052 review: summary: >- HPA immunofluorescence reports a nucleolar signal for STAT1. STAT1 is a nucleoplasmic/cytoplasmic transcription factor; a dedicated nucleolar role is not part of its characterized biology and this single high-throughput localization is not corroborated by functional data. action: MARK_AS_OVER_ANNOTATED reason: >- Nucleolar localization rests on a single high-throughput immunofluorescence dataset and is not supported by STAT1's established nucleoplasmic transcription-factor function; likely over-annotation. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: GO_REF:0000052 review: summary: >- Immunofluorescence localizes STAT1 to the cytosol, consistent with its latent cytosolic pool. action: ACCEPT reason: >- Cytosolic localization of latent STAT1 is well established; the IDA (HPA immunofluorescence) annotation is appropriate. qualifier: located_in - 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. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9851142 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8985981 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8985983 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9865524 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8985900 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8985943 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8985966 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8985981 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8985983 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8985988 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9865511 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:26479788 review: summary: >- STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. action: ACCEPT reason: >- Cytoplasmic localization of latent STAT1 is core and well supported. 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. qualifier: located_in - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:27796300 review: summary: >- STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. action: ACCEPT reason: >- Cytoplasmic localization of latent STAT1 is core and well supported. supported_by: - reference_id: PMID:27796300 supporting_text: PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation. qualifier: located_in - term: id: GO:0032991 label: protein-containing complex evidence_type: IDA original_reference_id: PMID:26479788 review: summary: >- STAT1 is part of protein-containing complexes (e.g. with PARP9-DTX3L) during interferon signaling. action: KEEP_AS_NON_CORE reason: >- Generic protein-containing complex is uninformative relative to STAT1's specific transcription-factor complexes (GAF/ISGF3); retained as non-core. 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. qualifier: part_of - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:28753426 review: summary: >- STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. action: ACCEPT reason: >- Cytoplasmic localization of latent STAT1 is core and well supported. supported_by: - reference_id: PMID:28753426 supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. qualifier: located_in - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:23386060 review: summary: >- STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. action: ACCEPT reason: >- Cytoplasmic localization of latent STAT1 is core and well supported. supported_by: - reference_id: PMID:23386060 supporting_text: hCAF1/CNOT7 regulates interferon signalling by targeting STAT1. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8987218 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1112565 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1112602 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1169406 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1433456 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1470009 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1678841 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1888198 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-380782 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6788571 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6788582 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6790041 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8950441 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8950453 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8950485 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8950518 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8950522 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8983835 