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.
| 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 |
KEEP AS NON CORE |
Summary: STAT3 acts downstream of hypothalamic leptin/JAK signalling, but as a highly pleiotropic transcription factor its link to feeding behaviour is an electronically-inferred, distal organismal output rather than a core STAT3 function.
Reason: Electronic (IEA/ISS) behavioural annotation on a pleiotropic transcription factor; distal to its core JAK-STAT signalling role; non-core.
|
|
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 MicroRNAโ4500 suppresses tumor progression in nonโsmall cell... |
UNDECIDED |
Summary: Experimental evidence (IMP) supports positive regulation of cell migration for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Real but borderline core vs non-core. STAT3's core molecular function is signal-dependent DNA-binding transcription factor activity (JAK-STAT); cell migration is a downstream transcriptional consequence rather than an activity STAT3 itself performs, and STAT3 is not part of the cytoskeletal/ adhesion motility machinery. The IMP evidence (knockdown/overexpression migration phenotype) is the classic indirect "perturb gene -> phenotype" inference. Flagged by the ASSAY_TO_FUNCTION CELL_MIGRATION_INVASION readout class; given STAT3 is high-profile and the call is genuinely contested (oncogenic migration driver vs downstream consequence), deferred to expert review rather than unilaterally demoted (issue #1422; staged OpenScientist hypothesis job under STAT3-hypotheses/). The OpenScientist cited adjudication (29 refs, verified) converged on NON-CORE (retain, not remove). Verification of its citations independently found that the supporting reference PMID:31638206 is indexed by PubMed as a RETRACTED publication, and surfaced a genuine non-transcriptional STAT3-stathmin microtubule mechanism (PMID:16401721) that currently has no GO cytoskeletal annotation - both noted for the expert (issue #1422).
Supporting Evidence:
PMID:31638206
Oct 11. MicroRNAโ4500 suppresses tumor progression in nonโsmall cell lung cancer by regulating STAT3.
file:human/STAT3/STAT3-hypotheses/readout-go-0030335/openscientist.md
Verdict NON-CORE (over-annotated as core): cell migration is a real, well-documented downstream consequence of STAT3's core transcription factor activity (e.g. transcriptional induction of Twist1, MMPs) rather than evidence STAT3 is part of the migration machinery; bidirectional context-dependent effects (also GO:2001223) are the hallmark of a transcription factor. Retain but reclassify non-core.
|
|
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 ... |
UNDECIDED |
Summary: Experimental evidence (IMP) supports positive regulation of cell migration for STAT3 [file:human/STAT3/STAT3-deep-research-falcon.md]
Reason: Real but borderline core vs non-core (companion IMP annotation to the GO:0030335 call on PMID:31638206). STAT3's core is signal-dependent DNA-binding TF activity; cell migration is a downstream transcriptional consequence, not in the motility machinery. Flagged by ASSAY_TO_FUNCTION (CELL_MIGRATION_INVASION); deferred to expert review rather than unilaterally demoted. See issue #1422.
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 GTPaseโlike 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 GTPaseโlike 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 |
KEEP AS NON CORE |
Summary: STAT3 acts downstream of hypothalamic leptin/JAK signalling, but as a highly pleiotropic transcription factor its link to feeding behaviour is an electronically-inferred, distal organismal output rather than a core STAT3 function.
Reason: Electronic (IEA/ISS) behavioural annotation on a pleiotropic transcription factor; distal to its core JAK-STAT signalling role; non-core.
|
|
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 |
KEEP AS NON CORE |
Summary: Eating-behaviour effects of STAT3 reflect its role in leptin-responsive hypothalamic transcription, a distal consequence of STAT3 signalling rather than a direct STAT3 function; evidence is ISS only.
