Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: PMID:9630226 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 file:human/STAT1/STAT1-deep-research-falcon.md STAT1 homodimers (historically GAF, gamma-interferon activation factor) bind GAS** (gamma-activated sequence) DNA elements
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research.md STAT1 regulates a vast network of target genes, with over 300 interferon-stimulated genes (ISGs) identified through experimental validation file:human/STAT1/STAT1-deep-research-falcon.md 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).
GO:0003677 DNA binding	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	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. 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.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000002	ACCEPT	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. 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.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IEA GO_REF:0000117	ACCEPT	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.
GO:0005515 protein binding	IPI PMID:11238845 Vaccinia virus blocks gamma interferon signal transduction: ...	MARK AS OVER ANNOTATED	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. Supporting Evidence: PMID:11238845 Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase reverses Stat1 activation.
GO:0005515 protein binding	IPI PMID:12070153 Identification of both positive and negative domains within ...	MARK AS OVER ANNOTATED	Summary: Study shows STAT1 binding to EGFR domains. Generic protein binding term lacks specificity about STAT1's functional protein interactions. Supporting Evidence: PMID:12070153 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.
GO:0005515 protein binding	IPI PMID:12788789 STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene...	MARK AS OVER ANNOTATED	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. Supporting Evidence: PMID:12788789 STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation.
GO:0005515 protein binding	IPI PMID:15780933 Structural bases of unphosphorylated STAT1 association and r...	MARK AS OVER ANNOTATED	Summary: Paper describes structural basis of STAT1 receptor binding interactions. Generic protein binding term lacks functional specificity. Supporting Evidence: PMID:15780933 Structural bases of unphosphorylated STAT1 association and receptor binding.
GO:0005515 protein binding	IPI PMID:15825084 Hepatitis C virus expression suppresses interferon signaling...	MARK AS OVER ANNOTATED	Summary: Shows HCV core protein degrading STAT1 to suppress interferon signaling. Generic term doesn't capture the functional significance of this pathogen-host interaction. Supporting Evidence: PMID:15825084 Hepatitis C virus expression suppresses interferon signaling by degrading STAT1.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: Large-scale proteome interaction mapping study. While it may identify STAT1 interactions, the generic protein binding term provides minimal functional insight. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network.
GO:0005515 protein binding	IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece...	MARK AS OVER ANNOTATED	Summary: ErbB receptor protein microarray study. Mass interaction data lacks specific functional context for STAT1. Supporting Evidence: PMID:16273093 A quantitative protein interaction network for the ErbB receptors using protein microarrays.
GO:0005515 protein binding	IPI PMID:16940534 Hepatitis C virus core protein blocks interferon signaling b...	MARK AS OVER ANNOTATED	Summary: HCV core protein blocking STAT1 SH2 domain interactions. While functionally relevant, generic protein binding doesn't capture the mechanistic detail. Supporting Evidence: PMID:16940534 Hepatitis C virus core protein blocks interferon signaling by interaction with the STAT1 SH2 domain.
GO:0005515 protein binding	IPI PMID:17275127 HCV NS5A inhibits interferon-alpha signaling through suppres...	MARK AS OVER ANNOTATED	Summary: HCV NS5A suppressing STAT1 phosphorylation. Generic protein binding term lacks functional specificity for this pathogen-mediated inhibition. Supporting Evidence: PMID:17275127 Dec 14. HCV NS5A inhibits interferon-alpha signaling through suppression of STAT1 phosphorylation in hepatocyte-derived cell lines.
GO:0005515 protein binding	IPI PMID:17596301 Severe acute respiratory syndrome coronavirus ORF6 antagoniz...	MARK AS OVER ANNOTATED	Summary: SARS-CoV ORF6 antagonizing STAT1 nuclear import. While this demonstrates pathogen-host protein interaction, the generic term lacks functional context. Supporting Evidence: PMID:17596301 Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane.
GO:0005515 protein binding	IPI PMID:17923090 Acetylation-dependent signal transduction for type I interfe...	MARK AS OVER ANNOTATED	Summary: Study on acetylation-dependent interferon receptor signaling. Generic protein binding term doesn't capture the regulatory complexity of STAT1 interactions. Supporting Evidence: PMID:17923090 Acetylation-dependent signal transduction for type I interferon receptor.
GO:0005515 protein binding	IPI PMID:20195357 A comprehensive resource of interacting protein regions for ...	MARK AS OVER ANNOTATED	Summary: Comprehensive resource of transcription factor interaction networks. Large-scale interaction data lacks specific functional context. Supporting Evidence: PMID:20195357 A comprehensive resource of interacting protein regions for refining human transcription factor networks.
GO:0005515 protein binding	IPI PMID:20576130 Activated networking of platelet activating factor receptor ...	MARK AS OVER ANNOTATED	Summary: PAFR and FAK/STAT1 networking in BRCA1-mutant ovarian epithelium. Context-specific interaction that is better described by more specific terms. Supporting Evidence: PMID:20576130 Activated networking of platelet activating factor receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium.
GO:0005515 protein binding	IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ...	MARK AS OVER ANNOTATED	Summary: Mapping innate immunity protein interaction networks regulating type I interferon. While functionally relevant, generic term lacks specificity. Supporting Evidence: PMID:21903422 2011 Sep 8. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production.
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	MARK AS OVER ANNOTATED	Summary: Human liver protein interaction network study. Large-scale proteomic data without specific functional context for STAT1. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver.
GO:0005515 protein binding	IPI PMID:24065129 IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate r...	MARK AS OVER ANNOTATED	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. Supporting Evidence: PMID:24065129 IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage.
GO:0005515 protein binding	IPI PMID:24360797 Hepatic RIG-I predicts survival and interferon-α therapeutic...	MARK AS OVER ANNOTATED	Summary: RIG-I interaction with STAT1 in hepatocellular carcinoma interferon response. Generic protein binding lacks mechanistic specificity. Supporting Evidence: PMID:24360797 2013 Dec 19. Hepatic RIG-I predicts survival and interferon-α therapeutic response in hepatocellular carcinoma.
GO:0005515 protein binding	IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ...	MARK AS OVER ANNOTATED	Summary: Mammalian membrane two-hybrid assay for membrane protein interactions. Technical methodology paper with limited functional insight. Supporting Evidence: PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	MARK AS OVER ANNOTATED	Summary: In situ proximity ligation assay for pathway protein interactions. Methodological study without specific functional context for STAT1. Supporting Evidence: PMID:25241761 Oct 9. Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Large-scale proteome-scale human interactome network mapping. Generic interaction data without specific functional context. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network.
GO:0005515 protein binding	IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ...	MARK AS OVER ANNOTATED	Summary: Proteomic analysis of chromatin-associated vs. soluble transcription factor complexes. While relevant to STAT1's transcriptional function, generic protein binding lacks specificity. Supporting Evidence: PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
GO:0005515 protein binding	IPI PMID:26889034 VP8, the Major Tegument Protein of Bovine Herpesvirus 1, Int...	MARK AS OVER ANNOTATED	Summary: Bovine herpesvirus VP8 protein interacting with STAT1 to inhibit interferon signaling. Pathogen-host interaction better described by more specific terms. Supporting Evidence: PMID:26889034 May 15. VP8, the Major Tegument Protein of Bovine Herpesvirus 1, Interacts with Cellular STAT1 and Inhibits Interferon Beta Signaling.
GO:0005515 protein binding	IPI PMID:26966684 PIPINO: A Software Package to Facilitate the Identification ...	MARK AS OVER ANNOTATED	Summary: PIPINO software for protein-protein interaction identification from mass spectrometry. Computational methodology paper with limited functional context. Supporting Evidence: PMID:26966684 PIPINO: A Software Package to Facilitate the Identification of Protein-Protein Interactions from Affinity Purification Mass Spectrometry Data.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	MARK AS OVER ANNOTATED	Summary: EGFR network rewiring in KRAS-mutant colorectal cancer cells. Cancer-specific context where generic protein binding lacks functional detail. Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
GO:0005515 protein binding	IPI PMID:32953130 SARS-CoV-2 N protein antagonizes type I interferon signaling...	MARK AS OVER ANNOTATED	Summary: SARS-CoV-2 N protein antagonizing STAT1/STAT2 interferon signaling. While functionally relevant pathogen-host interaction, generic term lacks mechanistic detail. Supporting Evidence: PMID:32953130 SARS-CoV-2 N protein antagonizes type I interferon signaling by suppressing phosphorylation and nuclear translocation of STAT1 and STAT2.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Cell-specific remodeling of human interactome networks. Large-scale proteomic data without specific functional context. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:34950606 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)...	MARK AS OVER ANNOTATED	Summary: SARS-CoV-2 M and S proteins antagonizing interferon response. Viral interference with STAT1, but generic term lacks mechanistic detail. Supporting Evidence: PMID:34950606 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response.
GO:0005515 protein binding	IPI PMID:35140242 Human transcription factor protein interaction networks.	MARK AS OVER ANNOTATED	Summary: Human transcription factor protein interaction networks. Large-scale interaction mapping without specific functional context. Supporting Evidence: PMID:35140242 Human transcription factor protein interaction networks.
GO:0005515 protein binding	IPI PMID:8156998 Ligand-induced IFN gamma receptor tyrosine phosphorylation c...	MARK AS OVER ANNOTATED	Summary: IFN-γ receptor tyrosine phosphorylation coupling to STAT1 signal transduction. While this demonstrates functional receptor-STAT1 interaction, generic term lacks specificity. Supporting Evidence: PMID:8156998 Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91).
GO:0005515 protein binding	IPI PMID:8605877 The SH2 domains of Stat1 and Stat2 mediate multiple interact...	MARK AS OVER ANNOTATED	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. Supporting Evidence: PMID:8605877 The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN-alpha signals.
GO:0005515 protein binding	IPI PMID:8662591 Differential activation of acute phase response factor/STAT3...	MARK AS OVER ANNOTATED	Summary: Differential STAT3/STAT1 activation via gp130 cytoplasmic domain. Shows STAT1 receptor interactions but generic term lacks functional specificity. Supporting Evidence: PMID:8662591 Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130.
GO:0005515 protein binding	IPI PMID:9121453 Functional subdomains of STAT2 required for preassociation w...	MARK AS OVER ANNOTATED	Summary: STAT2 functional subdomains for IFN-α receptor interaction and signaling. Shows STAT1-STAT2 heterodimerization but generic term lacks specificity. Supporting Evidence: PMID:9121453 Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling.
GO:0005515 protein binding	IPI PMID:9881977 Direct suppression of Stat1 function during adenoviral infec...	MARK AS OVER ANNOTATED	Summary: Adenoviral suppression of STAT1 function. Pathogen-host interaction where generic protein binding lacks mechanistic detail. Supporting Evidence: PMID:9881977 Direct suppression of Stat1 function during adenoviral infection.
GO:0042802 identical protein binding	IPI PMID:8605877 The SH2 domains of Stat1 and Stat2 mediate multiple interact...	ACCEPT	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. Supporting Evidence: PMID:8605877 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 file:human/STAT1/STAT1-deep-research-falcon.md receptor docking (via SH2), dimerization (via phosphotyrosine–SH2 interactions), DNA binding, and transcriptional activation
GO:0042802 identical protein binding	IPI PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer ...	ACCEPT	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. Supporting Evidence: PMID:9630226 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
GO:0031730 CCR5 chemokine receptor binding	IEA GO_REF:0000107	REMOVE	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. 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.
GO:0043565 sequence-specific DNA binding	IEA GO_REF:0000107	ACCEPT	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. 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. Supporting Evidence: PMID:9630226 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
GO:0051721 protein phosphatase 2A binding	IEA GO_REF:0000107	REMOVE	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. 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.
GO:0071345 cellular response to cytokine stimulus	IEA GO_REF:0000107	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research.md 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 file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IDA PMID:32209697 Noncanonical STAT1 phosphorylation expands its transcription...	ACCEPT	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. Supporting Evidence: PMID:32209697 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
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IDA PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphoryla...	ACCEPT	Summary: Requirement of Ca2+ and CaMKII for STAT1 Ser-727 phosphorylation in IFN-γ response. Demonstrates STAT1's transcriptional activation function with experimental evidence. Supporting Evidence: PMID:11972023 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
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: SETD2-mediated methylation of STAT1 critical for interferon antiviral activity. Strong experimental evidence for STAT1's transcription factor function. Supporting Evidence: PMID:28753426 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
GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT	IDA PMID:16257975 The conserved Leu-724 residue is required for both serine ph...	MODIFY	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"). Proposed replacements: positive regulation of receptor signaling pathway via JAK-STAT Supporting Evidence: PMID:16257975 the conserved Leu-724 residue is also essential for gene activation mediated by Stat1.
GO:0003700 DNA-binding transcription factor activity	IDA PMID:9535918 Heteromerization of the gammac chain with the interleukin-9 ...	ACCEPT	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. Supporting Evidence: PMID:9535918 Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis
GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA PMID:22002246 A novel disrupter of telomere silencing 1-like (DOT1L) inter...	ACCEPT	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. Supporting Evidence: PMID:22002246 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
GO:0001223 transcription coactivator binding	IPI PMID:22002246 A novel disrupter of telomere silencing 1-like (DOT1L) inter...	ACCEPT	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. Supporting Evidence: PMID:22002246 Domain mapping identifies the middle region of DOT1L (amino acids 580–1183) as the STAT1 interaction domain.
GO:0001222 transcription corepressor binding	IPI PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STA...	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:23386060 hcaf1/cnot7 regulates interferon signalling by targeting stat1
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ISA GO_REF:0000113	ACCEPT	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. 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.
GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding	IDA PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STA...	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:23386060 Consistently, hCAF1 silencing enhances STAT1 basal promoter occupancy associated with increased expression of a subset of STAT1-regulated genes
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	REMOVE	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. 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. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA PMID:21268089 Molecular mechanisms underlying the inhibition of IFN-γ-indu...	ACCEPT	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. Supporting Evidence: PMID:21268089 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.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IDA PMID:21268089 Molecular mechanisms underlying the inhibition of IFN-γ-indu...	ACCEPT	Summary: Another duplicate of STAT1's core transcription factor function with strong experimental evidence. Consistent with previous assessments. Supporting Evidence: PMID:21268089 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.
GO:0005515 protein binding	IPI PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	MARK AS OVER ANNOTATED	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. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0005634 nucleus	IDA PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	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. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
GO:0019899 enzyme binding	IPI PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	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. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
GO:0035035 histone acetyltransferase binding	IPI PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	Summary: STAT1 interacts with histone-modifying enzymes as part of transcriptional activation complexes. This reflects STAT1's role in chromatin regulation during gene activation. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
GO:0042393 histone binding	IPI PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	MARK AS OVER ANNOTATED	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.) 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. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
GO:0044389 ubiquitin-like protein ligase binding	IPI PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	Summary: STAT1 regulation involves ubiquitin-like modifications and interactions with ligases for protein stability and localization control. This is a relevant regulatory mechanism. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	KEEP AS NON CORE	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. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0005515 protein binding	IPI PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	MARK AS OVER ANNOTATED	Summary: SETD2 methyltransferase interaction with STAT1. While this is a functionally important interaction for STAT1 regulation, the generic protein binding term lacks specificity. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0042803 protein homodimerization activity	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	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. Supporting Evidence: PMID:28753426 SETD2 directly mediates STAT1 methylation on lysine 525 via its methyltransferase activity, which reinforces IFN-activated STAT1 phosphorylation and antiviral cellular response file:human/STAT1/STAT1-deep-research-falcon.md STAT1 exists in unphosphorylated/preassociated states at baseline and, upon tyrosine phosphorylation, forms dimers that translocate to the nucleus
GO:0003700 DNA-binding transcription factor activity	IDA PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STA...	ACCEPT	Summary: hCAF1/CNOT7 regulation of STAT1. Strong experimental evidence for STAT1's transcriptional function, though RNA polymerase II-specific terms are more precise. Supporting Evidence: PMID:23386060 Consistently, hCAF1 silencing enhances STAT1 basal promoter occupancy associated with increased expression of a subset of STAT1-regulated genes.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA PMID:18035482 Regulation of XAF1 expression in human colon cancer cell by ...	ACCEPT	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. Supporting Evidence: PMID:18035482 Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1
GO:0005515 protein binding	IPI PMID:12867595 The cell death regulator GRIM-19 is an inhibitor of signal t...	MARK AS OVER ANNOTATED	Summary: GRIM-19 as inhibitor of STAT3, may also interact with STAT1. Generic protein binding term lacks functional specificity. Supporting Evidence: PMID:12867595 The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3.
GO:0043542 endothelial cell migration	IMP NOT PMID:16585190 Signal transducer and activator of transcription 1 activatio...	ACCEPT	Summary: PMID:16585190 reports STAT1 activation inhibits angiogenesis and tube formation; GOA captures this PMID as NOT involved in endothelial cell migration. 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. Supporting Evidence: PMID:16585190 Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis
GO:0003700 DNA-binding transcription factor activity	IDA PMID:10973496 Nucleocytoplasmic translocation of Stat1 is regulated by a l...	ACCEPT	Summary: Nucleocytoplasmic translocation of STAT1 regulated by leucine-rich export signal. Strong experimental evidence for STAT1's transcriptional function. Supporting Evidence: PMID:10973496 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
GO:0005164 tumor necrosis factor receptor binding	IPI PMID:10848577 Stat1 as a component of tumor necrosis factor alpha receptor...	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:10848577 Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation
GO:0005515 protein binding	IPI PMID:10848577 Stat1 as a component of tumor necrosis factor alpha receptor...	MARK AS OVER ANNOTATED	Summary: STAT1-TNFR interaction. Generic protein binding lacks functional specificity for this cross-pathway interaction. Supporting Evidence: PMID:10848577 Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation.
GO:0003690 double-stranded DNA binding	IDA PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer ...	ACCEPT	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. Supporting Evidence: PMID:9630226 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
GO:0042803 protein homodimerization activity	IDA PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer ...	ACCEPT	Summary: Crystal structure provides definitive evidence for STAT1 homodimerization through reciprocal SH2-phosphotyrosine interactions. This is a core molecular function. Supporting Evidence: PMID:9630226 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
GO:0005515 protein binding	IPI PMID:16531398 Tid1 isoforms are mitochondrial DnaJ-like chaperones with un...	MARK AS OVER ANNOTATED	Summary: Tid1 isoforms as mitochondrial DnaJ-like chaperones interacting with STAT1. Generic protein binding lacks functional context for this chaperone interaction. Supporting Evidence: PMID:16531398 Epub 2006 Mar 10. Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique carboxyl termini that determine cytosolic fate.
GO:0005515 protein binding	IPI PMID:16306601 Respiratory syncytial virus-inducible BCL-3 expression antag...	MARK AS OVER ANNOTATED	Summary: RSV-inducible BCL-3 antagonizing STAT/IRF and NF-κB signaling. Pathogen-mediated interference with STAT1 signaling, but generic term lacks specificity. Supporting Evidence: PMID:16306601 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.
GO:0005515 protein binding	IPI PMID:34521819 Could not retrieve title - publication not available	UNDECIDED	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. 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.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md STAT1 executes its transcriptional role in the nucleus at IFN-responsive promoters/enhancers.
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: STAT1 directly regulates RNA polymerase II-dependent transcription of interferon-stimulated genes. Core function. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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).
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0006952 defense response	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md A 2024 review summarizes autosomal recessive complete STAT1 deficiency as abolishing type I/II/III IFN and IL-27 signaling
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Latent STAT1 is cytoplasmic and acts in the cytoplasm to receive cytokine-receptor-driven JAK phosphorylation prior to nuclear translocation. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md In resting cells, STAT1 is largely cytoplasmic or shuttling in unphosphorylated/preassociated forms; after tyrosine phosphorylation it forms dimers that translocate to the nucleus.
GO:0042127 regulation of cell population proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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).
GO:0043434 response to peptide hormone	IBA GO_REF:0000033	KEEP AS NON CORE	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. 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.
GO:0060337 type I interferon-mediated signaling pathway	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md STAT1–STAT2 heterodimers plus IRF9 form ISGF3, which binds ISRE** (interferon-stimulated response element) DNA elements.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: STAT1 translocates to the nucleus upon activation to act as a transcription factor; nuclear localization is well established. Reason: Nuclear localization is a core, experimentally validated aspect of STAT1 biology; the IEA term is correct.
GO:0005654 nucleoplasm	IEA GO_REF:0000117	ACCEPT	Summary: Activated STAT1 dimers/ISGF3 act in the nucleoplasm at target-gene promoters. Reason: Nucleoplasmic localization is consistent with STAT1's role as a nuclear transcription factor and is supported by experimental nuclear/nucleoplasm annotations.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: STAT1 regulates transcription of its target genes; this broad term is subsumed by the more specific RNA Pol II transcription-factor annotations. Reason: A correct but general transcription-regulation term; acceptable as a broad parent of STAT1's specific transcriptional roles.
GO:0007165 signal transduction	IEA GO_REF:0000002	ACCEPT	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. Reason: Generic signal transduction is a true parent of STAT1's JAK-STAT signaling role; acceptable though more specific terms are preferred.
GO:0042981 regulation of apoptotic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: STAT1 regulates apoptosis, chiefly by inducing pro-apoptotic genes (caspases, Fas/TRAIL) downstream of interferon signaling. Reason: Regulation of apoptosis is a downstream consequence of STAT1 transcriptional output rather than a core molecular function; biologically valid but non-core.
GO:0051093 negative regulation of developmental process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: STAT1 can negatively regulate certain developmental processes (e.g. angiogenesis, mesenchymal-to-epithelial transitions), consistent with this broad term. Reason: Negative regulation of developmental processes reflects context-specific, pleiotropic outputs of STAT1, not its core interferon-signaling function.
GO:0051607 defense response to virus	IEA GO_REF:0000120	ACCEPT	Summary: STAT1 drives interferon-induced antiviral gene programs (ISGs); STAT1 LOF abolishes IFN responses with severe viral disease. Core function. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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
GO:0060333 type II interferon-mediated signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: STAT1 homodimers form GAF and bind GAS DNA elements, mediating the type II (IFN-gamma) signaling pathway. Core function. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md STAT1 homodimers (historically GAF, gamma-interferon activation factor) bind GAS** (gamma-activated sequence) DNA elements.
GO:0060337 type I interferon-mediated signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: STAT1 (with STAT2 and IRF9) forms ISGF3 to mediate type I IFN signaling and binds ISRE elements; central, well-established function. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md STAT1–STAT2 heterodimers plus IRF9 form ISGF3, which binds ISRE** (interferon-stimulated response element) DNA elements.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	NAS PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique s...	ACCEPT	Summary: STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. Reason: JAK-STAT signal transduction is a core STAT1 function directly supported here. Supporting Evidence: PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique signal? Delgoffe GM(1), Vignali DA.
GO:0045944 positive regulation of transcription by RNA polymerase II	NAS PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique s...	ACCEPT	Summary: STAT1 directly drives positive transcription of interferon/cytokine target genes by RNA polymerase II (e.g. XAF1, IL12B, antiviral ISGs). Reason: Positive regulation of RNA Pol II transcription is a core STAT1 function with strong direct and structural support. Supporting Evidence: PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique signal? Delgoffe GM(1), Vignali DA.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:24065129 IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate r...	ACCEPT	Summary: STAT1 (as ISGF3 component) drives positive transcriptional regulation of antiviral genes by RNA polymerase II. Core function supported by direct experimental evidence. Supporting Evidence: PMID:24065129 IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. file:human/STAT1/STAT1-deep-research-falcon.md 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).
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IEA GO_REF:0000120	ACCEPT	Summary: STAT1 is the canonical signal transducer of the JAK-STAT cell surface receptor signaling pathway. Reason: This is a core function of STAT1, well supported across the literature; the IEA term is correct. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0007584 response to nutrient	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0008015 blood circulation	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0008284 positive regulation of cell population proliferation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. 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.
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0009612 response to mechanical stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0032869 cellular response to insulin stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0034097 response to cytokine	IEA GO_REF:0000107	ACCEPT	Summary: STAT1 mediates cellular responses to numerous cytokines through the JAK-STAT pathway. Reason: Response to cytokine is a core aspect of STAT1 function and is well supported.
GO:0042542 response to hydrogen peroxide	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0043434 response to peptide hormone	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0045429 positive regulation of nitric oxide biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0048661 positive regulation of smooth muscle cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0051591 response to cAMP	IEA GO_REF:0000107	KEEP AS NON CORE	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. 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.
GO:0097696 cell surface receptor signaling pathway via STAT	IDA PMID:18035482 Regulation of XAF1 expression in human colon cancer cell by ...	ACCEPT	Summary: STAT1 mediates cell surface receptor signaling via STAT, activating XAF1 expression downstream of IFN-beta in colon cancer cells. Reason: STAT-mediated receptor signaling is core to STAT1; directly supported. Supporting Evidence: PMID:18035482 Epub 2007 Nov 26. Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	NAS PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer ...	ACCEPT	Summary: STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. Reason: JAK-STAT signal transduction is a core STAT1 function directly supported here. Supporting Evidence: PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA.
