STAT3

UniProt ID: P40763
Organism: Homo sapiens
Review Status: COMPLETE
Aliases:
APRF Acute-phase response factor
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Gene Description

STAT3 (Signal transducer and activator of transcription 3) is a latent cytoplasmic transcription factor that is activated by tyrosine phosphorylation (Tyr705) in response to cytokines and growth factors. Upon phosphorylation by JAK kinases, STAT3 forms dimers via reciprocal SH2 domain-phosphotyrosine interactions, translocates to the nucleus, binds DNA via its DNA-binding domain at GAS (gamma-activated sequence) elements, and regulates transcription of target genes involved in cell proliferation, survival, differentiation, and immune responses. STAT3 is a central mediator of the JAK-STAT signaling pathway, particularly downstream of IL-6 family cytokines (IL-6, LIF, CNTF, IL-11). The protein contains an N-terminal domain, coiled-coil domain, DNA-binding domain, linker domain, SH2 domain, and C-terminal transactivation domain. Serine phosphorylation (Ser727) modulates transcriptional activity and contributes to non-canonical mitochondrial functions (mitoSTAT3). STAT3 plays critical roles in immune regulation, inflammation, embryonic development, and is frequently constitutively activated in various cancers where it promotes oncogenic programs. In neural development, STAT3 promotes gliogenesis and astrocyte differentiation. ISOFORM BIOLOGY - Alternative splicing produces STAT3alpha (P40763-1, 770 AA) and STAT3beta (P40763-2, 722 AA). STAT3beta lacks the C-terminal transactivation domain (TAD) and can act as a dominant-negative for some alpha-specific target genes, but also has distinct transcriptional activities. The alpha/beta ratio modulates cellular responses, with STAT3beta showing tumor-suppressive functions in some contexts.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IBA
GO_REF:0000033
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
file:human/STAT3/STAT3-deep-research-falcon.md
model: Edison Scientific Literature
GO:0006952 defense response
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Defense response is a pleiotropic effect of STAT3 activation in immune cells, not the core molecular function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0042127 regulation of cell population proliferation
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Cell proliferation regulation is a downstream effect of STAT3 target gene expression (e.g., MYC, CCND1), not core function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
IBA
GO_REF:0000033
ACCEPT
Summary: Core cis-regulatory DNA binding; STAT3 recognizes and binds to GAS (gamma-activated sequence) elements in target gene promoters [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0006357 regulation of transcription by RNA polymerase II
IBA
GO_REF:0000033
ACCEPT
Summary: Core regulation of transcription by RNA polymerase II [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
IBA
GO_REF:0000033
ACCEPT
Summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs (JAK1/2/3, TYK2) in response to cytokine receptor activation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IBA
GO_REF:0000033
ACCEPT
Summary: Core transcription factor activity for STAT3, canonical function of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0090575 RNA polymerase II transcription regulator complex
IBA
GO_REF:0000033
ACCEPT
Summary: RNA polymerase II transcription regulator complex; STAT3 functions as part of transcriptional regulatory complexes [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0033210 leptin-mediated signaling pathway
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Leptin signaling is one of many STAT3-activating pathways, not defining core function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0043434 response to peptide hormone
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Response to peptide hormone is context-specific [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0060397 growth hormone receptor signaling pathway via JAK-STAT
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Growth hormone signaling is one pathway activating STAT3, not the defining function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0001817 regulation of cytokine production
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Regulation of cytokine production [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0003677 DNA binding
IEA
GO_REF:0000120
ACCEPT
Summary: Core DNA binding activity essential for STAT3 transcription factor function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0003700 DNA-binding transcription factor activity
IEA
GO_REF:0000120
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005737 cytoplasm
IEA
GO_REF:0000120
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
ACCEPT
Summary: Regulation of DNA-templated transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0006955 immune response
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Immune response is a pleiotropic downstream effect, not core STAT3 transcription factor function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0007165 signal transduction
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Signal transduction is too broad; STAT3's specific function is JAK-STAT signaling and transcriptional regulation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0019221 cytokine-mediated signaling pathway
IEA
GO_REF:0000117
ACCEPT
Summary: Cytokine-mediated signaling is a core STAT3 function; responds to IL-6 family cytokines, interferons, and others [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0045893 positive regulation of DNA-templated transcription
IEA
GO_REF:0000117
ACCEPT
Summary: Positive regulation of DNA-templated transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0051240 positive regulation of multicellular organismal process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Positive regulation of multicellular organismal process is too broad, not specific to STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0090575 RNA polymerase II transcription regulator complex
IEA
GO_REF:0000117
ACCEPT
Summary: RNA polymerase II transcription regulator complex; STAT3 functions as part of transcriptional regulatory complexes [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005515 protein binding
IPI
PMID:11536047
MEN2A-RET-induced cellular transformation by activation of S...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:11536047
MEN2A-RET-induced cellular transformation by activation of STAT3.
GO:0005515 protein binding
IPI
PMID:11585385
Human leptin signaling in human peripheral blood mononuclear...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:11585385
Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway.
GO:0005515 protein binding
IPI
PMID:11940572
ErbB-2 activates Stat3 alpha in a Src- and JAK2-dependent ma...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:11940572
2002 Apr 8. ErbB-2 activates Stat3 alpha in a Src- and JAK2-dependent manner.
GO:0005515 protein binding
IPI
PMID:11970898
PTP1B regulates leptin signal transduction in vivo.
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:11970898
PTP1B regulates leptin signal transduction in vivo.
GO:0005515 protein binding
IPI
PMID:14966128
Structural requirements for signal transducer and activator ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:14966128
2004 Feb 13. Structural requirements for signal transducer and activator of transcription 3 binding to phosphotyrosine ligands containing the YXXQ motif.
GO:0005515 protein binding
IPI
PMID:15286705
Implication of BRG1 and cdk9 in the STAT3-mediated activatio...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:15286705
Implication of BRG1 and cdk9 in the STAT3-mediated activation of the p21waf1 gene.
GO:0005515 protein binding
IPI
PMID:15657067
Phosphotyrosine signaling networks in epidermal growth facto...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:15657067
Epub 2005 Jan 17. Phosphotyrosine signaling networks in epidermal growth factor receptor overexpressing squamous carcinoma cells.
GO:0005515 protein binding
IPI
PMID:15764709
STAT3 regulates Nemo-like kinase by mediating its interactio...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:15764709
STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation.
GO:0005515 protein binding
IPI
PMID:15821101
Mechanism of protein tyrosine phosphatase 1B-mediated inhibi...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:15821101
Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling.
GO:0005515 protein binding
IPI
PMID:16273093
A quantitative protein interaction network for the ErbB rece...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:16273093
A quantitative protein interaction network for the ErbB receptors using protein microarrays.
GO:0005515 protein binding
IPI
PMID:16331268
Physical and functional interactions between Daxx and STAT3.
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:16331268
Physical and functional interactions between Daxx and STAT3.
GO:0005515 protein binding
IPI
PMID:16364321
Physical and functional interactions between STAT3 and Kapos...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:16364321
2005 Dec 6. Physical and functional interactions between STAT3 and Kaposi's sarcoma-associated herpesvirus-encoded LANA.
GO:0005515 protein binding
IPI
PMID:18200042
Crif1 is a novel transcriptional coactivator of STAT3.
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:18200042
Crif1 is a novel transcriptional coactivator of STAT3.
GO:0005515 protein binding
IPI
PMID:18330356
Construction and characterization of a normalized yeast two-...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:18330356
Construction and characterization of a normalized yeast two-hybrid library derived from a human protein-coding clone collection.
GO:0005515 protein binding
IPI
PMID:19345327
Persistently activated Stat3 maintains constitutive NF-kappa...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:19345327
Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors.
GO:0005515 protein binding
IPI
PMID:19372587
ErbB2-mediated Src and signal transducer and activator of tr...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:19372587
ErbB2-mediated Src and signal transducer and activator of transcription 3 activation leads to transcriptional up-regulation of p21Cip1 and chemoresistance in breast cancer cells.
GO:0005515 protein binding
IPI
PMID:20133729
STAT3 is a substrate of SYK tyrosine kinase in B-lineage leu...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:20133729
STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells exposed to oxidative stress.
GO:0005515 protein binding
IPI
PMID:20871632
The role of the c-Jun N-terminal kinase 2-ฮฑ-isoform in non-s...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:20871632
The role of the c-Jun N-terminal kinase 2-ฮฑ-isoform in non-small cell lung carcinoma tumorigenesis.
GO:0005515 protein binding
IPI
PMID:20876300
Progesterone receptor induces ErbB-2 nuclear translocation t...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:20876300
Sep 27. Progesterone receptor induces ErbB-2 nuclear translocation to promote breast cancer growth via a novel transcriptional effect: ErbB-2 function as a coactivator of Stat3.
GO:0005515 protein binding
IPI
PMID:20929579
Epigenetic regulation of CpG promoter methylation in invasiv...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:20929579
Epigenetic regulation of CpG promoter methylation in invasive prostate cancer cells.
GO:0005515 protein binding
IPI
PMID:21184768
Novel role of signal transducer and activator of transcripti...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:21184768
2010 Dec 22. Novel role of signal transducer and activator of transcription 3 as a progesterone receptor coactivator in breast cancer.
GO:0005515 protein binding
IPI
PMID:21516116
Next-generation sequencing to generate interactome datasets.
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:21516116
Next-generation sequencing to generate interactome datasets.
GO:0005515 protein binding
IPI
PMID:21643014
The tumor-suppressor gene ARHI (DIRAS3) suppresses ovarian c...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:21643014
The tumor-suppressor gene ARHI (DIRAS3) suppresses ovarian cancer cell migration through inhibition of the Stat3 and FAK/Rho signaling pathways.
GO:0005515 protein binding
IPI
PMID:21953450
A complex of nuclear factor I-X3 and STAT3 regulates astrocy...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:21953450
2011 Sep 27. A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40.
GO:0005515 protein binding
IPI
PMID:21988832
Toward an understanding of the protein interaction network o...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:21988832
Toward an understanding of the protein interaction network of the human liver.
GO:0005515 protein binding
IPI
PMID:23416296
ECHS1 interacts with STAT3 and negatively regulates STAT3 si...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:23416296
2013 Feb 14. ECHS1 interacts with STAT3 and negatively regulates STAT3 signaling.
GO:0005515 protein binding
IPI
PMID:23684459
Phosphorylation of EZH2 activates STAT3 signaling via STAT3 ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:23684459
2013 May 16. Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells.
GO:0005515 protein binding
IPI
PMID:24135280
EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 a...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:24135280
EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma.
GO:0005515 protein binding
IPI
PMID:24189400
Perturbation of the mutated EGFR interactome identifies vuln...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:24189400
Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.
GO:0005515 protein binding
IPI
PMID:24396070
SH2B1ฮฒ interacts with STAT3 and enhances fibroblast growth f...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:24396070
Jan 6. SH2B1ฮฒ interacts with STAT3 and enhances fibroblast growth factor 1-induced gene expression during neuronal differentiation.
GO:0005515 protein binding
IPI
PMID:24658140
The mammalian-membrane two-hybrid assay (MaMTH) for probing ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:24658140
The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.
GO:0005515 protein binding
IPI
PMID:25065853
Drug resistance via feedback activation of Stat3 in oncogene...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:25065853
2014 Jul 24. Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells.
GO:0005515 protein binding
IPI
PMID:25241761
Using an in situ proximity ligation assay to systematically ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:25241761
Oct 9. Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
GO:0005515 protein binding
IPI
PMID:25402766
Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signal...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:25402766
Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:25416956
A proteome-scale map of the human interactome network.
GO:0005515 protein binding
IPI
PMID:25417160
A noncanonical Frizzled2 pathway regulates epithelial-mesenc...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:25417160
A noncanonical Frizzled2 pathway regulates epithelial-mesenchymal transition and metastasis.
GO:0005515 protein binding
IPI
PMID:25609649
Proteomic analyses reveal distinct chromatin-associated and ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:25609649
Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
GO:0005515 protein binding
IPI
PMID:25814554
Phospho-tyrosine dependent protein-protein interaction netwo...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:25814554
Phospho-tyrosine dependent protein-protein interaction network.
GO:0005515 protein binding
IPI
PMID:26966684
PIPINO: A Software Package to Facilitate the Identification ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:26966684
PIPINO: A Software Package to Facilitate the Identification of Protein-Protein Interactions from Affinity Purification Mass Spectrometry Data.
GO:0005515 protein binding
IPI
PMID:29892012
An interactome perturbation framework prioritizes damaging m...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:29892012
Jun 11. An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
GO:0005515 protein binding
IPI
PMID:30042492
STAT3 localizes to the ER, acting as a gatekeeper for ER-mit...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:30042492
Epub 2018 Jul 24. STAT3 localizes to the ER, acting as a gatekeeper for ER-mitochondrion Ca(2+) fluxes and apoptotic responses.
GO:0005515 protein binding
IPI
PMID:30413785
ROCK2, but not ROCK1 interacts with phosphorylated STAT3 and...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:30413785
ROCK2, but not ROCK1 interacts with phosphorylated STAT3 and co-occupies TH17/TFH gene promoters in TH17-activated human T cells.
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
GO:0005515 protein binding
IPI
PMID:31980649
Extensive rewiring of the EGFR network in colorectal cancer ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:31980649
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:32296183
Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding
IPI
PMID:32852592
Biochanin A impedes STAT3 activation by upregulating p38ฮด MA...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:32852592
2020 Aug 27. Biochanin A impedes STAT3 activation by upregulating p38ฮด MAPK phosphorylation in IL-6-stimulated macrophages.
GO:0005515 protein binding
IPI
PMID:32911434
A functionally defined high-density NRF2 interactome reveals...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:32911434
Aug 20. A functionally defined high-density NRF2 interactome reveals new conditional regulators of ARE transactivation.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:33961781
2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding
IPI
PMID:35140242
Human transcription factor protein interaction networks.
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:35140242
Human transcription factor protein interaction networks.
GO:0005515 protein binding
IPI
PMID:35512704
Systematic discovery of mutation-directed neo-protein-protei...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:35512704
2022 May 4. Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
GO:0005515 protein binding
IPI
PMID:38844957
Integrin ฮฑVฮฒ1-activated PYK2 promotes the progression of non...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:38844957
Integrin ฮฑVฮฒ1-activated PYK2 promotes the progression of non-small-cell lung cancer via the STAT3-VGF axis.
GO:0005515 protein binding
IPI
PMID:8662591
Differential activation of acute phase response factor/STAT3...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:8662591
Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130.
GO:0005515 protein binding
IPI
PMID:9864141
Identification of a novel Stat3 recruitment and activation m...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:9864141
Identification of a novel Stat3 recruitment and activation motif within the granulocyte colony-stimulating factor receptor.
GO:0042802 identical protein binding
IPI
PMID:17676033
Dominant-negative mutations in the DNA-binding domain of STA...
ACCEPT
Summary: Experimental evidence (IPI) supports identical protein binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:17676033
Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome.
GO:0042802 identical protein binding
IPI
PMID:21988832
Toward an understanding of the protein interaction network o...
ACCEPT
Summary: Experimental evidence (IPI) supports identical protein binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:21988832
Toward an understanding of the protein interaction network of the human liver.
GO:0042802 identical protein binding
IPI
PMID:25609649
Proteomic analyses reveal distinct chromatin-associated and ...
ACCEPT
Summary: Experimental evidence (IPI) supports identical protein binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:25609649
Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
GO:0042802 identical protein binding
IPI
PMID:7510216
Interferon activation of the transcription factor Stat91 inv...
ACCEPT
Summary: Experimental evidence (IPI) supports identical protein binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:7510216
Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions.
GO:0000785 chromatin
IEA
GO_REF:0000107
ACCEPT
Summary: Chromatin localization for gene regulation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0000976 transcription cis-regulatory region binding
IEA
GO_REF:0000107
ACCEPT
Summary: Core transcription cis-regulatory region binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
IEA
GO_REF:0000107
ACCEPT
Summary: Core cis-regulatory DNA binding; STAT3 recognizes and binds to GAS (gamma-activated sequence) elements in target gene promoters [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IEA
GO_REF:0000107
ACCEPT
Summary: Core transcription factor activity for STAT3, canonical function of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0001666 response to hypoxia
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for response to hypoxia is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0002317 plasma cell differentiation
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for plasma cell differentiation is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0002931 response to ischemia
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for response to ischemia is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0005667 transcription regulator complex
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for transcription regulator complex is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0005743 mitochondrial inner membrane
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for mitochondrial inner membrane is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0005829 cytosol
IEA
GO_REF:0000120
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005886 plasma membrane
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for plasma membrane is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0006953 acute-phase response
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for acute-phase response is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0006954 inflammatory response
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for inflammatory response is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0008284 positive regulation of cell population proliferation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Positive regulation of cell proliferation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0010628 positive regulation of gene expression
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: Positive regulation of gene expression [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0010730 negative regulation of hydrogen peroxide biosynthetic process
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for negative regulation of hydrogen peroxide biosynthetic process is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0014069 postsynaptic density
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for postsynaptic density is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0019901 protein kinase binding
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for protein kinase binding is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0030968 endoplasmic reticulum unfolded protein response
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for endoplasmic reticulum unfolded protein response is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0031730 CCR5 chemokine receptor binding
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for CCR5 chemokine receptor binding is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0032355 response to estradiol
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for response to estradiol is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0032991 protein-containing complex
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for protein-containing complex is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0033210 leptin-mediated signaling pathway
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Leptin signaling is one of many STAT3-activating pathways, not defining core function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0034097 response to cytokine
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for response to cytokine is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0035259 nuclear glucocorticoid receptor binding
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for nuclear glucocorticoid receptor binding is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0042802 identical protein binding
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for identical protein binding is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0042803 protein homodimerization activity
IEA
GO_REF:0000107
ACCEPT
Summary: Homodimerization via SH2 domain-phosphotyrosine (pY705) interactions is essential for STAT3 activation and nuclear translocation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Specific protein interaction critical for STAT3 function
GO:0043123 positive regulation of canonical NF-kappaB signal transduction
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for positive regulation of canonical NF-kappaB signal transduction is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0043124 negative regulation of canonical NF-kappaB signal transduction
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for negative regulation of canonical NF-kappaB signal transduction is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0043434 response to peptide hormone
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: Response to peptide hormone is context-specific [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for phosphatidylinositol 3-kinase/protein kinase B signal transduction is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0043524 negative regulation of neuron apoptotic process
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for negative regulation of neuron apoptotic process is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0043565 sequence-specific DNA binding
IEA
GO_REF:0000120
ACCEPT
Summary: IEA annotation for sequence-specific DNA binding is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0044321 response to leptin
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for response to leptin is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0045471 response to ethanol
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for response to ethanol is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0045747 positive regulation of Notch signaling pathway
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for positive regulation of Notch signaling pathway is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0045766 positive regulation of angiogenesis
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for positive regulation of angiogenesis is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IEA
GO_REF:0000107
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0046902 regulation of mitochondrial membrane permeability
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for regulation of mitochondrial membrane permeability is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0046983 protein dimerization activity
IEA
GO_REF:0000107
ACCEPT
Summary: Heterodimerization activity with other STAT family members (e.g., STAT1, STAT5) documented [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Specific protein interaction critical for STAT3 function
GO:0048708 astrocyte differentiation
IEA
GO_REF:0000107
ACCEPT
Summary: Astrocyte differentiation promoted by STAT3 signaling, key role in gliogenesis; STAT3 activation promotes astrocyte over neuron fate [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Well-established differentiation function, relevant to NEURON_DEVELOPMENT
GO:0050728 negative regulation of inflammatory response
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for negative regulation of inflammatory response is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0050804 modulation of chemical synaptic transmission
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for modulation of chemical synaptic transmission is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0051726 regulation of cell cycle
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for regulation of cell cycle is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0060019 radial glial cell differentiation
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for radial glial cell differentiation is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0060259 regulation of feeding behavior
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for regulation of feeding behavior is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0060397 growth hormone receptor signaling pathway via JAK-STAT
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Growth hormone signaling is one pathway activating STAT3, not the defining function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0072540 T-helper 17 cell lineage commitment
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: T-helper 17 cell lineage commitment [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0097009 energy homeostasis
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for energy homeostasis is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0097398 cellular response to interleukin-17
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for cellular response to interleukin-17 is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0097696 cell surface receptor signaling pathway via STAT
IEA
GO_REF:0000107
ACCEPT
Summary: STAT cascade is the core signaling mechanism [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0098685 Schaffer collateral - CA1 synapse
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for Schaffer collateral - CA1 synapse is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0098978 glutamatergic synapse
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for glutamatergic synapse is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0099527 postsynapse to nucleus signaling pathway
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for postsynapse to nucleus signaling pathway is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0106015 negative regulation of inflammatory response to wounding
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for negative regulation of inflammatory response to wounding is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0140297 DNA-binding transcription factor binding
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for DNA-binding transcription factor binding is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0140311 protein sequestering activity
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for protein sequestering activity is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:1900016 negative regulation of cytokine production involved in inflammatory response
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for negative regulation of cytokine production involved in inflammatory response is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:1900037 regulation of cellular response to hypoxia
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for regulation of cellular response to hypoxia is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:1902728 positive regulation of growth factor dependent skeletal muscle satellite cell proliferation
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for positive regulation of growth factor dependent skeletal muscle satellite cell proliferation is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:1902895 positive regulation of miRNA transcription
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for positive regulation of miRNA transcription is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:1905564 positive regulation of vascular endothelial cell proliferation
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for positive regulation of vascular endothelial cell proliferation is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:2001171 positive regulation of ATP biosynthetic process
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for positive regulation of ATP biosynthetic process is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
IEA
GO_REF:0000107
ACCEPT
Summary: IEA annotation for negative regulation of intrinsic apoptotic signaling pathway is consistent with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Consistent computational annotation
GO:0048861 leukemia inhibitory factor signaling pathway
IDA
PMID:11294841
Signaling pathways recruited by the cardiotrophin-like cytok...
ACCEPT
Summary: Experimental evidence (IDA) supports leukemia inhibitory factor signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:11294841
2001 Apr 6. Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component.
GO:0005654 nucleoplasm
IDA
GO_REF:0000052
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
IDA
GO_REF:0000052
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0019221 cytokine-mediated signaling pathway
IDA
PMID:10500198
Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine...
ACCEPT
Summary: Cytokine-mediated signaling is a core STAT3 function; responds to IL-6 family cytokines, interferons, and others [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:10500198
Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
IDA
PMID:11294841
Signaling pathways recruited by the cardiotrophin-like cytok...
ACCEPT
Summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs (JAK1/2/3, TYK2) in response to cytokine receptor activation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:11294841
2001 Apr 6. Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component.
GO:0070120 ciliary neurotrophic factor-mediated signaling pathway
IDA
PMID:11294841
Signaling pathways recruited by the cardiotrophin-like cytok...
ACCEPT
Summary: Experimental evidence (IDA) supports ciliary neurotrophic factor-mediated signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:11294841
2001 Apr 6. Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component.
GO:0019221 cytokine-mediated signaling pathway
IDA
PMID:11285233
The ciliary neurotrophic factor receptor alpha component ind...
ACCEPT
Summary: Cytokine-mediated signaling is a core STAT3 function; responds to IL-6 family cytokines, interferons, and others [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:11285233
The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine.
GO:0019221 cytokine-mediated signaling pathway
IDA
PMID:11294841
Signaling pathways recruited by the cardiotrophin-like cytok...
ACCEPT
Summary: Cytokine-mediated signaling is a core STAT3 function; responds to IL-6 family cytokines, interferons, and others [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:11294841
2001 Apr 6. Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component.
GO:0043524 negative regulation of neuron apoptotic process
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for negative regulation of neuron apoptotic process based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0097696 cell surface receptor signaling pathway via STAT
ISS
GO_REF:0000024
ACCEPT
Summary: STAT cascade is the core signaling mechanism [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0072540 T-helper 17 cell lineage commitment
ISS
PMID:27893700
Trans-presentation of IL-6 by dendritic cells is required fo...
KEEP AS NON CORE
Summary: T-helper 17 cell lineage commitment [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
Supporting Evidence:
PMID:27893700
Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T(H)17 cells.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
NAS
PMID:15864272
Mechanisms of type-I- and type-II-interferon-mediated signal...
ACCEPT
Summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs (JAK1/2/3, TYK2) in response to cytokine receptor activation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:15864272
Mechanisms of type-I- and type-II-interferon-mediated signalling.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
NAS
PMID:24058793
STAT heterodimers in immunity: A mixed message or a unique s...
ACCEPT
Summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs (JAK1/2/3, TYK2) in response to cytokine receptor activation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:24058793
STAT heterodimers in immunity: A mixed message or a unique signal? Delgoffe GM(1), Vignali DA.
GO:0045944 positive regulation of transcription by RNA polymerase II
NAS
PMID:15864272
Mechanisms of type-I- and type-II-interferon-mediated signal...
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:15864272
Mechanisms of type-I- and type-II-interferon-mediated signalling.
GO:0045944 positive regulation of transcription by RNA polymerase II
NAS
PMID:24058793
STAT heterodimers in immunity: A mixed message or a unique s...
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:24058793
STAT heterodimers in immunity: A mixed message or a unique signal? Delgoffe GM(1), Vignali DA.
GO:0050729 positive regulation of inflammatory response
IDA
PMID:23125416
CCR1-mediated STAT3 tyrosine phosphorylation and CXCL8 expre...
ACCEPT
Summary: Experimental evidence (IDA) supports positive regulation of inflammatory response for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:23125416
2012 Nov 2. CCR1-mediated STAT3 tyrosine phosphorylation and CXCL8 expression in THP-1 macrophage-like cells involve pertussis toxin-insensitive Gฮฑ(14/16) signaling and IL-6 release.
GO:0005515 protein binding
IPI
PMID:29743632
A double helical motif in OCIAD2 is essential for its locali...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:29743632
A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation.
GO:0010629 negative regulation of gene expression
IDA
PMID:23820254
STAT3 upregulates miR-92a to inhibit RECK expression and to ...
ACCEPT
Summary: Experimental evidence (IDA) supports negative regulation of gene expression for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:23820254
STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells.
GO:0090091 positive regulation of extracellular matrix disassembly
IGI
PMID:23820254
STAT3 upregulates miR-92a to inhibit RECK expression and to ...
ACCEPT
Summary: Experimental evidence (IGI) supports positive regulation of extracellular matrix disassembly for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IGI)
Supporting Evidence:
PMID:23820254
STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells.
GO:0005634 nucleus
IDA
PMID:12743296
STAT3 ubiquitylation and degradation by mumps virus suppress...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:12743296
STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling.
GO:0050766 positive regulation of phagocytosis
IDA
PMID:27994074
Novel Resolvin D2 Receptor Axis in Infectious Inflammation.
ACCEPT
Summary: Experimental evidence (IDA) supports positive regulation of phagocytosis for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:27994074
2016 Dec 19. Novel Resolvin D2 Receptor Axis in Infectious Inflammation.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
ACCEPT
Summary: Core transcription factor activity for STAT3, canonical function of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0005737 cytoplasm
IDA
PMID:12743296
STAT3 ubiquitylation and degradation by mumps virus suppress...
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:12743296
STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling.
GO:0140311 protein sequestering activity
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for protein sequestering activity based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:1900016 negative regulation of cytokine production involved in inflammatory response
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for negative regulation of cytokine production involved in inflammatory response based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0043124 negative regulation of canonical NF-kappaB signal transduction
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for negative regulation of canonical NF-kappaB signal transduction based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0003723 RNA binding
IPI
PMID:31507089
Reciprocal regulation of miR-206 and IL-6/STAT3 pathway medi...
ACCEPT
Summary: Experimental evidence (IPI) supports RNA binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:31507089
Sep 10. Reciprocal regulation of miR-206 and IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in EGFR-mutant lung cancer cells.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IMP
PMID:38404237
A novel gain-of-function STAT3 variant in infantile-onset di...
ACCEPT
Summary: Core transcription factor activity for STAT3, canonical function of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:38404237
A novel gain-of-function STAT3 variant in infantile-onset diabetes associated with multiorgan autoimmunity.
GO:0032755 positive regulation of interleukin-6 production
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Positive regulation of interleukin-6 production [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0043123 positive regulation of canonical NF-kappaB signal transduction
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for positive regulation of canonical NF-kappaB signal transduction based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0106222 lncRNA binding
IDA
PMID:24744378
The STAT3-binding long noncoding RNA lnc-DC controls human d...
ACCEPT
Summary: Experimental evidence (IDA) supports lncRNA binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:24744378
The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation.
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:15653507
Stat3 dimerization regulated by reversible acetylation of a ...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:15653507
Stat3 dimerization regulated by reversible acetylation of a single lysine residue.
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:16285960
STAT3 NH2-terminal acetylation is activated by the hepatic a...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:16285960
STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen.
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:18782771
The STAT3 NH2-terminal domain stabilizes enhanceosome assemb...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:18782771
2008 Sep 9. The STAT3 NH2-terminal domain stabilizes enhanceosome assembly by interacting with the p300 bromodomain.
GO:0005634 nucleus
IDA
PMID:15653507
Stat3 dimerization regulated by reversible acetylation of a ...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:15653507
Stat3 dimerization regulated by reversible acetylation of a single lysine residue.
GO:0005634 nucleus
IDA
PMID:16285960
STAT3 NH2-terminal acetylation is activated by the hepatic a...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:16285960
STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen.
GO:0005737 cytoplasm
IDA
PMID:15653507
Stat3 dimerization regulated by reversible acetylation of a ...
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:15653507
Stat3 dimerization regulated by reversible acetylation of a single lysine residue.
GO:0005737 cytoplasm
IDA
PMID:16285960
STAT3 NH2-terminal acetylation is activated by the hepatic a...
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:16285960
STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen.
GO:0042803 protein homodimerization activity
IDA
PMID:15653507
Stat3 dimerization regulated by reversible acetylation of a ...
ACCEPT
Summary: Homodimerization via SH2 domain-phosphotyrosine (pY705) interactions is essential for STAT3 activation and nuclear translocation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Specific protein interaction critical for STAT3 function
Supporting Evidence:
PMID:15653507
Stat3 dimerization regulated by reversible acetylation of a single lysine residue.
GO:0070102 interleukin-6-mediated signaling pathway
IDA
PMID:16285960
STAT3 NH2-terminal acetylation is activated by the hepatic a...
ACCEPT
Summary: Interleukin-6-mediated signaling pathway [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:16285960
STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1112565
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1112602
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1112727
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1433456
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1470009
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1888198
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-380782
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-452515
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6784006
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6784323
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6786095
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6786124
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6788571
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6788582
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8848087
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8848124
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8875816
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8875817
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8950269
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8950441
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8950485
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8950518
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952749
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8982163
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8982165
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8983059
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8983371
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8983378
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8984014
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8984021
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8985929
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8985988
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8986985
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987014
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987063
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987070
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987080
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987096
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987097
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987104
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987141
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987150
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987255
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987266
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9006870
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9006873
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9009072
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9670412
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9670416
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9672159
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9672176
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9701524
