Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: cytoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0006952 defense response	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: defense response pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0042127 regulation of cell population proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: regulation of cell population proliferation pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: nucleus localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling.
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: Direct STAT1 transcriptional regulation Reason: This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced activation.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IBA GO_REF:0000033	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling. Supporting Evidence: file:mouse/Stat1/Stat1-notes.md STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type I and type II interferon signaling. file:mouse/Stat1/Stat1-deep-research-falcon.md Falcon synthesis supports STAT1 as an interferon-activated STAT-family transcription factor that binds regulatory DNA after JAK-dependent phosphorylation.
GO:0070721 ISGF3 complex	IBA GO_REF:0000033	ACCEPT	Summary: ISGF3 complex interaction or complex context Reason: STAT1 is a core subunit of the STAT1/STAT2/IRF9 ISGF3 transcription factor complex during type I interferon signaling, so this complex-membership annotation is accurate even though the core molecular activity remains DNA-binding transcription factor activity.
GO:0043434 response to peptide hormone	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: response to peptide hormone pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0060337 type I interferon-mediated signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IEA GO_REF:0000117	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling. Supporting Evidence: file:mouse/Stat1/Stat1-notes.md STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type I and type II interferon signaling.
GO:0003677 DNA binding	IEA GO_REF:0000120	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000002	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: nucleus localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005654 nucleoplasm	IEA GO_REF:0000117	ACCEPT	Summary: nucleoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: cytoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	IEA GO_REF:0000117	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: DNA-templated transcription pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: Direct STAT1 transcriptional regulation Reason: This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced activation.
GO:0007165 signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: signal transduction pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IEA GO_REF:0000117	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling.
GO:0008283 cell population proliferation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: cell population proliferation pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0042981 regulation of apoptotic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: regulation of apoptotic process pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0051093 negative regulation of developmental process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: negative regulation of developmental process pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0051607 defense response to virus	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: defense response to virus pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0060333 type II interferon-mediated signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling.
GO:0060337 type I interferon-mediated signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling.
GO:0005515 protein binding	IPI PMID:22306691 The composition and signaling of the IL-35 receptor are unco...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding is too generic to describe STAT1 function and should be replaced by specific complex, DNA-binding, or transcription-factor annotations. Supporting Evidence: PMID:22306691 The composition and signaling of the IL-35 receptor are unconventional.
GO:0005515 protein binding	IPI PMID:23749757 Construction of a novel oligonucleotide array-based transcri...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding is too generic to describe STAT1 function and should be replaced by specific complex, DNA-binding, or transcription-factor annotations. Supporting Evidence: PMID:23749757 Jul 22. Construction of a novel oligonucleotide array-based transcription factor interaction assay platform and its uses for profiling STAT1 cofactors in mouse fibroblast cells.
GO:0005515 protein binding	IPI PMID:24360797 Hepatic RIG-I predicts survival and interferon-α therapeutic...	MARK AS OVER ANNOTATED	Summary: Generic protein binding Reason: Protein binding is too generic to describe STAT1 function and should be replaced by specific complex, DNA-binding, or transcription-factor annotations. Supporting Evidence: PMID:24360797 2013 Dec 19. Hepatic RIG-I predicts survival and interferon-α therapeutic response in hepatocellular carcinoma.
GO:0000785 chromatin	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: chromatin pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding	ISO GO_REF:0000119	ACCEPT	Summary: RNA polymerase II transcription regulatory region sequence-specific DNA binding directly captures STAT1 DNA-binding transcription-factor activity. Reason: STAT1 binds cytokine-responsive regulatory DNA as part of its core transcription factor function.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO GO_REF:0000119	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling.
GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding	ISO GO_REF:0000119	MODIFY	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 binds GAS and ISRE regulatory DNA elements downstream of interferon/cytokine signaling; these are better represented as RNA polymerase II cis-regulatory region sequence-specific DNA binding than as core-promoter binding. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ISO GO_REF:0000119	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling. Supporting Evidence: file:mouse/Stat1/Stat1-notes.md STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type I and type II interferon signaling.
GO:0001222 transcription corepressor binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: transcription corepressor binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0001223 transcription coactivator binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: transcription coactivator binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0001937 negative regulation of endothelial cell proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of endothelial cell proliferation pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0002230 positive regulation of defense response to virus by host	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of defense response to virus by host pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0003677 DNA binding	ISO GO_REF:0000096	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling.
GO:0003690 double-stranded DNA binding	ISO GO_REF:0000119	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling.
GO:0003700 DNA-binding transcription factor activity	ISO GO_REF:0000119	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling.
GO:0005164 tumor necrosis factor receptor binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: tumor necrosis factor receptor binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0005634 nucleus	ISO GO_REF:0000119	ACCEPT	Summary: nucleus localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005654 nucleoplasm	ISO GO_REF:0000119	ACCEPT	Summary: nucleoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005730 nucleolus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: nucleolus pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0005737 cytoplasm	ISO GO_REF:0000119	ACCEPT	Summary: cytoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	ISO GO_REF:0000119	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0006357 regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	ACCEPT	Summary: Direct STAT1 transcriptional regulation Reason: This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced activation.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	ISO GO_REF:0000119	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling.
GO:0016525 negative regulation of angiogenesis	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of angiogenesis pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0019899 enzyme binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic enzyme binding annotation Reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding and transcription-factor terms.
GO:0030424 axon	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: axon pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0030425 dendrite	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: dendrite pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0031730 CCR5 chemokine receptor binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: CCR5 chemokine receptor binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0032727 positive regulation of interferon-alpha production	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of interferon-alpha production pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0032991 protein-containing complex	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic protein-containing complex annotation Reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding and transcription-factor terms.
GO:0033209 tumor necrosis factor-mediated signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: tumor necrosis factor-mediated signaling pathway pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0034341 response to type II interferon	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: response to type II interferon pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0035035 histone acetyltransferase binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: histone acetyltransferase binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0035456 response to interferon-beta	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: response to interferon-beta pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0035458 cellular response to interferon-beta	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to interferon-beta pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0038111 interleukin-7-mediated signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: interleukin-7-mediated signaling pathway pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0038113 interleukin-9-mediated signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: interleukin-9-mediated signaling pathway pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0042393 histone binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: histone binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0042802 identical protein binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic identical protein binding annotation Reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding and transcription-factor terms.
GO:0042803 protein homodimerization activity	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic protein homodimerization activity annotation Reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding and transcription-factor terms.
GO:0043124 negative regulation of canonical NF-kappaB signal transduction	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of canonical NF-kappaB signal transduction pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0043565 sequence-specific DNA binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: sequence-specific DNA binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0044389 ubiquitin-like protein ligase binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: ubiquitin-like protein ligase binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0045648 positive regulation of erythrocyte differentiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of erythrocyte differentiation pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0045893 positive regulation of DNA-templated transcription	ISO GO_REF:0000119	ACCEPT	Summary: Direct STAT1 transcriptional regulation Reason: This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced activation.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of transcription by RNA polymerase II pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of receptor signaling pathway via JAK-STAT pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0046725 negative regulation by virus of viral protein levels in host cell	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation by virus of viral protein levels in host cell pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0048471 perinuclear region of cytoplasm	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: perinuclear region of cytoplasm pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0051607 defense response to virus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: defense response to virus pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0051721 protein phosphatase 2A binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: protein phosphatase 2A binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0060333 type II interferon-mediated signaling pathway	ISO GO_REF:0000119	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling.
GO:0060337 type I interferon-mediated signaling pathway	ISO GO_REF:0000119	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling.