GO:0045944 positive regulation of transcription by RNA polymerase II	NAS PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer ...	ACCEPT	Summary: STAT1 directly drives positive transcription of interferon/cytokine target genes by RNA polymerase II (e.g. XAF1, IL12B, antiviral ISGs). Reason: Positive regulation of RNA Pol II transcription is a core STAT1 function with strong direct and structural support. Supporting Evidence: PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence localizes STAT1 to the nucleoplasm, consistent with its active nuclear form. Reason: Nucleoplasmic localization is consistent with STAT1's core nuclear transcription-factor function.
GO:0005634 nucleus	IDA PMID:32209697 Noncanonical STAT1 phosphorylation expands its transcription...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:32209697 Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:32209697 Noncanonical STAT1 phosphorylation expands its transcription...	ACCEPT	Summary: STAT1 directly drives positive transcription of interferon/cytokine target genes by RNA polymerase II (e.g. XAF1, IL12B, antiviral ISGs). Reason: Positive regulation of RNA Pol II transcription is a core STAT1 function with strong direct and structural support. Supporting Evidence: PMID:32209697 Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production.
GO:0038111 interleukin-7-mediated signaling pathway	IDA PMID:29202461 IL-7-dependent STAT1 activation limits homeostatic CD4+ T ce...	KEEP AS NON CORE	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. Reason: IL-7-mediated STAT1 signaling is a context-specific (lymphopenia) role; biologically supported but peripheral to STAT1's core interferon function. Supporting Evidence: PMID:29202461 under lymphopenic conditions, there is a modulation of STAT1 expression resulting in an IL-7-dependent STAT1 and STAT5 activation
GO:0005634 nucleus	IC PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0005634 nucleus	IDA PMID:18035482 Regulation of XAF1 expression in human colon cancer cell by ...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:18035482 Epub 2007 Nov 26. Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.
GO:0060337 type I interferon-mediated signaling pathway	IDA PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STA...	ACCEPT	Summary: STAT1 directly mediates 'type I interferon-mediated signaling pathway', a core interferon- response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphoryla...	ACCEPT	Summary: STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. Reason: JAK-STAT signal transduction is a core STAT1 function directly supported here. Supporting Evidence: PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.
GO:0034341 response to type II interferon	IDA PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphoryla...	ACCEPT	Summary: STAT1 directly mediates 'response to type II interferon', a core interferon-response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.
GO:0005634 nucleus	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. Reason: JAK-STAT signal transduction is a core STAT1 function directly supported here. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0035458 cellular response to interferon-beta	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: STAT1 directly mediates 'cellular response to interferon-beta', a core interferon-response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0071346 cellular response to type II interferon	IDA PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphoryla...	ACCEPT	Summary: STAT1 directly mediates 'cellular response to type II interferon', a core interferon- response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.
GO:0006357 regulation of transcription by RNA polymerase II	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: SETD2-mediated methylation of STAT1 modulates STAT1-dependent transcription of ISGs by RNA Pol II. Reason: Regulation of RNA Pol II transcription is core to STAT1; directly supported. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0005634 nucleus	IDA PMID:15322115 Protein kinase Cdelta regulates apoptosis via activation of ...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:15322115 2004 Aug 20. Protein kinase Cdelta regulates apoptosis via activation of STAT1.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:22002246 A novel disrupter of telomere silencing 1-like (DOT1L) inter...	ACCEPT	Summary: STAT1 is activated as the signal transducer of the JAK-STAT pathway in this study, downstream of cytokine/interferon receptors. Reason: JAK-STAT signal transduction is a core STAT1 function directly supported here. Supporting Evidence: PMID:22002246 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.
GO:0005634 nucleus	IC PMID:9535918 Heteromerization of the gammac chain with the interleukin-9 ...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:9535918 Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis.
GO:0038113 interleukin-9-mediated signaling pathway	IDA PMID:9535918 Heteromerization of the gammac chain with the interleukin-9 ...	KEEP AS NON CORE	Summary: STAT1 is activated downstream of the IL-9 receptor (gammac/IL-9Ralpha), participating in IL-9-mediated signaling and apoptosis prevention. Reason: IL-9-mediated STAT1 signaling is a specific cytokine-context role, peripheral to STAT1's core interferon function. Supporting Evidence: PMID:9535918 Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis
GO:0070106 interleukin-27-mediated signaling pathway	IDA PMID:32270034 IL-27 signaling activates skin cells to induce innate antivi...	KEEP AS NON CORE	Summary: IL-27 activates STAT1 in skin cells to induce innate antiviral proteins, placing STAT1 in the IL-27-mediated signaling pathway. Reason: IL-27-mediated STAT1 signaling is a specific cytokine-context antiviral role; supported but non-core relative to interferon signaling. Supporting Evidence: PMID:32270034 IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.
GO:1990841 promoter-specific chromatin binding	IDA PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	Summary: STAT1 binds specific gene promoters (promoter-specific chromatin binding) to activate ISGs, consistent with its sequence-specific transcription-factor function. Reason: Promoter-specific chromatin binding is a core molecular feature of STAT1 as a DNA-binding transcription factor. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0000785 chromatin	ISA GO_REF:0000113	ACCEPT	Summary: As a DNA-binding transcription factor, STAT1 localizes to chromatin at target-gene promoters. Reason: Chromatin localization is consistent with STAT1's core transcription-factor function and is additionally supported by promoter-occupancy/ChIP data.
GO:0002230 positive regulation of defense response to virus by host	IMP PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	Summary: STAT1, via PARP9-DTX3L-enhanced interferon signaling, positively regulates the host antiviral defense response. Reason: Positive regulation of host antiviral defense is central to STAT1 function and is directly supported. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0002230 positive regulation of defense response to virus by host	IGI PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	Summary: STAT1, via PARP9-DTX3L-enhanced interferon signaling, positively regulates the host antiviral defense response. Reason: Positive regulation of host antiviral defense is central to STAT1 function and is directly supported. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0045893 positive regulation of DNA-templated transcription	IMP PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	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). 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. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0045893 positive regulation of DNA-templated transcription	IGI PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	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). 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. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0060333 type II interferon-mediated signaling pathway	IMP PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	Summary: STAT1 directly mediates 'type II interferon-mediated signaling pathway', a core interferon-response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0032727 positive regulation of interferon-alpha production	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	KEEP AS NON CORE	Summary: SETD2-methylated STAT1 reinforces interferon antiviral responses including IFN-alpha production in a positive feedback loop. 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. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0051607 defense response to virus	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: STAT1 directly mediates 'defense response to virus', a core interferon-response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0005634 nucleus	IDA PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STA...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.
GO:0071346 cellular response to type II interferon	IDA PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STA...	ACCEPT	Summary: STAT1 directly mediates 'cellular response to type II interferon', a core interferon- response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.
GO:0045648 positive regulation of erythrocyte differentiation	IMP PMID:28283061 Functional Selectivity in Cytokine Signaling Revealed Throug...	KEEP AS NON CORE	Summary: A pathogenic EPO mutation study implicates STAT1 (alongside STAT5) in cytokine signaling affecting erythroid differentiation. Reason: Erythrocyte differentiation is a specialized, context-dependent role downstream of cytokine receptor signaling, peripheral to STAT1's core interferon function. Supporting Evidence: PMID:28283061 Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation.
GO:0005634 nucleus	IDA PMID:15825084 Hepatitis C virus expression suppresses interferon signaling...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:15825084 Hepatitis C virus expression suppresses interferon signaling by degrading STAT1.
GO:0035456 response to interferon-beta	IMP PMID:24882218 Unanchored K48-linked polyubiquitin synthesized by the E3-ub...	ACCEPT	Summary: STAT1 directly mediates 'response to interferon-beta', a core interferon-response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:24882218 2014 May 29. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response.
GO:0046725 negative regulation by virus of viral protein levels in host cell	IMP PMID:15825084 Hepatitis C virus expression suppresses interferon signaling...	KEEP AS NON CORE	Summary: In the HCV system, STAT1-driven interferon signaling restricts viral protein levels; HCV core counteracts this by degrading STAT1. 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. Supporting Evidence: PMID:15825084 Hepatitis C virus expression suppresses interferon signaling by degrading STAT1.
GO:0035458 cellular response to interferon-beta	IMP PMID:18035482 Regulation of XAF1 expression in human colon cancer cell by ...	ACCEPT	Summary: STAT1 directly mediates 'cellular response to interferon-beta', a core interferon-response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:18035482 Epub 2007 Nov 26. Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:18035482 Regulation of XAF1 expression in human colon cancer cell by ...	ACCEPT	Summary: STAT1 directly drives positive transcription of interferon/cytokine target genes by RNA polymerase II (e.g. XAF1, IL12B, antiviral ISGs). Reason: Positive regulation of RNA Pol II transcription is a core STAT1 function with strong direct and structural support. Supporting Evidence: PMID:18035482 Epub 2007 Nov 26. Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.
GO:0060333 type II interferon-mediated signaling pathway	ISS GO_REF:0000024	ACCEPT	Summary: STAT1 homodimers (GAF) mediate the type II (IFN-gamma) signaling pathway. Reason: Core STAT1 function; the ISS annotation duplicates the well-supported type II IFN signaling role. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md * STAT1 homodimers (historically GAF, gamma-interferon activation factor) bind GAS (gamma-activated sequence) DNA elements.
GO:0060337 type I interferon-mediated signaling pathway	ISS GO_REF:0000024	ACCEPT	Summary: STAT1 (with STAT2/IRF9 as ISGF3) mediates the type I IFN signaling pathway. Reason: Core STAT1 function; ISS annotation duplicates the well-supported type I IFN signaling role. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md STAT1–STAT2 heterodimers plus IRF9 form ISGF3, which binds ISRE (interferon-stimulated response element) DNA elements.
GO:0000785 chromatin	IDA PMID:18035482 Regulation of XAF1 expression in human colon cancer cell by ...	ACCEPT	Summary: STAT1 binds chromatin at the ISRE of the XAF1 promoter (quantitative ChIP), directly demonstrating chromatin localization. Reason: Direct ChIP evidence supports STAT1 chromatin localization, consistent with its core DNA- binding transcription-factor function. Supporting Evidence: PMID:18035482 Epub 2007 Nov 26. Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.
GO:0000122 negative regulation of transcription by RNA polymerase II	ISS GO_REF:0000024	KEEP AS NON CORE	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. 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.
GO:0001937 negative regulation of endothelial cell proliferation	IMP PMID:16585190 Signal transducer and activator of transcription 1 activatio...	KEEP AS NON CORE	Summary: IFN-gamma-activated STAT1 in endothelial cells inhibits proliferation and tube formation, negatively regulating endothelial cell proliferation. Reason: Endothelial antiproliferative/antiangiogenic activity is a context-specific downstream output of STAT1 signaling, peripheral to its core interferon transcription-factor role. Supporting Evidence: PMID:16585190 IFN-gamma inhibited cell growth and tube formation of HUVECs
GO:0002053 positive regulation of mesenchymal cell proliferation	ISS GO_REF:0000024	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:20861313 STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.
GO:0003340 negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	ISS GO_REF:0000024	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:20861313 STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.
GO:0016525 negative regulation of angiogenesis	IMP PMID:16585190 Signal transducer and activator of transcription 1 activatio...	KEEP AS NON CORE	Summary: STAT1 activation in endothelial cells is a negative regulator of angiogenesis, suppressing VEGF-driven growth and tube formation. Reason: Negative regulation of angiogenesis is a documented but context-specific downstream effect of STAT1; retained as non-core. Supporting Evidence: PMID:16585190 Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis.
GO:0042981 regulation of apoptotic process	TAS PMID:12108949 The role of STATs in apoptosis.	KEEP AS NON CORE	Summary: STAT1 regulates apoptosis, predominantly transducing pro-apoptotic signals by inducing genes such as caspases, Fas and TRAIL. Reason: Regulation of apoptosis is a downstream transcriptional output of STAT1 rather than a core molecular function; supported as a non-core role. Supporting Evidence: PMID:12108949 STAT1 and, under some circums-tances. STAT3 are important for transducing pro-apoptotic signals
GO:0061326 renal tubule development	IMP PMID:20861313 STAT1 is required for redifferentiation during Madin-Darby c...	KEEP AS NON CORE	Summary: STAT1 is required for epithelial redifferentiation during MDCK kidney tubulogenesis, supporting a role in renal tubule development. Reason: Renal tubule development is a specialized morphogenetic role, peripheral to STAT1's core interferon function; supported but non-core. Supporting Evidence: PMID:20861313 STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.
GO:0072136 metanephric mesenchymal cell proliferation involved in metanephros development	ISS GO_REF:0000024	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:20861313 STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.
GO:0072162 metanephric mesenchymal cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:20861313 STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.
GO:0072308 negative regulation of metanephric nephron tubule epithelial cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:20861313 STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.
GO:0005634 nucleus	IDA PMID:10692450 Thrombin inhibits tumor cell growth in association with up-r...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:10692450 Thrombin inhibits tumor cell growth in association with up-regulation of p21(waf/cip1) and caspases via a p53-independent, STAT-1-dependent pathway.
GO:0045893 positive regulation of DNA-templated transcription	IDA PMID:10973496 Nucleocytoplasmic translocation of Stat1 is regulated by a l...	ACCEPT	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). 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. Supporting Evidence: PMID:10973496 Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain.
GO:0005634 nucleus	IDA PMID:10973496 Nucleocytoplasmic translocation of Stat1 is regulated by a l...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:10973496 Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain.
GO:0033209 tumor necrosis factor-mediated signaling pathway	IDA PMID:10848577 Stat1 as a component of tumor necrosis factor alpha receptor...	KEEP AS NON CORE	Summary: STAT1 is a component of the TNFR1-TRADD signaling complex, participating in TNF-alpha- mediated signaling. 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. Supporting Evidence: PMID:10848577 Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation.
GO:0043124 negative regulation of canonical NF-kappaB signal transduction	IMP PMID:10848577 Stat1 as a component of tumor necrosis factor alpha receptor...	KEEP AS NON CORE	Summary: STAT1 negatively regulates canonical NF-kappaB signaling as part of the TNFR1-TRADD complex. 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. Supporting Evidence: PMID:10848577 Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation.
GO:0005634 nucleus	IDA PMID:21268089 Molecular mechanisms underlying the inhibition of IFN-γ-indu...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:21268089 Molecular mechanisms underlying the inhibition of IFN-γ-induced, STAT1-mediated gene transcription in human macrophages by simvastatin and agonists of PPARs and LXRs.
GO:0060333 type II interferon-mediated signaling pathway	IDA PMID:21268089 Molecular mechanisms underlying the inhibition of IFN-γ-indu...	ACCEPT	Summary: STAT1 directly mediates 'type II interferon-mediated signaling pathway', a core interferon-response function demonstrated experimentally in this study. Reason: Interferon signaling/antiviral response is the central, non-redundant function of STAT1; directly supported. Supporting Evidence: PMID:21268089 Molecular mechanisms underlying the inhibition of IFN-γ-induced, STAT1-mediated gene transcription in human macrophages by simvastatin and agonists of PPARs and LXRs.
GO:0005634 nucleus	IDA PMID:16306601 Respiratory syncytial virus-inducible BCL-3 expression antag...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1. Supporting Evidence: PMID:16306601 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.
GO:0070721 ISGF3 complex	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md STAT1–STAT2 heterodimers plus IRF9 form ISGF3, which binds ISRE** (interferon-stimulated response element) DNA elements.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Latent STAT1 resides in the cytoplasm prior to cytokine-induced phosphorylation and nuclear import. Reason: Cytoplasmic localization of the latent pool is a core, well-established feature of STAT1 signaling.
GO:0005829 cytosol	IEA GO_REF:0000117	ACCEPT	Summary: STAT1's latent pool is cytosolic; this cytosol localization is consistent with established biology. Reason: Cytosolic localization of latent STAT1 is well supported; the IEA term is appropriate.
GO:0090575 RNA polymerase II transcription regulator complex	IEA GO_REF:0000117	ACCEPT	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). Reason: Membership in an RNA Pol II transcription regulator complex is consistent with STAT1's core transcription-factor function.
GO:0090575 RNA polymerase II transcription regulator complex	IPI PMID:8662591 Differential activation of acute phase response factor/STAT3...	ACCEPT	Summary: STAT1 assembles into RNA polymerase II transcription regulator complexes (e.g. STAT dimers and ISGF3) on target promoters. Reason: Membership in an RNA Pol II transcription regulator complex is consistent with STAT1's core transcription-factor function. Supporting Evidence: PMID:8662591 Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130.
GO:0070721 ISGF3 complex	IPI PMID:24065129 IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate r...	ACCEPT	Summary: Direct IPI evidence for STAT1's role in the ISGF3 complex (with STAT2 and IRF9). Core complex assignment. Supporting Evidence: PMID:24065129 IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage. file:human/STAT1/STAT1-deep-research-falcon.md STAT1–STAT2 heterodimers plus IRF9 form ISGF3, which binds ISRE** (interferon-stimulated response element) DNA elements.
GO:0090575 RNA polymerase II transcription regulator complex	NAS PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique s...	ACCEPT	Summary: STAT1 assembles into RNA polymerase II transcription regulator complexes (e.g. STAT dimers and ISGF3) on target promoters. Reason: Membership in an RNA Pol II transcription regulator complex is consistent with STAT1's core transcription-factor function. Supporting Evidence: PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique signal? Delgoffe GM(1), Vignali DA.
GO:0030424 axon	IEA GO_REF:0000107	REMOVE	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. 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.
GO:0030425 dendrite	IEA GO_REF:0000107	REMOVE	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. 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.
GO:0090575 RNA polymerase II transcription regulator complex	IPI PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer ...	ACCEPT	Summary: STAT1 assembles into RNA polymerase II transcription regulator complexes (e.g. STAT dimers and ISGF3) on target promoters. Reason: Membership in an RNA Pol II transcription regulator complex is consistent with STAT1's core transcription-factor function. Supporting Evidence: PMID:9630226 Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA.
GO:0005730 nucleolus	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	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. 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.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence localizes STAT1 to the cytosol, consistent with its latent cytosolic pool. Reason: Cytosolic localization of latent STAT1 is well established; the IDA (HPA immunofluorescence) annotation is appropriate.
GO:0005737 cytoplasm	IDA PMID:32209697 Noncanonical STAT1 phosphorylation expands its transcription...	ACCEPT	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. 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. Supporting Evidence: PMID:32209697 Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production.
GO:0005829 cytosol	TAS Reactome:R-HSA-9851142	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8985981	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8985983	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9865524	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8985900	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8985943	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8985966	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8985981	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8985983	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8985988	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9865511	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005737 cytoplasm	IDA PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	Summary: STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. Reason: Cytoplasmic localization of latent STAT1 is core and well supported. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0005737 cytoplasm	IDA PMID:27796300 PARP9 and PARP14 cross-regulate macrophage activation via ST...	ACCEPT	Summary: STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. Reason: Cytoplasmic localization of latent STAT1 is core and well supported. Supporting Evidence: PMID:27796300 PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation.
GO:0032991 protein-containing complex	IDA PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	KEEP AS NON CORE	Summary: STAT1 is part of protein-containing complexes (e.g. with PARP9-DTX3L) during interferon signaling. Reason: Generic protein-containing complex is uninformative relative to STAT1's specific transcription-factor complexes (GAF/ISGF3); retained as non-core. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0005737 cytoplasm	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. Reason: Cytoplasmic localization of latent STAT1 is core and well supported. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:0005737 cytoplasm	IDA PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STA...	ACCEPT	Summary: STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. Reason: Cytoplasmic localization of latent STAT1 is core and well supported. Supporting Evidence: PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8987218	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1112565	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1112602	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1169406	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1433456	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1470009	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1678841	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1888198	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-380782	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-6788571	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-6788582	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-6790041	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8950441	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8950453	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8950485	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8950518	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8950522	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8983835	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8983841	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8983845	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8983983	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8983996	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8984014	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8984021	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8984023	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8985929	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8986985	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987007	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987033	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987080	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987097	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987150	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987218	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987230	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987255	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987266	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8987270	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9006870	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9006873	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9670412	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9670416	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9672159	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9672176	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9729454	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9835443	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-1112587	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6788623	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8950522	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8950733	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9021334	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0048471 perinuclear region of cytoplasm	IDA PMID:17275127 HCV NS5A inhibits interferon-alpha signaling through suppres...	KEEP AS NON CORE	Summary: STAT1 was detected in the perinuclear region in hepatocytes where HCV NS5A suppresses STAT1 phosphorylation; this perinuclear pool is a context-specific observation. Reason: Perinuclear localization is a context-specific observation (HCV-infected hepatocytes) rather than a core STAT1 compartment; retained as non-core. Supporting Evidence: PMID:17275127 Dec 14. HCV NS5A inhibits interferon-alpha signaling through suppression of STAT1 phosphorylation in hepatocyte-derived cell lines.
GO:0005737 cytoplasm	IDA PMID:17275127 HCV NS5A inhibits interferon-alpha signaling through suppres...	ACCEPT	Summary: STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. Reason: Cytoplasmic localization of latent STAT1 is core and well supported. Supporting Evidence: PMID:17275127 Dec 14. HCV NS5A inhibits interferon-alpha signaling through suppression of STAT1 phosphorylation in hepatocyte-derived cell lines.
GO:0005737 cytoplasm	IDA PMID:15825084 Hepatitis C virus expression suppresses interferon signaling...	ACCEPT	Summary: STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. Reason: Cytoplasmic localization of latent STAT1 is core and well supported. Supporting Evidence: PMID:15825084 Hepatitis C virus expression suppresses interferon signaling by degrading STAT1.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-1015699	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-1031713	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-1470012	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-873917	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-877281	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-909721	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-913529	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9670426	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-997326	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1112727	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1470010	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1470012	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-873917	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-873921	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-873922	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-873927	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-909552	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-909718	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-909721	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-909722	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-909725	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-909726	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-913529	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9670417	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9670426	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9710959	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-9710963	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-997309	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1112538	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1112587	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-1112604	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-6788622	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-6788623	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-6788628	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8950733	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-8950782	ACCEPT	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. 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. Supporting Evidence: file:human/STAT1/STAT1-deep-research-falcon.md 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.
GO:0005737 cytoplasm	IDA PMID:10692450 Thrombin inhibits tumor cell growth in association with up-r...	ACCEPT	Summary: STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. Reason: Cytoplasmic localization of latent STAT1 is core and well supported. Supporting Evidence: PMID:10692450 Thrombin inhibits tumor cell growth in association with up-regulation of p21(waf/cip1) and caspases via a p53-independent, STAT-1-dependent pathway.
GO:0005737 cytoplasm	IDA PMID:10973496 Nucleocytoplasmic translocation of Stat1 is regulated by a l...	ACCEPT	Summary: STAT1 is observed in the cytoplasm, consistent with its latent cytoplasmic pool prior to nuclear translocation. Reason: Cytoplasmic localization of latent STAT1 is core and well supported. Supporting Evidence: PMID:10973496 Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain.
GO:0045087 innate immune response	IEA	NEW	Summary: Essential mediator of innate immune responses through interferon signaling pathway activation and antimicrobial gene expression 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. Supporting Evidence: PMID:21903422 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. PMID:23386060 hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.
GO:0005634 nucleus	IDA PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1.
GO:0005634 nucleus	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: STAT1 localizes to the nucleus upon activation, where it functions as a transcription factor; directly observed in this study. Reason: Nuclear localization is a core, repeatedly validated feature of activated STAT1.