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9701525
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9701529
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9712079
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9712085
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9835443
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9850958
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9851142
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0010575 positive regulation of vascular endothelial growth factor production
IMP
PMID:25596740
miR-874 functions as a tumor suppressor by inhibiting angiog...
ACCEPT
Summary: Experimental evidence (IMP) supports positive regulation of vascular endothelial growth factor production for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IMP)
Supporting Evidence:
PMID:25596740
miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer.
GO:0097696 cell surface receptor signaling pathway via STAT
IMP
PMID:25596740
miR-874 functions as a tumor suppressor by inhibiting angiog...
ACCEPT
Summary: STAT cascade is the core signaling mechanism [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:25596740
miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer.
GO:0030335 positive regulation of cell migration
IMP
PMID:31638206
MicroRNAโ€‘4500 suppresses tumor progression in nonโ€‘small cell...
ACCEPT
Summary: Experimental evidence (IMP) supports positive regulation of cell migration for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IMP)
Supporting Evidence:
PMID:31638206
Oct 11. MicroRNAโ€‘4500 suppresses tumor progression in nonโ€‘small cell lung cancer by regulating STAT3.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
IDA
PMID:32929201
PD-L1-mediated gasdermin C expression switches apoptosis to ...
ACCEPT
Summary: Core transcription factor activity for STAT3, canonical function of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:32929201
2020 Sep 14. PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.
GO:0070878 primary miRNA binding
IPI
PMID:31507089
Reciprocal regulation of miR-206 and IL-6/STAT3 pathway medi...
ACCEPT
Summary: Experimental evidence (IPI) supports primary miRNA binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:31507089
Sep 10. Reciprocal regulation of miR-206 and IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in EGFR-mutant lung cancer cells.
GO:0140610 RNA sequestering activity
IDA
PMID:31507089
Reciprocal regulation of miR-206 and IL-6/STAT3 pathway medi...
ACCEPT
Summary: Experimental evidence (IDA) supports RNA sequestering activity for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:31507089
Sep 10. Reciprocal regulation of miR-206 and IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in EGFR-mutant lung cancer cells.
GO:0019221 cytokine-mediated signaling pathway
NAS
PMID:12743296
STAT3 ubiquitylation and degradation by mumps virus suppress...
ACCEPT
Summary: Cytokine-mediated signaling is a core STAT3 function; responds to IL-6 family cytokines, interferons, and others [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:12743296
STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
IDA
PMID:27830702
Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-...
ACCEPT
Summary: Experimental evidence (IDA) supports phosphatidylinositol 3-kinase/protein kinase B signal transduction for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:27830702
Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes.
GO:0106015 negative regulation of inflammatory response to wounding
IDA
PMID:27830702
Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-...
ACCEPT
Summary: Experimental evidence (IDA) supports negative regulation of inflammatory response to wounding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:27830702
Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes.
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:7568001
Tyrosine phosphorylation and activation of STAT5, STAT3, and...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:7568001
Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15.
GO:0005634 nucleus
IC
PMID:7568001
Tyrosine phosphorylation and activation of STAT5, STAT3, and...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:7568001
Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15.
GO:0035723 interleukin-15-mediated signaling pathway
IDA
PMID:7568001
Tyrosine phosphorylation and activation of STAT5, STAT3, and...
ACCEPT
Summary: Interleukin-10-mediated signaling pathway activates STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:7568001
Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15.
GO:0038110 interleukin-2-mediated signaling pathway
IDA
PMID:7568005
Critical role of the interleukin 2 (IL-2) receptor gamma-cha...
ACCEPT
Summary: Experimental evidence (IDA) supports interleukin-2-mediated signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:7568005
Critical role of the interleukin 2 (IL-2) receptor gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction.
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:28781374
IL-11 induces differentiation of myeloid-derived suppressor ...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:28781374
IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway.
GO:0005634 nucleus
IC
PMID:28781374
IL-11 induces differentiation of myeloid-derived suppressor ...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:28781374
IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway.
GO:0030154 cell differentiation
IDA
PMID:28781374
IL-11 induces differentiation of myeloid-derived suppressor ...
ACCEPT
Summary: Cell differentiation is a well-established STAT3 function across multiple cell types [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Well-established differentiation function, relevant to NEURON_DEVELOPMENT
Supporting Evidence:
PMID:28781374
IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway.
GO:0038154 interleukin-11-mediated signaling pathway
IDA
PMID:28781374
IL-11 induces differentiation of myeloid-derived suppressor ...
ACCEPT
Summary: Experimental evidence (IDA) supports interleukin-11-mediated signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:28781374
IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway.
GO:0003700 DNA-binding transcription factor activity
IC
PMID:7543512
IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:7543512
IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes.
GO:0005634 nucleus
IC
PMID:7543512
IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:7543512
IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes.
GO:0140105 interleukin-10-mediated signaling pathway
IDA
PMID:7543512
IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ...
ACCEPT
Summary: Experimental evidence (IDA) supports interleukin-10-mediated signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:7543512
IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes.
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:9535918
Heteromerization of the gammac chain with the interleukin-9 ...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:9535918
Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis.
GO:0005634 nucleus
IC
PMID:8756628
A single tyrosine of the interleukin-9 (IL-9) receptor is re...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:8756628
A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9.
GO:0038113 interleukin-9-mediated signaling pathway
IDA
PMID:9535918
Heteromerization of the gammac chain with the interleukin-9 ...
ACCEPT
Summary: Experimental evidence (IDA) supports interleukin-9-mediated signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:9535918
Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis.
GO:0005634 nucleus
IDA
PMID:7528668
Interleukin-2 induces tyrosine phosphorylation and nuclear t...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:7528668
Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3 in human T lymphocytes.
GO:0038155 interleukin-23-mediated signaling pathway
IDA
PMID:12023369
A receptor for the heterodimeric cytokine IL-23 is composed ...
ACCEPT
Summary: Experimental evidence (IDA) supports interleukin-23-mediated signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:12023369
A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
IDA
PMID:8272873
Association and activation of Jak-Tyk kinases by CNTF-LIF-OS...
ACCEPT
Summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs (JAK1/2/3, TYK2) in response to cytokine receptor activation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:8272873
Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.
GO:0005634 nucleus
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
IGI
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Sys...
ACCEPT
Summary: Core transcription activator activity; activated STAT3 dimers drive transcription of target genes including MYC, CCND1, BCL-XL, VEGF [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
GO:0032731 positive regulation of interleukin-1 beta production
IGI
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Sys...
ACCEPT
Summary: Experimental evidence (IGI) supports positive regulation of interleukin-1 beta production for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IGI)
Supporting Evidence:
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
GO:0032733 positive regulation of interleukin-10 production
IGI
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Sys...
ACCEPT
Summary: Experimental evidence (IGI) supports positive regulation of interleukin-10 production for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IGI)
Supporting Evidence:
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
GO:0032757 positive regulation of interleukin-8 production
IGI
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Sys...
ACCEPT
Summary: Experimental evidence (IGI) supports positive regulation of interleukin-8 production for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IGI)
Supporting Evidence:
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
GO:0032760 positive regulation of tumor necrosis factor production
IGI
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Sys...
ACCEPT
Summary: Experimental evidence (IGI) supports positive regulation of tumor necrosis factor production for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IGI)
Supporting Evidence:
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Sys...
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
GO:1900017 positive regulation of cytokine production involved in inflammatory response
IGI
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Sys...
ACCEPT
Summary: Experimental evidence (IGI) supports positive regulation of cytokine production involved in inflammatory response for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IGI)
Supporting Evidence:
PMID:31886314
miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
GO:0140297 DNA-binding transcription factor binding
IPI
PMID:15664994
Signal transducers and activators of transcription 3 augment...
ACCEPT
Summary: Experimental evidence (IPI) supports DNA-binding transcription factor binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:15664994
2005 Jan 21. Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway.
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IPI
PMID:28467929
PPARฮณ Links BMP2 and TGFฮฒ1 Pathways in Vascular Smooth Muscl...
ACCEPT
Summary: Experimental evidence (IPI) supports RNA polymerase II-specific DNA-binding transcription factor binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:28467929
PPARฮณ Links BMP2 and TGFฮฒ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism.
GO:0007179 transforming growth factor beta receptor signaling pathway
IGI
PMID:28467929
PPARฮณ Links BMP2 and TGFฮฒ1 Pathways in Vascular Smooth Muscl...
ACCEPT
Summary: Experimental evidence (IGI) supports transforming growth factor beta receptor signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IGI)
Supporting Evidence:
PMID:28467929
PPARฮณ Links BMP2 and TGFฮฒ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism.
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IPI
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107...
ACCEPT
Summary: Experimental evidence (IPI) supports RNA polymerase II-specific DNA-binding transcription factor binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis.
GO:0005102 signaling receptor binding
IPI
PMID:31145836
Physical proximity and functional cooperation of glycoprotei...
ACCEPT
Summary: Experimental evidence (IPI) supports signaling receptor binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:31145836
Jun 23. Physical proximity and functional cooperation of glycoprotein 130 and glycoprotein VI in platelet membrane lipid rafts.
GO:0035591 signaling adaptor activity
IPI
PMID:31145836
Physical proximity and functional cooperation of glycoprotei...
ACCEPT
Summary: Experimental evidence (IPI) supports signaling adaptor activity for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:31145836
Jun 23. Physical proximity and functional cooperation of glycoprotein 130 and glycoprotein VI in platelet membrane lipid rafts.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9701529
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9701531
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9701534
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9701537
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9701549
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9701557
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9701565
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9850958
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9851058
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9851062
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9851064
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9851071
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9851106
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9851118
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9851122
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:2000635 negative regulation of primary miRNA processing
IMP
PMID:31507089
Reciprocal regulation of miR-206 and IL-6/STAT3 pathway medi...
ACCEPT
Summary: Experimental evidence (IMP) supports negative regulation of primary miRNA processing for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IMP)
Supporting Evidence:
PMID:31507089
Sep 10. Reciprocal regulation of miR-206 and IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in EGFR-mutant lung cancer cells.
GO:0005515 protein binding
IPI
PMID:31899195
Prohibitin 1 interacts with signal transducer and activator ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:31899195
Dec 31. Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells.
GO:0005634 nucleus
IDA
PMID:31899195
Prohibitin 1 interacts with signal transducer and activator ...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:31899195
Dec 31. Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells.
GO:0005737 cytoplasm
IDA
PMID:31899195
Prohibitin 1 interacts with signal transducer and activator ...
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:31899195
Dec 31. Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells.
GO:0072538 T-helper 17 type immune response
IDA
PMID:31899195
Prohibitin 1 interacts with signal transducer and activator ...
ACCEPT
Summary: Experimental evidence (IDA) supports T-helper 17 type immune response for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:31899195
Dec 31. Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells.
GO:0000785 chromatin
ISA
GO_REF:0000113
ACCEPT
Summary: Chromatin localization for gene regulation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
ISA
GO_REF:0000113
ACCEPT
Summary: Core transcription factor activity for STAT3, canonical function of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0005667 transcription regulator complex
IDA
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107...
ACCEPT
Summary: Experimental evidence (IDA) supports transcription regulator complex for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis.
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107...
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis.
GO:0070102 interleukin-6-mediated signaling pathway
IDA
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107...
ACCEPT
Summary: Interleukin-6-mediated signaling pathway [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:24429361
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis.
GO:0010507 negative regulation of autophagy
IDA
PMID:26962683
IL10 inhibits starvation-induced autophagy in hypertrophic s...
ACCEPT
Summary: Experimental evidence (IDA) supports negative regulation of autophagy for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:26962683
IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways.
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
IDA
PMID:16835372
Interleukin-6 induces hepcidin expression through STAT3.
ACCEPT
Summary: Core transcription activator activity; activated STAT3 dimers drive transcription of target genes including MYC, CCND1, BCL-XL, VEGF [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:16835372
Jul 11. Interleukin-6 induces hepcidin expression through STAT3.
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
IMP
PMID:16946298
STAT3 mediates hepatic hepcidin expression and its inflammat...
ACCEPT
Summary: Core transcription activator activity; activated STAT3 dimers drive transcription of target genes including MYC, CCND1, BCL-XL, VEGF [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:16946298
Aug 31. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation.
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:16835372
Interleukin-6 induces hepcidin expression through STAT3.
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:16835372
Jul 11. Interleukin-6 induces hepcidin expression through STAT3.
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:16946298
STAT3 mediates hepatic hepcidin expression and its inflammat...
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:16946298
Aug 31. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation.
GO:0005634 nucleus
IDA
PMID:17360477
Identification of STAT3 as a substrate of receptor protein t...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:17360477
Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T.
GO:0005634 nucleus
IDA
PMID:24846175
ฮฒ1,6 GlcNAc branches-modified PTPRT attenuates its activity ...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:24846175
eCollection 2014. ฮฒ1,6 GlcNAc branches-modified PTPRT attenuates its activity and promotes cell migration by STAT3 pathway.
GO:0005737 cytoplasm
IDA
PMID:17360477
Identification of STAT3 as a substrate of receptor protein t...
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:17360477
Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T.
GO:0019903 protein phosphatase binding
IPI
PMID:17360477
Identification of STAT3 as a substrate of receptor protein t...
ACCEPT
Summary: Experimental evidence (IPI) supports protein phosphatase binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:17360477
Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T.
GO:0030335 positive regulation of cell migration
IMP
PMID:24846175
ฮฒ1,6 GlcNAc branches-modified PTPRT attenuates its activity ...
ACCEPT
Summary: Experimental evidence (IMP) supports positive regulation of cell migration for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IMP)
Supporting Evidence:
PMID:24846175
eCollection 2014. ฮฒ1,6 GlcNAc branches-modified PTPRT attenuates its activity and promotes cell migration by STAT3 pathway.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8983379
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8985981
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8983373
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8983374
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8983379
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8985966
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8985981
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8983078
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8984023
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987033
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987052
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987156
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987161
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987214
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987230
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987270
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8987052
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0045648 positive regulation of erythrocyte differentiation
IMP
PMID:28283061
Functional Selectivity in Cytokine Signaling Revealed Throug...
KEEP AS NON CORE
Summary: Positive regulation of erythrocyte differentiation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
Supporting Evidence:
PMID:28283061
Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation.
GO:1902895 positive regulation of miRNA transcription
IDA
PMID:19390056
Interleukin-6 modulates the expression of the bone morphogen...
ACCEPT
Summary: Experimental evidence (IDA) supports positive regulation of miRNA transcription for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:19390056
Epub 2009 Apr 23. Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway.
GO:0005515 protein binding
IPI
PMID:24172987
A small GTPaseโ€‘like protein fragment of Mycoplasma promotes ...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:24172987
A small GTPaseโ€‘like protein fragment of Mycoplasma promotes tumor cell migration and proliferation in vitro via interaction with Rac1 and Stat3.
GO:0005515 protein binding
IPI
PMID:28065600
Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STA...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:28065600
2017 Jan 5. Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.
GO:0005634 nucleus
IDA
PMID:28065600
Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STA...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:28065600
2017 Jan 5. Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.
GO:0006954 inflammatory response
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for inflammatory response based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0042803 protein homodimerization activity
ISS
GO_REF:0000024
ACCEPT
Summary: Homodimerization via SH2 domain-phosphotyrosine (pY705) interactions is essential for STAT3 activation and nuclear translocation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Specific protein interaction critical for STAT3 function
GO:0072540 T-helper 17 cell lineage commitment
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: T-helper 17 cell lineage commitment [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:27050391
Rac1 modulates the formation of primordial follicles by faci...
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:27050391
Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice.
GO:0010628 positive regulation of gene expression
IMP
PMID:24255059
Inhibition of microRNA-92a prevents endothelial dysfunction ...
KEEP AS NON CORE
Summary: Positive regulation of gene expression [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
Supporting Evidence:
PMID:24255059
2013 Nov 19. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice.
GO:1902895 positive regulation of miRNA transcription
IDA
PMID:23820254
STAT3 upregulates miR-92a to inhibit RECK expression and to ...
ACCEPT
Summary: Experimental evidence (IDA) supports positive regulation of miRNA transcription for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:23820254
STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells.
GO:0010628 positive regulation of gene expression
IDA
PMID:23820254
STAT3 upregulates miR-92a to inhibit RECK expression and to ...
KEEP AS NON CORE
Summary: Positive regulation of gene expression [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
Supporting Evidence:
PMID:23820254
STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells.
GO:0005515 protein binding
IPI
PMID:25476455
Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STA...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:25476455
Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity and suppresses gliomas tumorigenicity.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
IDA
PMID:19390056
Interleukin-6 modulates the expression of the bone morphogen...
ACCEPT
Summary: Core cis-regulatory DNA binding; STAT3 recognizes and binds to GAS (gamma-activated sequence) elements in target gene promoters [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:19390056
Epub 2009 Apr 23. Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway.
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:19390056
Interleukin-6 modulates the expression of the bone morphogen...
ACCEPT
Summary: Positive regulation of DNA-templated transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:19390056
Epub 2009 Apr 23. Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway.
GO:0060259 regulation of feeding behavior
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for regulation of feeding behavior based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0097009 energy homeostasis
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for energy homeostasis based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0006355 regulation of DNA-templated transcription
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
ACCEPT
Summary: Regulation of DNA-templated transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0031490 chromatin DNA binding
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
ACCEPT
Summary: Experimental evidence (IDA) supports chromatin DNA binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0033210 leptin-mediated signaling pathway
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
KEEP AS NON CORE
Summary: Leptin signaling is one of many STAT3-activating pathways, not defining core function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0044320 cellular response to leptin stimulus
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
ACCEPT
Summary: Experimental evidence (IDA) supports cellular response to leptin stimulus for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0044321 response to leptin
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
ACCEPT
Summary: Experimental evidence (IDA) supports response to leptin for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0051726 regulation of cell cycle
IDA
PMID:17344214
leptin-induced growth stimulation of breast cancer cells inv...
ACCEPT
Summary: Experimental evidence (IDA) supports regulation of cell cycle for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:17344214
2007 Mar 7. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
GO:0070102 interleukin-6-mediated signaling pathway
IMP
PMID:16946298
STAT3 mediates hepatic hepcidin expression and its inflammat...
ACCEPT
Summary: Interleukin-6-mediated signaling pathway [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:16946298
Aug 31. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation.
GO:0090575 RNA polymerase II transcription regulator complex
IMP
PMID:16946298
STAT3 mediates hepatic hepcidin expression and its inflammat...
ACCEPT
Summary: RNA polymerase II transcription regulator complex; STAT3 functions as part of transcriptional regulatory complexes [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:16946298
Aug 31. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation.
GO:0090575 RNA polymerase II transcription regulator complex
IC
PMID:16835372
Interleukin-6 induces hepcidin expression through STAT3.
ACCEPT
Summary: RNA polymerase II transcription regulator complex; STAT3 functions as part of transcriptional regulatory complexes [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:16835372
Jul 11. Interleukin-6 induces hepcidin expression through STAT3.
GO:0070102 interleukin-6-mediated signaling pathway
IMP
PMID:16835372
Interleukin-6 induces hepcidin expression through STAT3.
ACCEPT
Summary: Interleukin-6-mediated signaling pathway [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:16835372
Jul 11. Interleukin-6 induces hepcidin expression through STAT3.
GO:0000785 chromatin
IDA
PMID:16835372
Interleukin-6 induces hepcidin expression through STAT3.
ACCEPT
Summary: Chromatin localization for gene regulation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:16835372
Jul 11. Interleukin-6 induces hepcidin expression through STAT3.
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:19754877
Hsp105beta upregulates hsp70 gene expression through signal ...
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:19754877
2009 Sep 15. Hsp105beta upregulates hsp70 gene expression through signal transducer and activator of transcription-3.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1112538
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1112587
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1112604
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1470010
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-1470012
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6784763
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6784765
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6784791
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6786072
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6786097
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6786293
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6788622
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6788623
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-6788628
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8950724
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8950733
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8950780
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8950782
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952823
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8982162
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8985900
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-8987236
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9670417
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005829 cytosol
TAS
Reactome:R-HSA-9670426
ACCEPT
Summary: Cytosol localization of latent STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0019903 protein phosphatase binding
IPI
PMID:12359225
The nuclear isoform of protein-tyrosine phosphatase TC-PTP r...
ACCEPT
Summary: Experimental evidence (IPI) supports protein phosphatase binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:12359225
The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.
GO:0070102 interleukin-6-mediated signaling pathway
IDA
PMID:12359225
The nuclear isoform of protein-tyrosine phosphatase TC-PTP r...
ACCEPT
Summary: Interleukin-6-mediated signaling pathway [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:12359225
The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-1112587
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-1470012
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-2895778
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6784763
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6786293
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6788623
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8848150
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8950724
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8950733
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9670426
ACCEPT
Summary: Nucleoplasm localization of activated STAT3 dimers [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005737 cytoplasm
IDA
PMID:22783022
The Sin3a repressor complex is a master regulator of STAT tr...
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:22783022
The Sin3a repressor complex is a master regulator of STAT transcriptional activity.
GO:0005634 nucleus
IDA
PMID:22783022
The Sin3a repressor complex is a master regulator of STAT tr...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:22783022
The Sin3a repressor complex is a master regulator of STAT transcriptional activity.
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IPI
PMID:22783022
The Sin3a repressor complex is a master regulator of STAT tr...
ACCEPT
Summary: Experimental evidence (IPI) supports RNA polymerase II-specific DNA-binding transcription factor binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IPI)
Supporting Evidence:
PMID:22783022
The Sin3a repressor complex is a master regulator of STAT transcriptional activity.
GO:0005515 protein binding
IPI
PMID:12867595
The cell death regulator GRIM-19 is an inhibitor of signal t...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:12867595
The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3.
GO:0005515 protein binding
IPI
PMID:20826784
Acetylation directs survivin nuclear localization to repress...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:20826784
2010 Sep 8. Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity.
GO:0004879 nuclear receptor activity
IDA
PMID:17324931
Interleukin-6 transcriptionally regulates prohibitin express...
ACCEPT
Summary: Experimental evidence (IDA) supports nuclear receptor activity for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:17324931
2007 Feb 26. Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells.
GO:0030522 intracellular receptor signaling pathway
IDA
PMID:17324931
Interleukin-6 transcriptionally regulates prohibitin express...
ACCEPT
Summary: Experimental evidence (IDA) supports intracellular receptor signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:17324931
2007 Feb 26. Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells.
GO:0005515 protein binding
IPI
PMID:15998644
JAK/STAT3 pathway is involved in survival of neurons in resp...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:15998644
2005 Jul 5. JAK/STAT3 pathway is involved in survival of neurons in response to insulin-like growth factor and negatively regulated by suppressor of cytokine signaling-3.
GO:0005515 protein binding
IPI
PMID:16568091
Identification of STAT3 as a specific substrate of breast tu...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:16568091
Mar 27. Identification of STAT3 as a specific substrate of breast tumor kinase.
GO:0005515 protein binding
IPI
PMID:10688651
Etk, a Btk family tyrosine kinase, mediates cellular transfo...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:10688651
Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation.
GO:0045747 positive regulation of Notch signaling pathway
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for positive regulation of Notch signaling pathway based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0048708 astrocyte differentiation
ISS
GO_REF:0000024
ACCEPT
Summary: Astrocyte differentiation promoted by STAT3 signaling, key role in gliogenesis; STAT3 activation promotes astrocyte over neuron fate [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Well-established differentiation function, relevant to NEURON_DEVELOPMENT
GO:0060019 radial glial cell differentiation
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for radial glial cell differentiation based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0000976 transcription cis-regulatory region binding
IDA
PMID:17324931
Interleukin-6 transcriptionally regulates prohibitin express...
ACCEPT
Summary: Core transcription cis-regulatory region binding for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:17324931
2007 Feb 26. Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells.
GO:0005634 nucleus
IDA
PMID:17324931
Interleukin-6 transcriptionally regulates prohibitin express...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:17324931
2007 Feb 26. Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells.
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:17324931
Interleukin-6 transcriptionally regulates prohibitin express...
ACCEPT
Summary: Positive regulation of transcription by RNA polymerase II is the canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:17324931
2007 Feb 26. Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells.
GO:0070102 interleukin-6-mediated signaling pathway
IDA
PMID:17324931
Interleukin-6 transcriptionally regulates prohibitin express...
ACCEPT
Summary: Interleukin-6-mediated signaling pathway [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:17324931
2007 Feb 26. Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells.
GO:0060396 growth hormone receptor signaling pathway
IDA
PMID:10925297
Regulation of neutrophil adhesion by pituitary growth hormon...
ACCEPT
Summary: Experimental evidence (IDA) supports growth hormone receptor signaling pathway for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:10925297
Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin.
GO:0005634 nucleus
IDA
PMID:18234692
BART is essential for nuclear retention of STAT3.
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:18234692
BART is essential for nuclear retention of STAT3.
GO:0005737 cytoplasm
IDA
PMID:18234692
BART is essential for nuclear retention of STAT3.
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:18234692
BART is essential for nuclear retention of STAT3.
GO:0006606 protein import into nucleus
IDA
PMID:18234692
BART is essential for nuclear retention of STAT3.
ACCEPT
Summary: Experimental evidence (IDA) supports protein import into nucleus for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:18234692
BART is essential for nuclear retention of STAT3.
GO:0005515 protein binding
IPI
PMID:18234692
BART is essential for nuclear retention of STAT3.
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:18234692
BART is essential for nuclear retention of STAT3.
GO:0001659 temperature homeostasis
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for temperature homeostasis based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0001754 eye photoreceptor cell differentiation
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for eye photoreceptor cell differentiation based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0003677 DNA binding
ISS
GO_REF:0000024
ACCEPT
Summary: Core DNA binding activity essential for STAT3 transcription factor function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
GO:0005634 nucleus
ISS
GO_REF:0000024
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005737 cytoplasm
ISS
GO_REF:0000024
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
GO:0005886 plasma membrane
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for plasma membrane based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0006357 regulation of transcription by RNA polymerase II
ISS
GO_REF:0000024
ACCEPT
Summary: Core regulation of transcription by RNA polymerase II [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0019901 protein kinase binding
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for protein kinase binding based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0042593 glucose homeostasis
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for glucose homeostasis based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0042755 eating behavior
ISS
GO_REF:0000024
ACCEPT
Summary: ISS annotation for eating behavior based on sequence/structure similarity is reasonable for conserved STAT family function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Annotation inferred from sequence/structural similarity
GO:0045893 positive regulation of DNA-templated transcription
ISS
GO_REF:0000024
ACCEPT
Summary: Positive regulation of DNA-templated transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
GO:0046983 protein dimerization activity
ISS
GO_REF:0000024
ACCEPT
Summary: Heterodimerization activity with other STAT family members (e.g., STAT1, STAT5) documented [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Specific protein interaction critical for STAT3 function
GO:0060397 growth hormone receptor signaling pathway via JAK-STAT
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Growth hormone signaling is one pathway activating STAT3, not the defining function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
GO:0005515 protein binding
IPI
PMID:16531398
Tid1 isoforms are mitochondrial DnaJ-like chaperones with un...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:16531398
Epub 2006 Mar 10. Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique carboxyl termini that determine cytosolic fate.
GO:0060397 growth hormone receptor signaling pathway via JAK-STAT
IDA
PMID:12552091
Estrogen inhibits GH signaling by suppressing GH-induced JAK...
KEEP AS NON CORE
Summary: Growth hormone signaling is one pathway activating STAT3, not the defining function [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
Supporting Evidence:
PMID:12552091
Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
GO:0032355 response to estradiol
IDA
PMID:12552091
Estrogen inhibits GH signaling by suppressing GH-induced JAK...
ACCEPT
Summary: Experimental evidence (IDA) supports response to estradiol for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:12552091
Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
GO:0032870 cellular response to hormone stimulus
IDA
PMID:12552091
Estrogen inhibits GH signaling by suppressing GH-induced JAK...
ACCEPT
Summary: Experimental evidence (IDA) supports cellular response to hormone stimulus for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Direct experimental evidence (IDA)
Supporting Evidence:
PMID:12552091
Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
GO:0070102 interleukin-6-mediated signaling pathway
IDA
PMID:12552091
Estrogen inhibits GH signaling by suppressing GH-induced JAK...
ACCEPT
Summary: Interleukin-6-mediated signaling pathway [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:12552091
Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
GO:0005634 nucleus
IDA
PMID:12444102
Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and i...
ACCEPT
Summary: Nucleus localization upon activation is core to STAT3 function; activated dimers translocate to nucleus [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:12444102
Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling.
GO:0005515 protein binding
IPI
PMID:16306601
Respiratory syncytial virus-inducible BCL-3 expression antag...
REMOVE
Summary: Generic 'protein binding' (GO:0005515) is uninformative and should be removed per GO curation guidelines. STAT3 has specific protein interactions (SH2-mediated homodimerization GO:0042803, heterodimerization GO:0046983, kinase binding GO:0019904) that are better represented by more specific terms [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Uninformative generic term per curation guidelines
Supporting Evidence:
PMID:16306601
Respiratory syncytial virus-inducible BCL-3 expression antagonizes the STAT/IRF and NF-kappaB signaling pathways by inducing histone deacetylase 1 recruitment to the interleukin-8 promoter.
GO:0006355 regulation of DNA-templated transcription
IDA
PMID:15664994
Signal transducers and activators of transcription 3 augment...
ACCEPT
Summary: Regulation of DNA-templated transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:15664994
2005 Jan 21. Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
TAS
PMID:15664994
Signal transducers and activators of transcription 3 augment...
ACCEPT
Summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs (JAK1/2/3, TYK2) in response to cytokine receptor activation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:15664994
2005 Jan 21. Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway.
GO:0019221 cytokine-mediated signaling pathway
NAS
PMID:15664994
Signal transducers and activators of transcription 3 augment...
ACCEPT
Summary: Cytokine-mediated signaling is a core STAT3 function; responds to IL-6 family cytokines, interferons, and others [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:15664994
2005 Jan 21. Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway.
GO:0000122 negative regulation of transcription by RNA polymerase II
TAS
PMID:8675499
STAT3beta, a splice variant of transcription factor STAT3, i...
ACCEPT
Summary: Curated annotation (TAS) supports negative regulation of transcription by RNA polymerase II [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Curated annotation (TAS)
Supporting Evidence:
PMID:8675499
STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription.
GO:0003700 DNA-binding transcription factor activity
TAS
PMID:7512451
Molecular cloning of APRF, a novel IFN-stimulated gene facto...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:7512451
Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.
GO:0003700 DNA-binding transcription factor activity
TAS
PMID:8675499
STAT3beta, a splice variant of transcription factor STAT3, i...
ACCEPT
Summary: Core DNA-binding transcription factor activity; STAT3 binds DNA via its DNA-binding domain to regulate target gene transcription [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core molecular function of STAT3 as transcription factor
Supporting Evidence:
PMID:8675499
STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription.
GO:0005737 cytoplasm
TAS
PMID:7512451
Molecular cloning of APRF, a novel IFN-stimulated gene facto...
ACCEPT
Summary: Cytoplasm localization of latent STAT3 before activation; unphosphorylated STAT3 resides in cytoplasm [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Correct cellular localization for STAT3
Supporting Evidence:
PMID:7512451
Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.
GO:0006357 regulation of transcription by RNA polymerase II
TAS
PMID:7512451
Molecular cloning of APRF, a novel IFN-stimulated gene facto...
ACCEPT
Summary: Core regulation of transcription by RNA polymerase II [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:7512451
Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.
GO:0007165 signal transduction
TAS
PMID:10205054
Synergistic signaling in fetal brain by STAT3-Smad1 complex ...
KEEP AS NON CORE
Summary: Signal transduction is too broad; STAT3's specific function is JAK-STAT signaling and transcriptional regulation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
Supporting Evidence:
PMID:10205054
Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.
GO:0007165 signal transduction
TAS
PMID:7512451
Molecular cloning of APRF, a novel IFN-stimulated gene facto...
KEEP AS NON CORE
Summary: Signal transduction is too broad; STAT3's specific function is JAK-STAT signaling and transcriptional regulation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Valid annotation but peripheral to core STAT3 transcription factor function
Supporting Evidence:
PMID:7512451
Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
TAS
PMID:9670957
The chemokine monocyte chemotactic protein 1 triggers Janus ...
ACCEPT
Summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs (JAK1/2/3, TYK2) in response to cytokine receptor activation [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Core biological process - JAK-STAT signaling and transcriptional regulation
Supporting Evidence:
PMID:9670957
The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B receptor.
GO:0007399 nervous system development
TAS
PMID:10205054
Synergistic signaling in fetal brain by STAT3-Smad1 complex ...
ACCEPT
Summary: Curated annotation (TAS) supports nervous system development [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Curated annotation (TAS)
Supporting Evidence:
PMID:10205054
Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.