GO:0061326 renal tubule development	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: renal tubule development pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0070106 interleukin-27-mediated signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: interleukin-27-mediated signaling pathway pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0070721 ISGF3 complex	ISO GO_REF:0000119	ACCEPT	Summary: ISGF3 complex interaction or complex context Reason: STAT1 is a core subunit of the STAT1/STAT2/IRF9 ISGF3 transcription factor complex during type I interferon signaling, so this complex-membership annotation is accurate even though the core molecular activity remains DNA-binding transcription factor activity.
GO:0071346 cellular response to type II interferon	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to type II interferon pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0090575 RNA polymerase II transcription regulator complex	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: RNA polymerase II transcription regulator complex pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0097696 cell surface receptor signaling pathway via STAT	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cell surface receptor signaling pathway via STAT pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:1990841 promoter-specific chromatin binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: promoter-specific chromatin binding pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0061326 renal tubule development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: renal tubule development pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0043065 positive regulation of apoptotic process	IMP PMID:10692450 Thrombin inhibits tumor cell growth in association with up-r...	KEEP AS NON CORE	Summary: positive regulation of apoptotic process pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function. 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:0045944 positive regulation of transcription by RNA polymerase II	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of transcription by RNA polymerase II pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0003700 DNA-binding transcription factor activity	IDA PMID:37327784 Gasdermin D licenses MHCII induction to maintain food tolera...	ACCEPT	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling. Supporting Evidence: file:mouse/Stat1/Stat1-uniprot.txt associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA
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: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling. Supporting Evidence: PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma. file:mouse/Stat1/Stat1-notes.md STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type I and type II interferon signaling.
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: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling. 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...	KEEP AS NON CORE	Summary: response to type II interferon pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity. Supporting Evidence: PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.
GO:0008283 cell population proliferation	IGI PMID:15781341 Differential effects of a novel IFN-zeta/limitin and IFN-alp...	KEEP AS NON CORE	Summary: cell population proliferation pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function. Supporting Evidence: PMID:15781341 Differential effects of a novel IFN-zeta/limitin and IFN-alpha on signals for Daxx induction and Crk phosphorylation that couple with growth control of megakaryocytes.
GO:0051607 defense response to virus	IMP PMID:32270034 IL-27 signaling activates skin cells to induce innate antivi...	KEEP AS NON CORE	Summary: defense response to virus pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity. Supporting Evidence: PMID:32270034 2020 Apr. IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.
GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding	ISS GO_REF:0000024	MODIFY	Summary: Core STAT1 DNA-binding transcription factor activity Reason: STAT1 binds GAS and ISRE regulatory DNA elements downstream of interferon/cytokine signaling; these are better represented as RNA polymerase II cis-regulatory region sequence-specific DNA binding than as core-promoter binding. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding
GO:0032727 positive regulation of interferon-alpha production	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of interferon-alpha production pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0042803 protein homodimerization activity	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Generic protein homodimerization activity annotation Reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding and transcription-factor terms.
GO:0051607 defense response to virus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: defense response to virus pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-9676907	ACCEPT	Summary: nucleoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-9705459	ACCEPT	Summary: nucleoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-9705472	ACCEPT	Summary: nucleoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-9943422	ACCEPT	Summary: nucleoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-9943424	ACCEPT	Summary: nucleoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0045648 positive regulation of erythrocyte differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of erythrocyte differentiation pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0071345 cellular response to cytokine stimulus	ISO PMID:19414010 JANEX-1, a JAK3 inhibitor, protects pancreatic islets from c...	KEEP AS NON CORE	Summary: cellular response to cytokine stimulus pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity. Supporting Evidence: PMID:19414010 Epub 2009 May 3. JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway.
GO:0034340 response to type I interferon	IDA PMID:24882218 Unanchored K48-linked polyubiquitin synthesized by the E3-ub...	KEEP AS NON CORE	Summary: response to type I interferon pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity. 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:0071222 cellular response to lipopolysaccharide	IMP PMID:21606371 Glucocorticoids target suppressor of cytokine signaling 1 (S...	KEEP AS NON CORE	Summary: cellular response to lipopolysaccharide pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity. Supporting Evidence: PMID:21606371 Glucocorticoids target suppressor of cytokine signaling 1 (SOCS1) and type 1 interferons to regulate Toll-like receptor-induced STAT1 activation.
GO:0005829 cytosol	TAS Reactome:R-MMU-1169206	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9674908	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9674931	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9676907	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9676912	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9680646	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9682158	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9682182	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0060337 type I interferon-mediated signaling pathway	IMP PMID:24598055 TLR ligands up-regulate Trex1 expression in murine conventio...	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling. Supporting Evidence: PMID:24598055 Mar 5. TLR ligands up-regulate Trex1 expression in murine conventional dendritic cells through type I Interferon and NF-κB-dependent signaling pathways.
GO:0034240 negative regulation of macrophage fusion	IMP PMID:22865856 An essential role for STAT6-STAT1 protein signaling in promo...	KEEP AS NON CORE	Summary: negative regulation of macrophage fusion pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function. Supporting Evidence: PMID:22865856 2012 Aug 3. An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion.
GO:0060333 type II interferon-mediated signaling pathway	IMP PMID:12138178 Identification of a nuclear Stat1 protein tyrosine phosphata...	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling. Supporting Evidence: PMID:12138178 Identification of a nuclear Stat1 protein tyrosine phosphatase.
GO:0060337 type I interferon-mediated signaling pathway	IMP PMID:12138178 Identification of a nuclear Stat1 protein tyrosine phosphata...	ACCEPT	Summary: Core interferon/JAK-STAT signaling role Reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT signaling. Supporting Evidence: PMID:12138178 Identification of a nuclear Stat1 protein tyrosine phosphatase.
GO:0000122 negative regulation of transcription by RNA polymerase II	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: negative regulation of transcription by RNA polymerase II pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0002053 positive regulation of mesenchymal cell proliferation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of mesenchymal cell proliferation pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0003340 negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0072136 metanephric mesenchymal cell proliferation involved in metanephros development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: metanephric mesenchymal cell proliferation involved in metanephros development pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0072162 metanephric mesenchymal cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: metanephric mesenchymal cell differentiation pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
GO:0072308 negative regulation of metanephric nephron tubule epithelial cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: negative regulation of metanephric nephron tubule epithelial cell differentiation pathway context Reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream than the core transcription-factor function.
GO:0005829 cytosol	TAS Reactome:R-MMU-1169142	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9008004	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005829 cytosol	TAS Reactome:R-MMU-9674959	ACCEPT	Summary: cytosol localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response.
GO:0005737 cytoplasm	IDA PMID:15661922 Immune activation of type I IFNs by Listeria monocytogenes o...	ACCEPT	Summary: cytoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response. Supporting Evidence: PMID:15661922 Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1.
GO:0009617 response to bacterium	IDA PMID:15661922 Immune activation of type I IFNs by Listeria monocytogenes o...	KEEP AS NON CORE	Summary: response to bacterium pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity. Supporting Evidence: PMID:15661922 Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1.
GO:0019221 cytokine-mediated signaling pathway	IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ...	KEEP AS NON CORE	Summary: cytokine-mediated signaling pathway pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function. Supporting Evidence: PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
GO:0031663 lipopolysaccharide-mediated signaling pathway	IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ...	KEEP AS NON CORE	Summary: lipopolysaccharide-mediated signaling pathway pathway context Reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function. Supporting Evidence: PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
GO:0032496 response to lipopolysaccharide	IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ...	KEEP AS NON CORE	Summary: response to lipopolysaccharide pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity. Supporting Evidence: PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
GO:0043330 response to exogenous dsRNA	IDA PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independ...	KEEP AS NON CORE	Summary: response to exogenous dsRNA pathway context Reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core molecular activity. Supporting Evidence: PMID:12872135 Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
GO:0003700 DNA-binding transcription factor activity	IMP PMID:15485925 Interferon-inducible ubiquitin E2, Ubc8, is a conjugating en...	UNDECIDED	Summary: PMID:15485925 supports Ubc8/ISGylation in the cached abstract but does not directly mention STAT1 DNA-binding transcription factor activity. Reason: Direct STAT1 evidence from full text or another source would be needed before accepting this PMID-specific annotation.
GO:0006351 DNA-templated transcription	IMP PMID:15485925 Interferon-inducible ubiquitin E2, Ubc8, is a conjugating en...	UNDECIDED	Summary: PMID:15485925 supports Ubc8/ISGylation in the cached abstract but does not directly mention STAT1-dependent transcription. Reason: Direct STAT1 transcription evidence from full text or another source would be needed before accepting this PMID-specific annotation.
GO:0005634 nucleus	IDA PMID:12957148 Erythrocyte and leukocyte dynamics in the retinal capillarie...	UNDECIDED	Summary: PMID:12957148 is a retinal capillary dynamics paper in the cached abstract and does not directly support STAT1 nuclear localization. Reason: Full-text or corrected evidence would be needed before accepting this evidence-specific nucleus annotation.
GO:0005737 cytoplasm	IDA PMID:14522949 Beta1 integrins regulate chondrocyte rotation, G1 progressio...	UNDECIDED	Summary: PMID:14522949 supports nuclear translocation of Stat1/Stat5a in the cached abstract, not cytoplasmic localization. Reason: Full-text or corrected cytoplasmic localization evidence would be needed before accepting this evidence-specific annotation.
GO:0005737 cytoplasm	IDA PMID:12634107 Expression and activation of STAT proteins during mouse reti...	ACCEPT	Summary: cytoplasm localization Reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional response. Supporting Evidence: PMID:12634107 Expression and activation of STAT proteins during mouse retina development.