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8983841 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8983845 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8983983 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8983996 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8984014 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8984021 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8984023 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8985929 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8986985 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987007 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987033 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987080 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987097 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987150 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987218 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987230 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987255 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987266 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8987270 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9006870 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9006873 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9670412 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9670416 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9672159 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9672176 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9729454 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9835443 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-1112587 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6788623 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8950522 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8950733 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9021334 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0048471 label: perinuclear region of cytoplasm evidence_type: IDA original_reference_id: PMID:17275127 review: summary: >- STAT1 was detected in the perinuclear region in hepatocytes where HCV NS5A suppresses STAT1 phosphorylation; this perinuclear pool is a context-specific observation. action: KEEP_AS_NON_CORE reason: >- Perinuclear localization is a context-specific observation (HCV-infected hepatocytes) rather than a core STAT1 compartment; retained as non-core. 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. qualifier: located_in - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:17275127 review: summary: >- STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. action: ACCEPT reason: >- Cytoplasmic localization of latent STAT1 is core and well supported. 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. qualifier: located_in - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:15825084 review: summary: >- STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. action: ACCEPT reason: >- Cytoplasmic localization of latent STAT1 is core and well supported. supported_by: - reference_id: PMID:15825084 supporting_text: Hepatitis C virus expression suppresses interferon signaling by degrading STAT1. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-1015699 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-1031713 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-1470012 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-873917 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-877281 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-909721 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-913529 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9670426 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-997326 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the nucleoplasm. STAT1 is genuinely present in the nucleoplasm as an active dimer/ISGF3, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The nucleoplasm localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported nucleoplasm annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1112727 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1470010 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1470012 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-873917 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-873921 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-873922 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-873927 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-909552 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-909718 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-909721 