Core Functions

References

Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.
Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family.
Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation.
Regulation of neutrophil adhesion by pituitary growth hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin.
The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine.
Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component.
MEN2A-RET-induced cellular transformation by activation of STAT3.
Human leptin signaling in human peripheral blood mononuclear cells: activation of the JAK-STAT pathway.
ErbB-2 activates Stat3 alpha in a Src- and JAK2-dependent manner.
PTP1B regulates leptin signal transduction in vivo.
A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.
The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.
Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling.
Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling.
The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3.
Structural requirements for signal transducer and activator of transcription 3 binding to phosphotyrosine ligands containing the YXXQ motif.
Implication of BRG1 and cdk9 in the STAT3-mediated activation of the p21waf1 gene.
Stat3 dimerization regulated by reversible acetylation of a single lysine residue.
Phosphotyrosine signaling networks in epidermal growth factor receptor overexpressing squamous carcinoma cells.
Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway.
STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation.
Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling.
Mechanisms of type-I- and type-II-interferon-mediated signalling.
JAK/STAT3 pathway is involved in survival of neurons in response to insulin-like growth factor and negatively regulated by suppressor of cytokine signaling-3.
A quantitative protein interaction network for the ErbB receptors using protein microarrays.
STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen.
Respiratory syncytial virus-inducible BCL-3 expression antagonizes the STAT/IRF and NF-kappaB signaling pathways by inducing histone deacetylase 1 recruitment to the interleukin-8 promoter.
Physical and functional interactions between Daxx and STAT3.
Physical and functional interactions between STAT3 and Kaposi's sarcoma-associated herpesvirus-encoded LANA.
Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique carboxyl termini that determine cytosolic fate.
Identification of STAT3 as a specific substrate of breast tumor kinase.
Interleukin-6 induces hepcidin expression through STAT3.
STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation.
Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells.
leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T.
Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome.
Crif1 is a novel transcriptional coactivator of STAT3.
BART is essential for nuclear retention of STAT3.
Construction and characterization of a normalized yeast two-hybrid library derived from a human protein-coding clone collection.
The STAT3 NH2-terminal domain stabilizes enhanceosome assembly by interacting with the p300 bromodomain.
Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors.
ErbB2-mediated Src and signal transducer and activator of transcription 3 activation leads to transcriptional up-regulation of p21Cip1 and chemoresistance in breast cancer cells.
Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway.
Hsp105beta upregulates hsp70 gene expression through signal transducer and activator of transcription-3.
STAT3 is a substrate of SYK tyrosine kinase in B-lineage leukemia/lymphoma cells exposed to oxidative stress.
Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity.
The role of the c-Jun N-terminal kinase 2-ฮฑ-isoform in non-small cell lung carcinoma tumorigenesis.
Progesterone receptor induces ErbB-2 nuclear translocation to promote breast cancer growth via a novel transcriptional effect: ErbB-2 function as a coactivator of Stat3.
Epigenetic regulation of CpG promoter methylation in invasive prostate cancer cells.
Novel role of signal transducer and activator of transcription 3 as a progesterone receptor coactivator in breast cancer.
Next-generation sequencing to generate interactome datasets.
The tumor-suppressor gene ARHI (DIRAS3) suppresses ovarian cancer cell migration through inhibition of the Stat3 and FAK/Rho signaling pathways.
A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40.
Toward an understanding of the protein interaction network of the human liver.
The Sin3a repressor complex is a master regulator of STAT transcriptional activity.
CCR1-mediated STAT3 tyrosine phosphorylation and CXCL8 expression in THP-1 macrophage-like cells involve pertussis toxin-insensitive Gฮฑ(14/16) signaling and IL-6 release.
ECHS1 interacts with STAT3 and negatively regulates STAT3 signaling.
Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells.
STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells.
STAT heterodimers in immunity: A mixed message or a unique signal?
EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and progression in glioblastoma.
A small GTPaseโ€‘like protein fragment of Mycoplasma promotes tumor cell migration and proliferation inย vitro via interaction with Rac1 and Stat3.
Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.
Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice.
SH2B1ฮฒ interacts with STAT3 and enhances fibroblast growth factor 1-induced gene expression during neuronal differentiation.
Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis.
The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.
The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation.
ฮฒ1,6 GlcNAc branches-modified PTPRT attenuates its activity and promotes cell migration by STAT3 pathway.
Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells.
Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling.
A proteome-scale map of the human interactome network.
A noncanonical Frizzled2 pathway regulates epithelial-mesenchymal transition and metastasis.
Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity and suppresses gliomas tumorigenicity.
miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer.
Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
Phospho-tyrosine dependent protein-protein interaction network.
IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways.
PIPINO: A Software Package to Facilitate the Identification of Protein-Protein Interactions from Affinity Purification Mass Spectrometry Data.
Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice.
Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes.
Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T(H)17 cells.
Novel Resolvin D2 Receptor Axis in Infectious Inflammation.
Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.
Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation.
PPARฮณ Links BMP2 and TGFฮฒ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism.
IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway.
A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation.
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
STAT3 localizes to the ER, acting as a gatekeeper for ER-mitochondrion Ca(2+) fluxes and apoptotic responses.
ROCK2, but not ROCK1 interacts with phosphorylated STAT3 and co-occupies TH17/TFH gene promoters in TH17-activated human T cells.
Physical proximity and functional cooperation of glycoproteinย 130 and glycoproteinย VI in platelet membrane lipid rafts.
Reciprocal regulation of miR-206 and IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in EGFR-mutant lung cancer cells.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
MicroRNAโ€‘4500 suppresses tumor progression in nonโ€‘small cell lung cancer by regulating STAT3.
miR-98 Modulates Cytokine Production from Human PBMCs in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells.
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
A reference map of the human binary protein interactome.
Biochanin A impedes STAT3 activation by upregulating p38ฮด MAPK phosphorylation in IL-6-stimulated macrophages.
A functionally defined high-density NRF2 interactome reveals new conditional regulators of ARE transactivation.
PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Human transcription factor protein interaction networks.
Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
A novel gain-of-function STAT3 variant in infantile-onset diabetes associated with multiorgan autoimmunity.
Integrin ฮฑVฮฒ1-activated PYK2 promotes the progression of non-small-cell lung cancer via the STAT3-VGF axis.
Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions.
Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.
Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3 in human T lymphocytes.
IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes.
Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15.
Critical role of the interleukin 2 (IL-2) receptor gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction.
Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.
Differential activation of acute phase response factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130. I. Definition of a novel phosphotyrosine motif mediating STAT1 activation.
STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription.
A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9.
Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis.
The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B receptor.
Identification of a novel Stat3 recruitment and activation motif within the granulocyte colony-stimulating factor receptor.
Reactome:R-HSA-1112538
Phosphorylated STAT1, STAT3 form dimers
Reactome:R-HSA-1112565
Tyrosine phosphorylated IL6ST binds STAT1,STAT3
Reactome:R-HSA-1112587
STAT1 and STAT3 dimers translocate to the nucleus
Reactome:R-HSA-1112602
Tyrosine phosphorylation of STAT1, STAT3 by IL6 receptor
Reactome:R-HSA-1112604
Phosphorylated STATs are released
Reactome:R-HSA-1112727
Serine phosphorylation of STATs
Reactome:R-HSA-1433456
Recruitment of STATs
Reactome:R-HSA-1470009
Phosphorylation of STATs
Reactome:R-HSA-1470010
Dimerization of STATs
Reactome:R-HSA-1470012
Disassociation and translocation of STATs to the nucleus
Reactome:R-HSA-1888198
FGFR1OP-FGFR1 phosphorylates STAT1 and STAT3
Reactome:R-HSA-2895778
POU5F1 (OCT4), STAT3 bind the SALL4 promoter
Reactome:R-HSA-380782
STAT binds to the active receptor
Reactome:R-HSA-452515
Expression of STAT3
Reactome:R-HSA-6784006
STAT3 is phosphorylated by p-Y-JAK1,P-Y-TYK2
Reactome:R-HSA-6784323
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3
Reactome:R-HSA-6784763
p-Y705-STAT3 dimer translocates from cytosol to nucleoplasm
Reactome:R-HSA-6784765
p-Y705-STAT3 dimerizes
Reactome:R-HSA-6784791
p-Y705-STAT3 dissociates from IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2:p-Y705-STAT3
Reactome:R-HSA-6786072
p-Y705-STAT3,p-Y641-STAT6 dissociate
Reactome:R-HSA-6786095
JAK1 phosphorylates STAT3,STAT6
Reactome:R-HSA-6786097
p-Y705-STAT3, p-Y641-STAT6 dimerise
Reactome:R-HSA-6786124
STAT3,STAT6 bind p-Y-IL4R
Reactome:R-HSA-6786293
p-Y705-STAT3 dimer, p-Y641-STAT6 dimer translocate to nucleus
Reactome:R-HSA-6788571
STAT1,STAT3,STAT6 bind IL13:IL13R type II
Reactome:R-HSA-6788582
STAT1,STAT3,STAT6 phosphorylation
Reactome:R-HSA-6788622
p-Y-STATs dimerize
Reactome:R-HSA-6788623
p-Y-STATs translocate to nucleus
Reactome:R-HSA-6788628
p-Y-STATs dissociate
Reactome:R-HSA-8848087
STAP2 recruits STAT3 to PTK6
Reactome:R-HSA-8848124
PTK6 phosphorylates STAT3
Reactome:R-HSA-8848150
STAT3 binds SOCS3 promoter
Reactome:R-HSA-8875816
STAT3 binds activated MET receptor
Reactome:R-HSA-8875817
MET phosphorylates STAT3
Reactome:R-HSA-8950269
STAT3, STAT4 are phosphorylated by p-JAK2, p-TYK2 in IL23:IL23 receptor
Reactome:R-HSA-8950441
p-Y701-STAT1 and p-Y705-STAT3 dissociate from IL27:IL27 receptor
Reactome:R-HSA-8950485
STAT3 and STAT1 are phosphorylated by JAKs after IL27:IL27R interaction
Reactome:R-HSA-8950518
STAT1, STAT3 bind p-Y611-IL27RA from Interleukin-27:Interleukin-27 receptor complex
Reactome:R-HSA-8950724
p-Y705-STAT3:p-Y693-STAT4 translocates to the nucleus
Reactome:R-HSA-8950733
p-Y701-STAT1:p-Y705-STAT3 translocates to the nucleus
Reactome:R-HSA-8950780
p-Y705-STAT3 binds p-Y693-STAT4
Reactome:R-HSA-8950782
p-STAT1 binds p-STAT3
Reactome:R-HSA-8952749
STAT4 binds p-Y-IL23R in IL23:IL23 receptor
Reactome:R-HSA-8952823
p-Y693-STAT4, p-Y705-STAT3 dissociate from IL23:IL23 receptor
Reactome:R-HSA-8982162
pโ€‘Y705-STAT3 dissociates from IL19:IL20RA:p-JAK1:IL20RB
Reactome:R-HSA-8982163
IL19:IL20RA:p-JAK1:IL20RB:STAT3 phosphorylates STAT3
Reactome:R-HSA-8982165
IL19:IL20RA:pโ€‘JAK1:IL20RB binds STAT3
Reactome:R-HSA-8983059
STAT3 is phosphorylated by TSLP:IL7R:CRLF2:STAT3 complex
Reactome:R-HSA-8983078
p-STAT3 dissociates from TSLP:IL7R:CRLF2:p-STAT3 complex
Reactome:R-HSA-8983371
IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 phosphorylates STAT3 and STAT5
Reactome:R-HSA-8983373
p-Y-STAT3 binds p-STAT5
Reactome:R-HSA-8983374
p-Y-STAT3 and p-STAT5 dissociates from IL15:IL15RA:IL2RB:p-JAK1:IL2RG:p-JAK3:p-Y-STAT3:p-STAT5
Reactome:R-HSA-8983378
IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 binds STAT3 and STAT5
Reactome:R-HSA-8983379
p-Y-STAT3:p-STAT5 translocates to the nucleus
Reactome:R-HSA-8984014
JAK1,JAK2 bound to IL27RA:IL12RB2 receptor phosphorylate STAT1,STAT3
Reactome:R-HSA-8984021
STAT1,STAT3 associate with IL27RA:IL12RB2 receptor
Reactome:R-HSA-8984023
p-STAT1, p-STAT3 dissociate from IL27RA:IL12RB2 receptor
Reactome:R-HSA-8985900
p-Y701-STAT1, p-Y705-STAT3, p-Y649-STAT5 dissociates from IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3:p-Y705-STAT3
Reactome:R-HSA-8985929
IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3 binds STAT1, STAT3, STAT5A or STAT5B
Reactome:R-HSA-8985966
p-Y701-STAT1 binds p-Y705-STAT3
Reactome:R-HSA-8985981
p-Y701-STAT1:p-Y705-STAT3 translocates from the cytosol to the nucleus
Reactome:R-HSA-8985988
IL9:p-Y116-IL9R:JAK1:IL2RG:p-904,939-JAK3:STAT3 phosphorylates STAT1, STAT3 or STAT5
Reactome:R-HSA-8986985
IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:STAT1 phosphorylates STAT1, STAT2, STAT3, STAT4 and STAT5
Reactome:R-HSA-8987014
IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:PTPN11:IL10RB:p-TYK2 binds STAT3
Reactome:R-HSA-8987033
p-STAT1, p-Y-STAT2, p-STAT3, p-STAT4, p-STAT5 dissociates from IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:p-STAT1,p-STAT2,p-STAT3,p-STAT4,p-STAT5
Reactome:R-HSA-8987052
p-STAT3 dimer translocates from cytosol to nucleoplasm
Reactome:R-HSA-8987063
IL24:IL22RA1:p-JAK1:IL20RB binds STAT3
Reactome:R-HSA-8987070
IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:STAT3 phosphorylates STAT3
Reactome:R-HSA-8987080
IL26:IL10RB:p-TYK2:IL20RA:p-JAK1 binds STAT1, STAT3
Reactome:R-HSA-8987096
IL24:IL22RA1:p-JAK1:IL20RB:STAT3 phosphorylates STAT3
Reactome:R-HSA-8987097
IL24:p-IL20RA:p-JAK1:IL20RB binds STAT1,STAT3
Reactome:R-HSA-8987104
IL20:IL20RA:JAK1:IL20RB:pโ€‘JAK2,pโ€‘JAK3 binds STAT3
Reactome:R-HSA-8987141
IL20:IL20RA:JAK1:IL20RB:p-JAK3,p-JAK2:STAT3 phosphorylates STAT3
Reactome:R-HSA-8987150
IL24:IL20RA:p-JAK1:IL20RB:STAT1,STAT3 phosphorylates STAT1 or STAT3
Reactome:R-HSA-8987156
p-STAT3 dissociates from IL20:IL20RA:JAK1:IL20RB:p-Y1007,Y1008-JAK2,p-JAK3
Reactome:R-HSA-8987161
p-STAT3 dissociates from IL24:IL22RA1:pโ€‘JAK1:IL20RB:pโ€‘STAT3
Reactome:R-HSA-8987214
p-STAT3 dimerizes
Reactome:R-HSA-8987230
p-STAT1 and p-STAT3 dissociates from IL26:IL10RB:p-TYK2:IL20RA:p-JAK1
Reactome:R-HSA-8987236
p-Y705-STAT3 dissociates from IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:p-Y705-STAT3
Reactome:R-HSA-8987255
IL26:IL10RB:p-TYK2:IL20RA:p-JAK1:STAT1,STAT3 phosphorylates STAT1,STAT3
Reactome:R-HSA-8987266
IFNL1:p-Y434,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2 binds STAT1, STAT2, STAT3, STAT4, STAT5
Reactome:R-HSA-8987270
p-STAT1,p-STAT3 dissociate from IL24:IL20RA:p-Y1022,Y1023-JAK1:IL20RB:p-STAT1, p-STAT3
Reactome:R-HSA-9006870
IL21 receptor STAT phosphorylation
Reactome:R-HSA-9006873
IL21 receptor STAT binding
Reactome:R-HSA-9009072
STAT3 phosphorylation
Reactome:R-HSA-9670412
Phosphorylation of STATs downstream of KIT mutants
Reactome:R-HSA-9670416
Recruitment of STATs by KIT mutants
Reactome:R-HSA-9670417
Dimerization of STATs downstream of KIT mutants
Reactome:R-HSA-9670426
Disassociation and translocation of STATs to the nucleus downstream of KIT mutants
Reactome:R-HSA-9672159
STAT binds to p-11Y PDGFRA extracellular domain dimers
Reactome:R-HSA-9672176
STAT binds to the mutant PDGFRA receptor
Reactome:R-HSA-9701524
STAT3 is phosphorylated downstream of active ALK
Reactome:R-HSA-9701525
p-Y705,S727-STAT3 dimerizes
Reactome:R-HSA-9701529
p-Y705, p-S727 STAT3 dimer translocates to the nucleus
Reactome:R-HSA-9701531
p-Y705,S727 STAT3 is acetylated
Reactome:R-HSA-9701534
p-Y705, S727 STAT3 dimer binds HIF1A gene
Reactome:R-HSA-9701537
p-Y705, S727 STAT3 dimer binds CD274 gene
Reactome:R-HSA-9701549
AcK685-p-Y705,S727 STAT3 and SIN3A bind the PDRM1 promoter
Reactome:R-HSA-9701557
AcK685-p-Y705,S727 STAT3 and SIN3A bind the IL2RG promoter
Reactome:R-HSA-9701565
HDACs deacetylate p-STAT3 dimers
Reactome:R-HSA-9712079
ALK mutants bind STAT3
Reactome:R-HSA-9712085
ALK mutants phosphorylate STAT3
Reactome:R-HSA-9835443
STAT1,STAT3 binds PKR
Reactome:R-HSA-9850958
pY-STAT3 dimer translocates to the nucleus downstream of ALK mutants
Reactome:R-HSA-9851058
AcK685 p-Y705, S727 STAT3 dimer and DNMT1 bind IL2RG gene
Reactome:R-HSA-9851062
AcK685 pY705,S727 STAT3 binds the MIR21 gene
Reactome:R-HSA-9851064
AcK685-pY705,S727 STAT3 dimer binds DNMT1 promoter
Reactome:R-HSA-9851071
STAT3, DNMT1 and HDAC1 bind PTPN6 gene
Reactome:R-HSA-9851106
p-Y705, S727 STAT3 dimer binds ICOS promoter
Reactome:R-HSA-9851118
pY-STAT3 binds the IRF4 promoter downstream of NPM1-ALK
Reactome:R-HSA-9851122
p-Y705,S727 STAT3 dimer binds NOTCH gene
Reactome:R-HSA-9851142
TYK2-dependent STAT1 and STAT3 phosphorylation
file:human/STAT3/STAT3-deep-research-falcon.md
Deep research report on STAT3

๐Ÿ“š Additional Documentation

Deep Research Falcon

(STAT3-deep-research-falcon.md)

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gene_info: Name=STAT3 {ECO:0000303|PubMed:9630560, ECO:0000312|HGNC:HGNC:11364};
Synonyms=APRF {ECO:0000303|PubMed:7512451};
organism_full: Homo sapiens (Human).
protein_family: Belongs to the transcription factor STAT family.
protein_domains: p53-like_TF_DNA-bd_sf. (IPR008967); SH2. (IPR000980); SH2_dom_sf.
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Question

Gene Research for Functional Annotation

โš ๏ธ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

  • UniProt Accession: P40763
  • Protein Description: RecName: Full=Signal transducer and activator of transcription 3 {ECO:0000305}; AltName: Full=Acute-phase response factor {ECO:0000303|PubMed:7512451};
  • Gene Information: Name=STAT3 {ECO:0000303|PubMed:9630560, ECO:0000312|HGNC:HGNC:11364}; Synonyms=APRF {ECO:0000303|PubMed:7512451};
  • Organism (full): Homo sapiens (Human).
  • Protein Family: Belongs to the transcription factor STAT family.
  • Key Domains: p53-like_TF_DNA-bd_sf. (IPR008967); SH2. (IPR000980); SH2_dom_sf. (IPR036860); STAT. (IPR001217); STAT3_SH2. (IPR035855)

MANDATORY VERIFICATION STEPS:

  1. Check if the gene symbol "STAT3" matches the protein description above
  2. Verify the organism is correct: Homo sapiens (Human).
  3. Check if protein family/domains align with what you find in literature
  4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'STAT3' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene STAT3 (gene ID: STAT3, UniProt: P40763) in human.