Core Functions

Master transcriptional regulator of interferon responses and cytokine signaling

Molecular Function:

DNA-binding transcription factor activity, RNA polymerase II-specific

Directly Involved In:

cellular response to cytokine stimulus type I interferon-mediated signaling pathway type II interferon-mediated signaling pathway innate immune response

Cellular Locations:

nucleus cytoplasm

Supporting Evidence:

file:human/STAT1/STAT1-deep-research.md
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
PMID:32209697
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

SH2 domain-mediated homodimerization and heterodimerization essential for transcriptional activation

Molecular Function:

protein homodimerization activity

Directly Involved In:

positive regulation of receptor signaling pathway via JAK-STAT

Cellular Locations:

nucleus

Supporting Evidence:

PMID:9630226
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
PMID:8605877
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

Sequence-specific DNA binding to interferon-responsive regulatory elements (GAS and ISRE)

Molecular Function:

RNA polymerase II cis-regulatory region sequence-specific DNA binding

Directly Involved In:

positive regulation of transcription by RNA polymerase II

Cellular Locations:

nucleus

Supporting Evidence:

PMID:9630226
STAT-1 utilizes a DNA-binding domain with an immunoglobulin fold, similar to that of NFkappaB and the p53 tumor suppressor protein
file:human/STAT1/STAT1-deep-research.md
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

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms.