Core Functions

STAT1 binds cytokine-responsive regulatory DNA as an RNA polymerase II transcription factor after interferon/JAK-STAT pathway activation.

Molecular Function:

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

Directly Involved In:

regulation of DNA-templated transcription cell surface receptor signaling pathway via JAK-STAT

Cellular Locations:

nucleus cytoplasm

Supporting Evidence:

file:mouse/Stat1/Stat1-notes.md
STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type I and type II interferon signaling.
file:mouse/Stat1/Stat1-deep-research-falcon.md
Falcon synthesis supports STAT1 as a cytokine/interferon-activated transcription factor that binds regulatory DNA downstream of JAK phosphorylation and nuclear translocation.

References

file:mouse/Stat1/Stat1-uniprot.txt

UniProtKB P42225 record for mouse Stat1

STAT1 associates with the 13 kDa Gasdermin-D cleavage product and promotes CIITA transcription in the small intestine.

"associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA"

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

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

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

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:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

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:11972023

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

PMID:12138178

Identification of a nuclear Stat1 protein tyrosine phosphatase.

PMID:12634107

Expression and activation of STAT proteins during mouse retina development.

PMID:12872135

Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.

PMID:12957148

Erythrocyte and leukocyte dynamics in the retinal capillaries of diabetic mice.

PMID:14522949

Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis.

PMID:15485925

Interferon-inducible ubiquitin E2, Ubc8, is a conjugating enzyme for protein ISGylation.

PMID:15661922

Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1.

PMID:15781341

Differential effects of a novel IFN-zeta/limitin and IFN-alpha on signals for Daxx induction and Crk phosphorylation that couple with growth control of megakaryocytes.

PMID:19414010

JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway.

PMID:21606371

Glucocorticoids target suppressor of cytokine signaling 1 (SOCS1) and type 1 interferons to regulate Toll-like receptor-induced STAT1 activation.

PMID:22306691

The composition and signaling of the IL-35 receptor are unconventional.

PMID:22865856

An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion.

PMID:23749757

Construction of a novel oligonucleotide array-based transcription factor interaction assay platform and its uses for profiling STAT1 cofactors in mouse fibroblast cells.

PMID:24360797

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

PMID:24598055

TLR ligands up-regulate Trex1 expression in murine conventional dendritic cells through type I Interferon and NF-κB-dependent signaling pathways.

PMID:24882218

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

PMID:32270034

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

PMID:37327784

Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine.

Reactome:R-MMU-1169142

Jak2 binds Stat1/Stat3

Reactome:R-MMU-1169206

Jak2 phosphorylates Stat1/Stat3

Reactome:R-MMU-9008004

Runx2 binds Stat1

Reactome:R-MMU-9674908

p-Y-Jak1,2 phosphorylates Stat1,3,5 in Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Y-Jak1:p-Jak2:p-Tyk2:Stat1,3,5

Reactome:R-MMU-9674931

Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Y-Jak1:p-Jak2:p-Syk:p-Hck:p-Tyk2:p-Y-Stat1,3,5 dissociates yielding Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Y-Jak1:p-Jak2:p-Syk:p-Hck:p-Tyk2 and p-Y-Stat1,3,5

Reactome:R-MMU-9674959

Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Jak1:p-Jak2:p-Syk:p-Hck:p-Tyk2 binds Stat1,3,5

Reactome:R-MMU-9676907

p-Y-Stat1,3,5 dimer translocates from the cytosol to the nucleus

Reactome:R-MMU-9676912

p-Y-Stat1,3,5 dimerize

Reactome:R-MMU-9680646

Pik3r11:Pik3ca,b,d (Pi3k), Plcg2 (PLCgamma2), Grb2:Sos1, Shc1 (Shc), Ptpn11 (Shp2), Grb2:Gab2, Grb2:Gab3, Grap2 (MONA), Cbl:Grb2, Inpp5d (SHIP1), Inppl1 (SHIP2) bind p-8Y-Csf1r and are activated

Reactome:R-MMU-9682158

Csf1r-associated Plcg2 hydrolyzes phosphatidylcholine yielding choline phosphate and 1,2-diacylglycerol

Reactome:R-MMU-9682182

Csf1r-associated PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate

Reactome:R-MMU-9705459

p-Y-Stat1,3,5 dimer binds Socs3 gene

Reactome:R-MMU-9705472

p-Y-Stat1,3,5 dimer binds Socs1 gene

Reactome:R-MMU-9943422

Stat4 binds the Tbx21 (T-bet) gene

Reactome:R-MMU-9943424

Stat1 and Nfatc1 bind the Tbx21 (T-bet) gene

file:mouse/Stat1/Stat1-deep-research-falcon.md

Falcon deep research summary for mouse Stat1

STAT1 is an interferon-activated STAT-family DNA-binding transcription factor.
Falcon synthesis supports JAK-dependent phosphorylation, dimerization, nuclear translocation, and regulatory DNA binding as the central STAT1 mechanism.

file:mouse/Stat1/Stat1-notes.md

AIGR curator notes for Stat1

Deep Research

Falcon

(Stat1-deep-research-falcon.md)

Research report: Mouse **Stat1** (STAT1) functional annotation (UniProt **P42225**) Falcon Edison Scientific Literature 22 citations 2026-05-04T01:13:02.759853

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: Mouse Stat1 (STAT1) functional annotation (UniProt P42225)

0) Identity verification (critical)

The target protein is Signal transducer and activator of transcription 1 (STAT1) encoded by Stat1 in Mus musculus (mouse), consistent with the canonical interferon-activated STAT family transcription factor. Multiple retrieved sources explicitly discuss STAT1’s conserved STAT-family domain architecture (NTD/CCD/DBD/linker/SH2/TAD) and canonical activation residues Tyr701 (Y701) and Ser727 (S727), and several studies use Stat1−/− or Stat1^fl/fl conditional mouse models, confirming the literature matches the intended gene/protein context. (hassani2024theroleof pages 14-17, hassani2024theroleof pages 11-14, hassani2024theroleof pages 17-20, nelson2025stat1mediatedinterferonsignaling pages 13-16)

1) Key concepts and definitions (current understanding)

1.1 What STAT1 is (molecular role)

STAT1 is a signal transducer and transcription factor that relays extracellular cytokine signals (especially type I and type II interferons) into the nucleus to regulate gene expression programs, notably interferon-stimulated genes (ISGs) that establish antiviral and immunomodulatory states. (hassani2024theroleof pages 11-14, zhao2023ubiquitinationnetworkin pages 3-3)

1.2 Domain architecture and functional modules

STAT1 has the typical STAT-family architecture: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), linker, SH2 domain, and transactivation domain (TAD). These domains coordinate dimerization, nuclear trafficking, DNA binding, and transcriptional activation. (hassani2024theroleof pages 14-17, hassani2024theroleof pages 17-20)

A recent structural review also illustrates the STAT domain organization schematically (visual evidence). (lv2024thejakstatpathway media 40acb29b)

1.3 Canonical activation: JAK-STAT signaling downstream of interferons

Upon interferon receptor engagement, associated Janus kinases (JAKs) phosphorylate STAT1:

Type I interferons (IFN-α/β) signal through IFNAR1/IFNAR2, associated with TYK2 (IFNAR1) and JAK1 (IFNAR2). Canonically, STAT1 is phosphorylated on Y701 (and STAT2 on Y690), forming STAT1–STAT2 heterodimers that recruit IRF9 to form ISGF3, which binds ISRE elements and drives ISG transcription. (liang2024ptpn2andantitumor pages 49-52, hassani2024theroleof pages 11-14, zhao2023ubiquitinationnetworkin pages 3-3)
Type II interferon (IFN-γ) signals via IFNGR1/IFNGR2 with JAK1/JAK2, producing phosphorylated STAT1 homodimers (often termed GAF) that bind GAS DNA elements to induce IFN-γ-responsive genes. (liang2024ptpn2andantitumor pages 49-52, hassani2024theroleof pages 11-14)

DNA motifs: GAS consensus is described as TTTCNNNGAAA in one review. (hassani2024theroleof pages 14-17)

1.4 Key phosphorylation sites and consequences

STAT1 Tyr701 phosphorylation (pY701): promotes dimerization, nuclear translocation, and DNA binding (core activation step). (liang2024ptpn2andantitumor pages 49-52, hassani2024theroleof pages 14-17)
STAT1 Ser727 phosphorylation (pS727): supports maximal transcriptional activity, including coactivator recruitment, and is discussed as required for full interferon activity. Kinases implicated include p38, PKC-δ, and CDK8; a pathway TYK2 → LATS1 → CDK8 → STAT1(S727) has been described in type I IFN signaling context. (zhao2023ubiquitinationnetworkin pages 3-3, liang2024ptpn2andantitumor pages 49-52)

1.5 Subcellular localization and trafficking

STAT1 is described as cytoplasmic at rest and translocates to the nucleus after activation; nuclear import can occur via importin-α/β. Reviews also note nuclear localization/export signals enabling cytoplasm–nucleus shuttling. (hassani2024theroleof pages 14-17, hassani2024theroleof pages 17-20)

1.6 Output programs (examples of STAT1-regulated genes)

Type I IFN-triggered ISGF3 signaling is described to activate >300 ISGs, with examples including ISG15, OAS1-3, IFIT1-3, MX1, and MX2. (hassani2024theroleof pages 11-14)