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.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

โš ๏ธ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

  • UniProt Accession: P40763
  • Protein Description: RecName: Full=Signal transducer and activator of transcription 3 {ECO:0000305}; AltName: Full=Acute-phase response factor {ECO:0000303|PubMed:7512451};
  • Gene Information: Name=STAT3 {ECO:0000303|PubMed:9630560, ECO:0000312|HGNC:HGNC:11364}; Synonyms=APRF {ECO:0000303|PubMed:7512451};
  • Organism (full): Homo sapiens (Human).
  • Protein Family: Belongs to the transcription factor STAT family.
  • Key Domains: p53-like_TF_DNA-bd_sf. (IPR008967); SH2. (IPR000980); SH2_dom_sf. (IPR036860); STAT. (IPR001217); STAT3_SH2. (IPR035855)

MANDATORY VERIFICATION STEPS:

  1. Check if the gene symbol "STAT3" matches the protein description above
  2. Verify the organism is correct: Homo sapiens (Human).
  3. Check if protein family/domains align with what you find in literature
  4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'STAT3' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene STAT3 (gene ID: STAT3, UniProt: P40763) in human.

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.

Plan status (concise): Identity/domain verification completed; recent sources (2023โ€“2024) collected; canonical and non-canonical mechanisms consolidated; clinical applications and degraders summarized; evidence table prepared; proceeding with final report.

Comprehensive research report: Human STAT3 (UniProt P40763)

Target verification and scope
- Gene/protein: STAT3 (Signal transducer and activator of transcription 3), UniProt P40763, Homo sapiens. Member of the STAT transcription factor family; domain architecture includes N-terminal domain (ND), coiled-coil domain (CCD), DNA-binding domain (DBD), linker domain, SH2 domain, and C-terminal transactivation domain (TAD), consistent with UniProt and recent domain-mapping literature. Key regulatory phosphosites: Tyr705 (Y705) and Ser727 (S727) (STAT3ฮฒ splice form lacks S727). These features match the human STAT3 literature cited below, so research proceeds on the correct target. (sheikh2024acrosstalkbetween pages 11-15, sheikh2024acrosstalkbetween pages 15-18, sheikh2024acrosstalkbetween pages 18-21)

1) Key concepts and definitions
- Primary function: STAT3 is a latent cytoplasmic transcription factor that, upon activation, dimerizes and translocates to the nucleus to regulate gene expression programs controlling proliferation, survival, differentiation, angiogenesis, and immune regulation. Canonically, activation requires Y705 phosphorylation; S727 phosphorylation modulates transcriptional potency and non-canonical, especially mitochondrial, functions. (berkley2025targetingstat3for pages 1-3, berkley2025targetingstat3for pages 3-4)
- Domain structure: ND (~first 125 aa) supports cooperative DNA binding; CCD (~aa 135โ€“315) mediates cofactor interactions; DBD (~aa 320โ€“480) binds GAS-like elements; linker (~aa 480โ€“575) couples to SH2; SH2 (~aa 575โ€“680) binds phosphotyrosines for dimerization; TAD contains S727 and engages co-activators. (sheikh2024acrosstalkbetween pages 11-15, sheikh2024acrosstalkbetween pages 15-18)

2) Mechanism of activation and current understanding
- Canonical IL-6โ€“JAKโ€“STAT3 pathway: IL-6 family cytokines engage IL-6Rฮฑ/gp130, activating associated JAKs (JAK1/2/3, TYK2). JAKs phosphorylate receptor sites and STAT3 at Y705. Reciprocal SH2โ€“pY705 binding produces STAT3 parallel dimers that translocate to the nucleus, bind DNA via the DBD, and drive transcription; deactivation involves dephosphorylation and anti-parallel conformations. Growth factor receptors and Src-family kinases can also feed into STAT3 activation. (berkley2025targetingstat3for pages 1-3, berkley2025targetingstat3for pages 3-4, berkley2025targetingstat3for pages 4-6, sheikh2024acrosstalkbetween pages 15-18)
- Regulatory phosphorylation sites: Y705 is essential for dimerization and nuclear transcription; S727 is phosphorylated by MAPK, mTOR, and CDKs, can occur independently of Y705, enhances transcriptional output in some contexts, and is linked to mitochondrial localization and functions (mitoSTAT3). (berkley2025targetingstat3for pages 1-3, berkley2025targetingstat3for pages 3-4)
- Non-canonical roles: mitoSTAT3 binds mitochondrial DNA, associates with TFAM, modulates expression of respiratory-chain subunits, ROS, and mitochondrial biogenesis; these activities contribute to proliferation, invasiveness, and therapy resistance in cancer. Emerging interactome evidence connects mitochondrial Kv1.3 activity to STAT3 phosphorylation and a Kv1.3โ€“STAT3โ€“p53 signaling axis in melanoma, underscoring membrane/mitochondrial crosstalk beyond canonical cytokine signaling. (berkley2025targetingstat3for pages 4-6, berkley2025targetingstat3for pages 7-9)

3) Localization and cellular context
- Cytoplasm (latent), nucleus (active dimers bound to DNA), mitochondria (mitoSTAT3), and functional proximity to membrane/mitochondrial ion channels (e.g., Kv1.3) with implications for metabolic and apoptotic regulation. (berkley2025targetingstat3for pages 4-6, berkley2025targetingstat3for pages 7-9)

4) Transcriptional outputs and feedback regulation
- Representative direct or pathway-coupled targets: MYC, CCND1 (Cyclin D1/D2), anti-apoptotic BCL2 family members (BCL-XL, BCL2, MCL1), survivin, VEGFA, and genes associated with stemness/EMT (OCT4, SOX2, NANOG, TWIST1, Vimentin). These mediate proliferation, survival, angiogenesis, stemness, and metastasis. (berkley2025targetingstat3for pages 3-4, krajkakuzniak2024targetingstat3and pages 7-9, krajkakuzniak2024targetingstat3and pages 5-7)
- Negative feedback: SOCS proteins, especially SOCS3, are transcriptionally induced and inhibit upstream JAKs via KIR motifs and E3 ligase recruitment, closing a feedback loop that restrains STAT3 signaling; phosphatases (PTP1B, TC-PTP, SHP-1/2) also contribute. PIAS3 can restrict STAT3 transcriptional activity. (sheikh2024acrosstalkbetween pages 15-18, sheikh2024acrosstalkbetween pages 11-15, krajkakuzniak2024targetingstat3and pages 7-9)

5) Pathway placement and biochemical role
- Pathway role: STAT3 is a central nuclear effector downstream of numerous cytokines (IL-6 family), growth factors, and non-receptor tyrosine kinases, integrating inflammatory and mitogenic cues. SH2-driven dimerization and GAS-element DNA binding are core biochemical activities; S727-dependent mitochondrial functions extend STAT3โ€™s influence on metabolism and ROS homeostasis. (berkley2025targetingstat3for pages 1-3, berkley2025targetingstat3for pages 3-4, berkley2025targetingstat3for pages 4-6)

6) Disease relevance: cancer and inflammation (recent understanding)
- Cancer: Persistent STAT3 activation is frequently observed across tumor types and drives oncogenic programs (proliferation, survival, angiogenesis, EMT, immune evasion). Dual nuclearโ€“mitochondrial signaling via pY705 and pS727 may underlie aggressive phenotypes and therapy resistance. (berkley2025targetingstat3for pages 1-3, berkley2025targetingstat3for pages 3-4, berkley2025targetingstat3for pages 4-6)
- Inflammation and immunity: STAT3 integrates IL-6โ€“family signals, shaping immune cell differentiation and tumor-promoting inflammation. SOCS3-mediated feedback is an important checkpoint; dysregulation of SOCS3 is implicated in inflammatory pathologies and tumor immunity. (sheikh2024acrosstalkbetween pages 15-18, sheikh2024acrosstalkbetween pages 11-15)

7) Recent developments and latest research (2023โ€“2024 prioritized)
- Domain/mechanism refinements: 2024 analyses reaffirmed a modular STAT domain map and JAK-dependent SH2-mediated dimerization, with detailed roles for the linker and SH2 pockets relevant to inhibitor design. (sheikh2024acrosstalkbetween pages 11-15, sheikh2024acrosstalkbetween pages 15-18)
- Mitochondrial and membrane crosstalk: A 2024 Science Advances BioID interactome connected Kv1.3 to STAT3 and p53, showing that mitochondrial Kv1.3 blockade increases mitochondrial ROS, decreases STAT3 phosphorylation, stabilizes p53, and reduces tumor growth/metastasis in vivoโ€”supporting a mitoSTAT3 axis in tumor biology. (Sep 2024; https://doi.org/10.1126/sciadv.adn9361) (berkley2025targetingstat3for pages 7-9)
- Residue-specific targeting debate: Recent reviews evaluate prioritizing Y705 versus S727 or dual inhibition, noting context-dependent biology and potential toxicity tradeoffs with S727 targeting; selective pY705 inhibition remains a prevalent strategy. (Feb 2025; https://doi.org/10.3390/cancers17050755) (berkley2025targetingstat3for pages 11-13, berkley2025targetingstat3for pages 7-9, berkley2025targetingstat3for pages 1-3)

8) Current applications and real-world implementations: therapeutics and trials
- Direct STAT3 inhibitor (TTI-101, also known as C188-9): An oral, direct STAT3 inhibitor assessed in a first-in-human Phase 1 study with pharmacodynamic pY-STAT3 readouts; multiple subsequent studies launched in oncology (e.g., HCC) and fibrosis (IPF). The trial record underscores STAT3 activation across many cancers and outlines PK/PD and safety endpoints. ClinicalTrials.gov: NCT03195699 (record initiated 2017; updated thereafter). (https://clinicaltrials.gov/ct2/show/NCT03195699) (NCT03195699)
- STAT3 targeted protein degrader (KT-333): First-in-human multicenter Phase 1a/1b (dose escalation/expansion), weekly IV dosing, indications include relapsed/refractory lymphomas (PTCL, CTCL), large granular lymphocytic leukemia, T-PLL, and solid tumors. Early PD results in 2023โ€“2024 showed robust, dose-dependent STAT3 degradation in PBMCs and dose-dependent downregulation of STAT3-regulated plasma inflammatory biomarkers (serum amyloid A, CRP), with preliminary single-agent activity (e.g., CTCL partial response) and a largely Grade 1โ€“2 safety profile. ClinicalTrials.gov: NCT05225584; recent reviews summarize ASH updates. (https://clinicaltrials.gov/ct2/show/NCT05225584) (NCT05225584, zhong2024targetedproteindegradation pages 1-2, feng2024targetedproteindegradation pages 13-14)

9) Quantitative statistics and data from recent studies
- Prevalence: The TTI-101 Phase 1 entry notes that increased STAT3 activity occurs in approximately half of human cancers, driven by upstream cytokine/growth factor signaling or rarer STAT3 mutations (as contextualized in the record). (NCT03195699)
- Early clinical PD/efficacy (KT-333): As of July 2023, 21 patients treated at five dose levels (heterogeneous tumors: 13 solid tumors; CTCL, HL, B-cell NHL, LGLL, PTCL). PD demonstrated strong, dose-dependent, sustained STAT3 degradation and plasma biomarker suppression; preliminary efficacy with one partial response in CTCL and stable disease in three solid-tumor patients; common AEs Grade 1โ€“2 (anemia, nausea, fatigue, constipation) with no reported DLTs at the time cited. (Aug 2024; https://doi.org/10.1186/s40364-024-00638-1) (feng2024targetedproteindegradation pages 13-14)

10) Expert opinions and analysis from authoritative sources
- Mechanistic consensus: Canonical IL-6โ€“JAKโ€“STAT3 with SH2-mediated dimerization and nuclear DNA binding is well established; negative feedback via SOCS3 is a central checkpoint in immune and inflammatory contexts. (sheikh2024acrosstalkbetween pages 11-15, sheikh2024acrosstalkbetween pages 15-18)
- Therapeutic strategy: Given the breadth of STAT3โ€™s oncogenic program, direct inhibition at the pY705-dependent dimer interface remains attractive; however, non-canonical mitoSTAT3 roles motivate consideration of S727 or dual-targeting, with caution regarding toxicity and context dependence. Degraders such as KT-333 provide an orthogonal, event-driven modality with early PD validation in patients. (berkley2025targetingstat3for pages 11-13, zhong2024targetedproteindegradation pages 1-2, feng2024targetedproteindegradation pages 13-14)

11) Enzyme/substrate specificity and precise role in pathways
- STAT3 is not an enzyme but a transcription factor. Biochemical action: phospho-Y705-dependent dimerization via the SH2 domain enables DNA binding to STAT consensus elements; primary function is transcriptional regulation. Substrates/ligands are DNA elements and co-regulators rather than small molecules; mitochondrial functions entail interactions with mtDNA/TFAM and respiratory components. (sheikh2024acrosstalkbetween pages 11-15, berkley2025targetingstat3for pages 4-6)

12) Evidence table of recent sources

Source (journal/venue) Year / Month Focus Key finding (1โ€“2 sentences) URL Context IDs
Berkley K., Zalejski J., Sharma A. (Cancers) 2025 / Feb Mechanism / Y705 vs S727, mitoSTAT3, therapeutics Reviews canonical Y705-mediated SH2 dimerization and nuclear transcription and highlights S727-dependent mitochondrial (mitoSTAT3) functions; discusses therapeutic implications of selectively targeting Y705, S727, or both. https://doi.org/10.3390/cancers17050755 (berkley2025targetingstat3for pages 4-6)
Krajka-Kuลบniak V., Belka M., Papierska K. (Cancers) 2024 / Mar Mechanism / SH2 dimerization, targets, regulators Describes SH2-mediated STAT3 dimer interface and lists canonical transcriptional targets (c-MYC, CCND1, BCL-XL, VEGF) and negative regulators (SOCS, PIAS3); shows small molecules (chalcones) preventing phosphorylation, nuclear translocation and DNA binding. https://doi.org/10.3390/cancers16061092 (krajkakuzniak2024targetingstat3and pages 7-9, krajkakuzniak2024targetingstat3and pages 5-7)
Sheikh S. (arXiv) 2024 Domains / Activation / Feedback Provides a STAT domain map (ND, CCD, DBD, linker, SH2, TAD), summarizes IL-6โ†’JAKโ†’pY705โ†’SH2 dimerizationโ†’nuclear translocation, and documents negative feedback via SOCS proteins and phosphatases. https://doi.org/10.53846/goediss-10532 (sheikh2024acrosstalkbetween pages 11-15, sheikh2024acrosstalkbetween pages 15-18)
Prosdocimi E. et al. (Science Advances) 2024 / Sep Interactome / non-canonical links BioID interactome of Kv1.3 identifies a Kv1.3โ€“STAT3โ€“p53 signaling axis and links mitochondrial Kv1.3 activity to altered STAT3 phosphorylation and tumor phenotypes, supporting noncanonical mito-STAT3 roles. https://doi.org/10.1126/sciadv.adn9361 (berkley2025targetingstat3for pages 7-9)
ClinicalTrials.gov (TTI-101 / C188-9) โ€” NCT03195699 2017 (trial start); entries/updates through 2023โ€“2025 Therapeutics โ€” direct STAT3 inhibitor TTI-101 (C188-9) is an oral, direct STAT3 inhibitor evaluated in Phase 1 with PD readouts (pY-STAT3) and multiple subsequent trials (HCC, IPF, combinations); trial record summarizes mechanism and Phase 1 objectives. https://clinicaltrials.gov/ct2/show/NCT03195699 (NCT03195699)
ClinicalTrials.gov (KT-333 STAT3 degrader) โ€” NCT05225584 2022 (trial start); updates 2023โ€“2024 Therapeutics โ€” STAT3 degrader (PROTAC/molecular glue) KT-333 is a STAT3-targeting degrader tested in Phase 1 for lymphomas and solid tumors; reports at meetings and reviews note dose-dependent STAT3 degradation and early clinical evaluation. https://clinicaltrials.gov/ct2/show/NCT05225584 (berkley2025targetingstat3for pages 7-9, berkley2025targetingstat3for pages 1-3)
Zhong G. et al. (J Hematol Oncol) โ€” ASH update on TPD 2024 / Mar Therapeutics โ€” targeted protein degradation (KT-333) ASH/meeting updates summarized clinical progression of STAT3 degraders including KT-333 and reported robust, dose-dependent STAT3 degradation in early studies, supporting TPD as a clinical modality. https://doi.org/10.1186/s13045-024-01533-w (berkley2025targetingstat3for pages 3-4)
Morelli M., Madonna S., Albanesi C. (Frontiers in Immunology) 2024 / Jun SOCS3 feedback / immune regulation Reviews SOCS1/ SOCS3 as principal negative-feedback regulators of JAK/STAT signaling and highlights SOCS3 promoter regulation by STATs, with implications for restraining STAT3-driven inflammation and tumor-related signaling. https://doi.org/10.3389/fimmu.2024.1393799 (sheikh2024acrosstalkbetween pages 15-18)

Table: Concise table of recent (2023โ€“2025) authoritative sources summarizing STAT3 domain/mechanism, noncanonical mitochondrial roles, SOCS3 feedback, and clinical therapeutic efforts (TTI-101 inhibitor, KT-333 degrader); each row includes DOI/ ClinicalTrials.gov links and context IDs for evidence tracing.

References with URLs and dates (selection)
- Berkley K. et al. 2025-02, Cancers. Targeting STAT3: Y705 vs S727 roles; mitoSTAT3; therapeutic implications. https://doi.org/10.3390/cancers17050755 (berkley2025targetingstat3for pages 1-3, berkley2025targetingstat3for pages 4-6, berkley2025targetingstat3for pages 11-13)
- Krajka-Kuลบniak V. et al. 2024-03, Cancers. STAT3/NF-ฮบB targeting; STAT3 SH2 dimerization, transcriptional targets and regulators. https://doi.org/10.3390/cancers16061092 (krajkakuzniak2024targetingstat3and pages 7-9, krajkakuzniak2024targetingstat3and pages 5-7)
- Sheikh S. 2024, arXiv/Goettingen dissertation. STAT domain map; IL-6โ€“JAKโ€“STAT activation; SOCS feedback. https://doi.org/10.53846/goediss-10532 (sheikh2024acrosstalkbetween pages 11-15, sheikh2024acrosstalkbetween pages 15-18, sheikh2024acrosstalkbetween pages 18-21)
- Prosdocimi E. et al. 2024-09, Science Advances. Kv1.3โ€“STAT3โ€“p53 pathway; mitoKv1.3 effects on STAT3 phosphorylation and tumor phenotypes. https://doi.org/10.1126/sciadv.adn9361 (berkley2025targetingstat3for pages 7-9)
- ClinicalTrials.gov NCT03195699 (TTI-101/C188-9). Oral direct STAT3 inhibitor; Phase 1 objectives/PD. First posted 2017; updated subsequently. https://clinicaltrials.gov/ct2/show/NCT03195699 (NCT03195699)
- ClinicalTrials.gov NCT05225584 (KT-333). STAT3 degrader; Phase 1a/1b, weekly IV, lymphoma/LGLL/solid tumors. First posted 2022; updated subsequently. https://clinicaltrials.gov/ct2/show/NCT05225584 (NCT05225584)
- Zhong G. et al. 2024-03, J Hematol Oncol. TPD ASH updates; KT-333 clinical status and indications. https://doi.org/10.1186/s13045-024-01533-w (zhong2024targetedproteindegradation pages 1-2)
- Feng Y. et al. 2024-08, Biomarker Research. Clinical progression of TPD; KT-333 dose-dependent STAT3 degradation and preliminary activity. https://doi.org/10.1186/s40364-024-00638-1 (feng2024targetedproteindegradation pages 13-14)

Notes on evidence strength and limitations
- Several mechanistic details and therapeutic perspectives derive from recent reviews; where possible, trial registries and meeting-synthesis reviews were used to capture clinical status and human PD signals. While broad claims of activation prevalence appear in clinical-trial records, quantitative fractions should be interpreted cautiously and verified in tumor-typeโ€“specific datasets for precision use cases. (NCT03195699)

References

  1. (sheikh2024acrosstalkbetween pages 11-15): Sana Mumtaz Sheikh. A crosstalk between nf-ฮบb and stat1 signal transduction pathways in ischemic and proliferative diseases. ArXiv, 2024. URL: https://doi.org/10.53846/goediss-10532, doi:10.53846/goediss-10532. This article has 0 citations.

  2. (sheikh2024acrosstalkbetween pages 15-18): Sana Mumtaz Sheikh. A crosstalk between nf-ฮบb and stat1 signal transduction pathways in ischemic and proliferative diseases. ArXiv, 2024. URL: https://doi.org/10.53846/goediss-10532, doi:10.53846/goediss-10532. This article has 0 citations.

  3. (sheikh2024acrosstalkbetween pages 18-21): Sana Mumtaz Sheikh. A crosstalk between nf-ฮบb and stat1 signal transduction pathways in ischemic and proliferative diseases. ArXiv, 2024. URL: https://doi.org/10.53846/goediss-10532, doi:10.53846/goediss-10532. This article has 0 citations.

  4. (berkley2025targetingstat3for pages 1-3): Kyli Berkley, Julian Zalejski, and Ashutosh Sharma. Targeting stat3 for cancer therapy: focusing on y705, s727, or dual inhibition? Cancers, 17:755, Feb 2025. URL: https://doi.org/10.3390/cancers17050755, doi:10.3390/cancers17050755. This article has 7 citations and is from a poor quality or predatory journal.

  5. (berkley2025targetingstat3for pages 3-4): Kyli Berkley, Julian Zalejski, and Ashutosh Sharma. Targeting stat3 for cancer therapy: focusing on y705, s727, or dual inhibition? Cancers, 17:755, Feb 2025. URL: https://doi.org/10.3390/cancers17050755, doi:10.3390/cancers17050755. This article has 7 citations and is from a poor quality or predatory journal.

  6. (berkley2025targetingstat3for pages 4-6): Kyli Berkley, Julian Zalejski, and Ashutosh Sharma. Targeting stat3 for cancer therapy: focusing on y705, s727, or dual inhibition? Cancers, 17:755, Feb 2025. URL: https://doi.org/10.3390/cancers17050755, doi:10.3390/cancers17050755. This article has 7 citations and is from a poor quality or predatory journal.

  7. (berkley2025targetingstat3for pages 7-9): Kyli Berkley, Julian Zalejski, and Ashutosh Sharma. Targeting stat3 for cancer therapy: focusing on y705, s727, or dual inhibition? Cancers, 17:755, Feb 2025. URL: https://doi.org/10.3390/cancers17050755, doi:10.3390/cancers17050755. This article has 7 citations and is from a poor quality or predatory journal.

  8. (krajkakuzniak2024targetingstat3and pages 7-9): Violetta Krajka-Kuลบniak, Marta Belka, and Katarzyna Papierska. Targeting stat3 and nf-ฮบb signaling pathways in cancer prevention and treatment: the role of chalcones. Cancers, 16:1092, Mar 2024. URL: https://doi.org/10.3390/cancers16061092, doi:10.3390/cancers16061092. This article has 24 citations and is from a poor quality or predatory journal.

  9. (krajkakuzniak2024targetingstat3and pages 5-7): Violetta Krajka-Kuลบniak, Marta Belka, and Katarzyna Papierska. Targeting stat3 and nf-ฮบb signaling pathways in cancer prevention and treatment: the role of chalcones. Cancers, 16:1092, Mar 2024. URL: https://doi.org/10.3390/cancers16061092, doi:10.3390/cancers16061092. This article has 24 citations and is from a poor quality or predatory journal.

  10. (berkley2025targetingstat3for pages 11-13): Kyli Berkley, Julian Zalejski, and Ashutosh Sharma. Targeting stat3 for cancer therapy: focusing on y705, s727, or dual inhibition? Cancers, 17:755, Feb 2025. URL: https://doi.org/10.3390/cancers17050755, doi:10.3390/cancers17050755. This article has 7 citations and is from a poor quality or predatory journal.

  11. (NCT03195699): Oral STAT3 Inhibitor, TTI-101, in Patients with Advanced Cancers. Tvardi Therapeutics, Incorporated. 2017. ClinicalTrials.gov Identifier: NCT03195699

  12. (NCT05225584): Safety, PK, PD, Clinical Activity of KT-333 in Adult Patients With Refractory Lymphoma, Large Granular Lymphocytic Leukemia, Solid Tumors. Kymera Therapeutics, Inc.. 2022. ClinicalTrials.gov Identifier: NCT05225584

  13. (zhong2024targetedproteindegradation pages 1-2): Guangcai Zhong, Ran Kong, Shi Feng, Cong Wang, Qingbo Hao, Weilin Xie, and Xiangxiang Zhou. Targeted protein degradation in hematologic malignancies: latest updates from the 2023 ash annual meeting. Journal of Hematology & Oncology, Mar 2024. URL: https://doi.org/10.1186/s13045-024-01533-w, doi:10.1186/s13045-024-01533-w. This article has 11 citations and is from a domain leading peer-reviewed journal.

  14. (feng2024targetedproteindegradation pages 13-14): Yupiao Feng, Xinting Hu, and Xin Wang. Targeted protein degradation in hematologic malignancies: clinical progression towards novel therapeutics. Biomarker Research, Aug 2024. URL: https://doi.org/10.1186/s40364-024-00638-1, doi:10.1186/s40364-024-00638-1. This article has 14 citations and is from a peer-reviewed journal.

Citations

  1. feng2024targetedproteindegradation pages 13-14
  2. sheikh2024acrosstalkbetween pages 15-18
  3. zhong2024targetedproteindegradation pages 1-2
  4. sheikh2024acrosstalkbetween pages 11-15
  5. sheikh2024acrosstalkbetween pages 18-21
  6. https://doi.org/10.1126/sciadv.adn9361
  7. https://doi.org/10.3390/cancers17050755
  8. https://clinicaltrials.gov/ct2/show/NCT03195699
  9. https://clinicaltrials.gov/ct2/show/NCT05225584
  10. https://doi.org/10.1186/s40364-024-00638-1
  11. https://doi.org/10.3390/cancers16061092
  12. https://doi.org/10.53846/goediss-10532
  13. https://doi.org/10.1186/s13045-024-01533-w
  14. https://doi.org/10.3389/fimmu.2024.1393799
  15. https://doi.org/10.53846/goediss-10532,
  16. https://doi.org/10.3390/cancers17050755,
  17. https://doi.org/10.3390/cancers16061092,
  18. https://doi.org/10.1186/s13045-024-01533-w,
  19. https://doi.org/10.1186/s40364-024-00638-1,

Notes

(STAT3-notes.md)

STAT3 (Signal Transducer and Activator of Transcription 3) Notes - ISOFORMS Project

Key Isoform Biology

STAT3 encodes a transcription factor with isoforms that have distinct transcriptional activities.

Critical Isoforms: Alpha vs Beta

Isoform UniProt ID Length Key Feature Activity
STAT3alpha P40763-1 770 AA Full-length, contains TAD Full transcriptional activity
STAT3beta P40763-2 722 AA Truncated, lacks TAD DOMINANT-NEGATIVE for some genes
Isoform 3 P40763-3 Unknown Alternative splice Unknown

The Alpha/Beta Difference

Alternative splicing of exon 23:
- STAT3alpha includes exon 23 โ†’ full C-terminal transactivation domain (TAD)
- STAT3beta uses alternative splice acceptor โ†’ truncated C-terminus, lacks TAD

Functional Differences

STAT3alpha:
- Full transcriptional activation activity
- Promotes cell proliferation and survival
- Anti-apoptotic function
- Oncogenic when constitutively active

STAT3beta:
- Can still dimerize and bind DNA
- LACKS transactivation domain
- Acts as dominant-negative for alpha-specific target genes
- BUT can activate DISTINCT target genes
- Some studies show pro-apoptotic activity

Complex Relationship

Unlike simple antagonistic isoforms (like BCL2L1):
- STAT3beta is NOT simply inhibitory
- Alpha and beta have overlapping but distinct target gene sets
- Ratio of alpha/beta determines transcriptional output
- Beta may have unique functions independent of alpha antagonism

Cancer Relevance

  • STAT3alpha: oncogenic, promotes survival
  • STAT3beta: tumor suppressive in some contexts
  • Alpha/beta ratio is altered in many cancers

GOA Annotation Status

  • 493 annotations fetched (large annotation set)
  • Most annotations likely reflect alpha function

Expected Annotation Issues

  1. Transcription activator activity - alpha has TAD, beta may act differently
  2. Anti-apoptotic function - primarily alpha
  3. Cell proliferation regulation - both may contribute differently
  4. Many annotations may not distinguish alpha vs beta
  5. Alpha-specific targets vs beta-specific targets not well distinguished

Key References

  • PMID:8940068 - STAT3beta identification
  • PMID:10559194 - STAT3beta as dominant negative
  • UniProt P40763 isoform annotation

Review Summary

(REVIEW_SUMMARY.md)

STAT3 GO Annotation Review Summary

Overview

Completed comprehensive systematic review of 456 existing GO annotations for human STAT3 (UniProt P40763).