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.

GO_REF:0000113

Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods.

PMID:10848577

Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation.

PMID:10973496

Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain.

PMID:11238845

Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase reverses Stat1 activation.

PMID:11972023

Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.

PMID:12070153

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.

PMID:12788789

STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation.

PMID:12867595

The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3.

PMID:15780933

Structural bases of unphosphorylated STAT1 association and receptor binding.

PMID:15825084

Hepatitis C virus expression suppresses interferon signaling by degrading STAT1.

PMID:16189514

Towards a proteome-scale map of the human protein-protein interaction network.

PMID:16257975

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.

PMID:16273093

A quantitative protein interaction network for the ErbB receptors using protein microarrays.

PMID:16306601

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.

PMID:16531398

Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique carboxyl termini that determine cytosolic fate.

PMID:16585190

Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis.

PMID:16940534

Hepatitis C virus core protein blocks interferon signaling by interaction with the STAT1 SH2 domain.

PMID:17275127

HCV NS5A inhibits interferon-alpha signaling through suppression of STAT1 phosphorylation in hepatocyte-derived cell lines.

PMID:17596301

Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane.

PMID:17923090

Acetylation-dependent signal transduction for type I interferon receptor.

PMID:18035482

Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.

PMID:20195357

A comprehensive resource of interacting protein regions for refining human transcription factor networks.

PMID:20576130

Activated networking of platelet activating factor receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium.

PMID:21268089

Molecular mechanisms underlying the inhibition of IFN-γ-induced, STAT1-mediated gene transcription in human macrophages by simvastatin and agonists of PPARs and LXRs.

PMID:21903422

Mapping a dynamic innate immunity protein interaction network regulating type I interferon production.

PMID:21988832

Toward an understanding of the protein interaction network of the human liver.

PMID:22002246

A novel disrupter of telomere silencing 1-like (DOT1L) interaction is required for signal transducer and activator of transcription 1 (STAT1)-activated gene expression.

PMID:23386060

hCAF1/CNOT7 regulates interferon signalling by targeting STAT1.

PMID:24065129

IFNβ-dependent increases in STAT1, STAT2, and IRF9 mediate resistance to viruses and DNA damage.

PMID:24360797

Hepatic RIG-I predicts survival and interferon-α therapeutic response in hepatocellular carcinoma.

PMID:24658140

The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.

PMID:25241761

Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:25468996

E-cadherin interactome complexity and robustness resolved by quantitative proteomics.

PMID:25609649

Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.

PMID:26479788

PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.

PMID:26889034

VP8, the Major Tegument Protein of Bovine Herpesvirus 1, Interacts with Cellular STAT1 and Inhibits Interferon Beta Signaling.

PMID:26966684

PIPINO: A Software Package to Facilitate the Identification of Protein-Protein Interactions from Affinity Purification Mass Spectrometry Data.

PMID:28753426

Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.

PMID:31980649

Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).

PMID:32209697

Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production.

PMID:32953130

SARS-CoV-2 N protein antagonizes type I interferon signaling by suppressing phosphorylation and nuclear translocation of STAT1 and STAT2.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34950606

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response.

PMID:35140242

Human transcription factor protein interaction networks.

PMID:8156998

Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91).

PMID:8605877

The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the transduction of IFN-alpha signals.

PMID:8662591

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.

PMID:9121453

Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling.

PMID:9535918

Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis.

PMID:9630226

Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA.

PMID:34521819

Could not retrieve title - publication not available

PMID:9881977

Direct suppression of Stat1 function during adenoviral infection.

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

PMID:10692450

Thrombin inhibits tumor cell growth in association with up-regulation of p21(waf/cip1) and caspases via a p53-independent, STAT-1-dependent pathway.

PMID:12108949

The role of STATs in apoptosis.

PMID:15322115

Protein kinase Cdelta regulates apoptosis via activation of STAT1.

PMID:20861313

STAT1 is required for redifferentiation during Madin-Darby canine kidney tubulogenesis.

PMID:24058793

STAT heterodimers in immunity: A mixed message or a unique signal?

PMID:24882218

Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response.

PMID:28283061

Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation.

PMID:29202461

IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion.

PMID:32270034

IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.

PMID:27796300

PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation.

Reactome:R-HSA-1015699

ISGF3 binds the ISRE promoter elements in IFN-stimulated genes

Reactome:R-HSA-1031713

GAF binds the GAS promoter elements in the IFNG-regulated genes

Reactome:R-HSA-1112538

Phosphorylated STAT1, STAT3 form dimers

Reactome:R-HSA-1112565

Tyrosine phosphorylated IL6ST binds STAT1,STAT3

Reactome:R-HSA-1112587

STAT1 and STAT3 dimers translocate to the nucleus

Reactome:R-HSA-1112602

Tyrosine phosphorylation of STAT1, STAT3 by IL6 receptor

Reactome:R-HSA-1112604

Phosphorylated STATs are released

Reactome:R-HSA-1112727

Serine phosphorylation of STATs

Reactome:R-HSA-1169406

ISGylation of host proteins

Reactome:R-HSA-1433456

Recruitment of STATs

Reactome:R-HSA-1470009

Phosphorylation of STATs

Reactome:R-HSA-1470010

Dimerization of STATs

Reactome:R-HSA-1470012

Disassociation and translocation of STATs to the nucleus

Reactome:R-HSA-1678841

Regulation of protein ISGylation by ISG15 deconjugating enzyme USP18

Reactome:R-HSA-1888198

FGFR1OP-FGFR1 phosphorylates STAT1 and STAT3

Reactome:R-HSA-380782

STAT binds to the active receptor

Reactome:R-HSA-6788571

STAT1,STAT3,STAT6 bind IL13:IL13R type II

Reactome:R-HSA-6788582

STAT1,STAT3,STAT6 phosphorylation

Reactome:R-HSA-6788622

p-Y-STATs dimerize

Reactome:R-HSA-6788623

p-Y-STATs translocate to nucleus

Reactome:R-HSA-6788628

p-Y-STATs dissociate

Reactome:R-HSA-6790041

Expression of STAT3-upregulated cytosolic proteins

Reactome:R-HSA-873917

Translocation of STAT1 dimer to nucleus

Reactome:R-HSA-873921

Binding of STAT1 to p-IFNGR1

Reactome:R-HSA-873922

Phosphorylation of STAT1 by JAK kinases

Reactome:R-HSA-873927

Release of STAT1 dimer from active receptor unit

Reactome:R-HSA-877281

PIAS1 binds p-STAT1 dimer

Reactome:R-HSA-8950441

p-Y701-STAT1 and p-Y705-STAT3 dissociate from IL27:IL27 receptor

Reactome:R-HSA-8950453

JAK1/JAK2 bound to IL12RB2:IL6ST receptor phosphorylates STAT1 and STAT4

Reactome:R-HSA-8950485

STAT3 and STAT1 are phosphorylated by JAKs after IL27:IL27R interaction

Reactome:R-HSA-8950518

STAT1, STAT3 bind p-Y611-IL27RA from Interleukin-27:Interleukin-27 receptor complex

Reactome:R-HSA-8950522

p-STAT1:p-STAT4 translocates to the nucleus

Reactome:R-HSA-8950733

p-Y701-STAT1:p-Y705-STAT3 translocates to the nucleus

Reactome:R-HSA-8950782

p-STAT1 binds p-STAT3

Reactome:R-HSA-8983835

JAK1/JAK2/TYK2 bound to IL6ST:IL6ST phosphorylate STAT1

Reactome:R-HSA-8983841

STAT1 associates with IL6ST:IL6ST

Reactome:R-HSA-8983845

p-STAT1 dissociates from IL6ST:IL6ST

Reactome:R-HSA-8983983

p-STAT1 and p-STAT4 dissociate from IL12RB2:IL6ST receptor

Reactome:R-HSA-8983996

STAT1 and STAT4 associate with IL12RB2:IL6ST receptor

Reactome:R-HSA-8984014

JAK1,JAK2 bound to IL27RA:IL12RB2 receptor phosphorylate STAT1,STAT3

Reactome:R-HSA-8984021

STAT1,STAT3 associate with IL27RA:IL12RB2 receptor

Reactome:R-HSA-8984023

p-STAT1, p-STAT3 dissociate from IL27RA:IL12RB2 receptor

Reactome:R-HSA-8985900

p-Y701-STAT1, p-Y705-STAT3, p-Y649-STAT5 dissociates from IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3:p-Y705-STAT3

Reactome:R-HSA-8985929

IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3 binds STAT1, STAT3, STAT5A or STAT5B

Reactome:R-HSA-8985943

p-Y701-STAT1 dimerizes

Reactome:R-HSA-8985966

p-Y701-STAT1 binds p-Y705-STAT3

Reactome:R-HSA-8985981

p-Y701-STAT1:p-Y705-STAT3 translocates from the cytosol to the nucleus

Reactome:R-HSA-8985983

p-Y701-STAT1 dimer translocates from the cytosol to the nucleus

Reactome:R-HSA-8985988

IL9:p-Y116-IL9R:JAK1:IL2RG:p-904,939-JAK3:STAT3 phosphorylates STAT1, STAT3 or STAT5

Reactome:R-HSA-8986985

IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:STAT1 phosphorylates STAT1, STAT2, STAT3, STAT4 and STAT5

Reactome:R-HSA-8987007

p-STAT1 dimerizes

Reactome:R-HSA-8987033

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

Reactome:R-HSA-8987080

IL26:IL10RB:p-TYK2:IL20RA:p-JAK1 binds STAT1, STAT3

Reactome:R-HSA-8987097

IL24:p-IL20RA:p-JAK1:IL20RB binds STAT1,STAT3

Reactome:R-HSA-8987150

IL24:IL20RA:p-JAK1:IL20RB:STAT1,STAT3 phosphorylates STAT1 or STAT3

Reactome:R-HSA-8987218

p-STAT1 dimer translocates from the cytosol to the nucleoplasm

Reactome:R-HSA-8987230

p-STAT1 and p-STAT3 dissociates from IL26:IL10RB:p-TYK2:IL20RA:p-JAK1

Reactome:R-HSA-8987255

IL26:IL10RB:p-TYK2:IL20RA:p-JAK1:STAT1,STAT3 phosphorylates STAT1,STAT3

Reactome:R-HSA-8987266

IFNL1:p-Y434,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2 binds STAT1, STAT2, STAT3, STAT4, STAT5

Reactome:R-HSA-8987270

p-STAT1,p-STAT3 dissociate from IL24:IL20RA:p-Y1022,Y1023-JAK1:IL20RB:p-STAT1, p-STAT3

Reactome:R-HSA-9006870

IL21 receptor STAT phosphorylation

Reactome:R-HSA-9006873

IL21 receptor STAT binding

Reactome:R-HSA-9021334

STAT1 binds HEY1 gene promoter

Reactome:R-HSA-909552

Phosphorylation of STAT1 at Ser727

Reactome:R-HSA-909718

Formation of p-STAT1 homodimer

Reactome:R-HSA-909721

Translocation of ISGF3 complex to nucleus

Reactome:R-HSA-909722

Release of p-STAT2:p-STAT1 dimer

Reactome:R-HSA-909725

Interaction of IRF9 with p-STAT2:p-STAT1

Reactome:R-HSA-909726

Phosphorylation of STAT1

Reactome:R-HSA-913529

Translocation of p-STAT1:p-STAT1 dimer to nucleus

Reactome:R-HSA-9670412

Phosphorylation of STATs downstream of KIT mutants

Reactome:R-HSA-9670416

Recruitment of STATs by KIT mutants

Reactome:R-HSA-9670417

Dimerization of STATs downstream of KIT mutants

Reactome:R-HSA-9670426

Disassociation and translocation of STATs to the nucleus downstream of KIT mutants

Reactome:R-HSA-9672159

STAT binds to p-11Y PDGFRA extracellular domain dimers

Reactome:R-HSA-9672176

STAT binds to the mutant PDGFRA receptor

Reactome:R-HSA-9710959

p-STAT1 dimer binds KPNA1

Reactome:R-HSA-9710963

p-STAT1dimer:KPNA1 binds KPNB1

Reactome:R-HSA-9729454

SARS-CoV-2 N protein binds STAT1, STAT2

Reactome:R-HSA-9835443

STAT1,STAT3 binds PKR

Reactome:R-HSA-9851142

TYK2-dependent STAT1 and STAT3 phosphorylation

Reactome:R-HSA-9865511

Phosphorylation of STAT1 on tyrosine-701 is enhanced by p-S172-IKBKE

Reactome:R-HSA-9865524

p-Y701-STAT1 binds the NLRP3 gene

Reactome:R-HSA-997309

Dephosphorylation of STAT1 by SHP2

Reactome:R-HSA-997326

Dephosphorylation of p-STAT1 dimer by nuclear isoform of TCPTP

file:human/STAT1/STAT1-deep-research-falcon.md

Falcon deep research report on STAT1

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.

"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."
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.

"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."
Tyr701 phosphorylation between SH2 and TAD enables STAT1 dimerization and nuclear translocation; Ser727 phosphorylation in the C-terminus modulates transcriptional activity.

"**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."
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).

"* **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."
STAT1's primary biochemical function is sequence-specific transcriptional regulation as part of IFN-activated transcription factor complexes (GAF and ISGF3) controlling ISG expression.

"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)."
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.

"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."
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.

"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."
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.

"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)."
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.

"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."
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.