In an antigen presentation / tumor immunity context, STAT1 activation is described to induce chemokines (e.g., Cxcl9/Cxcl10) and antigen presentation genes (e.g., Tap1/Tapbp, MHC genes such as H2-K1/H2-Ab1). (liang2024ptpn2andantitumor pages 49-52)

1.7 Non-canonical concepts: unphosphorylated STAT1 (U-STAT1)

Recent reviews highlight that unphosphorylated STATs, including U-STAT1, can form dimers, enter the nucleus, and contribute to constitutive expression of subsets of ISGs (e.g., OAS and Mx1) even without acute cytokine stimulation. (liu2024functionalinvolvementof pages 3-4)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 Post-translational regulation in interferon antiviral signaling (2023)

A 2023 review of ubiquitination networks in type I IFN signaling emphasizes that canonical IFN-I signaling drives STAT1 pY701 and requires pS727 for full activity, describing kinase routes including a TYK2–LATS1–CDK8–STAT1 axis for Ser727 phosphorylation. This reflects a continued trend in the field: moving beyond “Y701-only” activation toward integrated control via multi-site phosphorylation and broader post-translational networks. (Zhao et al., May 2023, European Journal of Immunology, https://doi.org/10.1002/eji.202350384) (zhao2023ubiquitinationnetworkin pages 3-3)

2.2 Structural biology and pathway-level synthesis (2024)

A 2024 structural review integrates interferon receptor complexes and JAK-STAT architecture; it includes a table mapping interferon cytokines to receptors, JAKs, and STATs, and depicts STAT domain organization (visual evidence). This reflects a “molecular mechanism → engineering/therapeutics” direction in current JAK-STAT research. (Lv et al., Aug 2024, Signal Transduction and Targeted Therapy, https://doi.org/10.1038/s41392-024-01934-w) (lv2024thejakstatpathway media 40acb29b, lv2024thejakstatpathway media c9783a5c, lv2024thejakstatpathway media 25a5c8c1)

2.3 Viral immune evasion targeting STAT1 trafficking (2024)

Mechanistic work in 2024 shows that viral proteins can antagonize interferon signaling not merely by blocking phosphorylation, but by interfering with STAT1 nuclear translocation. This reinforces nuclear import as a key actionable node in STAT1 function. (hassani2024theroleof pages 14-17)

2.4 STATs in infection biology reviews (2024)

A 2024 review on influenza A virus pathogenesis reiterates domain architecture and highlights STAT1 (including Y701) as central to interferon-mediated antiviral responses, underscoring that STAT1’s role spans type I, II, and III interferons. (Liu et al., Dec 2024, International Journal of Molecular Sciences, https://doi.org/10.3390/ijms252413589) (liu2024functionalinvolvementof pages 3-4)

3) Current applications and real-world implementations

3.1 Mouse models: infection susceptibility and tissue-specific interferon defense

Recent in vivo genetics demonstrate STAT1’s non-redundant role in antiviral defense with tissue- and compartment-specific requirements.

Usutu virus (USUV) infection model (2025, mouse genetics): Whole-body Stat1−/− mice showed 100% lethality (death at 6–7 dpi) vs 100% survival in controls. Hematopoietic Stat1 deletion (Vav-Cre; Stat1^fl/fl) reduced survival to 17% and produced a 35-fold serum viral RNA increase at 1–2 dpi, with high viral RNA across multiple organs by 4 dpi. By contrast, hepatocyte-specific deletion (Alb-Cre) showed 100% survival and undetectable serum viral RNA. These findings are widely used as a template for dissecting STAT1-dependent restriction across cell lineages. (Nelson et al., Jul 2025, PLOS Neglected Tropical Diseases, https://doi.org/10.1371/journal.pntd.0013317) (nelson2025stat1mediatedinterferonsignaling pages 13-16)

This study also provides a practical “intervention” demonstration: IFN-β pre-exposure rescued Vav-Cre mice (5/6 survived vs 0/4 untreated), illustrating that exogenous interferon can partially compensate when STAT1 is absent in specific compartments (with the important caveat that interferon signaling classically requires STAT1). (nelson2025stat1mediatedinterferonsignaling pages 13-16)

Machupo virus models using Stat1−/− mice: Stat1 knockout mice provide sensitive small-animal models for arenavirus pathogenesis, and viral adaptation can shift from partially lethal to fully lethal phenotypes, facilitating preclinical testing of antivirals and countermeasures (as an implementation of Stat1 KO for translational infection modeling). (Monticelli et al., Jul 2025, Viruses, https://doi.org/10.3390/v17070996) (monticelli2025characterizationofa pages 1-2)

3.2 Vaccinology: STAT1-dependent innate orchestration

A 2024 study of a heat-killed Cryptococcus vaccine candidate (HK-fbp1) reports that conditional Stat1 deletion in CD11c+ cells (including alveolar macrophages and monocyte-derived DC/macrophage populations) is essential for vaccine-induced protection, supporting the use of cell-specific Stat1 models to define which antigen-presenting/innate compartments must respond to IFNγ during effective vaccination. (Wang et al., Oct 2024, mBio, https://doi.org/10.1128/mbio.01944-24) (wang2024innatecellsand pages 1-2)

3.3 Inflammation and transplantation immunology

In a 2023 allogeneic BMT model, recipient Stat1 deficiency accelerated acute GVHD mortality (median survival 5 vs 7.5 days; log-rank P<0.0001), and Stat1-deficient antigen-presenting cells exhibited altered antigen presentation (impaired exogenous, increased endogenous), demonstrating STAT1 as an actionable checkpoint shaping APC function in severe inflammatory settings. (Lu et al., Feb 2023, Journal of Clinical Investigation, https://doi.org/10.1172/jci125986) (lu2023ifnγrstat1signalingin pages 1-2)

3.4 Oncology and immunotherapy context (STAT1 axis interactions)

STAT1 programs upregulate antigen presentation and chemokines that can support T cell recruitment; in tumor contexts, STAT1 can also induce immune checkpoints such as PD-L1 (reviewed). (liang2024ptpn2andantitumor pages 49-52)

4) Expert opinions and analysis (authoritative synthesis)

4.1 STAT1 as a “core interferon transcription factor” with modular outputs

Recent reviews converge on a model where STAT1 is not a simple on/off switch, but a modular transcription factor whose outputs are tuned by (i) which receptor/JAK pair is engaged (IFNAR vs IFNGR), (ii) which STAT complex forms (ISGF3 vs GAF), (iii) multi-site phosphorylation status (Y701 and S727), and (iv) nuclear trafficking dynamics. (liang2024ptpn2andantitumor pages 49-52, zhao2023ubiquitinationnetworkin pages 3-3, hassani2024theroleof pages 11-14)

4.2 Regulation and “signal shutoff” are essential to prevent immunopathology

Negative feedback by SOCS proteins is highlighted as important: insufficient SOCS1 is associated with continuous STAT1 phosphorylation and heightened inflammatory/autoimmune responses, emphasizing that STAT1 activity must be tightly regulated. (hassani2024theroleof pages 11-14)

4.3 The field’s direction: integrating structural biology with engineering/therapeutics

The 2024 structural review frames JAK-STAT as a mature pathway for therapeutic modulation and cytokine engineering, reflecting the broader expert consensus that mechanistic understanding (structures, interfaces, trafficking, PTMs) enables rational design of interventions. (lv2024thejakstatpathway media 40acb29b)

5) Relevant statistics and data (recent studies)

5.1 Quantitative genetic evidence in mouse infection models

Stat1−/− USUV: 100% lethality, deaths 6–7 dpi; controls 100% survival. (nelson2025stat1mediatedinterferonsignaling pages 13-16)
Hematopoietic Stat1 deletion (Vav-Cre): 17% survival, deaths 7–9 dpi; 35-fold serum viral RNA increase at 1–2 dpi; multi-organ high viral loads at 4 dpi. (nelson2025stat1mediatedinterferonsignaling pages 13-16)
Neuronal Stat1 deletion (Syn-Cre): 89% survival with 38-fold serum viral RNA increase at 1–2 dpi. (nelson2025stat1mediatedinterferonsignaling pages 13-16)
IFN-β intervention: Vav-Cre Stat1^fl/fl 5/6 survived with IFN-β pre-exposure vs 0/4 untreated. (nelson2025stat1mediatedinterferonsignaling pages 13-16)

5.2 Quantitative evidence in GVHD model

Recipient Stat1 deficiency: median survival 5 vs 7.5 days, P<0.0001. (lu2023ifnγrstat1signalingin pages 1-2)

5.3 Transcriptomic scale of ISG responses

Type I interferon signaling via STAT1/STAT2/IRF9 (ISGF3) is described as inducing >300 ISGs. (hassani2024theroleof pages 11-14)

6) Functional annotation summary (mouse STAT1; UniProt P42225)

Primary molecular function

STAT1 is a phosphorylation-activated transcription factor that binds DNA regulatory elements (GAS/ISRE via complexes) to induce interferon-responsive gene programs that mediate antiviral defense, antigen presentation, and immune regulation. (liang2024ptpn2andantitumor pages 49-52, hassani2024theroleof pages 11-14)