Reason: Electronic (ISS) behavioural annotation on a pleiotropic transcription factor; non-core.
|
|
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.
|
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 (2023โ2024) 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 135โ315) mediates cofactor interactions; DBD (~aa 320โ480) binds GAS-like elements; linker (~aa 480โ575) couples to SH2; SH2 (~aa 575โ680) 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-6โJAKโSTAT3 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 SH2โpY705 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 Kv1.3โSTAT3โp53 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 STAT3โs 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 nuclearโmitochondrial 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-6โfamily 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 (2023โ2024 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 vivoโsupporting 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 2023โ2024 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 1โ2 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 1โ2 (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-6โJAKโSTAT3 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 STAT3โs 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 (1โ2 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-6โJAKโpY705โSH2 dimerizationโnuclear 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 Kv1.3โSTAT3โp53 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 2023โ2025 | 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 2023โ2024 | 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 (2023โ2025) 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-6โJAKโSTAT 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. Kv1.3โSTAT3โp53 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-typeโspecific datasets for precision use cases. (NCT03195699)
References
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(NCT03195699): Oral STAT3 Inhibitor, TTI-101, in Patients with Advanced Cancers. Tvardi Therapeutics, Incorporated. 2017. ClinicalTrials.gov Identifier: NCT03195699
(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
(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.
(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.
Question: Is positive regulation of cell migration (GO:0030335) a core
function of STAT3, or a downstream / context-dependent consequence of its core
signal-dependent DNA-binding transcription-factor activity?
Why staged: Surfaced by the ASSAY_TO_FUNCTION CELL_MIGRATION_INVASION
readout class (catalog extension). The two GO:0030335 annotations (IMP;
PMID:31638206, PMID:24846175) were set to UNDECIDED (was ACCEPT) and
deferred to expert review (issue #1422) rather than unilaterally demoted,
because STAT3 is high-profile and the call is genuinely contested (oncogenic
EMT/invasion driver vs downstream transcriptional consequence).
Status: prompt staged via
projects/ASSAY_TO_FUNCTION/stage_hypotheses.py (human-gated generator).
Result, when run, lands in openscientist.md (+ openscientist.md.citations.md).
uv run deep-research-client research \
--input-file genes/human/STAT3/STAT3-hypotheses/readout-go-0030335/prompt.md \
--provider openscientist \
--output genes/human/STAT3/STAT3-hypotheses/readout-go-0030335/openscientist.md \
--separate-citations genes/human/STAT3/STAT3-hypotheses/readout-go-0030335/openscientist.md.citations.md
Treat the output as hypothesis-generating literature synthesis, not ground
truth โ verify snippets against the cited PMIDs before using them in curation.
The annotations remainUNDECIDEDpending expert adjudication on issue #1422;
fold only verified findings intoSTAT3-ai-review.yamlas afile:reference
with an extractedsupporting_text(the SCO1 review is the model).
Verdict: NON-CORE (over-annotated as core function). The GO annotation of STAT3 to positive regulation of cell migration (GO:0030335) should be retained as biologically accurate but reclassified as non-core โ a real, well-documented downstream consequence of STAT3's core transcription factor activity rather than a primary function the gene product evolved to perform.
Three convergent lines of evidence support this classification: (1) The dominant mechanism by which STAT3 promotes cell migration is transcriptional โ STAT3 drives expression of Twist1, MMPs, and EMT markers as downstream targets of its core DNA-binding transcription factor activity in the JAK-STAT pathway; (2) STAT3 exerts bidirectional effects on migration โ promoting it in cancer and wound healing contexts while inhibiting it in cortical neuron migration โ a hallmark of context-dependent downstream function that is incompatible with classification as core migration machinery; (3) Although a secondary non-transcriptional mechanism exists (STAT3-stathmin interaction stabilizing microtubules), this mechanism is context-limited, partially redundant, and was not tested in the reference paper's NSCLC context (PMID: 31638206). The reference paper itself employs classic indirect IMP evidence (miR-4500 targeting STAT3 โ reduced migration), which is the canonical "perturb gene โ observe phenotype" design that cannot distinguish core from downstream function.
The current UNDECIDED action should be resolved to ACCEPT as non-core. The annotation is scientifically valid and should not be removed, but it should be clearly flagged as a downstream consequence of STAT3's primary molecular function (signal-dependent DNA-binding transcription factor activity) rather than evidence that STAT3 is part of the cell migration machinery.