"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 Experiments

Experiment: ChIP-seq combined with RNA-seq to map genome-wide STAT1 binding sites and correlate with transcriptional outcomes in different immune contexts

Experiment: Single-molecule imaging of STAT1 nuclear translocation and chromatin binding dynamics in response to interferon stimulation

Experiment: Cryo-EM structural determination of STAT1 dimers bound to DNA and associated transcriptional co-regulators

Experiment: Mass spectrometry-based analysis of STAT1 post-translational modifications and their effects on protein stability and activity

Deep Research

Falcon

(STAT1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 42 citations 2 artifacts 2026-05-30T01:10:33.360962

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000030 Figure 3 illustrates potential therapeutic strategies to block HLA-I hyper-expression in beta cells by targeting the IFN/JAK/STAT s (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Human STAT1 (UniProt P42224) — Functional Annotation and Current Understanding

0. Target verification (mandatory)

The UniProt accession P42224 corresponds to human STAT1 (“signal transducer and activator of transcription 1-alpha/beta”; historically described as ISGF3 component p91/p84), a STAT-family transcription factor central to interferon (IFN) signaling, consistent with STAT-family domain architecture and STAT1’s role in IFN-induced transcriptional complexes. (babadei2024transcriptionalcontrolof pages 2-3, meesilpavikkai2024unravelingtheimmunogenetics pages 1-3)

1. Key concepts and definitions (current understanding)

1.1 STAT1 as a JAK–STAT pathway transcription factor

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. (ott2023jaksandstats pages 1-2, babadei2024transcriptionalcontrolof pages 2-3)

1.2 Domain architecture (functional implications)

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. (babadei2024transcriptionalcontrolof pages 2-3, meesilpavikkai2024unravelingtheimmunogenetics pages 1-3)

1.3 Activation, post-translational modification (PTM), and complex formation

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. (babadei2024transcriptionalcontrolof pages 2-3)
Serine phosphorylation: STAT1 also has a well-characterized C-terminal serine phosphorylation site (Ser727), which modulates transcriptional activity and can be induced by IFN-dependent and IFN-independent routes. (babadei2024transcriptionalcontrolof pages 2-3)
GAF vs ISGF3 (DNA response elements):
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.
These complexes provide a mechanistic basis for differences between IFNγ- and IFNα/β-driven transcriptional programs. (babadei2024transcriptionalcontrolof pages 2-3, efstathiou2024respiratorysyncytialvirus pages 1-2)

2. Molecular function, pathways, and cellular localization

2.1 Primary molecular function

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). (babadei2024transcriptionalcontrolof pages 2-3, babadei2024transcriptionalcontrolof pages 1-2)

2.2 Subcellular localization dynamics

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. (babadei2024transcriptionalcontrolof pages 1-2, babadei2024transcriptionalcontrolof pages 2-3)

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. (efstathiou2024respiratorysyncytialvirus pages 1-2)

3. Recent developments and latest research (prioritizing 2023–2024)

3.1 Quantitative, genome-scale characterization of ISG programs

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). (babadei2024transcriptionalcontrolof pages 1-2)

3.2 Time-resolved recruitment of STAT/IRF complexes to GAS/ISRE/composite sites (2023)

A 2023 time-resolved RNA-seq + ChIP-seq study in Huh7.5 cells integrated transcriptional induction with binding of pSTAT1, pSTAT2, IRF9, and IRF1, identifying 319 IFNα-responsive integrated genes and 286 IFNγ-inducible integrated genes with associated binding profiles. 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. (sekrecka2023timedependentrecruitmentof pages 8-9, sekrecka2023timedependentrecruitmentof pages 1-2)

3.3 Divergence of IFNβ vs IFNγ programs over time: ISGF3 versus IRF1 (2024)

A 2024 EMBO Journal study profiled nascent transcription over 48 hours and concluded that IFNβ and IFNγ programs overlap early but diverge over time, driven by differential deployment of ISGF3 and the “second-tier” transcription factor IRF1. Notably, the study reports a large nuclear interactome for STAT1 and provides quantitative proximity-labeling results: 184 STAT1 interactors vs 37 IRF1 interactors, with 127 STAT1-specific, 30 IRF1-specific, and 7 shared interactors. (geetha2024dynamiccontrolof pages 1-2, geetha2024dynamiccontrolof pages 8-10)

4. Human genetics and disease relevance (STAT1 LOF/GOF) with recent statistics

4.1 STAT1 gain-of-function (GOF): phenotype, mechanism, and prevalence statistics

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. Mechanistically, GOF variants often cause increased or prolonged STAT1 phosphorylation after cytokine stimulation (including variant-class-dependent effects on dephosphorylation). (meesilpavikkai2024unravelingtheimmunogenetics pages 4-7)

A 2024 infections-focused review summarizes a cohort description of 274 STAT1 GOF patients, reporting recurrent bacterial infections in ~75% and pneumonias in ~50%, with viral susceptibility in ~one-third (noting recurrent HSV/VZV and rare severe complications such as JCV-associated PML). (wang2024infectionsininborn pages 3-4)

4.2 STAT1 loss-of-function (LOF): severe inborn errors of immunity

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 and high mortality (“majority … died within the first year of life”) and severe vaccine reactions (e.g., 5 of 24 with severe reactions after live vaccination, as summarized). (meesilpavikkai2024unravelingtheimmunogenetics pages 4-7)

A 2023 clinical review similarly emphasizes that STAT1 LOF impairs IFN responses leading to severe infections and reports HSCT as a key intervention for severe deficiency; in one summary of 24 published patients, 10 received HSCT and 7 survived. (ott2023jaksandstats pages 13-14)

5. Current applications and real-world implementations

5.1 Targeted pathway modulation in STAT1 GOF (real-world care)

A 2023 case series reports three adults with STAT1 GOF and CMC treated with JAK inhibitors. In one detailed case, baricitinib 2 mg/day (initiated with prophylactic fluconazole and valacyclovir) led to marked improvement in mucocutaneous inflammation within a month and healing of aphthous ulcers by six months; infections/side effects were observed in some cases (e.g., herpes virus infection, sinusitis, bronchitis) and one patient did not tolerate ruxolitinib and required HSCT. (borgstrom2023threeadultcases pages 5-7, borgstrom2023threeadultcases pages 12-13)

5.2 IFN/JAK/STAT axis as a therapeutic target in type 1 diabetes (T1D)

A 2023 review argues that interferon-driven JAK–STAT signaling contributes to pancreatic islet HLA-I hyperexpression in T1D and frames JAK inhibition as a practical near-term approach to modulate this axis. It reports:
* In NOD mice, JAK inhibitors reduced insulitis, reduced islet HLA-I, and lowered diabetes incidence, with some evidence for reversal of new-onset disease. (russell2023theroleof pages 7-9)
* In human beta-cell/islet models, baricitinib prevented IFNα-induced HLA-I upregulation in EndoC-βH1 cells, and TYK2 inhibition (e.g., BMS-986165) or TYK2 knockdown prevented IFN-driven HLA-I upregulation in human islets. (russell2023theroleof pages 7-9)
* A translational clinical anecdote: a 15-year-old STAT1 GOF patient treated with ruxolitinib became euglycemic and discontinued insulin for 12 months. (russell2023theroleof pages 7-9, russell2023theroleof pages 9-10)

Figure evidence of proposed intervention points (receptors/JAKs/STATs/negative regulators) is available from this review. (russell2023theroleof media e63e0201)

5.3 Broader clinical landscape: JAK/TYK inhibitors

A 2024 Signal Transduction and Targeted Therapy review compiles a broad translational landscape of JAK/TYK inhibitors in clinical use and development, including long-term clinical data for widely used agents (e.g., ruxolitinib, tofacitinib) and multiple phase I/II studies for more selective inhibitors. This provides context for why repurposing JAK inhibitors is often proposed for IFN/STAT1-driven pathology: the pharmacologic class is mature and clinically accessible, though selectivity and infection risk remain central safety concerns. (lv2024thejakstatpathway pages 31-31)

6. Expert synthesis and analysis (authoritative perspectives)

Mechanistic modularity and context-dependence: Contemporary reviews emphasize that STAT1 functions are not monolithic; instead, pathway output depends on IFN type, complex composition (GAF vs ISGF3), promoter architecture (GAS/ISRE/composite), and additional transcription factors such as IRF1 that shape late phases of gene expression. (babadei2024transcriptionalcontrolof pages 2-3, sekrecka2023timedependentrecruitmentof pages 8-9, geetha2024dynamiccontrolof pages 1-2)
Clinical-genotype complexity: Recent clinical reviews stress that STAT1 GOF and LOF phenotypes cannot be inferred solely by variant location and that functional assays must measure phosphorylation and downstream transcription over time, due to time-dependent signaling and variant-class-specific effects on phosphorylation/dephosphorylation. (meesilpavikkai2024unravelingtheimmunogenetics pages 4-7, meesilpavikkai2024unravelingtheimmunogenetics pages 12-14)
Therapeutic tradeoffs: Reviews and clinical series converge on a key translational point: inhibiting JAK–STAT signaling can relieve STAT1 GOF-associated immune dysregulation (e.g., CMC), but also increases infection risk and must be deployed with careful antimicrobial prophylaxis and monitoring; HSCT remains essential in severe STAT1 deficiency and can be considered in refractory GOF cases. (wang2024infectionsininborn pages 3-4, borgstrom2023threeadultcases pages 12-13, ott2023jaksandstats pages 13-14)

7. Evidence summary table

The following table consolidates the most directly citable functional-annotation evidence gathered here (mechanism, localization, transcriptional programs, disease statistics, and applications) with URLs.

Aspect	Key points	Recent sources (2023-2024 with first author/year)	URLs
Identity / domains	• Verified target is human STAT1 matching UniProt P42224, a STAT-family transcription factor in IFN signaling. • Conserved STAT architecture: N-terminal, coiled-coil, DNA-binding, linker, SH2, C-terminal transactivation domain. • Canonical gene products include STAT1 homodimeric and STAT1-containing heterodimeric transcription factor functions, consistent with UniProt description of ISGF3 component p91/p84. (babadei2024transcriptionalcontrolof pages 2-3, meesilpavikkai2024unravelingtheimmunogenetics pages 1-3)	Babadei 2024; Meesilpavikkai 2024	https://doi.org/10.1016/j.jbc.2024.107771 https://doi.org/10.12932/ap-270124-1776
Activation / PTMs	• Receptor-associated JAKs phosphorylate STAT1 on Tyr701, enabling dimerization and transcriptional activation. • Ser727 phosphorylation in the C-terminal region modulates transcriptional output; recent review also highlights context-dependent Thr748 phosphorylation biology. • GOF alleles often show prolonged or increased pSTAT1 after cytokine stimulation due to altered phosphorylation/dephosphorylation dynamics. (babadei2024transcriptionalcontrolof pages 2-3, meesilpavikkai2024unravelingtheimmunogenetics pages 4-7)	Babadei 2024; Meesilpavikkai 2024	https://doi.org/10.1016/j.jbc.2024.107771 https://doi.org/10.12932/ap-270124-1776
Complexes & DNA elements	• STAT1 homodimers (GAF) bind GAS elements, especially downstream of IFN-γ. • STAT1-STAT2-IRF9 (ISGF3) binds ISRE elements, especially downstream of type I/III IFNs. • Composite ISRE+GAS promoters function as regulatory switches integrating pSTAT1, pSTAT2, IRF9, and IRF1. (babadei2024transcriptionalcontrolof pages 2-3, efstathiou2024respiratorysyncytialvirus pages 1-2, sekrecka2023timedependentrecruitmentof pages 1-2)	Babadei 2024; Efstathiou 2024; Sekrecka 2023	https://doi.org/10.1016/j.jbc.2024.107771 https://doi.org/10.3389/fimmu.2024.1395809 https://doi.org/10.1007/s00018-023-04830-8
Localization	• In resting cells, STAT1 is largely cytoplasmic or shuttling in unphosphorylated/preassociated forms; after tyrosine phosphorylation it forms dimers that translocate to the nucleus. • Nuclear import depends on interaction with importin α/KPNA1; RSV NS1 can block STAT1 nuclear translocation despite preserved phosphorylation. • STAT1 executes its transcriptional role in the nucleus at IFN-responsive promoters/enhancers. (babadei2024transcriptionalcontrolof pages 1-2, efstathiou2024respiratorysyncytialvirus pages 1-2)	Babadei 2024; Efstathiou 2024	https://doi.org/10.1016/j.jbc.2024.107771 https://doi.org/10.3389/fimmu.2024.1395809
Transcriptional programs / kinetics	• A cross-cell-type study summarized in review identified 975 ISGs, with 166 core ISGs robustly induced by IFN-I. • Time-resolved multi-omics identified 319 IFNα-responsive integrated genes and 286 IFNγ-inducible integrated genes bound by STAT/IRF complexes; 108 were IFNα-specific and 75 IFNγ-specific. • GAS genes tend to be early, ISRE genes more intermediate/late, while composite promoters show heterogeneous sustained responses driven by GAF, ISGF3, and IRF1. (sekrecka2023timedependentrecruitmentof pages 8-9, sekrecka2023timedependentrecruitmentof pages 1-2, babadei2024transcriptionalcontrolof pages 1-2)	Sekrecka 2023; Babadei 2024	https://doi.org/10.1007/s00018-023-04830-8 https://doi.org/10.1016/j.jbc.2024.107771
Human genetic disorders & stats	• STAT1 GOF is the most common STAT1 defect: >100 variants reported in >400 patients; CMC >60%, and one review notes 98% CMC in a series and ~half of all CMC attributable to STAT1 GOF. • A cohort of 274 patients with STAT1 GOF showed broad infectious phenotypes: recurrent bacterial infections in ~75%, pneumonias in ~50%, viral infections in ~one-third; another review notes bacterial infections in more than half and viral infections in about half. • AR complete STAT1 deficiency is rare but severe: 24 patients summarized in one review; a larger review cites 32 patients with severe viral/mycobacterial disease, including universal BCGosis in one series; among 24 HSCT cases, 10 transplanted and 7 survived. (meesilpavikkai2024unravelingtheimmunogenetics pages 4-7, wang2024infectionsininborn pages 3-4, ott2023jaksandstats pages 13-14)	Meesilpavikkai 2024; Wang 2024; Ott 2023	https://doi.org/10.12932/ap-270124-1776 https://doi.org/10.3390/pathogens13110955 https://doi.org/10.1007/s10875-023-01483-x
Therapeutic applications	• JAK inhibitors are the main targeted strategy in STAT1 GOF and related IFN-driven pathology; real-world adult case series showed baricitinib improved mucocutaneous disease, though infections/side effects occurred and one patient later required HSCT. • In T1D models, JAK inhibition reduced IFN-driven HLA-I hyperexpression: baricitinib protected human beta-cell models; TYK2 inhibition also blocked IFN-induced HLA-I upregulation. • Translational activity includes a reported 15-year-old STAT1 GOF patient who became euglycemic off insulin for 12 months on ruxolitinib, and the BANDIT placebo-controlled trial testing baricitinib in new-onset T1D. (borgstrom2023threeadultcases pages 12-13, russell2023theroleof pages 7-9, russell2023theroleof pages 9-10, russell2023theroleof media e63e0201)	Borgström 2023; Russell 2023	https://doi.org/10.1007/s10875-022-01351-0 https://doi.org/10.3389/fendo.2023.1270325

Table: This table summarizes verified functional annotation evidence for human STAT1 (UniProt P42224), spanning molecular mechanism, localization, transcriptional programs, disease genetics, and current therapeutic applications. It emphasizes recent 2023-2024 sources and key quantitative findings useful for evidence-based gene annotation.

8. Key references (with URLs and publication dates)

Babadei O. et al. “Transcriptional control of interferon-stimulated genes.” Journal of Biological Chemistry, Oct 2024. https://doi.org/10.1016/j.jbc.2024.107771 (babadei2024transcriptionalcontrolof pages 2-3, babadei2024transcriptionalcontrolof pages 1-2)
Geetha A.R.S.J. et al. “Dynamic control of gene expression by ISGF3 and IRF1 during IFNβ and IFNγ signaling.” The EMBO Journal, Apr 2024. https://doi.org/10.1038/s44318-024-00092-7 (geetha2024dynamiccontrolof pages 1-2, geetha2024dynamiccontrolof pages 8-10)
Sekrecka A. et al. “Time-dependent recruitment of GAF, ISGF3 and IRF1…” Cellular and Molecular Life Sciences, Jun 2023. https://doi.org/10.1007/s00018-023-04830-8 (sekrecka2023timedependentrecruitmentof pages 8-9, sekrecka2023timedependentrecruitmentof pages 1-2)
Wang C., Freeman A.F. “Infections in Inborn Errors of STATs.” Pathogens, Nov 2024. https://doi.org/10.3390/pathogens13110955 (wang2024infectionsininborn pages 3-4)
Meesilpavikkai K. et al. “Unraveling the Immunogenetics of STAT Proteins…” Asian Pacific Journal of Allergy and Immunology, May 2024. https://doi.org/10.12932/ap-270124-1776 (meesilpavikkai2024unravelingtheimmunogenetics pages 4-7)
Borgström E.W. et al. “Three Adult Cases of STAT1 Gain-of-Function… Treated with JAK Inhibitors.” Journal of Clinical Immunology, Sep 2023. https://doi.org/10.1007/s10875-022-01351-0 (borgstrom2023threeadultcases pages 5-7, borgstrom2023threeadultcases pages 12-13)
Russell M.A. et al. “The role of the interferon/JAK-STAT axis in driving islet HLA-I hyperexpression in type 1 diabetes.” Frontiers in Endocrinology, Oct 2023. https://doi.org/10.3389/fendo.2023.1270325 (russell2023theroleof pages 7-9, russell2023theroleof media e63e0201)
Efstathiou C. et al. “RSV NS1 inhibits anti-viral IFNα-induced JAK/STAT signaling by limiting nuclear translocation of STAT1.” Frontiers in Immunology, Jun 2024. https://doi.org/10.3389/fimmu.2024.1395809 (efstathiou2024respiratorysyncytialvirus pages 1-2)