Pathways

Type I IFN → IFNAR1/2 → JAK1/TYK2 → STAT1/STAT2/IRF9 (ISGF3) → ISRE → ISGs. (liang2024ptpn2andantitumor pages 49-52, hassani2024theroleof pages 11-14)
IFN-γ → IFNGR1/2 → JAK1/JAK2 → STAT1 homodimers (GAF) → GAS → IFN-γ-responsive genes. (liang2024ptpn2andantitumor pages 49-52, hassani2024theroleof pages 14-17)

Localization

STAT1 shuttles between cytoplasm and nucleus; upon phosphorylation (Y701, and S727 for maximal transcription), it translocates to the nucleus to regulate transcription. (hassani2024theroleof pages 14-17, hassani2024theroleof pages 17-20)

Regulation

Positive regulation: JAK-mediated phosphorylation at Y701; additional S727 phosphorylation via kinases including CDK8 (with upstream TYK2/LATS1 described). (zhao2023ubiquitinationnetworkin pages 3-3)
Negative regulation: SOCS-mediated feedback (SOCS1 highlighted). (hassani2024theroleof pages 11-14)
Protein stability/ubiquitin context: STAT TAD implicated in ubiquitin-mediated degradation in reviews of IFN responses. (hassani2024theroleof pages 14-17)

Visual evidence from a 2024 review

A 2024 structural review provides figures/tables showing (i) STAT domain architecture and (ii) interferon receptor/JAK/STAT mapping (including STAT1), supporting the mechanistic overview above. (lv2024thejakstatpathway media 40acb29b, lv2024thejakstatpathway media c9783a5c)

Source URLs (with publication dates where available)

Zhao Q et al. May 2023. European Journal of Immunology. “Ubiquitination network in the type I IFN-induced antiviral signaling pathway.” https://doi.org/10.1002/eji.202350384 (zhao2023ubiquitinationnetworkin pages 3-3)
Lu C et al. Feb 2023. Journal of Clinical Investigation. “IFN-γR/STAT1 signaling in recipient hematopoietic antigen-presenting cells suppresses graft-versus-host disease.” https://doi.org/10.1172/jci125986 (lu2023ifnγrstat1signalingin pages 1-2)
Lv Y et al. Aug 2024. Signal Transduction and Targeted Therapy. “The JAK-STAT pathway: from structural biology to cytokine engineering.” https://doi.org/10.1038/s41392-024-01934-w (lv2024thejakstatpathway media 40acb29b, lv2024thejakstatpathway media c9783a5c, lv2024thejakstatpathway media 25a5c8c1)
Liu S et al. Dec 2024. International Journal of Molecular Sciences. “Functional Involvement of Signal Transducers and Activators of Transcription in the Pathogenesis of Influenza A Virus.” https://doi.org/10.3390/ijms252413589 (liu2024functionalinvolvementof pages 3-4)
Wang K et al. Oct 2024. mBio. “Innate cells and STAT1-dependent signals orchestrate vaccine-induced protection against invasive Cryptococcus infection.” https://doi.org/10.1128/mbio.01944-24 (wang2024innatecellsand pages 1-2)
Nelson AN et al. Jul 2025. PLOS Neglected Tropical Diseases. “STAT1-mediated interferon signaling in the hematopoietic system is essential for restricting Usutu virus infection in vivo.” https://doi.org/10.1371/journal.pntd.0013317 (nelson2025stat1mediatedinterferonsignaling pages 13-16)

References

(hassani2024theroleof pages 14-17): S Hassani. The role of isre and gas composite-containing genes in long-term ifn-i and ifn-ii responsiveness. Unknown journal, 2024.
(hassani2024theroleof pages 11-14): S Hassani. The role of isre and gas composite-containing genes in long-term ifn-i and ifn-ii responsiveness. Unknown journal, 2024.
(hassani2024theroleof pages 17-20): S Hassani. The role of isre and gas composite-containing genes in long-term ifn-i and ifn-ii responsiveness. Unknown journal, 2024.
(nelson2025stat1mediatedinterferonsignaling pages 13-16): Amy N. Nelson, Saloni Sinha, Sydney J. Mullin, Sebastian S. Carver, Thomas R. Cafiero, Aaron E. Lin, Robert E. Schwartz, and Alexander Ploss. Stat1-mediated interferon signaling in the hematopoietic system is essential for restricting usutu virus infection in vivo. PLOS Neglected Tropical Diseases, 19:e0013317, Jul 2025. URL: https://doi.org/10.1371/journal.pntd.0013317, doi:10.1371/journal.pntd.0013317. This article has 0 citations and is from a domain leading peer-reviewed journal.
(zhao2023ubiquitinationnetworkin pages 3-3): Qian Zhao, Renxia Zhang, Caixia Qiao, Ying Miao, Yukang Yuan, and Huizhen Zheng. Ubiquitination network in the type i ifn‐induced antiviral signaling pathway. European Journal of Immunology, May 2023. URL: https://doi.org/10.1002/eji.202350384, doi:10.1002/eji.202350384. This article has 26 citations and is from a peer-reviewed journal.
(lv2024thejakstatpathway media 40acb29b): 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 111 citations and is from a peer-reviewed journal.
(liang2024ptpn2andantitumor pages 49-52): SHUWEI LIANG. Ptpn2 and anti-tumor immunity in triple-negative breast cancer. Text, Jan 2024. URL: https://doi.org/10.26180/25018109, doi:10.26180/25018109. This article has 0 citations and is from a peer-reviewed journal.
(liu2024functionalinvolvementof pages 3-4): Shasha Liu, Feng Qiu, Rongrong Gu, and Erying Xu. Functional involvement of signal transducers and activators of transcription in the pathogenesis of influenza a virus. International Journal of Molecular Sciences, 25:13589, Dec 2024. URL: https://doi.org/10.3390/ijms252413589, doi:10.3390/ijms252413589. This article has 5 citations.
(lv2024thejakstatpathway media c9783a5c): 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 111 citations and is from a peer-reviewed journal.
(lv2024thejakstatpathway media 25a5c8c1): 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 111 citations and is from a peer-reviewed journal.
(monticelli2025characterizationofa pages 1-2): S. R. Monticelli, A. Kuehne, Russell R. Bakken, Susan R. Coyne, Kenise D. Lewis, J. Raymond, Xiankun Zeng, Joshua B. Richardson, Zebulon Lapoint, Jennifer L. Williams, Christopher P. Stefan, Jeffrey R. Kugelman, Jeffrey W. Koehler, and Andrew S Herbert. Characterization of a stat-1 knockout mouse model for machupo virus infection and pathogenesis. Viruses, Jul 2025. URL: https://doi.org/10.3390/v17070996, doi:10.3390/v17070996. This article has 3 citations.
(wang2024innatecellsand pages 1-2): Keyi Wang, Vanessa Espinosa, Yina Wang, Alexander Lemenze, Yosuke Kumamoto, Chaoyang Xue, and Amariliz Rivera. Innate cells and stat1-dependent signals orchestrate vaccine-induced protection against invasive cryptococcus infection. mBio, Oct 2024. URL: https://doi.org/10.1128/mbio.01944-24, doi:10.1128/mbio.01944-24. This article has 10 citations and is from a domain leading peer-reviewed journal.
(lu2023ifnγrstat1signalingin pages 1-2): Caisheng Lu, Huihui Ma, Liangsong Song, Hui Wang, Lily Wang, Shirong Li, Stephen M. Lagana, Antonia R. Sepulveda, Kasper Hoebe, Samuel S. Pan, Yong-Guang Yang, Suzanne Lentzsch, and Markus Y. Mapara. Ifn-γr/stat1 signaling in recipient hematopoietic antigen-presenting cells suppresses graft-versus-host disease. Journal of Clinical Investigation, Feb 2023. URL: https://doi.org/10.1172/jci125986, doi:10.1172/jci125986. This article has 17 citations and is from a highest quality peer-reviewed journal.

Citations

hassani2024theroleof pages 14-17
hassani2024theroleof pages 11-14
liu2024functionalinvolvementof pages 3-4
zhao2023ubiquitinationnetworkin pages 3-3
monticelli2025characterizationofa pages 1-2
wang2024innatecellsand pages 1-2
hassani2024theroleof pages 17-20
https://doi.org/10.1002/eji.202350384
https://doi.org/10.1038/s41392-024-01934-w
https://doi.org/10.3390/ijms252413589
https://doi.org/10.1371/journal.pntd.0013317
https://doi.org/10.3390/v17070996
https://doi.org/10.1128/mbio.01944-24
https://doi.org/10.1172/jci125986
https://doi.org/10.1371/journal.pntd.0013317,
https://doi.org/10.1002/eji.202350384,
https://doi.org/10.1038/s41392-024-01934-w,
https://doi.org/10.26180/25018109,
https://doi.org/10.3390/ijms252413589,
https://doi.org/10.3390/v17070996,
https://doi.org/10.1128/mbio.01944-24,
https://doi.org/10.1172/jci125986,

📚 Additional Documentation

Notes

(Stat1-notes.md)

Stat1 review notes

Falcon deep research was unavailable for this corrected batch after the provider
timeout observed during the batch run; no Stat1-deep-research-falcon.md file
was produced. Review decisions used the cached UniProt record and publications.