Key caveats:
1. The STAT3-stathmin interaction means STAT3 IS capable of directly modulating cytoskeletal dynamics โ this is not purely a transcriptional relay
2. The non-core classification is strong but not absolute; the stathmin mechanism prevents a categorical "no direct involvement"
3. The annotation is biologically accurate regardless of core/non-core classification
4. STAT3 has BIDIRECTIONAL migration effects โ it promotes migration in cancer/wound healing (GO:0030335) but INHIBITS neuronal migration in developing cortex (GO:2001223, PMID: 22907754). Core migration machinery components do not show bidirectional effects; this is a hallmark of a context-dependent transcription factor whose migration effects depend on which target genes it activates in a given cellular context
STAT3 (Signal Transducer and Activator of Transcription 3) is a well-characterized intracellular transcription factor (~92 kDa, 750โ795 amino acids) whose core molecular function is signal-dependent DNA-binding transcription factor activity within the JAK-STAT signaling pathway. Constitutive STAT3 knockout in mice is embryonic lethal at E6.5โE7.5 (PMID: 30254684), underscoring its essential role in transcriptional regulation during development. The question under review is whether STAT3's documented role in promoting cell migration constitutes a core function (i.e., STAT3 is part of the migration machinery) or a downstream, context-dependent consequence of its transcription factor activity.
Our investigation, spanning 73 papers and 5 analytical iterations, establishes that STAT3 promotes cell migration primarily through transcriptional activation of pro-migratory target genes โ including Twist1, MMPs (MMP-1, -2, -3, -9, -10, -13), EMT transcription factors, and chemokines โ rather than through direct participation in the cytoskeletal or adhesion machinery that executes cell movement. A secondary, non-transcriptional mechanism involving direct STAT3-stathmin interaction and microtubule stabilization has been documented since 2006 (PMID: 16401721), but this mechanism is context-restricted (demonstrated primarily in T-cells, motoneurons, and fibroblasts) and was not evaluated in the NSCLC context of the reference paper. Critically, STAT3 has bidirectional effects on migration: it promotes migration in cancer cells, wound-healing keratinocytes, and T-cells, but inhibits radial neuronal migration in the developing cerebral cortex (PMID: 22907754). This bidirectionality is a defining feature of a context-dependent downstream effector, not a core component of the migration machinery.
The GO database itself reflects this picture: STAT3 carries 17+ annotations to transcription/signaling terms, exactly one annotation to positive regulation of cell migration (GO:0030335), one to negative regulation of neuron migration (GO:2001223), and zero annotations to microtubule, stathmin, cytoskeletal, or actin-related terms โ despite published biochemical evidence for the STAT3-stathmin interaction. This annotation profile is consistent with a transcription factor whose pleiotropic target genes include migration regulators, rather than a gene product whose primary function is in the migration pathway.
The predominant mechanism by which STAT3 influences cell migration is through its canonical role as a transcription factor. Multiple independent studies demonstrate that STAT3 directly binds the promoters of pro-migratory genes and drives their expression:
Twist1 transcription: STAT3 directly binds the Twist1 promoter to induce EMT transcription factor expression. In hepatocellular carcinoma cells, a dual-luciferase reporter assay confirmed that "STAT3 may bind the Twist promoter, mediate its transcriptional activity, and then promote the EMT process in HCC cells" (PMID: 25653024). Similarly, in prostate cancer, "STAT3 and HIF-1ฮฑ up-regulated TWIST1 expression by direct binding to a TWIST1 promoter" (PMID: 23623921). Additional ChIP evidence from colorectal cancer confirms IL-6 treatment promotes "recruitment of STAT3, ฮบB and C/EBPฮฒ toward the Twist promoter region" (PMID: 37047623).
Matrix metalloproteinase expression: STAT3 activation drives expression of multiple MMPs critical for extracellular matrix remodeling during migration. Knockdown of the lncRNA PRECSIT "inhibited expression of activated STAT3 and resulted in down-regulation of the expression of matrix metalloproteinase (MMP)-1, MMP-3, MMP-10, and MMP-13" in cutaneous squamous cell carcinoma (PMID: 31837949). PLOD3 interacts with STAT3 to express MMP-2 and MMP-9 for tumor metastasis (PMID: 30442941). The IL-6/STAT3/MMP signaling axis drives gastric cancer cell migration via paracrine activation (PMID: 30361813). EZH2 promotes renal cell carcinoma invasion through STAT3-mediated MMP-2 upregulation (PMID: 29286132).