References

(babadei2024transcriptionalcontrolof pages 2-3): Olga Babadei, Birgit Strobl, Mathias Müller, and Thomas Decker. Transcriptional control of interferon-stimulated genes. Journal of Biological Chemistry, 300:107771, Oct 2024. URL: https://doi.org/10.1016/j.jbc.2024.107771, doi:10.1016/j.jbc.2024.107771. This article has 22 citations and is from a domain leading peer-reviewed journal.
(meesilpavikkai2024unravelingtheimmunogenetics pages 1-3): Kornvalee Meesilpavikkai, N. Hirankarn, Virgil A.S.H. Dalm, P. M. Hagen, Willem A. Dik, and Hanna IJspeert. Unraveling the immunogenetics of stat proteins: clinical perspectives on gain-of-function and loss-of-function variants. Asian Pacific journal of allergy and immunology, May 2024. URL: https://doi.org/10.12932/ap-270124-1776, doi:10.12932/ap-270124-1776. This article has 7 citations and is from a peer-reviewed journal.
(ott2023jaksandstats pages 1-2): Nils Ott, Laura Faletti, Maximilian Heeg, Virginia Andreani, and Bodo Grimbacher. Jaks and stats from a clinical perspective: loss-of-function mutations, gain-of-function mutations, and their multidimensional consequences. Journal of Clinical Immunology, 43:1326-1359, May 2023. URL: https://doi.org/10.1007/s10875-023-01483-x, doi:10.1007/s10875-023-01483-x. This article has 97 citations and is from a domain leading peer-reviewed journal.
(efstathiou2024respiratorysyncytialvirus pages 1-2): Claudia Efstathiou, Yamei Zhang, Shubhangi Kandwal, Darren Fayne, Eleanor J. Molloy, and Nigel J. Stevenson. Respiratory syncytial virus ns1 inhibits anti-viral interferon-α-induced jak/stat signaling, by limiting the nuclear translocation of stat1. Frontiers in Immunology, Jun 2024. URL: https://doi.org/10.3389/fimmu.2024.1395809, doi:10.3389/fimmu.2024.1395809. This article has 16 citations and is from a peer-reviewed journal.
(babadei2024transcriptionalcontrolof pages 1-2): Olga Babadei, Birgit Strobl, Mathias Müller, and Thomas Decker. Transcriptional control of interferon-stimulated genes. Journal of Biological Chemistry, 300:107771, Oct 2024. URL: https://doi.org/10.1016/j.jbc.2024.107771, doi:10.1016/j.jbc.2024.107771. This article has 22 citations and is from a domain leading peer-reviewed journal.
(sekrecka2023timedependentrecruitmentof pages 8-9): Agata Sekrecka, Katarzyna Kluzek, Michal Sekrecki, Mahdi Eskandarian Boroujeni, Sanaz Hassani, Shota Yamauchi, Kiyonao Sada, Joanna Wesoly, and Hans A. R. Bluyssen. Time-dependent recruitment of gaf, isgf3 and irf1 complexes shapes ifnα and ifnγ-activated transcriptional responses and explains mechanistic and functional overlap. Cellular and Molecular Life Sciences: CMLS, Jun 2023. URL: https://doi.org/10.1007/s00018-023-04830-8, doi:10.1007/s00018-023-04830-8. This article has 37 citations.
(sekrecka2023timedependentrecruitmentof pages 1-2): Agata Sekrecka, Katarzyna Kluzek, Michal Sekrecki, Mahdi Eskandarian Boroujeni, Sanaz Hassani, Shota Yamauchi, Kiyonao Sada, Joanna Wesoly, and Hans A. R. Bluyssen. Time-dependent recruitment of gaf, isgf3 and irf1 complexes shapes ifnα and ifnγ-activated transcriptional responses and explains mechanistic and functional overlap. Cellular and Molecular Life Sciences: CMLS, Jun 2023. URL: https://doi.org/10.1007/s00018-023-04830-8, doi:10.1007/s00018-023-04830-8. This article has 37 citations.
(geetha2024dynamiccontrolof pages 1-2): Aarathy Ravi Sundar Jose Geetha, Katrin Fischer, Olga Babadei, Georg Smesnik, Alex Vogt, Ekaterini Platanitis, Mathias Müller, Matthias Farlik, and Thomas Decker. Dynamic control of gene expression by isgf3 and irf1 during ifnβ and ifnγ signaling. The EMBO Journal, 43:2233-2263, Apr 2024. URL: https://doi.org/10.1038/s44318-024-00092-7, doi:10.1038/s44318-024-00092-7. This article has 15 citations.
(geetha2024dynamiccontrolof pages 8-10): Aarathy Ravi Sundar Jose Geetha, Katrin Fischer, Olga Babadei, Georg Smesnik, Alex Vogt, Ekaterini Platanitis, Mathias Müller, Matthias Farlik, and Thomas Decker. Dynamic control of gene expression by isgf3 and irf1 during ifnβ and ifnγ signaling. The EMBO Journal, 43:2233-2263, Apr 2024. URL: https://doi.org/10.1038/s44318-024-00092-7, doi:10.1038/s44318-024-00092-7. This article has 15 citations.
(meesilpavikkai2024unravelingtheimmunogenetics pages 4-7): Kornvalee Meesilpavikkai, N. Hirankarn, Virgil A.S.H. Dalm, P. M. Hagen, Willem A. Dik, and Hanna IJspeert. Unraveling the immunogenetics of stat proteins: clinical perspectives on gain-of-function and loss-of-function variants. Asian Pacific journal of allergy and immunology, May 2024. URL: https://doi.org/10.12932/ap-270124-1776, doi:10.12932/ap-270124-1776. This article has 7 citations and is from a peer-reviewed journal.
(wang2024infectionsininborn pages 3-4): Chen Wang and Alexandra F. Freeman. Infections in inborn errors of stats. Pathogens, 13:955, Nov 2024. URL: https://doi.org/10.3390/pathogens13110955, doi:10.3390/pathogens13110955. This article has 0 citations.
(ott2023jaksandstats pages 13-14): Nils Ott, Laura Faletti, Maximilian Heeg, Virginia Andreani, and Bodo Grimbacher. Jaks and stats from a clinical perspective: loss-of-function mutations, gain-of-function mutations, and their multidimensional consequences. Journal of Clinical Immunology, 43:1326-1359, May 2023. URL: https://doi.org/10.1007/s10875-023-01483-x, doi:10.1007/s10875-023-01483-x. This article has 97 citations and is from a domain leading peer-reviewed journal.
(borgstrom2023threeadultcases pages 5-7): Emilie W. Borgström, Marie Edvinsson, Lucía P. Pérez, Anna C. Norlin, Sara L. Enoksson, Susanne Hansen, Anders Fasth, Vanda Friman, Olle Kämpe, Robert Månsson, Hernando Y. Estupiñán, Qing Wang, Tan Ziyang, Tadepally Lakshmikanth, Carl Inge E. Smith, Petter Brodin, and Peter Bergman. Three adult cases of stat1 gain-of-function with chronic mucocutaneous candidiasis treated with jak inhibitors. Journal of Clinical Immunology, 43:136-150, Sep 2023. URL: https://doi.org/10.1007/s10875-022-01351-0, doi:10.1007/s10875-022-01351-0. This article has 30 citations and is from a domain leading peer-reviewed journal.
(borgstrom2023threeadultcases pages 12-13): Emilie W. Borgström, Marie Edvinsson, Lucía P. Pérez, Anna C. Norlin, Sara L. Enoksson, Susanne Hansen, Anders Fasth, Vanda Friman, Olle Kämpe, Robert Månsson, Hernando Y. Estupiñán, Qing Wang, Tan Ziyang, Tadepally Lakshmikanth, Carl Inge E. Smith, Petter Brodin, and Peter Bergman. Three adult cases of stat1 gain-of-function with chronic mucocutaneous candidiasis treated with jak inhibitors. Journal of Clinical Immunology, 43:136-150, Sep 2023. URL: https://doi.org/10.1007/s10875-022-01351-0, doi:10.1007/s10875-022-01351-0. This article has 30 citations and is from a domain leading peer-reviewed journal.
(russell2023theroleof pages 7-9): Mark A. Russell, Sarah J. Richardson, and Noel G. Morgan. The role of the interferon/jak-stat axis in driving islet hla-i hyperexpression in type 1 diabetes. Frontiers in Endocrinology, Oct 2023. URL: https://doi.org/10.3389/fendo.2023.1270325, doi:10.3389/fendo.2023.1270325. This article has 30 citations.
(russell2023theroleof pages 9-10): Mark A. Russell, Sarah J. Richardson, and Noel G. Morgan. The role of the interferon/jak-stat axis in driving islet hla-i hyperexpression in type 1 diabetes. Frontiers in Endocrinology, Oct 2023. URL: https://doi.org/10.3389/fendo.2023.1270325, doi:10.3389/fendo.2023.1270325. This article has 30 citations.
(russell2023theroleof media e63e0201): Mark A. Russell, Sarah J. Richardson, and Noel G. Morgan. The role of the interferon/jak-stat axis in driving islet hla-i hyperexpression in type 1 diabetes. Frontiers in Endocrinology, Oct 2023. URL: https://doi.org/10.3389/fendo.2023.1270325, doi:10.3389/fendo.2023.1270325. This article has 30 citations.
(lv2024thejakstatpathway pages 31-31): You Lv, Jianxun Qi, Jeff J. Babon, Longxing Cao, Guohuang Fan, Jiajia Lang, Jin Zhang, Pengbing Mi, B. Kobe, and Faming Wang. The jak-stat pathway: from structural biology to cytokine engineering. Signal Transduction and Targeted Therapy, Aug 2024. URL: https://doi.org/10.1038/s41392-024-01934-w, doi:10.1038/s41392-024-01934-w. This article has 122 citations and is from a peer-reviewed journal.
(meesilpavikkai2024unravelingtheimmunogenetics pages 12-14): Kornvalee Meesilpavikkai, N. Hirankarn, Virgil A.S.H. Dalm, P. M. Hagen, Willem A. Dik, and Hanna IJspeert. Unraveling the immunogenetics of stat proteins: clinical perspectives on gain-of-function and loss-of-function variants. Asian Pacific journal of allergy and immunology, May 2024. URL: https://doi.org/10.12932/ap-270124-1776, doi:10.12932/ap-270124-1776. This article has 7 citations and is from a peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

babadei2024transcriptionalcontrolof pages 2-3
efstathiou2024respiratorysyncytialvirus pages 1-2
babadei2024transcriptionalcontrolof pages 1-2
meesilpavikkai2024unravelingtheimmunogenetics pages 4-7
wang2024infectionsininborn pages 3-4
ott2023jaksandstats pages 13-14
russell2023theroleof pages 7-9
lv2024thejakstatpathway pages 31-31
meesilpavikkai2024unravelingtheimmunogenetics pages 1-3
ott2023jaksandstats pages 1-2
sekrecka2023timedependentrecruitmentof pages 8-9
sekrecka2023timedependentrecruitmentof pages 1-2
geetha2024dynamiccontrolof pages 1-2
geetha2024dynamiccontrolof pages 8-10
borgstrom2023threeadultcases pages 5-7
borgstrom2023threeadultcases pages 12-13
russell2023theroleof pages 9-10
meesilpavikkai2024unravelingtheimmunogenetics pages 12-14
https://doi.org/10.1016/j.jbc.2024.107771
https://doi.org/10.12932/ap-270124-1776
https://doi.org/10.1016/j.jbc.2024.107771
https://doi.org/10.3389/fimmu.2024.1395809
https://doi.org/10.1007/s00018-023-04830-8
https://doi.org/10.1016/j.jbc.2024.107771
https://doi.org/10.3389/fimmu.2024.1395809
https://doi.org/10.1007/s00018-023-04830-8
https://doi.org/10.1016/j.jbc.2024.107771
https://doi.org/10.12932/ap-270124-1776
https://doi.org/10.3390/pathogens13110955
https://doi.org/10.1007/s10875-023-01483-x
https://doi.org/10.1007/s10875-022-01351-0
https://doi.org/10.3389/fendo.2023.1270325
https://doi.org/10.1016/j.jbc.2024.107771
https://doi.org/10.1038/s44318-024-00092-7
https://doi.org/10.1007/s00018-023-04830-8
https://doi.org/10.3390/pathogens13110955
https://doi.org/10.12932/ap-270124-1776
https://doi.org/10.1007/s10875-022-01351-0
https://doi.org/10.3389/fendo.2023.1270325
https://doi.org/10.3389/fimmu.2024.1395809
https://doi.org/10.1016/j.jbc.2024.107771,
https://doi.org/10.12932/ap-270124-1776,
https://doi.org/10.1007/s10875-023-01483-x,
https://doi.org/10.3389/fimmu.2024.1395809,
https://doi.org/10.1007/s00018-023-04830-8,
https://doi.org/10.1038/s44318-024-00092-7,
https://doi.org/10.3390/pathogens13110955,
https://doi.org/10.1007/s10875-022-01351-0,
https://doi.org/10.3389/fendo.2023.1270325,
https://doi.org/10.1038/s41392-024-01934-w,

Deep Research Report: STAT1 (human)

(STAT1-deep-research.md)

Deep Research Report: STAT1 (human)

Generated using comprehensive literature review and web search (September 2024)

STAT1 (Human) – Comprehensive Gene Report

Gene Overview and Core Functions

STAT1 (Signal Transducer and Activator of Transcription 1) is a critical transcription factor in the JAK-STAT pathway, serving as a master regulator of interferon signaling and immune responses. As described in recent comprehensive reviews, the JAK-STAT pathway represents "an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment" with "various cytokines, interferons, growth factors, and other specific molecules activat[ing] JAK-STAT signaling to drive a series of physiological and pathological processes."

Core Molecular Functions

STAT1 functions as a latent cytosolic transcription factor that becomes activated upon extracellular stimulation. The protein undergoes a well-characterized activation cycle: (1) Cytokine binding to membrane receptors activates receptor-associated Janus kinases (JAKs), (2) Tyrosine phosphorylation at Y701 by JAKs enables STAT1 dimerization through reciprocal SH2 domain interactions, (3) Nuclear translocation of activated dimers, and (4) DNA binding to specific response elements to regulate target gene transcription.

STAT1 demonstrates remarkable functional versatility through its ability to form different transcriptional complexes:
- STAT1 homodimers (GAF - gamma-activated factor) respond to IFN-γ and bind GAS elements
- STAT1:STAT2 heterodimers combine with IRF9 to form the ISGF3 complex, responding to type I interferons (IFN-α/β) and binding ISRE sequences
- Higher-order complexes with other transcription factors enable cooperative gene regulation

Recent research has confirmed that STAT1 and STAT2 are "key mediators of type I and type III interferon (IFN) signaling" and "associate with IFN regulatory factor 9 (IRF9) to form a heterotrimeric transcription factor complex known as ISGF3."

Cellular Localization and Subcellular Components

In resting cells, STAT1 resides predominantly in the cytoplasm (www.innatedb.com). Upon activation (tyrosine phosphorylation and dimerization), STAT1 undergoes a conformational change that exposes its nuclear localization signal, causing rapid translocation to the nucleus (www.innatedb.com). In the nucleus, STAT1 dimers bind DNA and assemble with co-activators on target gene promoters to initiate transcription (www.innatedb.com). After signal attenuation (e.g. by dephosphorylation), STAT1 can recycle back to the cytoplasm. Thus, STAT1 dynamically shuttles between the cytoplasm (inactive state) and the nucleus (active state) (www.innatedb.com). Consistent with its function as a transcription factor, STAT1 is commonly found in the nucleoplasm and associated with chromatin upon activation (a context captured by GO terms like transcription regulator complex). It is also a component of higher-order transcription factor complexes such as ISGF3 (in type I IFN signaling) and interacts with DNA-bound regulatory elements. Overall, STAT1’s subcellular distribution is tightly regulated by its phosphorylation state, ensuring it is present in the nucleus only when signals are present (www.innatedb.com).

STAT1 Target Genes and Interferon-Stimulated Gene Networks

STAT1 regulates a vast network of target genes, with over 300 interferon-stimulated genes (ISGs) identified through experimental validation. Recent ChIP-seq studies and functional analyses have provided comprehensive insights into STAT1's transcriptional targets and their roles in immune responses.

Core Interferon-Stimulated Genes

IRF1 (Interferon Regulatory Factor 1): A master transcriptional regulator and direct STAT1 target that amplifies interferon responses. IRF1 "binds to ISRE-only genes like ISG15, MX1, OAS3, and IFIT3 after both IFN-I and IFN-II stimulation" and serves as a critical mediator of STAT1-dependent gene expression. Experimental evidence shows that "STAT1 and IRF1 collaborate to induce interferon-γ stimulated genes, with IRF1 binding at ISG sites twice as often as STAT1, and STAT1 almost always binding together with IRF1."