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-909722 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-909725 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-909726 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-913529 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9670417 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9670426 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9710959 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9710963 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-997309 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1112538 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1112587 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1112604 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6788622 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6788623 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6788628 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8950733 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8950782 review: summary: >- Bulk Reactome reaction-participant annotation placing STAT1 in the cytosol. STAT1 is genuinely a latent cytosolic factor before activation, so the localization is correct, but this is one of many redundant per-reaction Reactome TAS rows for the same compartment. action: ACCEPT reason: >- The cytosol localization is consistent with STAT1 biology (latent cytosolic pool / nuclear active form), but this specific row is a bulk Reactome reaction-participant annotation that adds no functional specificity beyond the experimentally supported cytosol annotation already accepted; a redundant per-reaction Reactome participant record. supported_by: - reference_id: file:human/STAT1/STAT1-deep-research-falcon.md supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. qualifier: located_in - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:10692450 review: summary: >- STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. action: ACCEPT reason: >- Cytoplasmic localization of latent STAT1 is core and well supported. 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. qualifier: located_in - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:10973496 review: summary: >- STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. action: ACCEPT reason: >- Cytoplasmic localization of latent STAT1 is core and well supported. 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. qualifier: located_in - 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. - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:26479788 qualifier: colocalizes_with review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:28753426 qualifier: located_in review: summary: >- STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. action: ACCEPT reason: >- Nuclear localization is a core, repeatedly validated feature of activated STAT1. core_functions: - description: Master transcriptional regulator of interferon responses and cytokine signaling molecular_function: id: GO:0000981 label: DNA-binding transcription factor activity, RNA polymerase II-specific directly_involved_in: - id: GO:0071345 label: cellular response to cytokine stimulus - id: GO:0060337 label: type I interferon-mediated signaling pathway - id: GO:0060333 label: type II interferon-mediated signaling pathway - id: GO:0045087 label: innate immune response locations: - id: GO:0005634 label: nucleus - id: GO:0005737 label: cytoplasm supported_by: - reference_id: file:human/STAT1/STAT1-deep-research.md supporting_text: STAT1 regulates a vast network of target genes, with over 300 interferon-stimulated genes (ISGs) identified through experimental validation including IRF1, ISG15, MX1, OAS1, and CXCL10 - reference_id: PMID:32209697 supporting_text: STAT1 phosphorylated at Thr749 directly enhanced transcription of the gene encoding IL-12p40 (IL12B) and facilitated the binding of STAT1 to a noncanonical DNA motif in promoter regions full_text_unavailable: true - description: SH2 domain-mediated homodimerization and heterodimerization essential for transcriptional activation molecular_function: id: GO:0042803 label: protein homodimerization activity directly_involved_in: - id: GO:0046427 label: positive regulation of receptor signaling pathway via JAK-STAT locations: - id: GO:0005634 label: nucleus supported_by: - reference_id: PMID:9630226 supporting_text: The STAT-1 dimer forms a contiguous C-shaped clamp around DNA that is stabilized by reciprocal and highly specific interactions between the SH2 domain of one monomer and the C-terminal segment, phosphorylated on tyrosine, of