Core function judgment: STAT1 is a cytokine-activated DNA-binding transcription
factor, especially in type I and type II interferon signaling. UniProt describes
STAT1 as a signal transducer and transcription activator that forms ISGF3 or GAF
complexes, enters the nucleus, binds ISRE or GAS elements, and activates
interferon-stimulated genes [UniProt:P42225 "binds to the IFN stimulated
response element"; UniProt:P42225 "binds to the IFN gamma activated sequence"].
Experimental mouse/cell evidence supports interferon-dependent activation and
transcriptional output PMID:11972023.

Curation stance: RNA polymerase II-specific DNA-binding transcription factor
activity and regulation of DNA-templated transcription are core. JAK-STAT and
interferon pathway terms directly describe the activation context and are
retained, but immune defense, proliferation, development, apoptosis, and other
cellular response terms are kept as non-core downstream outcomes. Generic
protein binding and broad response/process terms are over-annotated when they
do not add mechanistic specificity.

📄 View Raw YAML

id: P42225
gene_symbol: Stat1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: STAT1 is a cytokine-activated signal transducer and RNA polymerase II transcription factor
  that mediates type I and type II interferon responses. After JAK-dependent phosphorylation it dimerizes,
  enters the nucleus, binds GAS or ISRE-associated regulatory DNA, and activates interferon-stimulated
  gene expression.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0006952
    label: defense response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: defense response pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: regulation of cell population proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: nucleus localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- 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: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Direct STAT1 transcriptional regulation
    action: ACCEPT
    reason: This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced
      activation.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
- 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: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
    supported_by:
    - reference_id: file:mouse/Stat1/Stat1-notes.md
      supporting_text: STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type
        I and type II interferon signaling.
    - reference_id: file:mouse/Stat1/Stat1-deep-research-falcon.md
      supporting_text: Falcon synthesis supports STAT1 as an interferon-activated STAT-family transcription
        factor that binds regulatory DNA after JAK-dependent phosphorylation.
- term:
    id: GO:0070721
    label: ISGF3 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ISGF3 complex interaction or complex context
    action: ACCEPT
    reason: STAT1 is a core subunit of the STAT1/STAT2/IRF9 ISGF3 transcription factor complex during
      type I interferon signaling, so this complex-membership annotation is accurate even though the
      core molecular activity remains DNA-binding transcription factor activity.
- term:
    id: GO:0043434
    label: response to peptide hormone
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: response to peptide hormone pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
- 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: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
    supported_by:
    - reference_id: file:mouse/Stat1/Stat1-notes.md
      supporting_text: STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type
        I and type II interferon signaling.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: nucleus localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: nucleoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: DNA-templated transcription pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Direct STAT1 transcriptional regulation
    action: ACCEPT
    reason: This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced
      activation.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: signal transduction pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
- term:
    id: GO:0008283
    label: cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: cell population proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: regulation of apoptotic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0051093
    label: negative regulation of developmental process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: negative regulation of developmental process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0051607
    label: defense response to virus
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: defense response to virus pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0060333
    label: type II interferon-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22306691
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding is too generic to describe STAT1 function and should be replaced by specific
      complex, DNA-binding, or transcription-factor annotations.
    supported_by:
    - reference_id: PMID:22306691
      supporting_text: The composition and signaling of the IL-35 receptor are unconventional.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23749757
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding is too generic to describe STAT1 function and should be replaced by specific
      complex, DNA-binding, or transcription-factor annotations.
    supported_by:
    - reference_id: PMID:23749757
      supporting_text: Jul 22. Construction of a novel oligonucleotide array-based transcription factor
        interaction assay platform and its uses for profiling STAT1 cofactors in mouse fibroblast cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24360797
  review:
    summary: Generic protein binding
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding is too generic to describe STAT1 function and should be replaced by specific
      complex, DNA-binding, or transcription-factor annotations.
    supported_by:
    - reference_id: PMID:24360797
      supporting_text: 2013 Dec 19. Hepatic RIG-I predicts survival and interferon-α therapeutic response
        in hepatocellular carcinoma.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: chromatin pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0000977
    label: RNA polymerase II transcription regulatory region sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: RNA polymerase II transcription regulatory region sequence-specific DNA binding directly
      captures STAT1 DNA-binding transcription-factor activity.
    action: ACCEPT
    reason: STAT1 binds cytokine-responsive regulatory DNA as part of its core transcription factor
      function.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
- term:
    id: GO:0000979
    label: RNA polymerase II core promoter sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: MODIFY
    reason: STAT1 binds GAS and ISRE regulatory DNA elements downstream of interferon/cytokine signaling;
      these are better represented as RNA polymerase II cis-regulatory region sequence-specific DNA
      binding than as core-promoter binding.
    proposed_replacement_terms:
    - id: GO:0000978
      label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
    supported_by:
    - reference_id: file:mouse/Stat1/Stat1-notes.md
      supporting_text: STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type
        I and type II interferon signaling.
- term:
    id: GO:0001222
    label: transcription corepressor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: transcription corepressor binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0001223
    label: transcription coactivator binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: transcription coactivator binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0001937
    label: negative regulation of endothelial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of endothelial cell proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0002230
    label: positive regulation of defense response to virus by host
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of defense response to virus by host pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
- term:
    id: GO:0003690
    label: double-stranded DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
- term:
    id: GO:0005164
    label: tumor necrosis factor receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: tumor necrosis factor receptor binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleus localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleolus pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Direct STAT1 transcriptional regulation
    action: ACCEPT
    reason: This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced
      activation.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
- term:
    id: GO:0016525
    label: negative regulation of angiogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of angiogenesis pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic enzyme binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding
      and transcription-factor terms.
- term:
    id: GO:0030424
    label: axon
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: axon pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: dendrite pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0031730
    label: CCR5 chemokine receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: CCR5 chemokine receptor binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0032727
    label: positive regulation of interferon-alpha production
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of interferon-alpha production pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic protein-containing complex annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding
      and transcription-factor terms.
- term:
    id: GO:0033209
    label: tumor necrosis factor-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: tumor necrosis factor-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0034341
    label: response to type II interferon
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: response to type II interferon pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0035035
    label: histone acetyltransferase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: histone acetyltransferase binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0035456
    label: response to interferon-beta
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: response to interferon-beta pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0035458
    label: cellular response to interferon-beta
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to interferon-beta pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0038111
    label: interleukin-7-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: interleukin-7-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0038113
    label: interleukin-9-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: interleukin-9-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0042393
    label: histone binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: histone binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic identical protein binding annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding
      and transcription-factor terms.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic protein homodimerization activity annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding
      and transcription-factor terms.
- term:
    id: GO:0043124
    label: negative regulation of canonical NF-kappaB signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of canonical NF-kappaB signal transduction pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: sequence-specific DNA binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0044389
    label: ubiquitin-like protein ligase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ubiquitin-like protein ligase binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0045648
    label: positive regulation of erythrocyte differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of erythrocyte differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Direct STAT1 transcriptional regulation
    action: ACCEPT
    reason: This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced
      activation.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of transcription by RNA polymerase II pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0046427
    label: positive regulation of receptor signaling pathway via JAK-STAT
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of receptor signaling pathway via JAK-STAT pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0046725
    label: negative regulation by virus of viral protein levels in host cell
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation by virus of viral protein levels in host cell pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: perinuclear region of cytoplasm pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0051607
    label: defense response to virus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: defense response to virus pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0051721
    label: protein phosphatase 2A binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein phosphatase 2A binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0060333
    label: type II interferon-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
- term:
    id: GO:0061326
    label: renal tubule development
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: renal tubule development pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0070106
    label: interleukin-27-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: interleukin-27-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0070721
    label: ISGF3 complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ISGF3 complex interaction or complex context
    action: ACCEPT
    reason: STAT1 is a core subunit of the STAT1/STAT2/IRF9 ISGF3 transcription factor complex during
      type I interferon signaling, so this complex-membership annotation is accurate even though the
      core molecular activity remains DNA-binding transcription factor activity.
- term:
    id: GO:0071346
    label: cellular response to type II interferon
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to type II interferon pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0090575
    label: RNA polymerase II transcription regulator complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: RNA polymerase II transcription regulator complex pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0097696
    label: cell surface receptor signaling pathway via STAT
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cell surface receptor signaling pathway via STAT pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:1990841
    label: promoter-specific chromatin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: promoter-specific chromatin binding pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0061326
    label: renal tubule development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: renal tubule development pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:10692450
  review:
    summary: positive regulation of apoptotic process pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
    supported_by:
    - reference_id: PMID:10692450
      supporting_text: Thrombin inhibits tumor cell growth in association with up-regulation of p21(waf/cip1)
        and caspases via a p53-independent, STAT-1-dependent pathway.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of transcription by RNA polymerase II pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:37327784
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
    supported_by:
    - reference_id: file:mouse/Stat1/Stat1-uniprot.txt
      supporting_text: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes
        transcription of CIITA
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: ACCEPT
    reason: STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream
      of interferon/cytokine signaling.
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to
        IFN-gamma.
    - reference_id: file:mouse/Stat1/Stat1-notes.md
      supporting_text: STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type
        I and type II interferon signaling.
- term:
    id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to
        IFN-gamma.
- term:
    id: GO:0034341
    label: response to type II interferon
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: response to type II interferon pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to
        IFN-gamma.
- term:
    id: GO:0008283
    label: cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:15781341
  review:
    summary: cell population proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
    supported_by:
    - reference_id: PMID:15781341
      supporting_text: Differential effects of a novel IFN-zeta/limitin and IFN-alpha on signals for Daxx
        induction and Crk phosphorylation that couple with growth control of megakaryocytes.
- term:
    id: GO:0051607
    label: defense response to virus
  evidence_type: IMP
  original_reference_id: PMID:32270034
  review:
    summary: defense response to virus pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
    supported_by:
    - reference_id: PMID:32270034
      supporting_text: 2020 Apr. IL-27 signaling activates skin cells to induce innate antiviral proteins
        and protects against Zika virus infection.