Non-canonical STAT3 roles are mitochondrial, not cytoskeletal: The well-documented non-transcriptional functions of STAT3 involve modulation of mitochondrial electron transport chain activity via S727 phosphorylation โ not cytoskeletal regulation. As stated in the literature: "STAT3 is increasingly becoming known for its non-transcriptional regulation of mitochondrial bioenergetic function upon activation of its S727 residue" (PMID: 27978828) and "STAT3 is a transcription factor involved in several cellular activities including inflammation, proliferation, and survival, but it also plays a non-transcriptional role in modulating mitochondrial metabolism" (PMID: 33305182). The mitochondrial role is the dominant non-transcriptional STAT3 activity discussed in the literature, far outweighing the stathmin interaction.
This evidence establishes that migration effects observed upon STAT3 perturbation are predominantly downstream transcriptional consequences, not evidence of STAT3 participation in the migration machinery itself.
STAT3's evolutionarily conserved primary function is as a transcription factor in the JAK-STAT signaling pathway:
The original reference supporting the GO:0030335 annotation uses a standard perturb-gene-observe-phenotype experimental design:
This is classic IMP evidence. Critically, migration was measured as one of several phenotypic readouts alongside proliferation and apoptosis. The paper does not distinguish whether STAT3's effect on migration is direct (via migration machinery) or indirect (via transcriptional targets). The experimental design cannot make this distinction.
A significant complication arises from the documented non-transcriptional role of STAT3 in microtubule regulation via direct interaction with stathmin (STMN1):
The seminal paper by Ng et al. (2006) demonstrated that STAT3 physically interacts with stathmin: "Previously, the function of Stat3 had been attributed exclusively to its transcriptional activity in the nucleus. In this study, we reveal an interaction between Stat3 and the microtubule (MT)-destabilizing protein stathmin." Furthermore, "Recombinant Stat3 was also capable of reversing stathmin inhibition of tubulin polymerization in vitro" (PMID: 16401721). This is a genuine biochemical interaction where STAT3 protein directly modulates cytoskeletal dynamics independent of transcription.
This mechanism was confirmed in migrating T-cells: "STAT3 physically interacts with stathmin to regulate microtubule dynamics in migrating T-cells" (PMID: 19251695).
It was observed in motoneuron axons: "activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity" (PMID: 23109669).
In gastric cancer: "STAT3 depletion inhibited the activity of RhoA and the interaction with stathmin, downregulated the expression of pFAK (phosphorylated focal adhesion kinase), acetylated-tubulin" (PMID: 23333463).
A commentary described the mechanism: "new evidence suggests a novel role for non-tyrosine-phosphorylated and cytoplasmically localized STAT3 in mediating cell migration by disrupting an interaction between microtubules and one of its partners, stathmin" (PMID: 16835434).
However, several factors limit the relevance of this mechanism for the annotation under review:
{{figure:evidence_comparison.png|caption=Quantitative comparison of evidence supporting transcriptional vs. stathmin-mediated STAT3 migration mechanisms. The transcriptional pathway has substantially more independent supporting studies across diverse cancer types and tissues, while the stathmin mechanism is documented in a limited number of cell type contexts.}}
The strongest evidence against core classification is STAT3's bidirectional effect on migration:
This bidirectionality is reflected in GO annotations: STAT3 carries both positive regulation of cell migration (GO:0030335) and negative regulation of neuron migration (GO:2001223). A gene product that is genuinely part of the migration machinery (e.g., a cytoskeletal motor, an adhesion receptor, or a Rho GTPase) would not exhibit opposing effects depending on cell context. The bidirectional phenotype is the hallmark of a transcription factor whose different target gene repertoires in different cell types lead to opposing downstream effects on the same biological process.
Conditional knockout studies provide important in vivo context:
This cell-type specificity further supports classification as a context-dependent downstream effect rather than a core function.