ISG15: A ubiquitin-like protein modifier that represents one of the most strongly induced ISGs. ISG15 is "instrumental in antiviral activity" and binds the ISGF3 complex in response to type I interferons.

MX1 (MX Dynamin Like GTPase 1): A key antiviral effector protein that "was induced by interferons, especially IFN-β" and represents an "ISRE-only gene that binds ISGF3 in response to IFN-I."

OAS1 (2'-5'-Oligoadenylate Synthetase 1): A critical component of the antiviral response, OAS1 is "a canonical ISGF3 target gene that was not induced in STAT2-deficient cells but was expressed in interferon-treated cells."

CXCL10: A chemokine involved in immune cell recruitment, CXCL10 "mRNA expression is upregulated during early pregnancy in maternal tissues" and represents a well-validated STAT1 target involved in inflammatory responses.

Experimental Validation and ChIP-seq Evidence

Multiple experimental approaches have confirmed STAT1's direct binding to target genes:
- ChIP-seq experiments performed on K562 cells treated with IFNα or IFNγ confirmed binding of STAT1, STAT2, and IRF1 to typical ISRE or GAS-containing genes
- Functional validation studies have identified "a set of five ISGs including GBP1, IFIT2, IRF1, APOL6, and OAS1" that are "known to increase at least twofold in human cells following either IFNα or IFNγ stimulation"
- Gene expression profiling using RT-qPCR, Western blot, and immunohistochemistry has validated the coordinate regulation of STAT1 target genes

Cooperative Transcriptional Networks

STAT1 functions within complex transcriptional networks involving multiple cooperating factors. Recent research has identified that "unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes," indicating that STAT1 regulation extends beyond simple phosphorylation-dependent activation.

Biological Processes Involvement

STAT1 orchestrates multiple critical biological processes through its transcriptional regulatory functions:

Antiviral and Antimicrobial Defense

STAT1's primary biological role involves coordinating cellular responses to pathogens. Upon interferon stimulation, STAT1 activates "over 300 ISGs, such as ISG15, OAS1-3, IFIT1-3, or MX1 and 2 that are instrumental in antiviral activity." This creates a comprehensive antiviral state that restricts viral replication through multiple mechanisms.

Immune System Regulation

STAT1 serves as a crucial mediator of both innate and adaptive immune responses. Through IFN-γ signaling, STAT1 is "required for macrophage activation and Th1-type immune responses, bridging innate and adaptive immunity." Recent studies have highlighted the importance of the "interferon/JAK-STAT axis in driving" various immune processes.

Cell Proliferation and Tumor Suppression

STAT1 generally exhibits antiproliferative and pro-apoptotic effects, contributing to tumor suppression. STAT1 "induces an anti-proliferative response and enhances anti-tumor immunity by stimulating immune cell activity and antigen presentation to immune cells."

Cellular Stress Responses

Beyond pathogen responses, STAT1 coordinates cellular responses to various stressors and developmental signals, participating in processes ranging from angiogenesis regulation to metabolic adaptation.

Disease Associations and Clinical Phenotypes

STAT1 mutations represent a significant cause of primary immunodeficiency, with both loss-of-function and gain-of-function variants causing distinct but severe clinical phenotypes. Recent comprehensive reviews have documented 442 unique patients with STAT1 mutations, highlighting the clinical spectrum and importance of this gene in human immunity.

Loss-of-Function Mutations and Immunodeficiency

Primary Immunodeficiency 31 (IMD31) results from autosomal recessive STAT1 loss-of-function mutations, causing "Mendelian susceptibility to mycobacterial diseases (MSMD)" and severe viral infections. The first description of "impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation" established the critical role of STAT1 in interferon signaling.

Patients with STAT1 deficiency cannot mount effective responses to IFN-α/β or IFN-γ, resulting in:
- Life-threatening disseminated atypical mycobacterial infections
- Severe viral diseases due to impaired type I interferon responses
- Normal development but profound immune dysfunction
- Complete failure to respond to interferons at the cellular level

Gain-of-Function Mutations and Chronic Mucocutaneous Candidiasis

Heterozygous missense STAT1 mutations leading to gain-of-function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). Recent systematic reviews have identified 108 publications describing these mutations with comprehensive clinical characterization.

Molecular Mechanisms of GOF Mutations

"Most of the STAT1 GOF variants are located in the coiled-coil and DNA-binding domains of STAT1" and result in:
- Enhanced STAT1 phosphorylation compared to wild-type STAT1
- Impaired nuclear dephosphorylation causing prolonged activation
- Enhanced STAT1 signaling downstream of multiple cytokines (IFN-α/β, IFN-γ, IL-27)
- Impaired Th17 cell development leading to reduced IL-17 production

Clinical Manifestations

Analysis of 442 patients revealed:
- CMC in nearly all cases (410/442 patients) - chronic Candida infections of skin, nails, and mucosa
- Lower respiratory tract infections (210/442 patients)
- Autoimmune thyroid disease (102/442 patients)
- Novel associations: Recent studies have identified "rosacea-like demodicosis as an emerging manifestation among patients with STAT1 GOF"

Genotype-Phenotype Correlations

Recent research has revealed important correlations:
- Sex differences: "Disrupted CD4+ T cell homeostasis occurred sooner and more robustly in females"
- Domain-specific effects: "Individuals with DNA binding domain (DBD) mutations had a higher prevalence of autoimmunity and aberrant B cell activation"
- Paradoxical immune dysfunction: GOF mutations "paradoxically impair IL-17-dependent antifungal immunity"

Autoimmunity and Immune Dysregulation

Recent studies have demonstrated that STAT1-GOF can cause autoimmunity even "in the absence of overt infection." Experimental models show that "STAT-GOF mice can disrupt naïve CD4+ T cell homeostasis and promote expansion and differentiation of abnormal T-follicular helper/T-helper 1-like (Tfh/Th1-like) T cells and germinal center-like (GC-like) B cells."

Clinical Implications and Treatment Considerations

Diagnostic importance: "Careful consideration to the possibility of STAT1 GOF mutations should be given at the time of CMC diagnosis since they are reported to be causative in more than half of CMC patients."

Therapeutic approaches: Recent case reports describe successful treatment with JAK inhibitors, with "treatment with baricitinib, an inhibitor of JAK1 and JAK2" showing clinical improvement in STAT1 GOF patients.

Protein Domains and Structural Features

The STAT1 protein (∼750 amino acids, 91 kDa for the α-isoform) has a modular structure with several conserved domains (www.innatedb.com):

N-terminal Domain (ND): Mediates STAT1’s cooperative interactions and tetramerization on DNA. This region (around amino acids 1–130) helps STAT1 dimers form higher-order oligomers on tandem DNA sites and regulates nuclear import/export.
Coiled-Coil Domain: Following the ND, STAT1 contains a coiled-coil region (~residues 136–315) that participates in protein–protein interactions, including binding of regulatory proteins (e.g. importins, other STATs, or cofactors). This domain is important for transcriptional coactivator recruitment and for negative regulators binding (e.g. some PIAS/SOCS may contact STATs here).
DNA-Binding Domain (DBD): A central globular domain (~residues 320–480) enables STAT1 to bind specific DNA sequences. It recognizes GAS elements (TTCCNNGGAA motifs) in gene promoters for IFN-γ responses, and, as part of ISGF3, helps bind ISRE sequences (www.innatedb.com). Mutations in the DBD can abrogate DNA binding and target gene activation.
Linker and SH2 Domain: STAT1’s linker region connects the DBD to the C-terminal SH2 domain (~residues 575–680 in STAT1). The SH2 domain (Src Homology 2 domain) is crucial for STAT1 activation – it binds to phosphotyrosine motifs, allowing STAT1 to dock at phosphorylated receptors/JAKs and to dimerize with another STAT1 (binding the partner’s pY701) (pmc.ncbi.nlm.nih.gov). The SH2 domain of STAT1 is highly conserved and is essential for its signal transducer function, as evidenced by point mutations here (e.g. STAT1 L706S) disrupting IFN signaling and causing IMD31A (www.omim.org).
Transactivation Domain (TAD): The C-terminus (∼ residues 700–750 in the full-length α isoform) contains the transcriptional activation segment. This region includes an important serine phosphorylation site at S727. Phosphorylation of S727 (often by kinases like p38 MAPK or CDK8 in the enhanceosome context) is required for maximal transcriptional activity of STAT1 (pmc.ncbi.nlm.nih.gov). The TAD interacts with coactivators such as CBP/p300 to initiate transcription. Notably, an alternative splice isoform of STAT1 (β isoform, ~84 kDa) lacks the last ~38 amino acids of the TAD (including S727). STAT1β can still form dimers and bind DNA but has reduced transcriptional activation potential (pmc.ncbi.nlm.nih.gov).

Post-translational modifications (PTMs) are key to STAT1 function: Y701 phosphorylation is mandatory for dimerization, while S727 phosphorylation enhances gene activation (pmc.ncbi.nlm.nih.gov). Other PTMs (e.g. Thr749 phosphorylation during LPS responses (www.genecards.org), acetylation, and methylation) modulate STAT1 activity and target selectivity. The domain architecture and critical phosphorylation sites of STAT1 are conserved across the STAT family, underscoring their importance (pmc.ncbi.nlm.nih.gov).

Expression Patterns and Regulation

STAT1 is expressed in a broad range of human tissues, consistent with its fundamental role in mediating responses to cytokines and pathogens. Basal expression is detectable in most cell types, but highest levels are observed in immune-related tissues such as spleen, lymph nodes, and circulating leukocytes (www.genecards.org). Proteomic surveys indicate STAT1 is notably abundant in lymphoid organs and T-cells (e.g. overexpressed in lymph node and spleen compared to other tissues) (www.genecards.org). This reflects the immune system’s reliance on STAT1 for cytokine signaling. STAT1 expression can be further upregulated by interferons themselves – IFN signaling induces STAT1 transcription as part of a positive feedback loop, thereby amplifying the cellular responsiveness to cytokines (www.genecards.org). For example, cells exposed to IFN-γ show increased STAT1 mRNA and protein levels, enhancing their ability to respond to sustained or subsequent cytokine stimulation (a mechanism to potentiate the cytokine-mediated signaling pathway (GO:0019221)). Regulation of STAT1 activity occurs at multiple levels:

Transcriptional regulation: Interferons and other stimuli can induce STAT1 gene expression via interferon-stimulated response elements in its promoter, while some growth factors or cellular conditions may downregulate STAT1 expression.
Post-transcriptional: Certain microRNAs (e.g. miR-145) have been reported to target STAT1 mRNA in specific contexts, fine-tuning protein levels during immune responses or in cancer.
Post-translational: Activated STAT1 is tightly controlled by negative regulators. Suppressor of cytokine signaling 1 (SOCS1) is induced by STAT1 activity and feeds back to inhibit JAK kinases, preventing further STAT1 phosphorylation (ncbi.nlm.nih.gov). Additionally, Protein Inhibitor of Activated STAT1 (PIAS1) binds to STAT1 dimers in the nucleus to block their DNA binding and limit transcription (pubmed.ncbi.nlm.nih.gov). These mechanisms ensure that STAT1 activation is transient and appropriately scaled, avoiding excessive inflammation. STAT1’s activity is also terminated by nuclear phosphatases (e.g. TC45/PTPN2) that dephosphorylate Y701, triggering STAT1 export from the nucleus and restoring the latent cytosolic pool. Together, inducible expression and multi-level regulation of STAT1 allow cells to rapidly mount, then resolve, STAT1-dependent responses.

Evolutionary Conservation

STAT1 is highly conserved across vertebrates, highlighting its fundamental biological importance. Orthologs of human STAT1 are found in all mammals and other jawed vertebrates, with strong sequence similarity (especially in the DNA-binding and SH2 domains). The STAT gene family expanded during early vertebrate evolution – two rounds of whole-genome duplication yielded multiple STAT paralogs (STAT1, 2, 3, 4, 5a, 5b, 6 in humans) from a likely single ancestral gene (pubmed.ncbi.nlm.nih.gov). STAT1 is most closely related to STAT4 (sharing similar domain architecture and function) (www.genecards.org). Notably, even in distantly related organisms, the core features of STAT1 are preserved: for example, the SH2 domain and the tyrosine phosphorylation site are present in STAT proteins of insects and nematodes, reflecting a conserved mechanism of JAK-STAT signaling in multicellular animals (pmc.ncbi.nlm.nih.gov). In invertebrates and early chordates, fewer STATs exist (Drosophila has a single Stat92E, and C. elegans has stat-like genes), which combine functions that in higher organisms are split among STAT1 and others (pubmed.ncbi.nlm.nih.gov). The presence of STAT1 in the common ancestor of chordates indicates an ancient origin (www.genecards.org). Functional conservation is evident: introducing human STAT1 into Stat1-knockout mice can restore interferon responsiveness, and conserved tyrosine motifs and DNA-binding preferences allow cross-species functionality (pmc.ncbi.nlm.nih.gov). This evolutionary preservation underlines that STAT1’s role in immune defense and cell regulation is indispensable and has been maintained by strong selective pressure.

Key Experimental Evidence and Landmark Studies

Research on STAT1 since the early 1990s has revealed its critical functions:

Discovery and Activation: STAT1 was first identified as a DNA-binding factor activated by interferons. Seminal studies in 1992 showed that interferon-α activates STAT1 and STAT2, whereas interferon-γ activates STAT1 alone (www.cell.com). These findings, by J. Darnell and colleagues, defined the STAT family as latent cytosolic factors activated by phosphorylation to become transcription factors. Shortly after, the JAK kinases (e.g. TYK2, JAK1) were found to be required for STAT activation, linking cytokine receptors to STAT1 function (www.cell.com).
Knockout Mouse Phenotype: A landmark study by Meraz et al. (1996) created Stat1-knockout mice, revealing STAT1’s essential role in immunity (www.cell.com). These mice appeared developmentally normal but failed to respond to IFN-α/β or IFN-γ, and were extremely susceptible to viral diseases and intracellular bacteria (www.cell.com) (www.cell.com). Cells from Stat1–/– mice could not induce typical interferon-responsive genes (e.g. IRF1, MHC molecules) and failed to clear infections (www.cell.com) (www.cell.com). This provided direct evidence that STAT1 is indispensable for interferon signaling and antimicrobial defense.
Human Immunodeficiency: Clinical genetics studies have identified human patients with STAT1 mutations, corroborating the mouse model. Holland et al. (2001) first described patients with loss-of-function STAT1 mutations who suffered fatal mycobacterial infections due to impaired IFN-γ immunity (www.innatedb.com). Subsequent reports characterized partial STAT1 deficiencies (autosomal dominant or recessive) as causes of Mendelian susceptibility to mycobacterial diseases and certain viral infections (www.innatedb.com) (www.innatedb.com). These human phenotypes established STAT1’s non-redundant role in host defense.
Gain-of-Function and CMC: In 2011–2013, teams led by Casanova and others discovered that autosomal dominant mutations causing STAT1 gain-of-function underlie many cases of chronic mucocutaneous candidiasis (www.innatedb.com). GOF mutations (often affecting the coiled-coil or CCD/DBD domains to impair dephosphorylation or increase dimer stability) result in hyperactivated STAT1. Surprisingly, this leads to selective susceptibility to chronic Candida infections because overactive STAT1 signaling suppresses IL-17–producing T cells, a key defense against fungi (www.innatedb.com). This was a breakthrough in understanding human Th17 immunity and showed the need for balanced STAT1 activity.
Negative Regulation: Research into STAT1’s regulation identified specific inhibitors. Shuai et al. (1997) isolated PIAS1, a nuclear protein that binds activated STAT1 and inhibits its DNA-binding and gene activation ability (pubmed.ncbi.nlm.nih.gov). Similarly, studies of cytokine signaling revealed SOCS1 as an interferon-inducible feedback inhibitor that binds JAKs to turn off STAT1 signaling (ncbi.nlm.nih.gov). These findings explained how cells avoid uncontrolled STAT1 activity and have informed therapeutic strategies (e.g. mimicking SOCS1 to dampen pathological STAT1 activation) (ncbi.nlm.nih.gov).
Structural and Mechanistic Insights: Crystallographic studies of STAT1 provided insight into its activation and DNA binding. For example, crystal structures of STAT1’s core (ND-DBD-SH2) illuminated how unphosphorylated STAT1 exists as antiparallel dimers and how phosphorylation induces a rearrangement to form active parallel dimers that bind DNA (pmc.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). Mutagenesis experiments have pinpointed key residues for function: Y701 and S727 for activation; the KXLN motif in the N-domain for nuclear import; and various interface residues for dimer stability and cooperative DNA binding (pmc.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). These studies built a molecular understanding of STAT1’s action.
Contemporary Research: Ongoing studies explore STAT1 in disease contexts – e.g. its role in cancer immunology, where STAT1 can promote tumor immune surveillance or, if dysregulated, contribute to resistance to therapy (ncbi.nlm.nih.gov). STAT1 is also being studied in the context of inflammatory disorders and as a potential drug target. The breadth of STAT1 research underscores its importance: as one of the first discovered STATs, it remains central in cytokine biology and a model for transcription factor regulation.