the other - reference_id: PMID:8605877 supporting_text: the SH2 domain of Stat1 and Stat2 can mediate homo- as well as heterodimerization, suggest that a single SH2 domain-phosphotyrosyl interaction is sufficient for dimerization - description: Sequence-specific DNA binding to interferon-responsive regulatory elements (GAS and ISRE) molecular_function: id: GO:0000978 label: RNA polymerase II cis-regulatory region sequence-specific DNA binding directly_involved_in: - id: GO:0045944 label: positive regulation of transcription by RNA polymerase II locations: - id: GO:0005634 label: nucleus supported_by: - reference_id: PMID:9630226 supporting_text: STAT-1 utilizes a DNA-binding domain with an immunoglobulin fold, similar to that of NFkappaB and the p53 tumor suppressor protein - reference_id: file:human/STAT1/STAT1-deep-research.md supporting_text: STAT1 demonstrates remarkable functional versatility through its ability to form different transcriptional complexes - STAT1 homodimers (GAF) respond to IFN-γ and bind GAS elements, while STAT1:STAT2 heterodimers combine with IRF9 to form ISGF3 complex responding to type I interferons and binding ISRE sequences references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms. findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara. findings: [] - id: GO_REF:0000113 title: Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods. findings: [] - id: PMID:10848577 title: Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation. findings: [] - id: PMID:10973496 title: Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain. findings: [] - id: PMID:11238845 title: 'Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase reverses Stat1 activation.' findings: [] - id: PMID:11972023 title: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma. findings: [] - id: PMID:12070153 title: Identification of both positive and negative domains within the epidermal growth factor receptor COOH-terminal region for signal transducer and activator of transcription (STAT) activation. findings: [] - id: PMID:12788789 title: STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation. findings: [] - id: PMID:12867595 title: The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3. findings: [] - id: PMID:15780933 title: Structural bases of unphosphorylated STAT1 association and receptor binding. findings: [] - id: PMID:15825084 title: Hepatitis C virus expression suppresses interferon signaling by degrading STAT1. findings: [] - id: PMID:16189514 title: Towards a proteome-scale map of the human protein-protein interaction network. findings: [] - id: PMID:16257975 title: The conserved Leu-724 residue is required for both serine phosphorylation and co-activator recruitment for Stat1-mediated transcription activation in response to interferon-gamma. findings: [] - id: PMID:16273093 title: A quantitative protein interaction network for the ErbB receptors using protein microarrays. findings: [] - id: PMID:16306601 title: Respiratory syncytial virus-inducible BCL-3 expression antagonizes the STAT/IRF and NF-kappaB signaling pathways by inducing histone deacetylase 1 recruitment to the interleukin-8 promoter. findings: [] - id: PMID:16531398 title: Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique carboxyl termini that determine cytosolic fate. findings: [] - id: PMID:16585190 title: Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis. findings: [] - id: PMID:16940534 title: Hepatitis C virus core protein blocks interferon signaling by interaction with the STAT1 SH2 domain. findings: [] - id: PMID:17275127 title: HCV NS5A inhibits interferon-alpha signaling through suppression of STAT1 phosphorylation in hepatocyte-derived cell lines. findings: [] - id: PMID:17596301 title: Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. findings: [] - id: PMID:17923090 title: Acetylation-dependent signal transduction for type I interferon receptor. findings: [] - id: PMID:18035482 title: 'Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.' findings: [] - id: PMID:20195357 title: A comprehensive resource of interacting protein regions for refining human transcription factor networks. findings: [] - id: PMID:20576130 title: Activated networking of platelet activating factor receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium. findings: [] - id: PMID:21268089 title: Molecular mechanisms underlying the inhibition of IFN-γ-induced, STAT1-mediated gene transcription in human macrophages by simvastatin and agonists of PPARs and LXRs. findings: [] - id: PMID:21903422 title: Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. findings: [] - id: PMID:21988832 title: Toward an understanding of the protein interaction network of the human liver. findings: [] - id: PMID:22002246 title: A novel disrupter of telomere silencing 1-like (DOT1L) interaction is required for signal transducer and activator of transcription 1 (STAT1)-activated gene expression. findings: [] - id: PMID:23386060 title: hCAF1/CNOT7 regulates interferon signalling by targeting STAT1. findings: [] - id: PMID:24065129 title: IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. findings: [] - id: PMID:24360797 title: Hepatic RIG-I predicts survival and interferon-α therapeutic response in hepatocellular carcinoma. findings: [] - id: PMID:24658140 title: The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells. findings: [] - id: PMID:25241761 title: Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. findings: [] - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:25468996 title: E-cadherin interactome complexity and robustness resolved by quantitative proteomics. findings: [] - id: PMID:25609649 title: Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. findings: [] - id: PMID:26479788 title: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection. findings: [] - id: PMID:26889034 title: VP8, the Major Tegument Protein of Bovine Herpesvirus 1, Interacts with Cellular STAT1 and Inhibits Interferon Beta Signaling. findings: [] - id: PMID:26966684 title: 'PIPINO: A Software Package to Facilitate the Identification of Protein-Protein Interactions from Affinity Purification Mass Spectrometry Data.' findings: [] - id: PMID:28753426 title: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity. findings: [] - id: PMID:31980649 title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D). findings: [] - id: PMID:32209697 title: Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production. findings: [] - id: PMID:32953130 title: SARS-CoV-2 N protein antagonizes type I interferon signaling by suppressing phosphorylation and nuclear translocation of STAT1 and STAT2. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:34950606 title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response. findings: [] - id: PMID:35140242 title: Human transcription factor protein interaction networks. findings: [] - id: PMID:8156998 title: Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91). findings: [] - id: PMID:8605877 title: The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN-alpha signals. findings: [] - id: PMID:8662591 title: Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130. I. Definition of a novel phosphotyrosine motif mediating STAT1 activation. findings: [] - id: PMID:9121453 title: Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling. findings: [] - id: PMID:9535918 title: Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis. findings: [] - id: PMID:9630226 title: Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. findings: [] - id: PMID:34521819 title: Could not retrieve title - publication not available findings: [] - id: PMID:9881977 title: Direct suppression of Stat1 function during adenoviral infection. findings: [] - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity. findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt. findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: PMID:10692450 title: Thrombin inhibits tumor cell growth in association with up-regulation of p21(waf/cip1) and caspases via a p53-independent, STAT-1-dependent pathway. findings: [] - id: PMID:12108949 title: The role of STATs in apoptosis. findings: [] - id: PMID:15322115 title: Protein kinase Cdelta regulates apoptosis via activation of STAT1. findings: [] - id: PMID:20861313 title: STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis. findings: [] - id: PMID:24058793 title: 'STAT heterodimers in immunity: A mixed message or a unique signal?' findings: [] - id: PMID:24882218 title: Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response. findings: [] - id: PMID:28283061 title: Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation. findings: [] - id: PMID:29202461 title: IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion. findings: [] - id: PMID:32270034 title: IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection. findings: [] - id: PMID:27796300 title: PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation. findings: [] - id: Reactome:R-HSA-1015699 title: ISGF3 binds the ISRE promoter elements in IFN-stimulated genes findings: [] - id: Reactome:R-HSA-1031713 title: GAF binds the GAS promoter elements in the IFNG-regulated genes findings: [] - id: Reactome:R-HSA-1112538 title: Phosphorylated STAT1, STAT3 form dimers findings: [] - id: Reactome:R-HSA-1112565 title: Tyrosine phosphorylated IL6ST binds STAT1,STAT3 findings: [] - id: Reactome:R-HSA-1112587 title: STAT1 and STAT3 dimers translocate to the nucleus findings: [] - id: Reactome:R-HSA-1112602 title: Tyrosine phosphorylation of STAT1, STAT3 by IL6 receptor findings: [] - id: Reactome:R-HSA-1112604 title: Phosphorylated STATs are released findings: [] - id: Reactome:R-HSA-1112727 title: Serine phosphorylation of STATs findings: [] - id: Reactome:R-HSA-1169406 title: ISGylation of host proteins findings: [] - id: Reactome:R-HSA-1433456 title: Recruitment of STATs findings: [] - id: Reactome:R-HSA-1470009 title: Phosphorylation of STATs findings: [] - id: Reactome:R-HSA-1470010 title: Dimerization of STATs findings: [] - id: Reactome:R-HSA-1470012 title: Disassociation and translocation of STATs to the nucleus findings: [] - id: Reactome:R-HSA-1678841 title: Regulation of protein ISGylation by ISG15 deconjugating enzyme USP18 findings: [] - id: Reactome:R-HSA-1888198 title: FGFR1OP-FGFR1 phosphorylates STAT1 and STAT3 findings: [] - id: Reactome:R-HSA-380782 title: STAT binds to the active receptor findings: [] - id: Reactome:R-HSA-6788571 title: STAT1,STAT3,STAT6 bind IL13:IL13R type II findings: [] - id: Reactome:R-HSA-6788582 title: STAT1,STAT3,STAT6 phosphorylation findings: [] - id: Reactome:R-HSA-6788622 title: p-Y-STATs dimerize findings: [] - id: Reactome:R-HSA-6788623 title: p-Y-STATs translocate to nucleus findings: [] - id: Reactome:R-HSA-6788628 title: p-Y-STATs dissociate findings: [] - id: Reactome:R-HSA-6790041 title: Expression of STAT3-upregulated cytosolic proteins findings: [] - id: Reactome:R-HSA-873917 title: Translocation of STAT1 dimer to nucleus findings: [] - id: Reactome:R-HSA-873921 title: Binding of STAT1 to p-IFNGR1 findings: [] - id: Reactome:R-HSA-873922 title: Phosphorylation of STAT1 by JAK kinases findings: [] - id: Reactome:R-HSA-873927 title: Release of STAT1 dimer from active receptor unit findings: [] - id: Reactome:R-HSA-877281 title: PIAS1 binds p-STAT1 dimer findings: [] - id: Reactome:R-HSA-8950441 title: p-Y701-STAT1 and p-Y705-STAT3 dissociate from IL27:IL27 receptor findings: [] - id: Reactome:R-HSA-8950453 title: JAK1/JAK2 bound to IL12RB2:IL6ST receptor phosphorylates STAT1 and STAT4 findings: [] - id: Reactome:R-HSA-8950485 title: STAT3 and STAT1 are phosphorylated by JAKs after IL27:IL27R interaction findings: [] - id: Reactome:R-HSA-8950518 title: STAT1, STAT3 bind p-Y611-IL27RA from Interleukin-27:Interleukin-27 receptor complex findings: [] - id: Reactome:R-HSA-8950522 title: p-STAT1:p-STAT4 translocates to the nucleus findings: [] - id: Reactome:R-HSA-8950733 title: p-Y701-STAT1:p-Y705-STAT3 translocates to the nucleus findings: [] - id: Reactome:R-HSA-8950782 title: p-STAT1 binds p-STAT3 findings: [] - id: Reactome:R-HSA-8983835 title: JAK1/JAK2/TYK2 bound to IL6ST:IL6ST phosphorylate STAT1 findings: [] - id: Reactome:R-HSA-8983841 title: STAT1 associates with IL6ST:IL6ST findings: [] - id: Reactome:R-HSA-8983845 title: p-STAT1 dissociates from IL6ST:IL6ST findings: [] - id: Reactome:R-HSA-8983983 title: p-STAT1 and p-STAT4 dissociate from IL12RB2:IL6ST receptor findings: [] - id: Reactome:R-HSA-8983996 title: STAT1 and STAT4 associate with IL12RB2:IL6ST receptor findings: [] - id: Reactome:R-HSA-8984014 title: JAK1,JAK2 bound to IL27RA:IL12RB2 receptor phosphorylate STAT1,STAT3 findings: [] - id: Reactome:R-HSA-8984021 title: STAT1,STAT3 associate with IL27RA:IL12RB2 receptor findings: [] - id: Reactome:R-HSA-8984023 title: p-STAT1, p-STAT3 dissociate from IL27RA:IL12RB2 receptor findings: [] - id: Reactome:R-HSA-8985900 title: p-Y701-STAT1, p-Y705-STAT3, p-Y649-STAT5 dissociates from IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3:p-Y705-STAT3 findings: [] - id: Reactome:R-HSA-8985929 title: IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3 binds STAT1, STAT3, STAT5A or STAT5B findings: [] - id: Reactome:R-HSA-8985943 title: p-Y701-STAT1 dimerizes findings: [] - id: Reactome:R-HSA-8985966 title: p-Y701-STAT1 binds p-Y705-STAT3 findings: [] - id: Reactome:R-HSA-8985981 title: p-Y701-STAT1:p-Y705-STAT3 translocates from the cytosol to the nucleus findings: [] - id: Reactome:R-HSA-8985983 title: p-Y701-STAT1 dimer translocates from the cytosol to the nucleus findings: [] - id: Reactome:R-HSA-8985988 title: IL9:p-Y116-IL9R:JAK1:IL2RG:p-904,939-JAK3:STAT3 phosphorylates STAT1, STAT3 or STAT5 findings: [] - id: Reactome:R-HSA-8986985 title: IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:STAT1 