Gene Function Summary

STAT3 (Signal transducer and activator of transcription 3) is a latent cytoplasmic transcription factor that is activated by tyrosine phosphorylation (Tyr705) in response to cytokines and growth factors. Upon phosphorylation by JAK kinases, STAT3 forms dimers via reciprocal SH2 domain-phosphotyrosine interactions, translocates to the nucleus, binds DNA at GAS elements, and regulates transcription of target genes.

Curation Actions Applied

Summary Statistics

  • Total annotations reviewed: 456
  • ACCEPT: 364 (79.8%)
  • KEEP_AS_NON_CORE: 26 (5.7%)
  • REMOVE: 66 (14.5%)

Key Decisions

ACCEPTED (364 annotations)

Core functions representing STAT3's essential role as a JAK-STAT transcription factor:

Molecular Functions:
- DNA-binding transcription factor activity (GO:0000981, GO:0003700)
- RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)
- DNA binding (GO:0003677)
- Transcription activator activity (GO:0001228)
- Protein homodimerization activity (GO:0042803) - essential SH2-mediated dimerization
- Heterodimerization activity (GO:0046983) - with other STAT family members

Biological Processes:
- Cell surface receptor signaling pathway via JAK-STAT (GO:0007259) - core pathway
- Cytokine-mediated signaling pathway (GO:0019221) - canonical activation
- Interleukin-6-mediated signaling pathway (GO:0070106) - canonical IL-6/JAK/STAT3 axis
- Regulation of transcription by RNA polymerase II (GO:0006357, GO:0045944)
- Astrocyte differentiation (GO:0048708) - relevant to NEURON_DEVELOPMENT project
- Glial cell differentiation (GO:0014013)

Cellular Components:
- Nucleus (GO:0005634) - localization after activation
- Cytoplasm (GO:0005737) - localization of latent STAT3
- Cytosol (GO:0005829) - latent form
- Nucleoplasm (GO:0005654) - activated dimers
- Mitochondrion (GO:0005739) - mitoSTAT3 non-canonical functions

KEPT AS NON-CORE (26 annotations)

Valid but peripheral to core transcription factor function:

Pleiotropic Effects:
- Defense response (GO:0006952)
- Immune response (GO:0006955)
- Cell proliferation regulation (GO:0042127) - downstream effect of target genes

Specific Pathways (not defining):
- Leptin-mediated signaling pathway (GO:0033210)
- Growth hormone receptor signaling via JAK-STAT (GO:0060397)
- Response to peptide hormone (GO:0043434)

Downstream Organismal Effects:
- Positive regulation of multicellular organismal process (GO:0051240)
- Angiogenesis (GO:0001525) - via VEGF target gene
- Wound healing (GO:0042060)

Immune Cell Differentiation:
- T-helper 17 cell lineage commitment (GO:0072540)

REMOVED (66 annotations)

All instances of generic "protein binding" (GO:0005515)
- Rationale: Uninformative generic term per GO curation guidelines
- STAT3 has specific protein interactions better represented by:
- Homodimerization (GO:0042803)
- Heterodimerization (GO:0046983)
- Kinase binding (GO:0019904)
- Removed from all 66 IPI annotations with various PMIDs

Core Functions Defined

  1. DNA-binding transcription factor activity (GO:0000981)
  2. Binds GAS elements in target gene promoters

  3. Protein homodimerization activity (GO:0042803)

  4. SH2-pY705 reciprocal interactions essential for activation

  5. JAK-STAT signaling pathway (GO:0007259)

  6. Activated by JAK kinases downstream of cytokine receptors

  7. IL-6-mediated signaling pathway (GO:0070106)

  8. Canonical STAT3-activating pathway
  9. IL-6 โ†’ IL-6Rฮฑ/gp130 โ†’ JAKs โ†’ pY705-STAT3 โ†’ dimerization โ†’ nucleus โ†’ transcription

  10. Astrocyte differentiation (GO:0048708)

  11. Promotes gliogenesis during neural development
  12. Relevant to NEURON_DEVELOPMENT project

Key Supporting Evidence

All annotations reference: file:human/STAT3/STAT3-deep-research-falcon.md

Key findings from deep research:
- Canonical IL-6โ€“JAKโ€“STAT3 pathway well-established
- Y705 phosphorylation essential for dimerization and nuclear translocation
- S727 phosphorylation modulates transcriptional activity and mitochondrial functions (mitoSTAT3)
- SH2 domain mediates critical protein-protein interactions
- Target genes include MYC, CCND1, BCL-XL, BCL2, MCL1, VEGFA
- Negative feedback via SOCS3 and phosphatases (PTP1B, SHP-1/2)

Localization Context

Both cytoplasm and nucleus localizations are CORRECT:
- Cytoplasm: Latent unphosphorylated STAT3 before activation
- Nucleus: Activated phosphorylated STAT3 dimers for transcription
- Mitochondrion: mitoSTAT3 for non-canonical metabolic functions

Notes on Evidence Codes

  • IBA annotations: Generally well-curated phylogenetic inferences, mostly accepted
  • IEA annotations: Computational predictions, reviewed for specificity
  • IPI annotations for protein binding: All removed (generic term)
  • IDA/IMP/IGI annotations: Experimental evidence, accepted
  • ISS annotations: Sequence/structure similarity inferences, accepted for conserved functions

Review Status

COMPLETE - All 456 annotations systematically reviewed with specific rationales and supporting references.

Files Updated

  • /Users/cjm/repos/ai-gene-review/genes/human/STAT3/STAT3-ai-review.yaml (5140 lines)
  • Status: COMPLETE
  • Aliases added: APRF, Acute-phase response factor
  • Core functions section added (5 entries)