Each of these findings has been captured in Gene Ontology annotations. For example, the requirement of STAT1 for IFN signaling is annotated as "response to interferon-gamma" (GO:0034341) and "type I interferon signaling pathway" (GO:0060337), supported by the knockout studies. The discovery of PIAS1 contributes to annotations like "negative regulation of STAT1 signaling" (part of GO:0042509), and the STAT1 structural studies inform annotations of its molecular function in sequence-specific DNA binding and transcriptional activation. These accumulated experimental evidences ensure that the GO curation for STAT1 is well-founded in the literature.

Therapeutic Implications and STAT1 Targeting

Recent advances in understanding STAT1 function have opened new therapeutic avenues, particularly through JAK-STAT pathway modulation. The clinical success of JAK inhibitors has demonstrated the therapeutic potential of targeting this pathway in various disease contexts.

JAK Inhibitors and Cancer Immunotherapy (2023-2024)

Breakthrough Clinical Results: Two separate clinical trials in 2024 found that "combining JAK inhibitors with immune checkpoint inhibitors significantly improved treatment outcomes, with the combination shrinking tumors in more than half of participants with lung cancer and lymphoma."

Hodgkin Lymphoma: A phase I clinical trial of ruxolitinib with nivolumab in 19 Hodgkin lymphoma patients "achieved a best overall response rate of 53% (10/19)" in patients who had previously failed checkpoint inhibitor therapy. Remarkably, "two years after the start of the trial, 46% of participants had no sign of their cancer growing back."

Mechanistic Rationale: The therapeutic benefit stems from the recognition that "cytokine signaling through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway correlates with checkpoint immunotherapy resistance."

Current JAK Inhibitor Arsenal

Approved Therapeutics: "Twelve JAK inhibitors have been approved for clinical use against autoimmune diseases: ruxolitinib, pacritinib, fedratinib, tofacitinib, baricitinib, abrocitinib, filgotinib, oclacitinib, peficitinib, upadacitinib, deucravacitinib, and delgocitinib."

STAT1-Specific Targeting: These inhibitors demonstrate "varying specificities for JAK1, JAK2, JAK3, and TYK2," allowing for tailored therapeutic approaches depending on the specific STAT pathway involved.

Clinical Applications

STAT1 Gain-of-Function Treatment: Recent case reports demonstrate successful treatment of STAT1 GOF patients with baricitinib, showing normalization of liver biochemical parameters and spleen size reduction from 11.0 cm to 7.1 cm diameter after 44 months of treatment.

Cutaneous T-Cell Lymphoma: JAK inhibitors have shown promise in treating CTCL, with drugs like ruxolitinib and cerdulatinib demonstrating potential therapeutic benefit with manageable side effects.

Autoimmune Applications: JAK inhibition has proven effective in "treatment-resistant autoimmune hepatitis" associated with STAT1 gain-of-function mutations.

Safety Considerations

Infection Risk: "Risk of serious infections and opportunistic infections has been reported with JAK inhibitors," with tofacitinib showing "doubled rate of herpes zoster infection compared to patients using biologics."

Malignancy Risk: While some reports suggested increased tumorigenesis risk with tofacitinib, "a meta-analysis found no increased risk of malignancy in patients with rheumatoid arthritis treated with tofacitinib."

Future Therapeutic Directions

The success of JAK inhibitor combinations with checkpoint inhibitors represents "significant advances in understanding how JAK-STAT pathway inhibition can enhance cancer immunotherapy, particularly in previously treatment-resistant cases." This research has opened new avenues for:
- Combination immunotherapy approaches
- Precision medicine based on STAT1 mutation status
- Novel therapeutic strategies for primary immunodeficiencies
- Targeted treatment of autoimmune disorders with STAT1 dysregulation

Post-Translational Modifications and Regulation

STAT1 function is precisely controlled through multiple post-translational modifications that regulate its activity, localization, and target gene specificity.

Phosphorylation

Y701 (Tyrosine 701): The critical activating phosphorylation site required for STAT1 dimerization and transcriptional activity. Recent studies have also identified "several phosphorylatable residues in STAT1, including Y68 and Y106," though these remain to be fully characterized.

S727 (Serine 727): Located in the transactivation domain, S727 phosphorylation "is required for maximal transcriptional activity of STAT1" and is mediated by kinases including p38 MAPK and CDK8.

T749 (Threonine 749): Phosphorylated during LPS responses, contributing to STAT1 activation in inflammatory contexts.

Beyond Phosphorylation

While specific recent data on STAT1 acetylation and methylation remains limited, research on the broader STAT family indicates extensive regulation through these modifications. Studies on STAT3 have identified "10 documented sites for acetylation" and multiple methylation sites, suggesting similar regulatory complexity for STAT1.

Negative Regulation

STAT1 activity is tightly controlled by several negative regulators:
- SOCS1: Provides feedback inhibition by targeting JAK kinases
- PIAS1: Blocks STAT1 DNA binding in the nucleus
- Nuclear phosphatases (TC45/PTPN2): Dephosphorylate Y701 to terminate signaling

This multi-layered regulation ensures that STAT1 responses are appropriately scaled and terminated, preventing excessive inflammation while maintaining effective immune responses.

Summary and Research Conclusions

This comprehensive analysis of STAT1 reveals its fundamental importance as a master regulator of interferon signaling and immune responses. The accumulated evidence from decades of research, including recent advances in 2023-2024, establishes several key conclusions:

Core Functions (Well-Established)

Critical transcription factor in the JAK-STAT pathway mediating interferon responses
Master regulator of over 300 interferon-stimulated genes including IRF1, ISG15, MX1, OAS1, and CXCL10
Essential mediator of both type I (IFN-α/β) and type II (IFN-γ) interferon signaling
Key coordinator of antiviral, antimicrobial, and immune regulatory responses

Disease Relevance (Clinically Validated)

Loss-of-function mutations cause severe primary immunodeficiency (MSMD) with mycobacterial and viral susceptibility
Gain-of-function mutations represent the most frequent cause of chronic mucocutaneous candidiasis (CMC)
Therapeutic target for cancer immunotherapy through JAK inhibitor combinations
Clinical biomarker for precision medicine approaches in immunology and oncology

Commonly Over-Annotated Aspects

Based on this comprehensive review, potential over-annotations might include:
- Non-specific "protein binding" annotations that don't capture STAT1's specific transcription factor functions
- Overly broad inflammatory process annotations that don't distinguish STAT1's specific role from general inflammation
- Generic "signal transduction" terms that miss the specificity of JAK-STAT pathway signaling
- Non-immune cellular processes where STAT1's role may be secondary or contextual rather than core

Research Priorities and Future Directions

Mechanistic understanding of post-translational modifications beyond phosphorylation
Therapeutic development of selective STAT1 modulators for precision medicine
Clinical translation of JAK inhibitor combinations in various cancer types
Functional genomics of STAT1 target gene networks in different cellular contexts

This research establishes STAT1 as a critical hub in immune signaling with well-defined core functions in interferon responses, validated disease associations, and emerging therapeutic importance in cancer immunotherapy and autoimmune disorders.

📚 Additional Documentation

Notes

(STAT1-notes.md)

STAT1 Gene Review Notes

2025-01-14 - Retired Annotation Fix

Issue: Validation failure due to 1 annotation not found in the current GOA file.

Root Cause: PMID:16257975 that was referenced in one annotation (GO:0046427 - positive regulation of receptor signaling pathway via JAK-STAT) has been removed from the current GOA database.

Action Taken: Marked the annotation with PMID:16257975 as retired: true to exclude it from GOA validation while preserving the annotation review work.

Validation Status: After marking the retired annotation, the gene now passes validation with only warnings about PENDING annotations and an invalid PMID:34521819 that couldn't be fetched.

Outstanding Issues:
- PMID:34521819 cannot be verified - may need manual checking or correction
- Large number of PENDING annotations require review

Note: STAT1 is a key transcription factor in the JAK-STAT signaling pathway, particularly important for interferon signaling and immune responses. The single retired annotation represents ongoing curation changes in the GOA database.

2026-05-29 - PROTEOSTASIS PN autophagy-gene-expression pass

The PN workbook places STAT1 under Autophagy-Lysosome Pathway > Autophagy gene expression > Transcriptional repressor with the note that STAT1 binds a regulatory sequence in the ULK1 5' flanking region; mutating that sequence increased ULK1 promoter activity and made the promoter unresponsive to mTOR inhibition.

The underlying paper supports a real, context-specific STAT1 role in suppressing ULK1 expression and autophagic activity, but it should not be promoted to a generic core STAT1 proteostasis function. It also does not cleanly support group-level propagation to GO:0003714 transcription corepressor activity for STAT1, because STAT1 is a DNA-binding transcription factor and the evidence is specific to ULK1/autophagy regulation rather than generic corepressor activity. [PMID:28011640 "STAT1-deficient human fibrosarcoma cells exhibited enhanced autophagic flux"; PMID:28011640 "STAT1 bound a putative regulatory sequence in the ULK1 5'-flanking region"; PMID:28011640 "These results demonstrate a novel mechanism by which STAT1 negatively regulates ULK1 expression and autophagy."]

Working curation conclusion: keep the PN placement as useful context for evaluating autophagy-gene-expression biology, but do not automatically propagate GO:0003714 from the PN group to STAT1. A gene-level annotation, if pursued, should capture the specific ULK1/autophagy repression evidence rather than a broad corepressor claim.

Pn Notes

(STAT1-pn-notes.md)

STAT1 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: priority-only PN rereview against local AIGR review and available deep-research artifacts
UniProt: P42224
AIGR review status: COMPLETE
Priority category: context_specific_ALP
Local AIGR project status: local_review_complete_not_phase1
Related project: INTEGRATED_STRESS_RESPONSE.md

Source Files Checked

AIGR review YAML: present - genes/human/STAT1/STAT1-ai-review.yaml
AIGR review HTML: present - genes/human/STAT1/STAT1-ai-review.html
Gene notes: present - genes/human/STAT1/STAT1-notes.md
GOA TSV: present - genes/human/STAT1/STAT1-goa.tsv
UniProt record: present - genes/human/STAT1/STAT1-uniprot.txt
PROTEOSTASIS priority table: projects/PROTEOSTASIS/priority_genes.tsv
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv
PN mapping file: none from current projection rows.

Deep Research Files

AIGR Review Snapshot

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/core annotation action counts: ACCEPT: 205; KEEP_AS_NON_CORE: 38; MARK_AS_OVER_ANNOTATED: 43; MODIFY: 1; NEW: 1; REMOVE: 5; UNDECIDED: 1

PN Consistency Summary

Consistency: Priority-only record; no phase-1 dossier section exists yet. Local review status is local_review_complete_not_phase1. PN placement: ALP > Autophagy gene expression > Transcriptional repressor. Main issue: Workbook has an explicit ULK1-promoter note, but this likely remains a contextual non-core role
PN story / NEW pressure: No current projected GO row; the value is exception/context tracking.
Mapping strategy: Treat the PN ALP placement as context-specific regulatory biology. A non-core GO annotation may be warranted only if the gene-specific evidence supports it.
Verdict: Create boundary/phase1 dossier and decide whether a non-core ALP regulatory annotation is warranted

Priority Review Context

Category: context_specific_ALP
PN annotations: ALP > Autophagy gene expression > Transcriptional repressor
Why interesting: Workbook has an explicit ULK1-promoter note, but this likely remains a contextual non-core role
Suggested next step: Create boundary/phase1 dossier and decide whether a non-core ALP regulatory annotation is warranted
Related project: INTEGRATED_STRESS_RESPONSE.md

PN Projection Rows

No current PN projected GO row for this gene. Treat this priority item as an exception, boundary, or context-tracking case rather than a direct GO propagation candidate.

PN Dossier Context

No phase-1 dossier exists for this priority-only gene. This note preserves the current PROTEOSTASIS boundary or exception decision and should be superseded by a dossier section if the gene is promoted into a full phase-1 batch.

Note

This file is generated from the current PROTEOSTASIS priority table, PN projection outputs, and local gene-review artifacts. Edit those source records rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

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

STAT1

Gene Description

Existing Annotations Review

Core Functions

Master transcriptional regulator of interferon responses and cytokine signaling

SH2 domain-mediated homodimerization and heterodimerization essential for transcriptional activation

Sequence-specific DNA binding to interferon-responsive regulatory elements (GAS and ISRE)

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Human STAT1 (UniProt P42224) — Functional Annotation and Current Understanding

0. Target verification (mandatory)

1. Key concepts and definitions (current understanding)

1.1 STAT1 as a JAK–STAT pathway transcription factor

1.2 Domain architecture (functional implications)

1.3 Activation, post-translational modification (PTM), and complex formation

2. Molecular function, pathways, and cellular localization

2.1 Primary molecular function

2.2 Subcellular localization dynamics

3. Recent developments and latest research (prioritizing 2023–2024)

3.1 Quantitative, genome-scale characterization of ISG programs

3.2 Time-resolved recruitment of STAT/IRF complexes to GAS/ISRE/composite sites (2023)

3.3 Divergence of IFNβ vs IFNγ programs over time: ISGF3 versus IRF1 (2024)

4. Human genetics and disease relevance (STAT1 LOF/GOF) with recent statistics

4.1 STAT1 gain-of-function (GOF): phenotype, mechanism, and prevalence statistics

4.2 STAT1 loss-of-function (LOF): severe inborn errors of immunity

5. Current applications and real-world implementations

5.1 Targeted pathway modulation in STAT1 GOF (real-world care)

5.2 IFN/JAK/STAT axis as a therapeutic target in type 1 diabetes (T1D)

5.3 Broader clinical landscape: JAK/TYK inhibitors

6. Expert synthesis and analysis (authoritative perspectives)

7. Evidence summary table

8. Key references (with URLs and publication dates)

Artifacts

Citations

Deep Research Report: STAT1 (human)

Deep Research Report: STAT1 (human)

STAT1 (Human) – Comprehensive Gene Report

Gene Overview and Core Functions

Core Molecular Functions

Cellular Localization and Subcellular Components

STAT1 Target Genes and Interferon-Stimulated Gene Networks

Core Interferon-Stimulated Genes

Experimental Validation and ChIP-seq Evidence

Cooperative Transcriptional Networks

Biological Processes Involvement

Antiviral and Antimicrobial Defense

Immune System Regulation

Cell Proliferation and Tumor Suppression

Cellular Stress Responses

Disease Associations and Clinical Phenotypes

Loss-of-Function Mutations and Immunodeficiency

Gain-of-Function Mutations and Chronic Mucocutaneous Candidiasis

Molecular Mechanisms of GOF Mutations

Clinical Manifestations

Genotype-Phenotype Correlations

Autoimmunity and Immune Dysregulation

Clinical Implications and Treatment Considerations

Protein Domains and Structural Features

Expression Patterns and Regulation

Evolutionary Conservation

Key Experimental Evidence and Landmark Studies

Therapeutic Implications and STAT1 Targeting

JAK Inhibitors and Cancer Immunotherapy (2023-2024)

Current JAK Inhibitor Arsenal

Clinical Applications

Safety Considerations

Future Therapeutic Directions

Post-Translational Modifications and Regulation

Phosphorylation

Beyond Phosphorylation

Negative Regulation

Summary and Research Conclusions

Core Functions (Well-Established)

Disease Relevance (Clinically Validated)

Commonly Over-Annotated Aspects

Research Priorities and Future Directions

📚 Additional Documentation