- term:
    id: GO:0000979
    label: RNA polymerase II core promoter sequence-specific DNA binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Core STAT1 DNA-binding transcription factor activity
    action: MODIFY
    reason: STAT1 binds GAS and ISRE regulatory DNA elements downstream of interferon/cytokine signaling;
      these are better represented as RNA polymerase II cis-regulatory region sequence-specific DNA
      binding than as core-promoter binding.
    proposed_replacement_terms:
    - id: GO:0000978
      label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
- term:
    id: GO:0032727
    label: positive regulation of interferon-alpha production
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of interferon-alpha production pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Generic protein homodimerization activity annotation
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is too broad to add useful information for STAT1 relative to specific DNA-binding
      and transcription-factor terms.
- term:
    id: GO:0051607
    label: defense response to virus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: defense response to virus pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9676907
  review:
    summary: nucleoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9705459
  review:
    summary: nucleoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9705472
  review:
    summary: nucleoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9943422
  review:
    summary: nucleoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9943424
  review:
    summary: nucleoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0045648
    label: positive regulation of erythrocyte differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of erythrocyte differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0071345
    label: cellular response to cytokine stimulus
  evidence_type: ISO
  original_reference_id: PMID:19414010
  review:
    summary: cellular response to cytokine stimulus pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
    supported_by:
    - reference_id: PMID:19414010
      supporting_text: Epub 2009 May 3. JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine
        toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway.
- term:
    id: GO:0034340
    label: response to type I interferon
  evidence_type: IDA
  original_reference_id: PMID:24882218
  review:
    summary: response to type I interferon pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
    supported_by:
    - reference_id: PMID:24882218
      supporting_text: 2014 May 29. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin
        ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response.
- term:
    id: GO:0071222
    label: cellular response to lipopolysaccharide
  evidence_type: IMP
  original_reference_id: PMID:21606371
  review:
    summary: cellular response to lipopolysaccharide pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
    supported_by:
    - reference_id: PMID:21606371
      supporting_text: Glucocorticoids target suppressor of cytokine signaling 1 (SOCS1) and type 1 interferons
        to regulate Toll-like receptor-induced STAT1 activation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-1169206
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9674908
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9674931
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9676907
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9676912
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9680646
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9682158
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9682182
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:24598055
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
    supported_by:
    - reference_id: PMID:24598055
      supporting_text: Mar 5. TLR ligands up-regulate Trex1 expression in murine conventional dendritic
        cells through type I Interferon and NF-κB-dependent signaling pathways.
- term:
    id: GO:0034240
    label: negative regulation of macrophage fusion
  evidence_type: IMP
  original_reference_id: PMID:22865856
  review:
    summary: negative regulation of macrophage fusion pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
    supported_by:
    - reference_id: PMID:22865856
      supporting_text: 2012 Aug 3. An essential role for STAT6-STAT1 protein signaling in promoting macrophage
        cell-cell fusion.
- term:
    id: GO:0060333
    label: type II interferon-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:12138178
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
    supported_by:
    - reference_id: PMID:12138178
      supporting_text: Identification of a nuclear Stat1 protein tyrosine phosphatase.
- term:
    id: GO:0060337
    label: type I interferon-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:12138178
  review:
    summary: Core interferon/JAK-STAT signaling role
    action: ACCEPT
    reason: STAT1 is a direct transcription factor effector of type I and type II interferon JAK-STAT
      signaling.
    supported_by:
    - reference_id: PMID:12138178
      supporting_text: Identification of a nuclear Stat1 protein tyrosine phosphatase.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: negative regulation of transcription by RNA polymerase II pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0002053
    label: positive regulation of mesenchymal cell proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of mesenchymal cell proliferation pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- 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: negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis
      pathway context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0072136
    label: metanephric mesenchymal cell proliferation involved in metanephros development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: metanephric mesenchymal cell proliferation involved in metanephros development pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- term:
    id: GO:0072162
    label: metanephric mesenchymal cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: metanephric mesenchymal cell differentiation pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
- 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: negative regulation of metanephric nephron tubule epithelial cell differentiation pathway
      context
    action: KEEP_AS_NON_CORE
    reason: This regulatory annotation is plausible for STAT1 biology but is broader or more downstream
      than the core transcription-factor function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-1169142
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9008004
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9674959
  review:
    summary: cytosol localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15661922
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
    supported_by:
    - reference_id: PMID:15661922
      supporting_text: Immune activation of type I IFNs by Listeria monocytogenes occurs independently
        of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding
        kinase 1.
- term:
    id: GO:0009617
    label: response to bacterium
  evidence_type: IDA
  original_reference_id: PMID:15661922
  review:
    summary: response to bacterium pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
    supported_by:
    - reference_id: PMID:15661922
      supporting_text: Immune activation of type I IFNs by Listeria monocytogenes occurs independently
        of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding
        kinase 1.
- term:
    id: GO:0019221
    label: cytokine-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:12872135
  review:
    summary: cytokine-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
    supported_by:
    - reference_id: PMID:12872135
      supporting_text: Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
- term:
    id: GO:0031663
    label: lipopolysaccharide-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:12872135
  review:
    summary: lipopolysaccharide-mediated signaling pathway pathway context
    action: KEEP_AS_NON_CORE
    reason: The annotation is compatible with STAT1 cytokine-response biology but represents a pathway,
      localization, or downstream process rather than the core molecular function.
    supported_by:
    - reference_id: PMID:12872135
      supporting_text: Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
- term:
    id: GO:0032496
    label: response to lipopolysaccharide
  evidence_type: IDA
  original_reference_id: PMID:12872135
  review:
    summary: response to lipopolysaccharide pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
    supported_by:
    - reference_id: PMID:12872135
      supporting_text: Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
- term:
    id: GO:0043330
    label: response to exogenous dsRNA
  evidence_type: IDA
  original_reference_id: PMID:12872135
  review:
    summary: response to exogenous dsRNA pathway context
    action: KEEP_AS_NON_CORE
    reason: This term describes an upstream stimulus or immune outcome of STAT1 activation, not its core
      molecular activity.
    supported_by:
    - reference_id: PMID:12872135
      supporting_text: Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IMP
  original_reference_id: PMID:15485925
  review:
    summary: PMID:15485925 supports Ubc8/ISGylation in the cached abstract but does not directly mention
      STAT1 DNA-binding transcription factor activity.
    action: UNDECIDED
    reason: Direct STAT1 evidence from full text or another source would be needed before accepting
      this PMID-specific annotation.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:15485925
  review:
    summary: PMID:15485925 supports Ubc8/ISGylation in the cached abstract but does not directly mention
      STAT1-dependent transcription.
    action: UNDECIDED
    reason: Direct STAT1 transcription evidence from full text or another source would be needed before
      accepting this PMID-specific annotation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12957148
  review:
    summary: PMID:12957148 is a retinal capillary dynamics paper in the cached abstract and does not
      directly support STAT1 nuclear localization.
    action: UNDECIDED
    reason: Full-text or corrected evidence would be needed before accepting this evidence-specific
      nucleus annotation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:14522949
  review:
    summary: PMID:14522949 supports nuclear translocation of Stat1/Stat5a in the cached abstract, not
      cytoplasmic localization.
    action: UNDECIDED
    reason: Full-text or corrected cytoplasmic localization evidence would be needed before accepting
      this evidence-specific annotation.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12634107
  review:
    summary: cytoplasm localization
    action: ACCEPT
    reason: STAT1 shuttles between cytoplasm/cytosol and nucleus during activation and transcriptional
      response.
    supported_by:
    - reference_id: PMID:12634107
      supporting_text: Expression and activation of STAT proteins during mouse retina development.
references:
- id: file:mouse/Stat1/Stat1-uniprot.txt
  title: UniProtKB P42225 record for mouse Stat1
  findings:
  - statement: STAT1 associates with the 13 kDa Gasdermin-D cleavage product and promotes CIITA transcription
      in the small intestine.
    supporting_text: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes
      transcription of CIITA
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  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:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  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:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  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:11972023
  title: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.
  findings: []
- id: PMID:12138178
  title: Identification of a nuclear Stat1 protein tyrosine phosphatase.
  findings: []
- id: PMID:12634107
  title: Expression and activation of STAT proteins during mouse retina development.
  findings: []
- id: PMID:12872135
  title: Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.
  findings: []
- id: PMID:12957148
  title: Erythrocyte and leukocyte dynamics in the retinal capillaries of diabetic mice.
  findings: []
- id: PMID:14522949
  title: Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis.
  findings: []
- id: PMID:15485925
  title: Interferon-inducible ubiquitin E2, Ubc8, is a conjugating enzyme for protein ISGylation.
  findings: []
- id: PMID:15661922
  title: Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2,
    and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1.
  findings: []
- id: PMID:15781341
  title: Differential effects of a novel IFN-zeta/limitin and IFN-alpha on signals for Daxx induction
    and Crk phosphorylation that couple with growth control of megakaryocytes.
  findings: []
- id: PMID:19414010
  title: JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation
    of NF-kappaB activation and the JAK/STAT pathway.
  findings: []
- id: PMID:21606371
  title: Glucocorticoids target suppressor of cytokine signaling 1 (SOCS1) and type 1 interferons to regulate
    Toll-like receptor-induced STAT1 activation.
  findings: []
- id: PMID:22306691
  title: The composition and signaling of the IL-35 receptor are unconventional.
  findings: []
- id: PMID:22865856
  title: An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion.
  findings: []
- id: PMID:23749757
  title: Construction of a novel oligonucleotide array-based transcription factor interaction assay platform
    and its uses for profiling STAT1 cofactors in mouse fibroblast cells.
  findings: []
- id: PMID:24360797
  title: Hepatic RIG-I predicts survival and interferon-α therapeutic response in hepatocellular carcinoma.
  findings: []
- id: PMID:24598055
  title: TLR ligands up-regulate Trex1 expression in murine conventional dendritic cells through type
    I Interferon and NF-κB-dependent signaling pathways.
  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:32270034
  title: IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against
    Zika virus infection.
  findings: []
- id: PMID:37327784
  title: Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine.
  findings: []
- id: Reactome:R-MMU-1169142
  title: Jak2 binds Stat1/Stat3
  findings: []
- id: Reactome:R-MMU-1169206
  title: Jak2 phosphorylates Stat1/Stat3
  findings: []
- id: Reactome:R-MMU-9008004
  title: Runx2 binds Stat1
  findings: []
- id: Reactome:R-MMU-9674908
  title: p-Y-Jak1,2 phosphorylates Stat1,3,5 in Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Y-Jak1:p-Jak2:p-Tyk2:Stat1,3,5
  findings: []
- id: Reactome:R-MMU-9674931
  title: Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Y-Jak1:p-Jak2:p-Syk:p-Hck:p-Tyk2:p-Y-Stat1,3,5 dissociates yielding
    Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Y-Jak1:p-Jak2:p-Syk:p-Hck:p-Tyk2 and p-Y-Stat1,3,5
  findings: []
- id: Reactome:R-MMU-9674959
  title: Csf3 dimer:2xp-4Y-Csf3r:Lyn:p-Jak1:p-Jak2:p-Syk:p-Hck:p-Tyk2 binds Stat1,3,5
  findings: []
- id: Reactome:R-MMU-9676907
  title: p-Y-Stat1,3,5 dimer translocates from the cytosol to the nucleus
  findings: []
- id: Reactome:R-MMU-9676912
  title: p-Y-Stat1,3,5 dimerize
  findings: []
- id: Reactome:R-MMU-9680646
  title: Pik3r11:Pik3ca,b,d (Pi3k), Plcg2 (PLCgamma2), Grb2:Sos1, Shc1 (Shc), Ptpn11 (Shp2), Grb2:Gab2,
    Grb2:Gab3, Grap2 (MONA), Cbl:Grb2, Inpp5d (SHIP1), Inppl1 (SHIP2)  bind p-8Y-Csf1r and are activated
  findings: []
- id: Reactome:R-MMU-9682158
  title: Csf1r-associated Plcg2 hydrolyzes phosphatidylcholine yielding choline phosphate and 1,2-diacylglycerol
  findings: []
- id: Reactome:R-MMU-9682182
  title: Csf1r-associated PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate
  findings: []
- id: Reactome:R-MMU-9705459
  title: p-Y-Stat1,3,5 dimer binds Socs3 gene
  findings: []
- id: Reactome:R-MMU-9705472
  title: p-Y-Stat1,3,5 dimer binds Socs1 gene
  findings: []
- id: Reactome:R-MMU-9943422
  title: Stat4 binds the Tbx21 (T-bet) gene
  findings: []
- id: Reactome:R-MMU-9943424
  title: Stat1 and Nfatc1 bind the Tbx21 (T-bet) gene
  findings: []
- id: file:mouse/Stat1/Stat1-deep-research-falcon.md
  title: Falcon deep research summary for mouse Stat1
  findings:
  - statement: STAT1 is an interferon-activated STAT-family DNA-binding transcription factor.
  - statement: Falcon synthesis supports JAK-dependent phosphorylation, dimerization,
      nuclear translocation, and regulatory DNA binding as the central STAT1 mechanism.
- id: file:mouse/Stat1/Stat1-notes.md
  title: AIGR curator notes for Stat1
  findings: []
core_functions:
- molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  description: STAT1 binds cytokine-responsive regulatory DNA as an RNA polymerase II transcription factor
    after interferon/JAK-STAT pathway activation.
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005737
    label: cytoplasm
  directly_involved_in:
  - id: GO:0006355
    label: regulation of DNA-templated transcription
  - id: GO:0007259
    label: cell surface receptor signaling pathway via JAK-STAT
  supported_by:
  - reference_id: file:mouse/Stat1/Stat1-notes.md
    supporting_text: STAT1 is a cytokine-activated DNA-binding transcription factor, especially in type
      I and type II interferon signaling.
  - reference_id: file:mouse/Stat1/Stat1-deep-research-falcon.md
    supporting_text: Falcon synthesis supports STAT1 as a cytokine/interferon-activated transcription
      factor that binds regulatory DNA downstream of JAK phosphorylation and nuclear translocation.