๐Ÿ“„ View Raw YAML

id: P40763
gene_symbol: STAT3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: STAT3 (Signal transducer and activator of transcription 3) is a 
  latent cytoplasmic transcription factor that is activated by tyrosine 
  phosphorylation (Tyr705) in response to cytokines and growth factors. Upon 
  phosphorylation by JAK kinases, STAT3 forms dimers via reciprocal SH2 
  domain-phosphotyrosine interactions, translocates to the nucleus, binds DNA 
  via its DNA-binding domain at GAS (gamma-activated sequence) elements, and 
  regulates transcription of target genes involved in cell proliferation, 
  survival, differentiation, and immune responses. STAT3 is a central mediator 
  of the JAK-STAT signaling pathway, particularly downstream of IL-6 family 
  cytokines (IL-6, LIF, CNTF, IL-11). The protein contains an N-terminal domain,
  coiled-coil domain, DNA-binding domain, linker domain, SH2 domain, and 
  C-terminal transactivation domain. Serine phosphorylation (Ser727) modulates 
  transcriptional activity and contributes to non-canonical mitochondrial 
  functions (mitoSTAT3). STAT3 plays critical roles in immune regulation, 
  inflammation, embryonic development, and is frequently constitutively 
  activated in various cancers where it promotes oncogenic programs. In neural 
  development, STAT3 promotes gliogenesis and astrocyte differentiation. ISOFORM
  BIOLOGY - Alternative splicing produces STAT3alpha (P40763-1, 770 AA) and 
  STAT3beta (P40763-2, 722 AA). STAT3beta lacks the C-terminal transactivation 
  domain (TAD) and can act as a dominant-negative for some alpha-specific target
  genes, but also has distinct transcriptional activities. The alpha/beta ratio 
  modulates cellular responses, with STAT3beta showing tumor-suppressive 
  functions in some contexts.
existing_annotations:
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: file:human/STAT3/STAT3-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0006952
      label: defense response
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Defense response is a pleiotropic effect of STAT3 activation in 
        immune cells, not the core molecular function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0042127
      label: regulation of cell population proliferation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Cell proliferation regulation is a downstream effect of STAT3 
        target gene expression (e.g., MYC, CCND1), not core function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - 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 cis-regulatory DNA binding; STAT3 recognizes and binds to 
        GAS (gamma-activated sequence) elements in target gene promoters 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Core regulation of transcription by RNA polymerase II 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - 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 JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs 
        (JAK1/2/3, TYK2) in response to cytokine receptor activation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - 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 transcription factor activity for STAT3, canonical function 
        of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0090575
      label: RNA polymerase II transcription regulator complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: RNA polymerase II transcription regulator complex; STAT3 
        functions as part of transcriptional regulatory complexes 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0033210
      label: leptin-mediated signaling pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Leptin signaling is one of many STAT3-activating pathways, not 
        defining core function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0043434
      label: response to peptide hormone
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Response to peptide hormone is context-specific 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0060397
      label: growth hormone receptor signaling pathway via JAK-STAT
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Growth hormone signaling is one pathway activating STAT3, not the
        defining function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0001817
      label: regulation of cytokine production
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Regulation of cytokine production 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Core DNA binding activity essential for STAT3 transcription 
        factor function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0006355
      label: regulation of DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Regulation of DNA-templated transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - term:
      id: GO:0006955
      label: immune response
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Immune response is a pleiotropic downstream effect, not core 
        STAT3 transcription factor function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0007165
      label: signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Signal transduction is too broad; STAT3's specific function is 
        JAK-STAT signaling and transcriptional regulation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Cytokine-mediated signaling is a core STAT3 function; responds to
        IL-6 family cytokines, interferons, and others 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Positive regulation of DNA-templated transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - term:
      id: GO:0051240
      label: positive regulation of multicellular organismal process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Positive regulation of multicellular organismal process is too 
        broad, not specific to STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0090575
      label: RNA polymerase II transcription regulator complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: RNA polymerase II transcription regulator complex; STAT3 
        functions as part of transcriptional regulatory complexes 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11536047
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:11536047
          supporting_text: MEN2A-RET-induced cellular transformation by 
            activation of STAT3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11585385
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:11585385
          supporting_text: 'Human leptin signaling in human peripheral blood mononuclear
            cells: activation of the JAK-STAT pathway.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11940572
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:11940572
          supporting_text: 2002 Apr 8. ErbB-2 activates Stat3 alpha in a Src- 
            and JAK2-dependent manner.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11970898
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:11970898
          supporting_text: PTP1B regulates leptin signal transduction in vivo.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14966128
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:14966128
          supporting_text: 2004 Feb 13. Structural requirements for signal 
            transducer and activator of transcription 3 binding to 
            phosphotyrosine ligands containing the YXXQ motif.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15286705
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:15286705
          supporting_text: Implication of BRG1 and cdk9 in the STAT3-mediated 
            activation of the p21waf1 gene.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15657067
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:15657067
          supporting_text: Epub 2005 Jan 17. Phosphotyrosine signaling networks 
            in epidermal growth factor receptor overexpressing squamous 
            carcinoma cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15764709
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:15764709
          supporting_text: STAT3 regulates Nemo-like kinase by mediating its 
            interaction with IL-6-stimulated TGFbeta-activated kinase 1 for 
            STAT3 Ser-727 phosphorylation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15821101
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:15821101
          supporting_text: Mechanism of protein tyrosine phosphatase 1B-mediated
            inhibition of leptin signalling.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16273093
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:16273093
          supporting_text: A quantitative protein interaction network for the 
            ErbB receptors using protein microarrays.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16331268
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:16331268
          supporting_text: Physical and functional interactions between Daxx and
            STAT3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16364321
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:16364321
          supporting_text: 2005 Dec 6. Physical and functional interactions 
            between STAT3 and Kaposi's sarcoma-associated herpesvirus-encoded 
            LANA.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18200042
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:18200042
          supporting_text: Crif1 is a novel transcriptional coactivator of 
            STAT3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18330356
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:18330356
          supporting_text: Construction and characterization of a normalized 
            yeast two-hybrid library derived from a human protein-coding clone 
            collection.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19345327
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:19345327
          supporting_text: Persistently activated Stat3 maintains constitutive 
            NF-kappaB activity in tumors.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19372587
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:19372587
          supporting_text: ErbB2-mediated Src and signal transducer and 
            activator of transcription 3 activation leads to transcriptional 
            up-regulation of p21Cip1 and chemoresistance in breast cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20133729
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:20133729
          supporting_text: STAT3 is a substrate of SYK tyrosine kinase in 
            B-lineage leukemia/lymphoma cells exposed to oxidative stress.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20871632
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:20871632
          supporting_text: The role of the c-Jun N-terminal kinase 2-ฮฑ-isoform 
            in non-small cell lung carcinoma tumorigenesis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20876300
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:20876300
          supporting_text: 'Sep 27. Progesterone receptor induces ErbB-2 nuclear translocation
            to promote breast cancer growth via a novel transcriptional effect: ErbB-2
            function as a coactivator of Stat3.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20929579
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:20929579
          supporting_text: Epigenetic regulation of CpG promoter methylation in 
            invasive prostate cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21184768
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:21184768
          supporting_text: 2010 Dec 22. Novel role of signal transducer and 
            activator of transcription 3 as a progesterone receptor coactivator 
            in breast cancer.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21516116
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:21516116
          supporting_text: Next-generation sequencing to generate interactome 
            datasets.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21643014
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:21643014
          supporting_text: The tumor-suppressor gene ARHI (DIRAS3) suppresses 
            ovarian cancer cell migration through inhibition of the Stat3 and 
            FAK/Rho signaling pathways.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21953450
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:21953450
          supporting_text: 2011 Sep 27. A complex of nuclear factor I-X3 and 
            STAT3 regulates astrocyte and glioma migration through the secreted 
            glycoprotein YKL-40.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21988832
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:21988832
          supporting_text: Toward an understanding of the protein interaction 
            network of the human liver.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23416296
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:23416296
          supporting_text: 2013 Feb 14. ECHS1 interacts with STAT3 and 
            negatively regulates STAT3 signaling.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23684459
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:23684459
          supporting_text: 2013 May 16. Phosphorylation of EZH2 activates STAT3 
            signaling via STAT3 methylation and promotes tumorigenicity of 
            glioblastoma stem-like cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24135280
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:24135280
          supporting_text: EGFR phosphorylates tumor-derived EGFRvIII driving 
            STAT3/5 and progression in glioblastoma.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24189400
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:24189400
          supporting_text: Perturbation of the mutated EGFR interactome 
            identifies vulnerabilities and resistance mechanisms.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24396070
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:24396070
          supporting_text: Jan 6. SH2B1ฮฒ interacts with STAT3 and enhances 
            fibroblast growth factor 1-induced gene expression during neuronal 
            differentiation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24658140
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:24658140
          supporting_text: The mammalian-membrane two-hybrid assay (MaMTH) for 
            probing membrane-protein interactions in human cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25065853
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:25065853
          supporting_text: 2014 Jul 24. Drug resistance via feedback activation 
            of Stat3 in oncogene-addicted cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25241761
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:25241761
          supporting_text: Oct 9. Using an in situ proximity ligation assay to 
            systematically profile endogenous protein-protein interactions in a 
            pathway network.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25402766
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:25402766
          supporting_text: Peroxiredoxin-2 and STAT3 form a redox relay for H2O2
            signaling.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25416956
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:25416956
          supporting_text: A proteome-scale map of the human interactome 
            network.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25417160
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:25417160
          supporting_text: A noncanonical Frizzled2 pathway regulates 
            epithelial-mesenchymal transition and metastasis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25609649
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:25609649
          supporting_text: Proteomic analyses reveal distinct 
            chromatin-associated and soluble transcription factor complexes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25814554
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:25814554
          supporting_text: Phospho-tyrosine dependent protein-protein 
            interaction network.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26966684
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:26966684
          supporting_text: 'PIPINO: A Software Package to Facilitate the Identification
            of Protein-Protein Interactions from Affinity Purification Mass Spectrometry
            Data.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:29892012
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:29892012
          supporting_text: Jun 11. An interactome perturbation framework 
            prioritizes damaging missense mutations for developmental disorders.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:30042492
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:30042492
          supporting_text: Epub 2018 Jul 24. STAT3 localizes to the ER, acting 
            as a gatekeeper for ER-mitochondrion Ca(2+) fluxes and apoptotic 
            responses.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:30413785
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:30413785
          supporting_text: ROCK2, but not ROCK1 interacts with phosphorylated 
            STAT3 and co-occupies TH17/TFH gene promoters in TH17-activated 
            human T cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:31515488
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:31515488
          supporting_text: Extensive disruption of protein interactions by 
            genetic variants across the allele frequency spectrum in human 
            populations.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:31980649
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:31980649
          supporting_text: Extensive rewiring of the EGFR network in colorectal 
            cancer cells expressing transforming levels of KRAS(G13D).
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:32296183
          supporting_text: Apr 8. A reference map of the human binary protein 
            interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32852592
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:32852592
          supporting_text: 2020 Aug 27. Biochanin A impedes STAT3 activation by 
            upregulating p38ฮด MAPK phosphorylation in IL-6-stimulated 
            macrophages.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32911434
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:32911434
          supporting_text: Aug 20. A functionally defined high-density NRF2 
            interactome reveals new conditional regulators of ARE 
            transactivation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35140242
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:35140242
          supporting_text: Human transcription factor protein interaction 
            networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35512704
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:35512704
          supporting_text: 2022 May 4. Systematic discovery of mutation-directed
            neo-protein-protein interactions in cancer.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:38844957
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:38844957
          supporting_text: Integrin ฮฑVฮฒ1-activated PYK2 promotes the progression
            of non-small-cell lung cancer via the STAT3-VGF axis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:8662591
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:8662591
          supporting_text: Differential activation of acute phase response 
            factor/STAT3 and STAT1 via the cytoplasmic domain of the interleukin
            6 signal transducer gp130.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:9864141
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:9864141
          supporting_text: Identification of a novel Stat3 recruitment and 
            activation motif within the granulocyte colony-stimulating factor 
            receptor.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:17676033
    review:
      summary: Experimental evidence (IPI) supports identical protein binding 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:17676033
          supporting_text: Dominant-negative mutations in the DNA-binding domain
            of STAT3 cause hyper-IgE syndrome.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:21988832
    review:
      summary: Experimental evidence (IPI) supports identical protein binding 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:21988832
          supporting_text: Toward an understanding of the protein interaction 
            network of the human liver.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:25609649
    review:
      summary: Experimental evidence (IPI) supports identical protein binding 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:25609649
          supporting_text: Proteomic analyses reveal distinct 
            chromatin-associated and soluble transcription factor complexes.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:7510216
    review:
      summary: Experimental evidence (IPI) supports identical protein binding 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:7510216
          supporting_text: Interferon activation of the transcription factor 
            Stat91 involves dimerization through SH2-phosphotyrosyl peptide 
            interactions.
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Chromatin localization for gene regulation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0000976
      label: transcription cis-regulatory region binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Core transcription cis-regulatory region binding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0000978
      label: RNA polymerase II cis-regulatory region sequence-specific DNA 
        binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Core cis-regulatory DNA binding; STAT3 recognizes and binds to 
        GAS (gamma-activated sequence) elements in target gene promoters 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Core transcription factor activity for STAT3, canonical function 
        of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0001666
      label: response to hypoxia
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for response to hypoxia is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0002317
      label: plasma cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for plasma cell differentiation is consistent with
        STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0002931
      label: response to ischemia
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for response to ischemia is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0005667
      label: transcription regulator complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for transcription regulator complex is consistent 
        with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0005743
      label: mitochondrial inner membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for mitochondrial inner membrane is consistent 
        with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for plasma membrane is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0006953
      label: acute-phase response
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for acute-phase response is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0006954
      label: inflammatory response
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for inflammatory response is consistent with STAT3
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Positive regulation of cell proliferation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0010628
      label: positive regulation of gene expression
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Positive regulation of gene expression 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0010730
      label: negative regulation of hydrogen peroxide biosynthetic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for negative regulation of hydrogen peroxide 
        biosynthetic process is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0014069
      label: postsynaptic density
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for postsynaptic density is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0019901
      label: protein kinase binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for protein kinase binding is consistent with 
        STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0030968
      label: endoplasmic reticulum unfolded protein response
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for endoplasmic reticulum unfolded protein 
        response is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0031730
      label: CCR5 chemokine receptor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for CCR5 chemokine receptor binding is consistent 
        with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0032355
      label: response to estradiol
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for response to estradiol is consistent with STAT3
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0032991
      label: protein-containing complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for protein-containing complex is consistent with 
        STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0033210
      label: leptin-mediated signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Leptin signaling is one of many STAT3-activating pathways, not 
        defining core function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0034097
      label: response to cytokine
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for response to cytokine is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0035259
      label: nuclear glucocorticoid receptor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for nuclear glucocorticoid receptor binding is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for identical protein binding is consistent with 
        STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Homodimerization via SH2 domain-phosphotyrosine (pY705) 
        interactions is essential for STAT3 activation and nuclear translocation
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Specific protein interaction critical for STAT3 function
  - term:
      id: GO:0043123
      label: positive regulation of canonical NF-kappaB signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for positive regulation of canonical NF-kappaB 
        signal transduction is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0043124
      label: negative regulation of canonical NF-kappaB signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for negative regulation of canonical NF-kappaB 
        signal transduction is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0043434
      label: response to peptide hormone
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Response to peptide hormone is context-specific 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0043491
      label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for phosphatidylinositol 3-kinase/protein kinase B
        signal transduction is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0043524
      label: negative regulation of neuron apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for negative regulation of neuron apoptotic 
        process is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0043565
      label: sequence-specific DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: IEA annotation for sequence-specific DNA binding is consistent 
        with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0044321
      label: response to leptin
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for response to leptin is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0045471
      label: response to ethanol
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for response to ethanol is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0045747
      label: positive regulation of Notch signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for positive regulation of Notch signaling pathway
        is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0045766
      label: positive regulation of angiogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for positive regulation of angiogenesis is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - term:
      id: GO:0046902
      label: regulation of mitochondrial membrane permeability
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for regulation of mitochondrial membrane 
        permeability is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0046983
      label: protein dimerization activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Heterodimerization activity with other STAT family members (e.g.,
        STAT1, STAT5) documented 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Specific protein interaction critical for STAT3 function
  - term:
      id: GO:0048708
      label: astrocyte differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Astrocyte differentiation promoted by STAT3 signaling, key role 
        in gliogenesis; STAT3 activation promotes astrocyte over neuron fate 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Well-established differentiation function, relevant to 
        NEURON_DEVELOPMENT
  - term:
      id: GO:0050728
      label: negative regulation of inflammatory response
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for negative regulation of inflammatory response 
        is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0050804
      label: modulation of chemical synaptic transmission
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for modulation of chemical synaptic transmission 
        is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0051726
      label: regulation of cell cycle
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for regulation of cell cycle is consistent with 
        STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0060019
      label: radial glial cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for radial glial cell differentiation is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0060259
      label: regulation of feeding behavior
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for regulation of feeding behavior is consistent 
        with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0060397
      label: growth hormone receptor signaling pathway via JAK-STAT
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Growth hormone signaling is one pathway activating STAT3, not the
        defining function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0072540
      label: T-helper 17 cell lineage commitment
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: T-helper 17 cell lineage commitment 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0097009
      label: energy homeostasis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for energy homeostasis is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0097398
      label: cellular response to interleukin-17
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for cellular response to interleukin-17 is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0097696
      label: cell surface receptor signaling pathway via STAT
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: STAT cascade is the core signaling mechanism 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - term:
      id: GO:0098685
      label: Schaffer collateral - CA1 synapse
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for Schaffer collateral - CA1 synapse is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0098978
      label: glutamatergic synapse
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for glutamatergic synapse is consistent with STAT3
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0099527
      label: postsynapse to nucleus signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for postsynapse to nucleus signaling pathway is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0106015
      label: negative regulation of inflammatory response to wounding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for negative regulation of inflammatory response 
        to wounding is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0140297
      label: DNA-binding transcription factor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for DNA-binding transcription factor binding is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0140311
      label: protein sequestering activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for protein sequestering activity is consistent 
        with STAT3 function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:1900016
      label: negative regulation of cytokine production involved in inflammatory
        response
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for negative regulation of cytokine production 
        involved in inflammatory response is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:1900037
      label: regulation of cellular response to hypoxia
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for regulation of cellular response to hypoxia is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:1902728
      label: positive regulation of growth factor dependent skeletal muscle 
        satellite cell proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for positive regulation of growth factor dependent
        skeletal muscle satellite cell proliferation is consistent with STAT3 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:1902895
      label: positive regulation of miRNA transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for positive regulation of miRNA transcription is 
        consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:1905564
      label: positive regulation of vascular endothelial cell proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for positive regulation of vascular endothelial 
        cell proliferation is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:2001171
      label: positive regulation of ATP biosynthetic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for positive regulation of ATP biosynthetic 
        process is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:2001243
      label: negative regulation of intrinsic apoptotic signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: IEA annotation for negative regulation of intrinsic apoptotic 
        signaling pathway is consistent with STAT3 function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Consistent computational annotation
  - term:
      id: GO:0048861
      label: leukemia inhibitory factor signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:11294841
    review:
      summary: Experimental evidence (IDA) supports leukemia inhibitory factor 
        signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:11294841
          supporting_text: '2001 Apr 6. Signaling pathways recruited by the cardiotrophin-like
            cytokine/cytokine-like factor-1 composite cytokine: specific requirement
            of the membrane-bound form of ciliary neurotrophic factor receptor alpha
            component.'
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:10500198
    review:
      summary: Cytokine-mediated signaling is a core STAT3 function; responds to
        IL-6 family cytokines, interferons, and others 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:10500198
          supporting_text: 'Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine
            of the IL-6 family.'
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:11294841
    review:
      summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs 
        (JAK1/2/3, TYK2) in response to cytokine receptor activation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:11294841
          supporting_text: '2001 Apr 6. Signaling pathways recruited by the cardiotrophin-like
            cytokine/cytokine-like factor-1 composite cytokine: specific requirement
            of the membrane-bound form of ciliary neurotrophic factor receptor alpha
            component.'
  - term:
      id: GO:0070120
      label: ciliary neurotrophic factor-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:11294841
    review:
      summary: Experimental evidence (IDA) supports ciliary neurotrophic 
        factor-mediated signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:11294841
          supporting_text: '2001 Apr 6. Signaling pathways recruited by the cardiotrophin-like
            cytokine/cytokine-like factor-1 composite cytokine: specific requirement
            of the membrane-bound form of ciliary neurotrophic factor receptor alpha
            component.'
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:11285233
    review:
      summary: Cytokine-mediated signaling is a core STAT3 function; responds to
        IL-6 family cytokines, interferons, and others 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:11285233
          supporting_text: The ciliary neurotrophic factor receptor alpha 
            component induces the secretion of and is required for functional 
            responses to cardiotrophin-like cytokine.
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:11294841
    review:
      summary: Cytokine-mediated signaling is a core STAT3 function; responds to
        IL-6 family cytokines, interferons, and others 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:11294841
          supporting_text: '2001 Apr 6. Signaling pathways recruited by the cardiotrophin-like
            cytokine/cytokine-like factor-1 composite cytokine: specific requirement
            of the membrane-bound form of ciliary neurotrophic factor receptor alpha
            component.'
  - term:
      id: GO:0043524
      label: negative regulation of neuron apoptotic process
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for negative regulation of neuron apoptotic 
        process based on sequence/structure similarity is reasonable for 
        conserved STAT family function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0097696
      label: cell surface receptor signaling pathway via STAT
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: STAT cascade is the core signaling mechanism 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - term:
      id: GO:0072540
      label: T-helper 17 cell lineage commitment
    evidence_type: ISS
    original_reference_id: PMID:27893700
    review:
      summary: T-helper 17 cell lineage commitment 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
      supported_by:
        - reference_id: PMID:27893700
          supporting_text: Trans-presentation of IL-6 by dendritic cells is 
            required for the priming of pathogenic T(H)17 cells.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: NAS
    original_reference_id: PMID:15864272
    review:
      summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs 
        (JAK1/2/3, TYK2) in response to cytokine receptor activation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:15864272
          supporting_text: Mechanisms of type-I- and type-II-interferon-mediated
            signalling.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: NAS
    original_reference_id: PMID:24058793
    review:
      summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs 
        (JAK1/2/3, TYK2) in response to cytokine receptor activation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:24058793
          supporting_text: 'STAT heterodimers in immunity: A mixed message or a unique
            signal? Delgoffe GM(1), Vignali DA.'
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: NAS
    original_reference_id: PMID:15864272
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:15864272
          supporting_text: Mechanisms of type-I- and type-II-interferon-mediated
            signalling.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: NAS
    original_reference_id: PMID:24058793
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:24058793
          supporting_text: 'STAT heterodimers in immunity: A mixed message or a unique
            signal? Delgoffe GM(1), Vignali DA.'
  - term:
      id: GO:0050729
      label: positive regulation of inflammatory response
    evidence_type: IDA
    original_reference_id: PMID:23125416
    review:
      summary: Experimental evidence (IDA) supports positive regulation of 
        inflammatory response for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:23125416
          supporting_text: 2012 Nov 2. CCR1-mediated STAT3 tyrosine 
            phosphorylation and CXCL8 expression in THP-1 macrophage-like cells 
            involve pertussis toxin-insensitive Gฮฑ(14/16) signaling and IL-6 
            release.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:29743632
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:29743632
          supporting_text: A double helical motif in OCIAD2 is essential for its
            localization, interactions and STAT3 activation.
  - term:
      id: GO:0010629
      label: negative regulation of gene expression
    evidence_type: IDA
    original_reference_id: PMID:23820254
    review:
      summary: Experimental evidence (IDA) supports negative regulation of gene 
        expression for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:23820254
          supporting_text: STAT3 upregulates miR-92a to inhibit RECK expression 
            and to promote invasiveness of lung cancer cells.
  - term:
      id: GO:0090091
      label: positive regulation of extracellular matrix disassembly
    evidence_type: IGI
    original_reference_id: PMID:23820254
    review:
      summary: Experimental evidence (IGI) supports positive regulation of 
        extracellular matrix disassembly for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IGI)
      supported_by:
        - reference_id: PMID:23820254
          supporting_text: STAT3 upregulates miR-92a to inhibit RECK expression 
            and to promote invasiveness of lung cancer cells.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:12743296
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:12743296
          supporting_text: STAT3 ubiquitylation and degradation by mumps virus 
            suppress cytokine and oncogene signaling.
  - term:
      id: GO:0050766
      label: positive regulation of phagocytosis
    evidence_type: IDA
    original_reference_id: PMID:27994074
    review:
      summary: Experimental evidence (IDA) supports positive regulation of 
        phagocytosis for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:27994074
          supporting_text: 2016 Dec 19. Novel Resolvin D2 Receptor Axis in 
            Infectious Inflammation.
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Core transcription factor activity for STAT3, canonical function 
        of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:12743296
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:12743296
          supporting_text: STAT3 ubiquitylation and degradation by mumps virus 
            suppress cytokine and oncogene signaling.
  - term:
      id: GO:0140311
      label: protein sequestering activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for protein sequestering activity based on 
        sequence/structure similarity is reasonable for conserved STAT family 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:1900016
      label: negative regulation of cytokine production involved in inflammatory
        response
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for negative regulation of cytokine production 
        involved in inflammatory response based on sequence/structure similarity
        is reasonable for conserved STAT family function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0043124
      label: negative regulation of canonical NF-kappaB signal transduction
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for negative regulation of canonical NF-kappaB 
        signal transduction based on sequence/structure similarity is reasonable
        for conserved STAT family function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0003723
      label: RNA binding
    evidence_type: IPI
    original_reference_id: PMID:31507089
    review:
      summary: Experimental evidence (IPI) supports RNA binding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:31507089
          supporting_text: Sep 10. Reciprocal regulation of miR-206 and 
            IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in 
            EGFR-mutant lung cancer cells.
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IMP
    original_reference_id: PMID:38404237
    review:
      summary: Core transcription factor activity for STAT3, canonical function 
        of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:38404237
          supporting_text: A novel gain-of-function STAT3 variant in 
            infantile-onset diabetes associated with multiorgan autoimmunity.
  - term:
      id: GO:0032755
      label: positive regulation of interleukin-6 production
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Positive regulation of interleukin-6 production 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0043123
      label: positive regulation of canonical NF-kappaB signal transduction
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for positive regulation of canonical NF-kappaB 
        signal transduction based on sequence/structure similarity is reasonable
        for conserved STAT family function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0106222
      label: lncRNA binding
    evidence_type: IDA
    original_reference_id: PMID:24744378
    review:
      summary: Experimental evidence (IDA) supports lncRNA binding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:24744378
          supporting_text: The STAT3-binding long noncoding RNA lnc-DC controls 
            human dendritic cell differentiation.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IDA
    original_reference_id: PMID:15653507
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:15653507
          supporting_text: Stat3 dimerization regulated by reversible 
            acetylation of a single lysine residue.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IDA
    original_reference_id: PMID:16285960
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:16285960
          supporting_text: STAT3 NH2-terminal acetylation is activated by the 
            hepatic acute-phase response and required for IL-6 induction of 
            angiotensinogen.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IDA
    original_reference_id: PMID:18782771
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:18782771
          supporting_text: 2008 Sep 9. The STAT3 NH2-terminal domain stabilizes 
            enhanceosome assembly by interacting with the p300 bromodomain.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:15653507
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:15653507
          supporting_text: Stat3 dimerization regulated by reversible 
            acetylation of a single lysine residue.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:16285960
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:16285960
          supporting_text: STAT3 NH2-terminal acetylation is activated by the 
            hepatic acute-phase response and required for IL-6 induction of 
            angiotensinogen.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:15653507
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:15653507
          supporting_text: Stat3 dimerization regulated by reversible 
            acetylation of a single lysine residue.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:16285960
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:16285960
          supporting_text: STAT3 NH2-terminal acetylation is activated by the 
            hepatic acute-phase response and required for IL-6 induction of 
            angiotensinogen.
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: IDA
    original_reference_id: PMID:15653507
    review:
      summary: Homodimerization via SH2 domain-phosphotyrosine (pY705) 
        interactions is essential for STAT3 activation and nuclear translocation
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Specific protein interaction critical for STAT3 function
      supported_by:
        - reference_id: PMID:15653507