The following model synthesizes the evidence into a coherent framework for understanding STAT3's relationship to cell migration:
CORE FUNCTION DOWNSTREAM EFFECTS
โโโโโโโโโโโโโ โโโโโโโโโโโโโโโโโโ
Cytokine/Growth Factor
โ
โผ
JAK phosphorylation
โ
โผ
โโโโโโโโโโโโโโโโโโโโ
โ STAT3 (Y705-P) โโโโโ Core MF: DNA-binding
โ Transcription โ transcription factor
โ Factor Activity โ activity (GO:0003700)
โโโโโโโโฌโโโโโโโโโโโโ
โ
โโโโบ Twist1, Snail, Slug โโโบ EMT โโโบ Migration โ (cancer)
โโโโบ MMP-1/2/3/9/10/13 โโโบ ECM remodeling โโโบ Invasion โ
โโโโบ VEGFA, iNOS โโโบ Angiogenesis
โโโโบ Bcl-2, survivin โโโบ Survival
โโโโบ SPRR1B โโโบ Keratinocyte migration โ (wound)
โโโโบ Neuronal gene targets โโโบ Migration โ (cortex)
โโโโบ Chemokines, cytokines โโโบ Immune cell migration
โโโโโโโโโโโโโโโโโโโโ
โ STAT3 (unP, cyto)โโโโโ Secondary/Accessory:
โ Stathmin binding โ stathmin sequestration
โโโโโโโโฌโโโโโโโโโโโโ (context-limited)
โ
โโโโบ MT stabilization โโโบ Migration โ (T-cells,
fibroblasts,
some cancers)
Key insight: The same transcription factor (STAT3) drives different transcriptional programs in different cellular contexts, leading to opposing effects on migration. This is the defining signature of a downstream, context-dependent function โ not a core migration function. A core migration gene (e.g., RAC1, CDC42, ACTN1, the Arp2/3 complex) does not switch between pro- and anti-migratory roles based on cell type. The fact that STAT3 promotes migration in cancer cells but inhibits it in cortical neurons (PMID: 22907754) definitively establishes that STAT3 is not part of the universal migration machinery.
The secondary stathmin mechanism represents a genuine direct participation in cytoskeletal dynamics, but it is (a) context-limited, (b) partially redundant with other stathmin regulators, (c) uses a distinct STAT3 pool (unphosphorylated, cytoplasmic), and (d) was not tested in the reference paper's context. It constitutes a moonlighting function rather than the primary evolved activity of STAT3.
| Citation | Evidence Type | Direction | Claim Tested | Key Finding | Context | Confidence & Limitations |
|---|---|---|---|---|---|---|
| PMID: 31638206 | Mutant phenotype (IMP) | Supports annotation | STAT3 knockdown reduces migration | miR-4500 targets STAT3 3'UTR; knockdown reduces migration in NSCLC | Human, NSCLC (A549, H1975) | Moderate; classic IMP, cannot distinguish mechanism |
| PMID: 23623921 | Direct assay (ChIP) | Qualifies as transcriptional | STAT3 directly activates Twist1 | STAT3+HIF-1ฮฑ bind TWIST1 promoter directly | Human, prostate cancer | High; direct promoter binding |
| PMID: 25653024 | Direct assay (reporter) | Qualifies as transcriptional | STAT3 drives Twist transcription | Luciferase confirms STAT3-Twist promoter activity โ EMT | Human, HCC | High; reporter assay |
| PMID: 31837949 | Mutant phenotype | Qualifies as transcriptional | STAT3 drives MMP expression | STAT3 activation โ MMP-1, -3, -10, -13 in cSCC | Human, cutaneous SCC | High |
| PMID: 30442941 | Mutant phenotype + interaction | Qualifies as transcriptional | PLOD3-STAT3 drives metastasis | PLOD3 interacts with STAT3 โ MMP-2, MMP-9 โ metastasis | Human, lung cancer + xenograft | High |
| PMID: 30361813 | Mutant phenotype | Qualifies as transcriptional | IL-6/STAT3/MMP pathway | IL-6 from fibroblasts activates STAT3โMMPโmigration | Human, gastric cancer | High |
| PMID: 29286132 | Mutant phenotype | Qualifies as transcriptional | EZH2-STAT3-MMP axis | EZH2 increases p-STAT3 โ MMP-2 โ invasion | Human, RCC | High |
| PMID: 16401721 | Direct assay (co-IP, in vitro polymerization) | Competing (supports core) | STAT3 directly antagonizes stathmin | Recombinant STAT3 reverses stathmin inhibition of tubulin polymerization; stathmin KD partially rescues migration in STAT3-null cells | Mouse fibroblasts (MEFs) | High; strongest evidence for non-transcriptional mechanism; partial rescue only |
| PMID: 19251695 | Direct assay (co-IP) | Competing (supports core) | STAT3-stathmin in T-cell migration | STAT3 physically interacts with stathmin to regulate MT dynamics in migrating T-cells | Human, Hut78 T-lymphoma | High; direct non-transcriptional mechanism |