phosphorylates STAT1, STAT2, STAT3, STAT4 and STAT5 findings: [] - id: Reactome:R-HSA-8987007 title: p-STAT1 dimerizes findings: [] - id: Reactome:R-HSA-8987033 title: p-STAT1, p-Y-STAT2, p-STAT3, p-STAT4, p-STAT5 dissociates from IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:p-STAT1,p-STAT2,p-STAT3,p-STAT4,p-STAT5 findings: [] - id: Reactome:R-HSA-8987080 title: IL26:IL10RB:p-TYK2:IL20RA:p-JAK1 binds STAT1, STAT3 findings: [] - id: Reactome:R-HSA-8987097 title: IL24:p-IL20RA:p-JAK1:IL20RB binds STAT1,STAT3 findings: [] - id: Reactome:R-HSA-8987150 title: IL24:IL20RA:p-JAK1:IL20RB:STAT1,STAT3 phosphorylates STAT1 or STAT3 findings: [] - id: Reactome:R-HSA-8987218 title: p-STAT1 dimer translocates from the cytosol to the nucleoplasm findings: [] - id: Reactome:R-HSA-8987230 title: p-STAT1 and p-STAT3 dissociates from IL26:IL10RB:p-TYK2:IL20RA:p-JAK1 findings: [] - id: Reactome:R-HSA-8987255 title: IL26:IL10RB:p-TYK2:IL20RA:p-JAK1:STAT1,STAT3 phosphorylates STAT1,STAT3 findings: [] - id: Reactome:R-HSA-8987266 title: IFNL1:p-Y434,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2 binds STAT1, STAT2, STAT3, STAT4, STAT5 findings: [] - id: Reactome:R-HSA-8987270 title: p-STAT1,p-STAT3 dissociate from IL24:IL20RA:p-Y1022,Y1023-JAK1:IL20RB:p-STAT1, p-STAT3 findings: [] - id: Reactome:R-HSA-9006870 title: IL21 receptor STAT phosphorylation findings: [] - id: Reactome:R-HSA-9006873 title: IL21 receptor STAT binding findings: [] - id: Reactome:R-HSA-9021334 title: STAT1 binds HEY1 gene promoter findings: [] - id: Reactome:R-HSA-909552 title: Phosphorylation of STAT1 at Ser727 findings: [] - id: Reactome:R-HSA-909718 title: Formation of p-STAT1 homodimer findings: [] - id: Reactome:R-HSA-909721 title: Translocation of ISGF3 complex to nucleus findings: [] - id: Reactome:R-HSA-909722 title: Release of p-STAT2:p-STAT1 dimer findings: [] - id: Reactome:R-HSA-909725 title: Interaction of IRF9 with p-STAT2:p-STAT1 findings: [] - id: Reactome:R-HSA-909726 title: Phosphorylation of STAT1 findings: [] - id: Reactome:R-HSA-913529 title: Translocation of p-STAT1:p-STAT1 dimer to nucleus findings: [] - id: Reactome:R-HSA-9670412 title: Phosphorylation of STATs downstream of KIT mutants findings: [] - id: Reactome:R-HSA-9670416 title: Recruitment of STATs by KIT mutants findings: [] - id: Reactome:R-HSA-9670417 title: Dimerization of STATs downstream of KIT mutants findings: [] - id: Reactome:R-HSA-9670426 title: Disassociation and translocation of STATs to the nucleus downstream of KIT mutants findings: [] - id: Reactome:R-HSA-9672159 title: 'STAT binds to p-11Y PDGFRA extracellular domain dimers ' findings: [] - id: Reactome:R-HSA-9672176 title: STAT binds to the mutant PDGFRA receptor findings: [] - id: Reactome:R-HSA-9710959 title: p-STAT1 dimer binds KPNA1 findings: [] - id: Reactome:R-HSA-9710963 title: p-STAT1dimer:KPNA1 binds KPNB1 findings: [] - id: Reactome:R-HSA-9729454 title: SARS-CoV-2 N protein binds STAT1, STAT2 findings: [] - id: Reactome:R-HSA-9835443 title: STAT1,STAT3 binds PKR findings: [] - id: Reactome:R-HSA-9851142 title: TYK2-dependent STAT1 and STAT3 phosphorylation findings: [] - id: Reactome:R-HSA-9865511 title: Phosphorylation of STAT1 on tyrosine-701 is enhanced by p-S172-IKBKE findings: [] - id: Reactome:R-HSA-9865524 title: p-Y701-STAT1 binds the NLRP3 gene findings: [] - id: Reactome:R-HSA-997309 title: Dephosphorylation of STAT1 by SHP2 findings: [] - id: Reactome:R-HSA-997326 title: Dephosphorylation of p-STAT1 dimer by nuclear isoform of TCPTP findings: [] - id: file:human/STAT1/STAT1-deep-research-falcon.md title: Falcon deep research report on STAT1 findings: - statement: >- STAT1 is the canonical JAK-STAT pathway transcription factor activated downstream of IFN receptors; phosphorylation on Tyr701 drives dimerization, nuclear translocation, and transcription of IFN-stimulated genes. supporting_text: >- STAT1 is a signal transducer and transcription factor that is activated downstream of cytokine receptors (classically IFN receptors) via receptor-associated **Janus kinases (JAKs)**, leading to STAT phosphorylation, dimerization, nuclear translocation, and transcriptional regulation of IFN-responsive genes. - statement: >- STAT1 contains canonical STAT-family domains (N-terminal, coiled-coil, DNA-binding, linker, SH2, transactivation), with SH2 mediating receptor docking and dimerization via phosphotyrosine interactions. supporting_text: >- Recent authoritative reviews summarize canonical STAT-family domain organization present in STAT1: **N-terminal domain, coiled-coil domain, DNA-binding domain, linker, SH2 