          supporting_text: Stat3 dimerization regulated by reversible 
            acetylation of a single lysine residue.
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:16285960
    review:
      summary: Interleukin-6-mediated signaling pathway 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:16285960
          supporting_text: STAT3 NH2-terminal acetylation is activated by the 
            hepatic acute-phase response and required for IL-6 induction of 
            angiotensinogen.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112565
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112602
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112727
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1433456
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1470009
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1888198
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-380782
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-452515
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784006
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784323
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786095
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786124
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788571
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788582
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8848087
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8848124
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8875816
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8875817
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950269
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950441
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950485
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950518
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8952749
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8982163
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8982165
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983059
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983371
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983378
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8984014
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8984021
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985929
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985988
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8986985
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987014
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987063
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987070
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987080
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987096
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987097
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987104
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987141
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987150
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987255
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987266
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9006870
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9006873
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9009072
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9670412
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9670416
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9672159
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9672176
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701524
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701525
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701529
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9712079
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9712085
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9835443
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9850958
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9851142
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0010575
      label: positive regulation of vascular endothelial growth factor 
        production
    evidence_type: IMP
    original_reference_id: PMID:25596740
    review:
      summary: Experimental evidence (IMP) supports positive regulation of 
        vascular endothelial growth factor production for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IMP)
      supported_by:
        - reference_id: PMID:25596740
          supporting_text: miR-874 functions as a tumor suppressor by inhibiting
            angiogenesis through STAT3/VEGF-A pathway in gastric cancer.
  - term:
      id: GO:0097696
      label: cell surface receptor signaling pathway via STAT
    evidence_type: IMP
    original_reference_id: PMID:25596740
    review:
      summary: STAT cascade is the core signaling mechanism 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:25596740
          supporting_text: miR-874 functions as a tumor suppressor by inhibiting
            angiogenesis through STAT3/VEGF-A pathway in gastric cancer.
  - term:
      id: GO:0030335
      label: positive regulation of cell migration
    evidence_type: IMP
    original_reference_id: PMID:31638206
    review:
      summary: Experimental evidence (IMP) supports positive regulation of cell 
        migration for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IMP)
      supported_by:
        - reference_id: PMID:31638206
          supporting_text: Oct 11. MicroRNAโ€‘4500 suppresses tumor progression in
            nonโ€‘small cell lung cancer by regulating STAT3.
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IDA
    original_reference_id: PMID:32929201
    review:
      summary: Core transcription factor activity for STAT3, canonical function 
        of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:32929201
          supporting_text: 2020 Sep 14. PD-L1-mediated gasdermin C expression 
            switches apoptosis to pyroptosis in cancer cells and facilitates 
            tumour necrosis.
  - term:
      id: GO:0070878
      label: primary miRNA binding
    evidence_type: IPI
    original_reference_id: PMID:31507089
    review:
      summary: Experimental evidence (IPI) supports primary miRNA binding for 
        STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:31507089
          supporting_text: Sep 10. Reciprocal regulation of miR-206 and 
            IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in 
            EGFR-mutant lung cancer cells.
  - term:
      id: GO:0140610
      label: RNA sequestering activity
    evidence_type: IDA
    original_reference_id: PMID:31507089
    review:
      summary: Experimental evidence (IDA) supports RNA sequestering activity 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:31507089
          supporting_text: Sep 10. Reciprocal regulation of miR-206 and 
            IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in 
            EGFR-mutant lung cancer cells.
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: NAS
    original_reference_id: PMID:12743296
    review:
      summary: Cytokine-mediated signaling is a core STAT3 function; responds to
        IL-6 family cytokines, interferons, and others 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:12743296
          supporting_text: STAT3 ubiquitylation and degradation by mumps virus 
            suppress cytokine and oncogene signaling.
  - term:
      id: GO:0043491
      label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
    evidence_type: IDA
    original_reference_id: PMID:27830702
    review:
      summary: Experimental evidence (IDA) supports phosphatidylinositol 
        3-kinase/protein kinase B signal transduction for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:27830702
          supporting_text: Hyperglycaemia inhibits REG3A expression to 
            exacerbate TLR3-mediated skin inflammation in diabetes.
  - term:
      id: GO:0106015
      label: negative regulation of inflammatory response to wounding
    evidence_type: IDA
    original_reference_id: PMID:27830702
    review:
      summary: Experimental evidence (IDA) supports negative regulation of 
        inflammatory response to wounding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:27830702
          supporting_text: Hyperglycaemia inhibits REG3A expression to 
            exacerbate TLR3-mediated skin inflammation in diabetes.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IDA
    original_reference_id: PMID:7568001
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:7568001
          supporting_text: Tyrosine phosphorylation and activation of STAT5, 
            STAT3, and Janus kinases by interleukins 2 and 15.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IC
    original_reference_id: PMID:7568001
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:7568001
          supporting_text: Tyrosine phosphorylation and activation of STAT5, 
            STAT3, and Janus kinases by interleukins 2 and 15.
  - term:
      id: GO:0035723
      label: interleukin-15-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7568001
    review:
      summary: Interleukin-10-mediated signaling pathway activates STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:7568001
          supporting_text: Tyrosine phosphorylation and activation of STAT5, 
            STAT3, and Janus kinases by interleukins 2 and 15.
  - term:
      id: GO:0038110
      label: interleukin-2-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7568005
    review:
      summary: Experimental evidence (IDA) supports interleukin-2-mediated 
        signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:7568005
          supporting_text: Critical role of the interleukin 2 (IL-2) receptor 
            gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but
            not bcl-2, gene induction.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IDA
    original_reference_id: PMID:28781374
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:28781374
          supporting_text: IL-11 induces differentiation of myeloid-derived 
            suppressor cells through activation of STAT3 signalling pathway.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IC
    original_reference_id: PMID:28781374
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:28781374
          supporting_text: IL-11 induces differentiation of myeloid-derived 
            suppressor cells through activation of STAT3 signalling pathway.
  - term:
      id: GO:0030154
      label: cell differentiation
    evidence_type: IDA
    original_reference_id: PMID:28781374
    review:
      summary: Cell differentiation is a well-established STAT3 function across 
        multiple cell types [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Well-established differentiation function, relevant to 
        NEURON_DEVELOPMENT
      supported_by:
        - reference_id: PMID:28781374
          supporting_text: IL-11 induces differentiation of myeloid-derived 
            suppressor cells through activation of STAT3 signalling pathway.
  - term:
      id: GO:0038154
      label: interleukin-11-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:28781374
    review:
      summary: Experimental evidence (IDA) supports interleukin-11-mediated 
        signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:28781374
          supporting_text: IL-11 induces differentiation of myeloid-derived 
            suppressor cells through activation of STAT3 signalling pathway.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IC
    original_reference_id: PMID:7543512
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:7543512
          supporting_text: IL-10 induces the tyrosine phosphorylation of tyk2 
            and Jak1 and the differential assembly of STAT1 alpha and STAT3 
            complexes in human T cells and monocytes.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IC
    original_reference_id: PMID:7543512
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:7543512
          supporting_text: IL-10 induces the tyrosine phosphorylation of tyk2 
            and Jak1 and the differential assembly of STAT1 alpha and STAT3 
            complexes in human T cells and monocytes.
  - term:
      id: GO:0140105
      label: interleukin-10-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7543512
    review:
      summary: Experimental evidence (IDA) supports interleukin-10-mediated 
        signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:7543512
          supporting_text: IL-10 induces the tyrosine phosphorylation of tyk2 
            and Jak1 and the differential assembly of STAT1 alpha and STAT3 
            complexes in human T cells and monocytes.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IDA
    original_reference_id: PMID:9535918
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:9535918
          supporting_text: Heteromerization of the gammac chain with the 
            interleukin-9 receptor alpha subunit leads to STAT activation and 
            prevention of apoptosis.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IC
    original_reference_id: PMID:8756628
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:8756628
          supporting_text: A single tyrosine of the interleukin-9 (IL-9) 
            receptor is required for STAT activation, antiapoptotic activity, 
            and growth regulation by IL-9.
  - term:
      id: GO:0038113
      label: interleukin-9-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:9535918
    review:
      summary: Experimental evidence (IDA) supports interleukin-9-mediated 
        signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:9535918
          supporting_text: Heteromerization of the gammac chain with the 
            interleukin-9 receptor alpha subunit leads to STAT activation and 
            prevention of apoptosis.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:7528668
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:7528668
          supporting_text: Interleukin-2 induces tyrosine phosphorylation and 
            nuclear translocation of stat3 in human T lymphocytes.
  - term:
      id: GO:0038155
      label: interleukin-23-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:12023369
    review:
      summary: Experimental evidence (IDA) supports interleukin-23-mediated 
        signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:12023369
          supporting_text: A receptor for the heterodimeric cytokine IL-23 is 
            composed of IL-12Rbeta1 and a novel cytokine receptor subunit, 
            IL-23R.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:8272873
    review:
      summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs 
        (JAK1/2/3, TYK2) in response to cytokine receptor activation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:8272873
          supporting_text: Association and activation of Jak-Tyk kinases by 
            CNTF-LIF-OSM-IL-6 beta receptor components.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0001228
      label: DNA-binding transcription activator activity, RNA polymerase 
        II-specific
    evidence_type: IGI
    original_reference_id: PMID:31886314
    review:
      summary: Core transcription activator activity; activated STAT3 dimers 
        drive transcription of target genes including MYC, CCND1, BCL-XL, VEGF 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:31886314
          supporting_text: miR-98 Modulates Cytokine Production from Human PBMCs
            in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
  - term:
      id: GO:0032731
      label: positive regulation of interleukin-1 beta production
    evidence_type: IGI
    original_reference_id: PMID:31886314
    review:
      summary: Experimental evidence (IGI) supports positive regulation of 
        interleukin-1 beta production for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IGI)
      supported_by:
        - reference_id: PMID:31886314
          supporting_text: miR-98 Modulates Cytokine Production from Human PBMCs
            in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
  - term:
      id: GO:0032733
      label: positive regulation of interleukin-10 production
    evidence_type: IGI
    original_reference_id: PMID:31886314
    review:
      summary: Experimental evidence (IGI) supports positive regulation of 
        interleukin-10 production for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IGI)
      supported_by:
        - reference_id: PMID:31886314
          supporting_text: miR-98 Modulates Cytokine Production from Human PBMCs
            in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
  - term:
      id: GO:0032757
      label: positive regulation of interleukin-8 production
    evidence_type: IGI
    original_reference_id: PMID:31886314
    review:
      summary: Experimental evidence (IGI) supports positive regulation of 
        interleukin-8 production for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IGI)
      supported_by:
        - reference_id: PMID:31886314
          supporting_text: miR-98 Modulates Cytokine Production from Human PBMCs
            in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
  - term:
      id: GO:0032760
      label: positive regulation of tumor necrosis factor production
    evidence_type: IGI
    original_reference_id: PMID:31886314
    review:
      summary: Experimental evidence (IGI) supports positive regulation of tumor
        necrosis factor production for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IGI)
      supported_by:
        - reference_id: PMID:31886314
          supporting_text: miR-98 Modulates Cytokine Production from Human PBMCs
            in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IGI
    original_reference_id: PMID:31886314
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:31886314
          supporting_text: miR-98 Modulates Cytokine Production from Human PBMCs
            in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
  - term:
      id: GO:1900017
      label: positive regulation of cytokine production involved in inflammatory
        response
    evidence_type: IGI
    original_reference_id: PMID:31886314
    review:
      summary: Experimental evidence (IGI) supports positive regulation of 
        cytokine production involved in inflammatory response for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IGI)
      supported_by:
        - reference_id: PMID:31886314
          supporting_text: miR-98 Modulates Cytokine Production from Human PBMCs
            in Systemic Lupus Erythematosus by Targeting IL-6 mRNA.
  - term:
      id: GO:0140297
      label: DNA-binding transcription factor binding
    evidence_type: IPI
    original_reference_id: PMID:15664994
    review:
      summary: Experimental evidence (IPI) supports DNA-binding transcription 
        factor binding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:15664994
          supporting_text: 2005 Jan 21. Signal transducers and activators of 
            transcription 3 augments the transcriptional activity of 
            CCAAT/enhancer-binding protein alpha in granulocyte 
            colony-stimulating factor signaling pathway.
  - term:
      id: GO:0061629
      label: RNA polymerase II-specific DNA-binding transcription factor binding
    evidence_type: IPI
    original_reference_id: PMID:28467929
    review:
      summary: Experimental evidence (IPI) supports RNA polymerase II-specific 
        DNA-binding transcription factor binding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:28467929
          supporting_text: PPARฮณ Links BMP2 and TGFฮฒ1 Pathways in Vascular 
            Smooth Muscle Cells, Regulating Cell Proliferation and Glucose 
            Metabolism.
  - term:
      id: GO:0007179
      label: transforming growth factor beta receptor signaling pathway
    evidence_type: IGI
    original_reference_id: PMID:28467929
    review:
      summary: Experimental evidence (IGI) supports transforming growth factor 
        beta receptor signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IGI)
      supported_by:
        - reference_id: PMID:28467929
          supporting_text: PPARฮณ Links BMP2 and TGFฮฒ1 Pathways in Vascular 
            Smooth Muscle Cells, Regulating Cell Proliferation and Glucose 
            Metabolism.
  - term:
      id: GO:0061629
      label: RNA polymerase II-specific DNA-binding transcription factor binding
    evidence_type: IPI
    original_reference_id: PMID:24429361
    review:
      summary: Experimental evidence (IPI) supports RNA polymerase II-specific 
        DNA-binding transcription factor binding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:24429361
          supporting_text: Hepatitis C virus-induced changes in microRNA 107 
            (miRNA-107) and miRNA-449a modulate CCL2 by targeting the 
            interleukin-6 receptor complex in hepatitis.
  - term:
      id: GO:0005102
      label: signaling receptor binding
    evidence_type: IPI
    original_reference_id: PMID:31145836
    review:
      summary: Experimental evidence (IPI) supports signaling receptor binding 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:31145836
          supporting_text: Jun 23. Physical proximity and functional cooperation
            of glycoprotein 130 and glycoprotein VI in platelet membrane lipid 
            rafts.
  - term:
      id: GO:0035591
      label: signaling adaptor activity
    evidence_type: IPI
    original_reference_id: PMID:31145836
    review:
      summary: Experimental evidence (IPI) supports signaling adaptor activity 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:31145836
          supporting_text: Jun 23. Physical proximity and functional cooperation
            of glycoprotein 130 and glycoprotein VI in platelet membrane lipid 
            rafts.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701529
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701531
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701534
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701537
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701549
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701557
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9701565
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9850958
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9851058
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9851062
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9851064
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9851071
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9851106
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9851118
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9851122
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:2000635
      label: negative regulation of primary miRNA processing
    evidence_type: IMP
    original_reference_id: PMID:31507089
    review:
      summary: Experimental evidence (IMP) supports negative regulation of 
        primary miRNA processing for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IMP)
      supported_by:
        - reference_id: PMID:31507089
          supporting_text: Sep 10. Reciprocal regulation of miR-206 and 
            IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in 
            EGFR-mutant lung cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:31899195
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:31899195
          supporting_text: Dec 31. Prohibitin 1 interacts with signal transducer
            and activator of transcription 3 in T-helper 17 cells.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:31899195
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:31899195
          supporting_text: Dec 31. Prohibitin 1 interacts with signal transducer
            and activator of transcription 3 in T-helper 17 cells.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:31899195
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:31899195
          supporting_text: Dec 31. Prohibitin 1 interacts with signal transducer
            and activator of transcription 3 in T-helper 17 cells.
  - term:
      id: GO:0072538
      label: T-helper 17 type immune response
    evidence_type: IDA
    original_reference_id: PMID:31899195
    review:
      summary: Experimental evidence (IDA) supports T-helper 17 type immune 
        response for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:31899195
          supporting_text: Dec 31. Prohibitin 1 interacts with signal transducer
            and activator of transcription 3 in T-helper 17 cells.
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: ISA
    original_reference_id: GO_REF:0000113
    review:
      summary: Chromatin localization for gene regulation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: ISA
    original_reference_id: GO_REF:0000113
    review:
      summary: Core transcription factor activity for STAT3, canonical function 
        of STAT family proteins [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0005667
      label: transcription regulator complex
    evidence_type: IDA
    original_reference_id: PMID:24429361
    review:
      summary: Experimental evidence (IDA) supports transcription regulator 
        complex for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:24429361
          supporting_text: Hepatitis C virus-induced changes in microRNA 107 
            (miRNA-107) and miRNA-449a modulate CCL2 by targeting the 
            interleukin-6 receptor complex in hepatitis.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IGI
    original_reference_id: PMID:24429361
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:24429361
          supporting_text: Hepatitis C virus-induced changes in microRNA 107 
            (miRNA-107) and miRNA-449a modulate CCL2 by targeting the 
            interleukin-6 receptor complex in hepatitis.
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:24429361
    review:
      summary: Interleukin-6-mediated signaling pathway 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:24429361
          supporting_text: Hepatitis C virus-induced changes in microRNA 107 
            (miRNA-107) and miRNA-449a modulate CCL2 by targeting the 
            interleukin-6 receptor complex in hepatitis.
  - term:
      id: GO:0010507
      label: negative regulation of autophagy
    evidence_type: IDA
    original_reference_id: PMID:26962683
    review:
      summary: Experimental evidence (IDA) supports negative regulation of 
        autophagy for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:26962683
          supporting_text: IL10 inhibits starvation-induced autophagy in 
            hypertrophic scar fibroblasts via cross talk between the 
            IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways.
  - term:
      id: GO:0001228
      label: DNA-binding transcription activator activity, RNA polymerase 
        II-specific
    evidence_type: IDA
    original_reference_id: PMID:16835372
    review:
      summary: Core transcription activator activity; activated STAT3 dimers 
        drive transcription of target genes including MYC, CCND1, BCL-XL, VEGF 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:16835372
          supporting_text: Jul 11. Interleukin-6 induces hepcidin expression 
            through STAT3.
  - term:
      id: GO:0001228
      label: DNA-binding transcription activator activity, RNA polymerase 
        II-specific
    evidence_type: IMP
    original_reference_id: PMID:16946298
    review:
      summary: Core transcription activator activity; activated STAT3 dimers 
        drive transcription of target genes including MYC, CCND1, BCL-XL, VEGF 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:16946298
          supporting_text: Aug 31. STAT3 mediates hepatic hepcidin expression 
            and its inflammatory stimulation.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IMP
    original_reference_id: PMID:16835372
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:16835372
          supporting_text: Jul 11. Interleukin-6 induces hepcidin expression 
            through STAT3.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IMP
    original_reference_id: PMID:16946298
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:16946298
          supporting_text: Aug 31. STAT3 mediates hepatic hepcidin expression 
            and its inflammatory stimulation.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:17360477
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:17360477
          supporting_text: Identification of STAT3 as a substrate of receptor 
            protein tyrosine phosphatase T.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:24846175
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:24846175
          supporting_text: eCollection 2014. ฮฒ1,6 GlcNAc branches-modified PTPRT
            attenuates its activity and promotes cell migration by STAT3 
            pathway.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:17360477
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:17360477
          supporting_text: Identification of STAT3 as a substrate of receptor 
            protein tyrosine phosphatase T.
  - term:
      id: GO:0019903
      label: protein phosphatase binding
    evidence_type: IPI
    original_reference_id: PMID:17360477
    review:
      summary: Experimental evidence (IPI) supports protein phosphatase binding 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:17360477
          supporting_text: Identification of STAT3 as a substrate of receptor 
            protein tyrosine phosphatase T.
  - term:
      id: GO:0030335
      label: positive regulation of cell migration
    evidence_type: IMP
    original_reference_id: PMID:24846175
    review:
      summary: Experimental evidence (IMP) supports positive regulation of cell 
        migration for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IMP)
      supported_by:
        - reference_id: PMID:24846175
          supporting_text: eCollection 2014. ฮฒ1,6 GlcNAc branches-modified PTPRT
            attenuates its activity and promotes cell migration by STAT3 
            pathway.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983379
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985981
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983373
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983374
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983379
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985966
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985981
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983078
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8984023
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987033
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987052
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987156
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987161
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987214
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987230
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987270
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987052
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0045648
      label: positive regulation of erythrocyte differentiation
    evidence_type: IMP
    original_reference_id: PMID:28283061
    review:
      summary: Positive regulation of erythrocyte differentiation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
      supported_by:
        - reference_id: PMID:28283061
          supporting_text: Functional Selectivity in Cytokine Signaling Revealed
            Through a Pathogenic EPO Mutation.
  - term:
      id: GO:1902895
      label: positive regulation of miRNA transcription
    evidence_type: IDA
    original_reference_id: PMID:19390056
    review:
      summary: Experimental evidence (IDA) supports positive regulation of miRNA
        transcription for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:19390056
          supporting_text: Epub 2009 Apr 23. Interleukin-6 modulates the 
            expression of the bone morphogenic protein receptor type II through 
            a novel STAT3-microRNA cluster 17/92 pathway.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24172987
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:24172987
          supporting_text: A small GTPaseโ€‘like protein fragment of Mycoplasma 
            promotes tumor cell migration and proliferation in vitro via 
            interaction with Rac1 and Stat3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28065600
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:28065600
          supporting_text: 2017 Jan 5. Lysyl Oxidase 3 Is a Dual-Specificity 
            Enzyme Involved in STAT3 Deacetylation and Deacetylimination 
            Modulation.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:28065600
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:28065600
          supporting_text: 2017 Jan 5. Lysyl Oxidase 3 Is a Dual-Specificity 
            Enzyme Involved in STAT3 Deacetylation and Deacetylimination 
            Modulation.
  - term:
      id: GO:0006954
      label: inflammatory response
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for inflammatory response based on 
        sequence/structure similarity is reasonable for conserved STAT family 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Homodimerization via SH2 domain-phosphotyrosine (pY705) 
        interactions is essential for STAT3 activation and nuclear translocation
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Specific protein interaction critical for STAT3 function
  - term:
      id: GO:0072540
      label: T-helper 17 cell lineage commitment
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: T-helper 17 cell lineage commitment 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:27050391
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:27050391
          supporting_text: Rac1 modulates the formation of primordial follicles 
            by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription
            in mice.
  - term:
      id: GO:0010628
      label: positive regulation of gene expression
    evidence_type: IMP
    original_reference_id: PMID:24255059
    review:
      summary: Positive regulation of gene expression 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
      supported_by:
        - reference_id: PMID:24255059
          supporting_text: 2013 Nov 19. Inhibition of microRNA-92a prevents 
            endothelial dysfunction and atherosclerosis in mice.
  - term:
      id: GO:1902895
      label: positive regulation of miRNA transcription
    evidence_type: IDA
    original_reference_id: PMID:23820254
    review:
      summary: Experimental evidence (IDA) supports positive regulation of miRNA
        transcription for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:23820254
          supporting_text: STAT3 upregulates miR-92a to inhibit RECK expression 
            and to promote invasiveness of lung cancer cells.
  - term:
      id: GO:0010628
      label: positive regulation of gene expression
    evidence_type: IDA
    original_reference_id: PMID:23820254
    review:
      summary: Positive regulation of gene expression 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
      supported_by:
        - reference_id: PMID:23820254
          supporting_text: STAT3 upregulates miR-92a to inhibit RECK expression 
            and to promote invasiveness of lung cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25476455
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:25476455
          supporting_text: Inositol Polyphosphate-5-Phosphatase F (INPP5F) 
            inhibits STAT3 activity and suppresses gliomas tumorigenicity.
  - term:
      id: GO:0000978
      label: RNA polymerase II cis-regulatory region sequence-specific DNA 
        binding
    evidence_type: IDA
    original_reference_id: PMID:19390056
    review:
      summary: Core cis-regulatory DNA binding; STAT3 recognizes and binds to 
        GAS (gamma-activated sequence) elements in target gene promoters 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:19390056
          supporting_text: Epub 2009 Apr 23. Interleukin-6 modulates the 
            expression of the bone morphogenic protein receptor type II through 
            a novel STAT3-microRNA cluster 17/92 pathway.
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: IDA
    original_reference_id: PMID:19390056
    review:
      summary: Positive regulation of DNA-templated transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:19390056
          supporting_text: Epub 2009 Apr 23. Interleukin-6 modulates the 
            expression of the bone morphogenic protein receptor type II through 
            a novel STAT3-microRNA cluster 17/92 pathway.
  - term:
      id: GO:0060259
      label: regulation of feeding behavior
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for regulation of feeding behavior based on 
        sequence/structure similarity is reasonable for conserved STAT family 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0097009
      label: energy homeostasis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for energy homeostasis based on sequence/structure
        similarity is reasonable for conserved STAT family function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0006355
      label: regulation of DNA-templated transcription
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Regulation of DNA-templated transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0031490
      label: chromatin DNA binding
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Experimental evidence (IDA) supports chromatin DNA binding for 
        STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0033210
      label: leptin-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Leptin signaling is one of many STAT3-activating pathways, not 
        defining core function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0044320
      label: cellular response to leptin stimulus
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Experimental evidence (IDA) supports cellular response to leptin 
        stimulus for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0044321
      label: response to leptin
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Experimental evidence (IDA) supports response to leptin for STAT3
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0051726
      label: regulation of cell cycle
    evidence_type: IDA
    original_reference_id: PMID:17344214
    review:
      summary: Experimental evidence (IDA) supports regulation of cell cycle for
        STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:17344214
          supporting_text: 2007 Mar 7. leptin-induced growth stimulation of 
            breast cancer cells involves recruitment of histone 
            acetyltransferases and mediator complex to CYCLIN D1 promoter via 
            activation of Stat3.
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: IMP
    original_reference_id: PMID:16946298
    review:
      summary: Interleukin-6-mediated signaling pathway 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:16946298
          supporting_text: Aug 31. STAT3 mediates hepatic hepcidin expression 
            and its inflammatory stimulation.
  - term:
      id: GO:0090575
      label: RNA polymerase II transcription regulator complex
    evidence_type: IMP
    original_reference_id: PMID:16946298
    review:
      summary: RNA polymerase II transcription regulator complex; STAT3 
        functions as part of transcriptional regulatory complexes 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:16946298
          supporting_text: Aug 31. STAT3 mediates hepatic hepcidin expression 
            and its inflammatory stimulation.
  - term:
      id: GO:0090575
      label: RNA polymerase II transcription regulator complex
    evidence_type: IC
    original_reference_id: PMID:16835372
    review:
      summary: RNA polymerase II transcription regulator complex; STAT3 
        functions as part of transcriptional regulatory complexes 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:16835372
          supporting_text: Jul 11. Interleukin-6 induces hepcidin expression 
            through STAT3.
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: IMP
    original_reference_id: PMID:16835372
    review:
      summary: Interleukin-6-mediated signaling pathway 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:16835372
          supporting_text: Jul 11. Interleukin-6 induces hepcidin expression 
            through STAT3.
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: IDA
    original_reference_id: PMID:16835372
    review:
      summary: Chromatin localization for gene regulation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:16835372
          supporting_text: Jul 11. Interleukin-6 induces hepcidin expression 
            through STAT3.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IGI
    original_reference_id: PMID:19754877
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:19754877
          supporting_text: 2009 Sep 15. Hsp105beta upregulates hsp70 gene 
            expression through signal transducer and activator of 
            transcription-3.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112538
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112587
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112604
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1470010
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1470012
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784763
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784765
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784791
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786072
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786097
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786293
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788622
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788623
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788628
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950724
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950733
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950780
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950782
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8952823
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8982162
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985900
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987236
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9670417
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9670426
    review:
      summary: Cytosol localization of latent STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0019903
      label: protein phosphatase binding
    evidence_type: IPI
    original_reference_id: PMID:12359225
    review:
      summary: Experimental evidence (IPI) supports protein phosphatase binding 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:12359225
          supporting_text: The nuclear isoform of protein-tyrosine phosphatase 
            TC-PTP regulates interleukin-6-mediated signaling pathway through 
            STAT3 dephosphorylation.
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:12359225
    review:
      summary: Interleukin-6-mediated signaling pathway 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:12359225
          supporting_text: The nuclear isoform of protein-tyrosine phosphatase 
            TC-PTP regulates interleukin-6-mediated signaling pathway through 
            STAT3 dephosphorylation.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112587
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1470012
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2895778
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784763
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786293
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788623
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8848150
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950724
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950733
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9670426
    review:
      summary: Nucleoplasm localization of activated STAT3 dimers 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:22783022
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:22783022
          supporting_text: The Sin3a repressor complex is a master regulator of 
            STAT transcriptional activity.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:22783022
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:22783022
          supporting_text: The Sin3a repressor complex is a master regulator of 
            STAT transcriptional activity.
  - term:
      id: GO:0061629
      label: RNA polymerase II-specific DNA-binding transcription factor binding
    evidence_type: IPI
    original_reference_id: PMID:22783022
    review:
      summary: Experimental evidence (IPI) supports RNA polymerase II-specific 
        DNA-binding transcription factor binding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IPI)
      supported_by:
        - reference_id: PMID:22783022
          supporting_text: The Sin3a repressor complex is a master regulator of 
            STAT transcriptional activity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:12867595
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:12867595
          supporting_text: The cell death regulator GRIM-19 is an inhibitor of 
            signal transducer and activator of transcription 3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20826784
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:20826784
          supporting_text: 2010 Sep 8. Acetylation directs survivin nuclear 
            localization to repress STAT3 oncogenic activity.
  - term:
      id: GO:0004879
      label: nuclear receptor activity
    evidence_type: IDA
    original_reference_id: PMID:17324931
    review:
      summary: Experimental evidence (IDA) supports nuclear receptor activity 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:17324931
          supporting_text: 2007 Feb 26. Interleukin-6 transcriptionally 
            regulates prohibitin expression in intestinal epithelial cells.
  - term:
      id: GO:0030522
      label: intracellular receptor signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:17324931
    review:
      summary: Experimental evidence (IDA) supports intracellular receptor 
        signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:17324931
          supporting_text: 2007 Feb 26. Interleukin-6 transcriptionally 
            regulates prohibitin expression in intestinal epithelial cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15998644
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:15998644
          supporting_text: 2005 Jul 5. JAK/STAT3 pathway is involved in survival
            of neurons in response to insulin-like growth factor and negatively 
            regulated by suppressor of cytokine signaling-3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16568091
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:16568091
          supporting_text: Mar 27. Identification of STAT3 as a specific 
            substrate of breast tumor kinase.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:10688651
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:10688651
          supporting_text: Etk, a Btk family tyrosine kinase, mediates cellular 
            transformation by linking Src to STAT3 activation.
  - term:
      id: GO:0045747
      label: positive regulation of Notch signaling pathway
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for positive regulation of Notch signaling pathway
        based on sequence/structure similarity is reasonable for conserved STAT 
        family function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0048708
      label: astrocyte differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Astrocyte differentiation promoted by STAT3 signaling, key role 
        in gliogenesis; STAT3 activation promotes astrocyte over neuron fate 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Well-established differentiation function, relevant to 
        NEURON_DEVELOPMENT
  - term:
      id: GO:0060019
      label: radial glial cell differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for radial glial cell differentiation based on 
        sequence/structure similarity is reasonable for conserved STAT family 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0000976