Stat1

Gene Description

Existing Annotations Review

Core Functions

STAT1 binds cytokine-responsive regulatory DNA as an RNA polymerase II transcription factor after interferon/JAK-STAT pathway activation.

References

Deep Research

Falcon

Research report: Mouse Stat1 (STAT1) functional annotation (UniProt P42225)

0) Identity verification (critical)

1) Key concepts and definitions (current understanding)

1.1 What STAT1 is (molecular role)

1.2 Domain architecture and functional modules

1.3 Canonical activation: JAK-STAT signaling downstream of interferons

1.4 Key phosphorylation sites and consequences

1.5 Subcellular localization and trafficking

1.6 Output programs (examples of STAT1-regulated genes)

1.7 Non-canonical concepts: unphosphorylated STAT1 (U-STAT1)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 Post-translational regulation in interferon antiviral signaling (2023)

2.2 Structural biology and pathway-level synthesis (2024)

2.3 Viral immune evasion targeting STAT1 trafficking (2024)

2.4 STATs in infection biology reviews (2024)

3) Current applications and real-world implementations

3.1 Mouse models: infection susceptibility and tissue-specific interferon defense

3.2 Vaccinology: STAT1-dependent innate orchestration

3.3 Inflammation and transplantation immunology

3.4 Oncology and immunotherapy context (STAT1 axis interactions)

4) Expert opinions and analysis (authoritative synthesis)

4.1 STAT1 as a “core interferon transcription factor” with modular outputs

4.2 Regulation and “signal shutoff” are essential to prevent immunopathology

4.3 The field’s direction: integrating structural biology with engineering/therapeutics

5) Relevant statistics and data (recent studies)

5.1 Quantitative genetic evidence in mouse infection models

5.2 Quantitative evidence in GVHD model

5.3 Transcriptomic scale of ISG responses

6) Functional annotation summary (mouse STAT1; UniProt P42225)

Primary molecular function

Pathways

Localization

Regulation

Visual evidence from a 2024 review

Source URLs (with publication dates where available)

Citations

📚 Additional Documentation

Notes

Stat1 review notes

📄 View Raw YAML