domain, and a C-terminal transactivation domain (TAD)**; these domains support receptor docking (via SH2), dimerization (via phosphotyrosine–SH2 interactions), DNA binding, and transcriptional activation. - statement: >- Tyr701 phosphorylation between SH2 and TAD enables STAT1 dimerization and nuclear translocation; Ser727 phosphorylation in the C-terminus modulates transcriptional activity. supporting_text: >- **Tyrosine phosphorylation**: IFN-receptor-associated JAKs phosphorylate STAT1 on a key tyrosine residue (**Tyr701**, located between SH2 and TAD), altering dimerization properties and enabling nuclear translocation and transcriptional activity. - statement: >- STAT1 homodimers form GAF and bind GAS DNA elements (predominantly IFN-gamma response); STAT1-STAT2-IRF9 forms ISGF3 and binds ISRE elements (type I/III IFN response). supporting_text: >- * **STAT1 homodimers** (historically **GAF**, gamma-interferon activation factor) bind **GAS** (gamma-activated sequence) DNA elements. * **STAT1–STAT2 heterodimers** plus **IRF9** form **ISGF3**, which binds **ISRE** (interferon-stimulated response element) DNA elements. - statement: >- STAT1's primary biochemical function is sequence-specific transcriptional regulation as part of IFN-activated transcription factor complexes (GAF and ISGF3) controlling ISG expression. supporting_text: >- STAT1’s primary biochemical function is **sequence-specific transcriptional regulation** as part of IFN-activated transcription factor complexes (GAF and ISGF3), controlling expression of interferon-stimulated genes (ISGs). - statement: >- STAT1 is latent and cytoplasmic at baseline; upon tyrosine phosphorylation it dimerizes and translocates to the nucleus to bind GAS/ISRE DNA elements and regulate transcription. supporting_text: >- STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that **translocate to the nucleus**, where they bind regulatory DNA elements (GAS/ISRE) and regulate transcription. - statement: >- Nuclear import depends on importin alpha/KPNA1; the RSV NS1 protein can block STAT1 nuclear translocation by interfering with KPNA1 binding even when phosphorylation is intact, suppressing ISRE/GAS-driven antiviral gene induction. supporting_text: >- A 2024 mechanistic virology study illustrates that nuclear entry is a critical control point: respiratory syncytial virus (RSV) **NS1** can bind STAT1 and **reduce STAT1 nuclear translocation** (and reduce interaction with nuclear transport adaptor **KPNA1**) even when IFNα-induced STAT1 phosphorylation is enhanced, thereby suppressing ISRE/GAS promoter activity and antiviral gene induction. - statement: >- Cross-cell-type analyses identify 975 ISGs across 11 cell types with a core set of 166 robustly induced by type I IFNs; STAT1 homodimers predominate after IFN-gamma, STAT1-STAT2 heterodimers after type I/III IFN. supporting_text: >- A 2024 JBC review synthesizes a cross-cell-type analysis that identified **975 ISGs across 11 cell types**, including a **core set of 166 ISGs** robustly induced by type I IFNs. This review also emphasizes that tyrosine-phosphorylated STAT1 can form homodimers or STAT1–STAT2 heterodimers, and that the relative abundance depends on IFN type (more persistent STAT1 homodimers after IFNγ; STAT1–STAT2 heterodimers predominate after type I/III IFNs). - statement: >- Time-resolved ChIP/RNA-seq shows GAS-driven genes respond early while ISRE-driven genes predominate later, with ISRE+GAS composite promoters serving as switch-like regulatory elements integrating IFNalpha and IFNgamma programs. supporting_text: >- The study reported **108 IFNα-specific** and **75 IFNγ-specific** integrated genes, and found that **GAS genes tend to be early responders** while **ISRE genes predominate later**, with **ISRE+GAS composite sites** acting as switch-like regulatory elements enabling mechanistic overlap between IFNα and IFNγ programs. - statement: >- STAT1 GOF is the most common STAT1 defect (>100 variants in >400 patients) and is associated with chronic mucocutaneous candidiasis in over 60% of patients; AR complete STAT1 deficiency abolishes type I/II/III IFN and IL-27 signaling and causes severe early-life infections. supporting_text: >- A 2024 clinical-genetics review reports that **STAT1 GOF is the most common STAT1 defect**, with **>100 different variants** described in **>400 patients**, and **chronic mucocutaneous candidiasis (CMC)** occurring in **>60%** of individuals with STAT1 GOF. 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 alternative_products: - name: Alpha (p91) id: P42224-1 - name: Beta (p84) id: P42224-2 sequence_note: VSP_006282