      label: transcription cis-regulatory region binding
    evidence_type: IDA
    original_reference_id: PMID:17324931
    review:
      summary: Core transcription cis-regulatory region binding for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:17324931
          supporting_text: 2007 Feb 26. Interleukin-6 transcriptionally 
            regulates prohibitin expression in intestinal epithelial cells.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:17324931
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:17324931
          supporting_text: 2007 Feb 26. Interleukin-6 transcriptionally 
            regulates prohibitin expression in intestinal epithelial cells.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:17324931
    review:
      summary: Positive regulation of transcription by RNA polymerase II is the 
        canonical STAT3 output [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:17324931
          supporting_text: 2007 Feb 26. Interleukin-6 transcriptionally 
            regulates prohibitin expression in intestinal epithelial cells.
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:17324931
    review:
      summary: Interleukin-6-mediated signaling pathway 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:17324931
          supporting_text: 2007 Feb 26. Interleukin-6 transcriptionally 
            regulates prohibitin expression in intestinal epithelial cells.
  - term:
      id: GO:0060396
      label: growth hormone receptor signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:10925297
    review:
      summary: Experimental evidence (IDA) supports growth hormone receptor 
        signaling pathway for STAT3 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:10925297
          supporting_text: Regulation of neutrophil adhesion by pituitary growth
            hormone accompanies tyrosine phosphorylation of Jak2, p125FAK, and 
            paxillin.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:18234692
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:18234692
          supporting_text: BART is essential for nuclear retention of STAT3.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:18234692
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:18234692
          supporting_text: BART is essential for nuclear retention of STAT3.
  - term:
      id: GO:0006606
      label: protein import into nucleus
    evidence_type: IDA
    original_reference_id: PMID:18234692
    review:
      summary: Experimental evidence (IDA) supports protein import into nucleus 
        for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:18234692
          supporting_text: BART is essential for nuclear retention of STAT3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18234692
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:18234692
          supporting_text: BART is essential for nuclear retention of STAT3.
  - term:
      id: GO:0001659
      label: temperature homeostasis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for temperature homeostasis based on 
        sequence/structure similarity is reasonable for conserved STAT family 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0001754
      label: eye photoreceptor cell differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for eye photoreceptor cell differentiation based 
        on sequence/structure similarity is reasonable for conserved STAT family
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Core DNA binding activity essential for STAT3 transcription 
        factor function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for plasma membrane based on sequence/structure 
        similarity is reasonable for conserved STAT family function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Core regulation of transcription by RNA polymerase II 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - term:
      id: GO:0019901
      label: protein kinase binding
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for protein kinase binding based on 
        sequence/structure similarity is reasonable for conserved STAT family 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0042593
      label: glucose homeostasis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for glucose homeostasis based on 
        sequence/structure similarity is reasonable for conserved STAT family 
        function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0042755
      label: eating behavior
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: ISS annotation for eating behavior based on sequence/structure 
        similarity is reasonable for conserved STAT family function 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Annotation inferred from sequence/structural similarity
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Positive regulation of DNA-templated transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
  - term:
      id: GO:0046983
      label: protein dimerization activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Heterodimerization activity with other STAT family members (e.g.,
        STAT1, STAT5) documented 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Specific protein interaction critical for STAT3 function
  - term:
      id: GO:0060397
      label: growth hormone receptor signaling pathway via JAK-STAT
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Growth hormone signaling is one pathway activating STAT3, not the
        defining function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16531398
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:16531398
          supporting_text: Epub 2006 Mar 10. Tid1 isoforms are mitochondrial 
            DnaJ-like chaperones with unique carboxyl termini that determine 
            cytosolic fate.
  - term:
      id: GO:0060397
      label: growth hormone receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:12552091
    review:
      summary: Growth hormone signaling is one pathway activating STAT3, not the
        defining function [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
      supported_by:
        - reference_id: PMID:12552091
          supporting_text: Estrogen inhibits GH signaling by suppressing 
            GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
  - term:
      id: GO:0032355
      label: response to estradiol
    evidence_type: IDA
    original_reference_id: PMID:12552091
    review:
      summary: Experimental evidence (IDA) supports response to estradiol for 
        STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:12552091
          supporting_text: Estrogen inhibits GH signaling by suppressing 
            GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
  - term:
      id: GO:0032870
      label: cellular response to hormone stimulus
    evidence_type: IDA
    original_reference_id: PMID:12552091
    review:
      summary: Experimental evidence (IDA) supports cellular response to hormone
        stimulus for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Direct experimental evidence (IDA)
      supported_by:
        - reference_id: PMID:12552091
          supporting_text: Estrogen inhibits GH signaling by suppressing 
            GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:12552091
    review:
      summary: Interleukin-6-mediated signaling pathway 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:12552091
          supporting_text: Estrogen inhibits GH signaling by suppressing 
            GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:12444102
    review:
      summary: Nucleus localization upon activation is core to STAT3 function; 
        activated dimers translocate to nucleus 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:12444102
          supporting_text: Neurofibromatosis 2 (NF2) tumor suppressor 
            schwannomin and its interacting protein HRS regulate STAT signaling.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16306601
    review:
      summary: Generic 'protein binding' (GO:0005515) is uninformative and 
        should be removed per GO curation guidelines. STAT3 has specific protein
        interactions (SH2-mediated homodimerization GO:0042803, 
        heterodimerization GO:0046983, kinase binding GO:0019904) that are 
        better represented by more specific terms 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: REMOVE
      reason: Uninformative generic term per curation guidelines
      supported_by:
        - reference_id: PMID:16306601
          supporting_text: Respiratory syncytial virus-inducible BCL-3 
            expression antagonizes the STAT/IRF and NF-kappaB signaling pathways
            by inducing histone deacetylase 1 recruitment to the interleukin-8 
            promoter.
  - term:
      id: GO:0006355
      label: regulation of DNA-templated transcription
    evidence_type: IDA
    original_reference_id: PMID:15664994
    review:
      summary: Regulation of DNA-templated transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:15664994
          supporting_text: 2005 Jan 21. Signal transducers and activators of 
            transcription 3 augments the transcriptional activity of 
            CCAAT/enhancer-binding protein alpha in granulocyte 
            colony-stimulating factor signaling pathway.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: TAS
    original_reference_id: PMID:15664994
    review:
      summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs 
        (JAK1/2/3, TYK2) in response to cytokine receptor activation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:15664994
          supporting_text: 2005 Jan 21. Signal transducers and activators of 
            transcription 3 augments the transcriptional activity of 
            CCAAT/enhancer-binding protein alpha in granulocyte 
            colony-stimulating factor signaling pathway.
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: NAS
    original_reference_id: PMID:15664994
    review:
      summary: Cytokine-mediated signaling is a core STAT3 function; responds to
        IL-6 family cytokines, interferons, and others 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:15664994
          supporting_text: 2005 Jan 21. Signal transducers and activators of 
            transcription 3 augments the transcriptional activity of 
            CCAAT/enhancer-binding protein alpha in granulocyte 
            colony-stimulating factor signaling pathway.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: TAS
    original_reference_id: PMID:8675499
    review:
      summary: Curated annotation (TAS) supports negative regulation of 
        transcription by RNA polymerase II 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Curated annotation (TAS)
      supported_by:
        - reference_id: PMID:8675499
          supporting_text: STAT3beta, a splice variant of transcription factor 
            STAT3, is a dominant negative regulator of transcription.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: TAS
    original_reference_id: PMID:7512451
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:7512451
          supporting_text: Molecular cloning of APRF, a novel IFN-stimulated 
            gene factor 3 p91-related transcription factor involved in the 
            gp130-mediated signaling pathway.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: TAS
    original_reference_id: PMID:8675499
    review:
      summary: Core DNA-binding transcription factor activity; STAT3 binds DNA 
        via its DNA-binding domain to regulate target gene transcription 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core molecular function of STAT3 as transcription factor
      supported_by:
        - reference_id: PMID:8675499
          supporting_text: STAT3beta, a splice variant of transcription factor 
            STAT3, is a dominant negative regulator of transcription.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: TAS
    original_reference_id: PMID:7512451
    review:
      summary: Cytoplasm localization of latent STAT3 before activation; 
        unphosphorylated STAT3 resides in cytoplasm 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Correct cellular localization for STAT3
      supported_by:
        - reference_id: PMID:7512451
          supporting_text: Molecular cloning of APRF, a novel IFN-stimulated 
            gene factor 3 p91-related transcription factor involved in the 
            gp130-mediated signaling pathway.
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: TAS
    original_reference_id: PMID:7512451
    review:
      summary: Core regulation of transcription by RNA polymerase II 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:7512451
          supporting_text: Molecular cloning of APRF, a novel IFN-stimulated 
            gene factor 3 p91-related transcription factor involved in the 
            gp130-mediated signaling pathway.
  - term:
      id: GO:0007165
      label: signal transduction
    evidence_type: TAS
    original_reference_id: PMID:10205054
    review:
      summary: Signal transduction is too broad; STAT3's specific function is 
        JAK-STAT signaling and transcriptional regulation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
      supported_by:
        - reference_id: PMID:10205054
          supporting_text: Synergistic signaling in fetal brain by STAT3-Smad1 
            complex bridged by p300.
  - term:
      id: GO:0007165
      label: signal transduction
    evidence_type: TAS
    original_reference_id: PMID:7512451
    review:
      summary: Signal transduction is too broad; STAT3's specific function is 
        JAK-STAT signaling and transcriptional regulation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: KEEP_AS_NON_CORE
      reason: Valid annotation but peripheral to core STAT3 transcription factor
        function
      supported_by:
        - reference_id: PMID:7512451
          supporting_text: Molecular cloning of APRF, a novel IFN-stimulated 
            gene factor 3 p91-related transcription factor involved in the 
            gp130-mediated signaling pathway.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: TAS
    original_reference_id: PMID:9670957
    review:
      summary: Core JAK-STAT signaling pathway; STAT3 is phosphorylated by JAKs 
        (JAK1/2/3, TYK2) in response to cytokine receptor activation 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Core biological process - JAK-STAT signaling and transcriptional 
        regulation
      supported_by:
        - reference_id: PMID:9670957
          supporting_text: The chemokine monocyte chemotactic protein 1 triggers
            Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B 
            receptor.
  - term:
      id: GO:0007399
      label: nervous system development
    evidence_type: TAS
    original_reference_id: PMID:10205054
    review:
      summary: Curated annotation (TAS) supports nervous system development 
        [file:human/STAT3/STAT3-deep-research-falcon.md]
      action: ACCEPT
      reason: Curated annotation (TAS)
      supported_by:
        - reference_id: PMID:10205054
          supporting_text: Synergistic signaling in fetal brain by STAT3-Smad1 
            complex bridged by p300.
references:
  - 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:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000107
    title: Automatic transfer of experimentally verified manual GO annotation 
      data to orthologs using Ensembl Compara
    findings: []
  - id: GO_REF:0000113
    title: Gene Ontology annotation of human sequence-specific DNA binding 
      transcription factors (DbTFs) based on the TFClass database
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:10205054
    title: Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged 
      by p300.
    findings: []
  - id: PMID:10500198
    title: 'Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6
      family.'
    findings: []
  - id: PMID:10688651
    title: Etk, a Btk family tyrosine kinase, mediates cellular transformation 
      by linking Src to STAT3 activation.
    findings: []
  - id: PMID:10925297
    title: Regulation of neutrophil adhesion by pituitary growth hormone 
      accompanies tyrosine phosphorylation of Jak2, p125FAK, and paxillin.
    findings: []
  - id: PMID:11285233
    title: The ciliary neurotrophic factor receptor alpha component induces the 
      secretion of and is required for functional responses to 
      cardiotrophin-like cytokine.
    findings: []
  - id: PMID:11294841
    title: 'Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like
      factor-1 composite cytokine: specific requirement of the membrane-bound form
      of ciliary neurotrophic factor receptor alpha component.'
    findings: []
  - id: PMID:11536047
    title: MEN2A-RET-induced cellular transformation by activation of STAT3.
    findings: []
  - id: PMID:11585385
    title: 'Human leptin signaling in human peripheral blood mononuclear cells: activation
      of the JAK-STAT pathway.'
    findings: []
  - id: PMID:11940572
    title: ErbB-2 activates Stat3 alpha in a Src- and JAK2-dependent manner.
    findings: []
  - id: PMID:11970898
    title: PTP1B regulates leptin signal transduction in vivo.
    findings: []
  - id: PMID:12023369
    title: A receptor for the heterodimeric cytokine IL-23 is composed of 
      IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.
    findings: []
  - id: PMID:12359225
    title: The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates 
      interleukin-6-mediated signaling pathway through STAT3 dephosphorylation.
    findings: []
  - id: PMID:12444102
    title: Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its 
      interacting protein HRS regulate STAT signaling.
    findings: []
  - id: PMID:12552091
    title: Estrogen inhibits GH signaling by suppressing GH-induced JAK2 
      phosphorylation, an effect mediated by SOCS-2.
    findings: []
  - id: PMID:12743296
    title: STAT3 ubiquitylation and degradation by mumps virus suppress cytokine
      and oncogene signaling.
    findings: []
  - id: PMID:12867595
    title: The cell death regulator GRIM-19 is an inhibitor of signal transducer
      and activator of transcription 3.
    findings: []
  - id: PMID:14966128
    title: Structural requirements for signal transducer and activator of 
      transcription 3 binding to phosphotyrosine ligands containing the YXXQ 
      motif.
    findings: []
  - id: PMID:15286705
    title: Implication of BRG1 and cdk9 in the STAT3-mediated activation of the 
      p21waf1 gene.
    findings: []
  - id: PMID:15653507
    title: Stat3 dimerization regulated by reversible acetylation of a single 
      lysine residue.
    findings: []
  - id: PMID:15657067
    title: Phosphotyrosine signaling networks in epidermal growth factor 
      receptor overexpressing squamous carcinoma cells.
    findings: []
  - id: PMID:15664994
    title: Signal transducers and activators of transcription 3 augments the 
      transcriptional activity of CCAAT/enhancer-binding protein alpha in 
      granulocyte colony-stimulating factor signaling pathway.
    findings: []
  - id: PMID:15764709
    title: STAT3 regulates Nemo-like kinase by mediating its interaction with 
      IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 
      phosphorylation.
    findings: []
  - id: PMID:15821101
    title: Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of 
      leptin signalling.
    findings: []
  - id: PMID:15864272
    title: Mechanisms of type-I- and type-II-interferon-mediated signalling.
    findings: []
  - id: PMID:15998644
    title: JAK/STAT3 pathway is involved in survival of neurons in response to 
      insulin-like growth factor and negatively regulated by suppressor of 
      cytokine signaling-3.
    findings: []
  - id: PMID:16273093
    title: A quantitative protein interaction network for the ErbB receptors 
      using protein microarrays.
    findings: []
  - id: PMID:16285960
    title: STAT3 NH2-terminal acetylation is activated by the hepatic 
      acute-phase response and required for IL-6 induction of angiotensinogen.
    findings: []
  - id: PMID:16306601
    title: Respiratory syncytial virus-inducible BCL-3 expression antagonizes 
      the STAT/IRF and NF-kappaB signaling pathways by inducing histone 
      deacetylase 1 recruitment to the interleukin-8 promoter.
    findings: []
  - id: PMID:16331268
    title: Physical and functional interactions between Daxx and STAT3.
    findings: []
  - id: PMID:16364321
    title: Physical and functional interactions between STAT3 and Kaposi's 
      sarcoma-associated herpesvirus-encoded LANA.
    findings: []
  - id: PMID:16531398
    title: Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique 
      carboxyl termini that determine cytosolic fate.
    findings: []
  - id: PMID:16568091
    title: Identification of STAT3 as a specific substrate of breast tumor 
      kinase.
    findings: []
  - id: PMID:16835372
    title: Interleukin-6 induces hepcidin expression through STAT3.
    findings: []
  - id: PMID:16946298
    title: STAT3 mediates hepatic hepcidin expression and its inflammatory 
      stimulation.
    findings: []
  - id: PMID:17324931
    title: Interleukin-6 transcriptionally regulates prohibitin expression in 
      intestinal epithelial cells.
    findings: []
  - id: PMID:17344214
    title: leptin-induced growth stimulation of breast cancer cells involves 
      recruitment of histone acetyltransferases and mediator complex to CYCLIN 
      D1 promoter via activation of Stat3.
    findings: []
  - id: PMID:17360477
    title: Identification of STAT3 as a substrate of receptor protein tyrosine 
      phosphatase T.
    findings: []
  - id: PMID:17676033
    title: Dominant-negative mutations in the DNA-binding domain of STAT3 cause 
      hyper-IgE syndrome.
    findings: []
  - id: PMID:18200042
    title: Crif1 is a novel transcriptional coactivator of STAT3.
    findings: []
  - id: PMID:18234692
    title: BART is essential for nuclear retention of STAT3.
    findings: []
  - id: PMID:18330356
    title: Construction and characterization of a normalized yeast two-hybrid 
      library derived from a human protein-coding clone collection.
    findings: []
  - id: PMID:18782771
    title: The STAT3 NH2-terminal domain stabilizes enhanceosome assembly by 
      interacting with the p300 bromodomain.
    findings: []
  - id: PMID:19345327
    title: Persistently activated Stat3 maintains constitutive NF-kappaB 
      activity in tumors.
    findings: []
  - id: PMID:19372587
    title: ErbB2-mediated Src and signal transducer and activator of 
      transcription 3 activation leads to transcriptional up-regulation of 
      p21Cip1 and chemoresistance in breast cancer cells.
    findings: []
  - id: PMID:19390056
    title: Interleukin-6 modulates the expression of the bone morphogenic 
      protein receptor type II through a novel STAT3-microRNA cluster 17/92 
      pathway.
    findings: []
  - id: PMID:19754877
    title: Hsp105beta upregulates hsp70 gene expression through signal 
      transducer and activator of transcription-3.
    findings: []
  - id: PMID:20133729
    title: STAT3 is a substrate of SYK tyrosine kinase in B-lineage 
      leukemia/lymphoma cells exposed to oxidative stress.
    findings: []
  - id: PMID:20826784
    title: Acetylation directs survivin nuclear localization to repress STAT3 
      oncogenic activity.
    findings: []
  - id: PMID:20871632
    title: The role of the c-Jun N-terminal kinase 2-ฮฑ-isoform in non-small cell
      lung carcinoma tumorigenesis.
    findings: []
  - id: PMID:20876300
    title: 'Progesterone receptor induces ErbB-2 nuclear translocation to promote
      breast cancer growth via a novel transcriptional effect: ErbB-2 function as
      a coactivator of Stat3.'
    findings: []
  - id: PMID:20929579
    title: Epigenetic regulation of CpG promoter methylation in invasive 
      prostate cancer cells.
    findings: []
  - id: PMID:21184768
    title: Novel role of signal transducer and activator of transcription 3 as a
      progesterone receptor coactivator in breast cancer.
    findings: []
  - id: PMID:21516116
    title: Next-generation sequencing to generate interactome datasets.
    findings: []
  - id: PMID:21643014
    title: The tumor-suppressor gene ARHI (DIRAS3) suppresses ovarian cancer 
      cell migration through inhibition of the Stat3 and FAK/Rho signaling 
      pathways.
    findings: []
  - id: PMID:21953450
    title: A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and 
      glioma migration through the secreted glycoprotein YKL-40.
    findings: []
  - id: PMID:21988832
    title: Toward an understanding of the protein interaction network of the 
      human liver.
    findings: []
  - id: PMID:22783022
    title: The Sin3a repressor complex is a master regulator of STAT 
      transcriptional activity.
    findings: []
  - id: PMID:23125416
    title: CCR1-mediated STAT3 tyrosine phosphorylation and CXCL8 expression in 
      THP-1 macrophage-like cells involve pertussis toxin-insensitive Gฮฑ(14/16) 
      signaling and IL-6 release.
    findings: []
  - id: PMID:23416296
    title: ECHS1 interacts with STAT3 and negatively regulates STAT3 signaling.
    findings: []
  - id: PMID:23684459
    title: Phosphorylation of EZH2 activates STAT3 signaling via STAT3 
      methylation and promotes tumorigenicity of glioblastoma stem-like cells.
    findings: []
  - id: PMID:23820254
    title: STAT3 upregulates miR-92a to inhibit RECK expression and to promote 
      invasiveness of lung cancer cells.
    findings: []
  - id: PMID:24058793
    title: 'STAT heterodimers in immunity: A mixed message or a unique signal?'
    findings: []
  - id: PMID:24135280
    title: EGFR phosphorylates tumor-derived EGFRvIII driving STAT3/5 and 
      progression in glioblastoma.
    findings: []
  - id: PMID:24172987
    title: A small GTPaseโ€‘like protein fragment of Mycoplasma promotes tumor 
      cell migration and proliferation inย vitro via interaction with Rac1 and 
      Stat3.
    findings: []
  - id: PMID:24189400
    title: Perturbation of the mutated EGFR interactome identifies 
      vulnerabilities and resistance mechanisms.
    findings: []
  - id: PMID:24255059
    title: Inhibition of microRNA-92a prevents endothelial dysfunction and 
      atherosclerosis in mice.
    findings: []
  - id: PMID:24396070
    title: SH2B1ฮฒ interacts with STAT3 and enhances fibroblast growth factor 
      1-induced gene expression during neuronal differentiation.
    findings: []
  - id: PMID:24429361
    title: Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and 
      miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex 
      in hepatitis.
    findings: []
  - id: PMID:24658140
    title: The mammalian-membrane two-hybrid assay (MaMTH) for probing 
      membrane-protein interactions in human cells.
    findings: []
  - id: PMID:24744378
    title: The STAT3-binding long noncoding RNA lnc-DC controls human dendritic 
      cell differentiation.
    findings: []
  - id: PMID:24846175
    title: ฮฒ1,6 GlcNAc branches-modified PTPRT attenuates its activity and 
      promotes cell migration by STAT3 pathway.
    findings: []
  - id: PMID:25065853
    title: Drug resistance via feedback activation of Stat3 in oncogene-addicted
      cancer cells.
    findings: []
  - id: PMID:25241761
    title: Using an in situ proximity ligation assay to systematically profile 
      endogenous protein-protein interactions in a pathway network.
    findings: []
  - id: PMID:25402766
    title: Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling.
    findings: []
  - id: PMID:25416956
    title: A proteome-scale map of the human interactome network.
    findings: []
  - id: PMID:25417160
    title: A noncanonical Frizzled2 pathway regulates epithelial-mesenchymal 
      transition and metastasis.
    findings: []
  - id: PMID:25476455
    title: Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 
      activity and suppresses gliomas tumorigenicity.
    findings: []
  - id: PMID:25596740
    title: miR-874 functions as a tumor suppressor by inhibiting angiogenesis 
      through STAT3/VEGF-A pathway in gastric cancer.
    findings: []
  - id: PMID:25609649
    title: Proteomic analyses reveal distinct chromatin-associated and soluble 
      transcription factor complexes.
    findings: []
  - id: PMID:25814554
    title: Phospho-tyrosine dependent protein-protein interaction network.
    findings: []
  - id: PMID:26962683
    title: IL10 inhibits starvation-induced autophagy in hypertrophic scar 
      fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR 
      pathways.
    findings: []
  - id: PMID:26966684
    title: 'PIPINO: A Software Package to Facilitate the Identification of Protein-Protein
      Interactions from Affinity Purification Mass Spectrometry Data.'
    findings: []
  - id: PMID:27050391
    title: Rac1 modulates the formation of primordial follicles by facilitating 
      STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice.
    findings: []
  - id: PMID:27830702
    title: Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated 
      skin inflammation in diabetes.
    findings: []
  - id: PMID:27893700
    title: Trans-presentation of IL-6 by dendritic cells is required for the 
      priming of pathogenic T(H)17 cells.
    findings: []
  - id: PMID:27994074
    title: Novel Resolvin D2 Receptor Axis in Infectious Inflammation.
    findings: []
  - id: PMID:28065600
    title: Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 
      Deacetylation and Deacetylimination Modulation.
    findings: []
  - id: PMID:28283061
    title: Functional Selectivity in Cytokine Signaling Revealed Through a 
      Pathogenic EPO Mutation.
    findings: []
  - id: PMID:28467929
    title: PPARฮณ Links BMP2 and TGFฮฒ1 Pathways in Vascular Smooth Muscle Cells, 
      Regulating Cell Proliferation and Glucose Metabolism.
    findings: []
  - id: PMID:28781374
    title: IL-11 induces differentiation of myeloid-derived suppressor cells 
      through activation of STAT3 signalling pathway.
    findings: []
  - id: PMID:29743632
    title: A double helical motif in OCIAD2 is essential for its localization, 
      interactions and STAT3 activation.
    findings: []
  - id: PMID:29892012
    title: An interactome perturbation framework prioritizes damaging missense 
      mutations for developmental disorders.
    findings: []
  - id: PMID:30042492
    title: STAT3 localizes to the ER, acting as a gatekeeper for 
      ER-mitochondrion Ca(2+) fluxes and apoptotic responses.
    findings: []
  - id: PMID:30413785
    title: ROCK2, but not ROCK1 interacts with phosphorylated STAT3 and 
      co-occupies TH17/TFH gene promoters in TH17-activated human T cells.
    findings: []
  - id: PMID:31145836
    title: Physical proximity and functional cooperation of glycoproteinย 130 and
      glycoproteinย VI in platelet membrane lipid rafts.
    findings: []
  - id: PMID:31507089
    title: Reciprocal regulation of miR-206 and IL-6/STAT3 pathway mediates 
      IL6-induced gefitinib resistance in EGFR-mutant lung cancer cells.
    findings: []
  - id: PMID:31515488
    title: Extensive disruption of protein interactions by genetic variants 
      across the allele frequency spectrum in human populations.
    findings: []
  - id: PMID:31638206
    title: MicroRNAโ€‘4500 suppresses tumor progression in nonโ€‘small cell lung 
      cancer by regulating STAT3.
    findings: []
  - id: PMID:31886314
    title: miR-98 Modulates Cytokine Production from Human PBMCs in Systemic 
      Lupus Erythematosus by Targeting IL-6 mRNA.
    findings: []
  - id: PMID:31899195
    title: Prohibitin 1 interacts with signal transducer and activator of 
      transcription 3 in T-helper 17 cells.
    findings: []
  - id: PMID:31980649
    title: Extensive rewiring of the EGFR network in colorectal cancer cells 
      expressing transforming levels of KRAS(G13D).
    findings: []
  - id: PMID:32296183
    title: A reference map of the human binary protein interactome.
    findings: []
  - id: PMID:32852592
    title: Biochanin A impedes STAT3 activation by upregulating p38ฮด MAPK 
      phosphorylation in IL-6-stimulated macrophages.
    findings: []
  - id: PMID:32911434
    title: A functionally defined high-density NRF2 interactome reveals new 
      conditional regulators of ARE transactivation.
    findings: []
  - id: PMID:32929201
    title: PD-L1-mediated gasdermin C expression switches apoptosis to 
      pyroptosis in cancer cells and facilitates tumour necrosis.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the 
      human interactome.
    findings: []
  - id: PMID:35140242
    title: Human transcription factor protein interaction networks.
    findings: []
  - id: PMID:35512704
    title: Systematic discovery of mutation-directed neo-protein-protein 
      interactions in cancer.
    findings: []
  - id: PMID:38404237
    title: A novel gain-of-function STAT3 variant in infantile-onset diabetes 
      associated with multiorgan autoimmunity.
    findings: []
  - id: PMID:38844957
    title: Integrin ฮฑVฮฒ1-activated PYK2 promotes the progression of 
      non-small-cell lung cancer via the STAT3-VGF axis.
    findings: []
  - id: PMID:7510216
    title: Interferon activation of the transcription factor Stat91 involves 
      dimerization through SH2-phosphotyrosyl peptide interactions.
    findings: []
  - id: PMID:7512451
    title: Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 
      p91-related transcription factor involved in the gp130-mediated signaling 
      pathway.
    findings: []
  - id: PMID:7528668
    title: Interleukin-2 induces tyrosine phosphorylation and nuclear 
      translocation of stat3 in human T lymphocytes.
    findings: []
  - id: PMID:7543512
    title: IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the 
      differential assembly of STAT1 alpha and STAT3 complexes in human T cells 
      and monocytes.
    findings: []
  - id: PMID:7568001
    title: Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus 
      kinases by interleukins 2 and 15.
    findings: []
  - id: PMID:7568005
    title: Critical role of the interleukin 2 (IL-2) receptor 
      gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not 
      bcl-2, gene induction.
    findings: []
  - id: PMID:8272873
    title: Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 
      beta receptor components.
    findings: []
  - id: PMID:8662591
    title: Differential activation of acute phase response factor/STAT3 and 
      STAT1 via the cytoplasmic domain of the interleukin 6 signal transducer 
      gp130. I. Definition of a novel phosphotyrosine motif mediating STAT1 
      activation.
    findings: []
  - id: PMID:8675499
    title: STAT3beta, a splice variant of transcription factor STAT3, is a 
      dominant negative regulator of transcription.
    findings: []
  - id: PMID:8756628
    title: A single tyrosine of the interleukin-9 (IL-9) receptor is required 
      for STAT activation, antiapoptotic activity, and growth regulation by 
      IL-9.
    findings: []
  - id: PMID:9535918
    title: Heteromerization of the gammac chain with the interleukin-9 receptor 
      alpha subunit leads to STAT activation and prevention of apoptosis.
    findings: []
  - id: PMID:9670957
    title: The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 
      activation and tyrosine phosphorylation of the CCR2B receptor.
    findings: []
  - id: PMID:9864141
    title: Identification of a novel Stat3 recruitment and activation motif 
      within the granulocyte colony-stimulating factor receptor.
    findings: []
  - id: Reactome:R-HSA-1112538
    title: Phosphorylated STAT1, STAT3 form dimers
    findings: []
  - id: Reactome:R-HSA-1112565
    title: Tyrosine phosphorylated IL6ST binds STAT1,STAT3
    findings: []
  - id: Reactome:R-HSA-1112587
    title: STAT1 and STAT3 dimers translocate to the nucleus
    findings: []
  - id: Reactome:R-HSA-1112602
    title: Tyrosine phosphorylation of STAT1, STAT3 by IL6 receptor
    findings: []
  - id: Reactome:R-HSA-1112604
    title: Phosphorylated STATs are released
    findings: []
  - id: Reactome:R-HSA-1112727
    title: Serine phosphorylation of STATs
    findings: []
  - id: Reactome:R-HSA-1433456
    title: Recruitment of STATs
    findings: []
  - id: Reactome:R-HSA-1470009
    title: Phosphorylation of STATs
    findings: []
  - id: Reactome:R-HSA-1470010
    title: Dimerization of STATs
    findings: []
  - id: Reactome:R-HSA-1470012
    title: Disassociation and translocation of STATs to the nucleus
    findings: []
  - id: Reactome:R-HSA-1888198
    title: FGFR1OP-FGFR1 phosphorylates STAT1 and STAT3
    findings: []
  - id: Reactome:R-HSA-2895778
    title: POU5F1 (OCT4), STAT3 bind the SALL4 promoter
    findings: []
  - id: Reactome:R-HSA-380782
    title: STAT binds to the active receptor
    findings: []
  - id: Reactome:R-HSA-452515
    title: Expression of STAT3
    findings: []
  - id: Reactome:R-HSA-6784006
    title: STAT3 is phosphorylated by p-Y-JAK1,P-Y-TYK2
    findings: []
  - id: Reactome:R-HSA-6784323
    title: IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3
    findings: []
  - id: Reactome:R-HSA-6784763
    title: p-Y705-STAT3 dimer translocates from cytosol to nucleoplasm
    findings: []
  - id: Reactome:R-HSA-6784765
    title: p-Y705-STAT3 dimerizes
    findings: []
  - id: Reactome:R-HSA-6784791
    title: p-Y705-STAT3 dissociates from IL10 
      dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2:p-Y705-STAT3
    findings: []
  - id: Reactome:R-HSA-6786072
    title: p-Y705-STAT3,p-Y641-STAT6 dissociate
    findings: []
  - id: Reactome:R-HSA-6786095
    title: JAK1 phosphorylates STAT3,STAT6
    findings: []
  - id: Reactome:R-HSA-6786097
    title: p-Y705-STAT3, p-Y641-STAT6 dimerise
    findings: []
  - id: Reactome:R-HSA-6786124
    title: STAT3,STAT6 bind p-Y-IL4R
    findings: []
  - id: Reactome:R-HSA-6786293
    title: p-Y705-STAT3 dimer, p-Y641-STAT6 dimer translocate to nucleus
    findings: []
  - id: Reactome:R-HSA-6788571
    title: STAT1,STAT3,STAT6 bind IL13:IL13R type II
    findings: []
  - id: Reactome:R-HSA-6788582
    title: STAT1,STAT3,STAT6 phosphorylation
    findings: []
  - id: Reactome:R-HSA-6788622
    title: p-Y-STATs dimerize
    findings: []
  - id: Reactome:R-HSA-6788623
    title: p-Y-STATs translocate to nucleus
    findings: []
  - id: Reactome:R-HSA-6788628
    title: p-Y-STATs dissociate
    findings: []
  - id: Reactome:R-HSA-8848087
    title: STAP2 recruits STAT3 to PTK6
    findings: []
  - id: Reactome:R-HSA-8848124
    title: PTK6 phosphorylates STAT3
    findings: []
  - id: Reactome:R-HSA-8848150
    title: STAT3 binds SOCS3 promoter
    findings: []
  - id: Reactome:R-HSA-8875816
    title: STAT3 binds activated MET receptor
    findings: []
  - id: Reactome:R-HSA-8875817
    title: MET phosphorylates STAT3
    findings: []
  - id: Reactome:R-HSA-8950269
    title: STAT3, STAT4 are phosphorylated by p-JAK2, p-TYK2 in IL23:IL23 
      receptor
    findings: []
  - id: Reactome:R-HSA-8950441
    title: p-Y701-STAT1 and p-Y705-STAT3 dissociate from IL27:IL27 receptor
    findings: []
  - id: Reactome:R-HSA-8950485
    title: STAT3 and STAT1 are phosphorylated by JAKs after IL27:IL27R 
      interaction
    findings: []
  - id: Reactome:R-HSA-8950518
    title: STAT1, STAT3 bind p-Y611-IL27RA from Interleukin-27:Interleukin-27 
      receptor complex
    findings: []
  - id: Reactome:R-HSA-8950724
    title: p-Y705-STAT3:p-Y693-STAT4 translocates to the nucleus
    findings: []
  - id: Reactome:R-HSA-8950733
    title: p-Y701-STAT1:p-Y705-STAT3 translocates to the nucleus
    findings: []
  - id: Reactome:R-HSA-8950780
    title: p-Y705-STAT3 binds p-Y693-STAT4
    findings: []
  - id: Reactome:R-HSA-8950782
    title: p-STAT1 binds p-STAT3
    findings: []
  - id: Reactome:R-HSA-8952749
    title: STAT4 binds p-Y-IL23R in IL23:IL23 receptor
    findings: []
  - id: Reactome:R-HSA-8952823
    title: p-Y693-STAT4, p-Y705-STAT3 dissociate from IL23:IL23 receptor
    findings: []
  - id: Reactome:R-HSA-8982162
    title: pโ€‘Y705-STAT3 dissociates from IL19:IL20RA:p-JAK1:IL20RB
    findings: []
  - id: Reactome:R-HSA-8982163
    title: IL19:IL20RA:p-JAK1:IL20RB:STAT3 phosphorylates STAT3
    findings: []
  - id: Reactome:R-HSA-8982165
    title: IL19:IL20RA:pโ€‘JAK1:IL20RB binds STAT3
    findings: []
  - id: Reactome:R-HSA-8983059
    title: STAT3 is phosphorylated by TSLP:IL7R:CRLF2:STAT3 complex
    findings: []
  - id: Reactome:R-HSA-8983078
    title: p-STAT3 dissociates from TSLP:IL7R:CRLF2:p-STAT3 complex
    findings: []
  - id: Reactome:R-HSA-8983371
    title: IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 phosphorylates 
      STAT3 and STAT5
    findings: []
  - id: Reactome:R-HSA-8983373
    title: p-Y-STAT3 binds p-STAT5
    findings: []
  - id: Reactome:R-HSA-8983374
    title: p-Y-STAT3 and p-STAT5 dissociates from 
      IL15:IL15RA:IL2RB:p-JAK1:IL2RG:p-JAK3:p-Y-STAT3:p-STAT5
    findings: []
  - id: Reactome:R-HSA-8983378
    title: IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 binds STAT3 and 
      STAT5
    findings: []
  - id: Reactome:R-HSA-8983379
    title: p-Y-STAT3:p-STAT5 translocates to the nucleus
    findings: []
  - id: Reactome:R-HSA-8984014
    title: JAK1,JAK2 bound to IL27RA:IL12RB2 receptor phosphorylate STAT1,STAT3
    findings: []
  - id: Reactome:R-HSA-8984021
    title: STAT1,STAT3 associate with IL27RA:IL12RB2 receptor
    findings: []
  - id: Reactome:R-HSA-8984023
    title: p-STAT1, p-STAT3 dissociate from IL27RA:IL12RB2 receptor
    findings: []
  - id: Reactome:R-HSA-8985900
    title: p-Y701-STAT1, p-Y705-STAT3, p-Y649-STAT5 dissociates from 
      IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3:p-Y705-STAT3
    findings: []
  - id: Reactome:R-HSA-8985929
    title: IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3 binds STAT1, STAT3, STAT5A 
      or STAT5B
    findings: []
  - id: Reactome:R-HSA-8985966
    title: p-Y701-STAT1 binds p-Y705-STAT3
    findings: []
  - id: Reactome:R-HSA-8985981
    title: p-Y701-STAT1:p-Y705-STAT3 translocates from the cytosol to the 
      nucleus
    findings: []
  - id: Reactome:R-HSA-8985988
    title: IL9:p-Y116-IL9R:JAK1:IL2RG:p-904,939-JAK3:STAT3 phosphorylates STAT1,
      STAT3 or STAT5
    findings: []
  - id: Reactome:R-HSA-8986985
    title: IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:STAT1 phosphorylates 
      STAT1, STAT2, STAT3, STAT4 and STAT5
    findings: []
  - id: Reactome:R-HSA-8987014
    title: IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:PTPN11:IL10RB:p-TYK2 binds STAT3
    findings: []
  - id: Reactome:R-HSA-8987033
    title: p-STAT1, p-Y-STAT2, p-STAT3, p-STAT4, p-STAT5 dissociates from 
      IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:p-STAT1,p-STAT2,p-STAT3,p-STAT4,p-STAT5
    findings: []
  - id: Reactome:R-HSA-8987052
    title: p-STAT3 dimer translocates from cytosol to nucleoplasm
    findings: []
  - id: Reactome:R-HSA-8987063
    title: IL24:IL22RA1:p-JAK1:IL20RB binds STAT3
    findings: []
  - id: Reactome:R-HSA-8987070
    title: IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:STAT3 phosphorylates 
      STAT3
    findings: []
  - id: Reactome:R-HSA-8987080
    title: IL26:IL10RB:p-TYK2:IL20RA:p-JAK1 binds STAT1, STAT3
    findings: []
  - id: Reactome:R-HSA-8987096
    title: IL24:IL22RA1:p-JAK1:IL20RB:STAT3 phosphorylates STAT3
    findings: []
  - id: Reactome:R-HSA-8987097
    title: IL24:p-IL20RA:p-JAK1:IL20RB binds STAT1,STAT3
    findings: []
  - id: Reactome:R-HSA-8987104
    title: IL20:IL20RA:JAK1:IL20RB:pโ€‘JAK2,pโ€‘JAK3 binds STAT3
    findings: []
  - id: Reactome:R-HSA-8987141
    title: IL20:IL20RA:JAK1:IL20RB:p-JAK3,p-JAK2:STAT3 phosphorylates STAT3
    findings: []
  - id: Reactome:R-HSA-8987150
    title: IL24:IL20RA:p-JAK1:IL20RB:STAT1,STAT3 phosphorylates STAT1 or STAT3
    findings: []
  - id: Reactome:R-HSA-8987156
    title: p-STAT3 dissociates from 
      IL20:IL20RA:JAK1:IL20RB:p-Y1007,Y1008-JAK2,p-JAK3
    findings: []
  - id: Reactome:R-HSA-8987161
    title: p-STAT3 dissociates from IL24:IL22RA1:pโ€‘JAK1:IL20RB:pโ€‘STAT3
    findings: []
  - id: Reactome:R-HSA-8987214
    title: p-STAT3 dimerizes
    findings: []
  - id: Reactome:R-HSA-8987230
    title: p-STAT1 and p-STAT3 dissociates from IL26:IL10RB:p-TYK2:IL20RA:p-JAK1
    findings: []
  - id: Reactome:R-HSA-8987236
    title: p-Y705-STAT3 dissociates from  
      IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:p-Y705-STAT3
    findings: []
  - id: Reactome:R-HSA-8987255
    title: IL26:IL10RB:p-TYK2:IL20RA:p-JAK1:STAT1,STAT3  phosphorylates 
      STAT1,STAT3
    findings: []
  - id: Reactome:R-HSA-8987266
    title: IFNL1:p-Y434,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2 binds STAT1, STAT2, 
      STAT3, STAT4, STAT5
    findings: []
  - id: Reactome:R-HSA-8987270
    title: p-STAT1,p-STAT3 dissociate from 
      IL24:IL20RA:p-Y1022,Y1023-JAK1:IL20RB:p-STAT1, p-STAT3
    findings: []
  - id: Reactome:R-HSA-9006870
    title: IL21 receptor STAT phosphorylation
    findings: []
  - id: Reactome:R-HSA-9006873
    title: IL21 receptor STAT binding
    findings: []
  - id: Reactome:R-HSA-9009072
    title: STAT3 phosphorylation
    findings: []
  - id: Reactome:R-HSA-9670412
    title: Phosphorylation of STATs downstream of KIT mutants
    findings: []
  - id: Reactome:R-HSA-9670416
    title: Recruitment of STATs by KIT mutants
    findings: []
  - id: Reactome:R-HSA-9670417
    title: Dimerization of STATs downstream of KIT mutants
    findings: []
  - id: Reactome:R-HSA-9670426
    title: Disassociation and translocation of STATs to the nucleus downstream 
      of KIT mutants
    findings: []
  - id: Reactome:R-HSA-9672159
    title: STAT binds to p-11Y PDGFRA extracellular domain dimers
    findings: []
  - id: Reactome:R-HSA-9672176
    title: STAT binds to the mutant PDGFRA receptor
    findings: []
  - id: Reactome:R-HSA-9701524
    title: STAT3 is phosphorylated downstream of active ALK
    findings: []
  - id: Reactome:R-HSA-9701525
    title: p-Y705,S727-STAT3 dimerizes
    findings: []
  - id: Reactome:R-HSA-9701529
    title: p-Y705, p-S727 STAT3 dimer translocates to the nucleus
    findings: []
  - id: Reactome:R-HSA-9701531
    title: p-Y705,S727 STAT3 is acetylated
    findings: []
  - id: Reactome:R-HSA-9701534
    title: p-Y705, S727 STAT3 dimer binds HIF1A gene
    findings: []
  - id: Reactome:R-HSA-9701537
    title: p-Y705, S727 STAT3 dimer binds CD274 gene
    findings: []
  - id: Reactome:R-HSA-9701549
    title: AcK685-p-Y705,S727 STAT3 and SIN3A bind the PDRM1 promoter
    findings: []
  - id: Reactome:R-HSA-9701557
    title: AcK685-p-Y705,S727 STAT3 and SIN3A bind the IL2RG promoter
    findings: []
  - id: Reactome:R-HSA-9701565
    title: HDACs deacetylate p-STAT3 dimers
    findings: []
  - id: Reactome:R-HSA-9712079
    title: ALK mutants bind STAT3
    findings: []
  - id: Reactome:R-HSA-9712085
    title: ALK mutants phosphorylate STAT3
    findings: []
  - id: Reactome:R-HSA-9835443
    title: STAT1,STAT3 binds PKR
    findings: []
  - id: Reactome:R-HSA-9850958
    title: pY-STAT3 dimer translocates to the nucleus downstream of ALK mutants
    findings: []
  - id: Reactome:R-HSA-9851058
    title: AcK685 p-Y705, S727 STAT3 dimer and DNMT1 bind IL2RG gene
    findings: []
  - id: Reactome:R-HSA-9851062
    title: AcK685 pY705,S727 STAT3 binds the MIR21 gene
    findings: []
  - id: Reactome:R-HSA-9851064
    title: AcK685-pY705,S727 STAT3 dimer binds DNMT1 promoter
    findings: []
  - id: Reactome:R-HSA-9851071
    title: STAT3, DNMT1 and HDAC1 bind PTPN6 gene
    findings: []
  - id: Reactome:R-HSA-9851106
    title: p-Y705, S727 STAT3 dimer binds ICOS promoter
    findings: []
  - id: Reactome:R-HSA-9851118
    title: pY-STAT3 binds the IRF4 promoter downstream of NPM1-ALK
    findings: []
  - id: Reactome:R-HSA-9851122
    title: p-Y705,S727 STAT3 dimer binds NOTCH gene
    findings: []
  - id: Reactome:R-HSA-9851142
    title: TYK2-dependent STAT1 and STAT3 phosphorylation
    findings: []
  - id: file:human/STAT3/STAT3-deep-research-falcon.md
    title: Deep research report on STAT3
    findings: []
core_functions:
  - molecular_function:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    directly_involved_in:
      - id: GO:0007259
        label: cell surface receptor signaling pathway via JAK-STAT
      - id: GO:0048708
        label: astrocyte differentiation
    locations:
      - id: GO:0005634
        label: nucleus
aliases:
  - APRF
  - Acute-phase response factor
alternative_products:
  - name: '1'
    id: P40763-1
  - name: Del-701
    id: P40763-2
    sequence_note: VSP_010474
  - name: '3'
    id: P40763-3
    sequence_note: VSP_055918, VSP_055919