| PMID: 16835434 | Commentary | Competing (supports core) | Non-transcriptional STAT3 migration | Non-tyrosine-phosphorylated, cytoplasmic STAT3 mediates migration via stathmin-MT disruption | Commentary | Moderate |
| PMID: 23109669 | Direct assay | Competing (supports core) | STAT3-stathmin in axons | Activated STAT3 interacts with stathmin, inhibits MT-destabilizing activity in motoneurons | Mouse, motoneurons | High; but axon context, not classical cell migration |
| PMID: 23333463 | Knockdown phenotype | Supports both mechanisms | STAT3 in gastric cancer motility | STAT3 depletion impairs RhoA, stathmin interaction, pFAK, microtubules AND MMP activity | Human, gastric cancer | High; shows dual mechanisms |
| PMID: 22907754 | Mutant phenotype | Supports non-core (bidirectional) | STAT3 inhibits neuron migration | STAT3 activation INHIBITS radial neuronal migration in cortex; DN-STAT3 rescues | Mouse, developing cerebral cortex | High; bidirectionality clinches non-core |
| PMID: 17601706 | Review (conditional KO) | Supports annotation | STAT3 in keratinocyte migration in vivo | Keratinocyte-specific Stat3 KO: impaired wound healing and migration | Mouse, keratinocyte KO | High; in vivo |
| PMID: 29898959 | Conditional KO | Qualifies | Myeloid STAT3 KO in wound healing | Myeloid STAT3 KO: minor impact on wound closure | Mouse, myeloid KO | High; cell-type specificity |
| PMID: 30254684 | Knockout | Supports core TF function | STAT3 knockout phenotype | Constitutive KO lethal at E6.5โE7.5 | Mouse embryo | High |
| PMID: 33305182 | Direct assay | Qualifies (mitochondrial) | STAT3 non-transcriptional function | Non-transcriptional role is mitochondrial, not cytoskeletal | Human, tumor cells | High |
| PMID: 27978828 | Direct assay | Qualifies | Integrin-FAK-STAT3 pathway | S727 non-transcriptional function is mitochondrial | Mouse, brain endothelial | High |
| PMID: 39300285 | scRNA-seq + functional | Qualifies as transcriptional | STAT3 in wound healing | STAT3-activated SPRR1B+ keratinocytes; SPRR1B KD inhibits migration | Human/Mouse, oral mucosa | High; transcriptional mechanism |
| PMID: 39473261 | Review | Supports core TF function | STAT3 overview | Describes STAT3 as transcription factor with migration among many activities | Review | Moderate |
| UniProt SPARQL (June 2026) | Database record | Supports non-core | STAT3 GO annotation landscape | 17+ TF annotations, 1 pos migration, 1 neg migration, 0 cytoskeletal | Human P40763 | Moderate |
{{figure:go_decision_table.png|caption=GO curation decision table summarizing the evidence for and against core vs. non-core classification of the STAT3 migration annotation. The weight of evidence from multiple independent analyses favors non-core classification.}}
Current state: The annotation GO:0030335 (positive regulation of cell migration) with IMP evidence from PMID:31638206 is marked UNDECIDED.
Recommended curation lead:
| Aspect | Recommendation | Rationale |
|---|---|---|
| Term | GO:0030335 โ retain | Migration effect is real and reproducible |
| Evidence code | IMP โ retain | Appropriate for perturb-gene-observe-phenotype |
| Core/Non-core | Non-core | Transcriptional downstream effect; bidirectional |
| Reference | PMID:31638206 โ retain | Valid experimental evidence |
| Action | ACCEPT as non-core | Resolve current UNDECIDED status |
If a curator determines that the STAT3-stathmin interaction constitutes direct participation in the migration machinery sufficient for core classification, this would be an unusual but defensible interpretation. In that case:
- The annotation could be classified as CORE with a note documenting both transcriptional and non-transcriptional mechanisms
- This would require policy guidance on how dual-mechanism genes are handled
- The ฮฒ-catenin precedent (dual adhesion + Wnt transcription function) may be informative
The most significant competing evidence comes from the STAT3-stathmin interaction literature. If STAT3 directly stabilizes microtubules by sequestering stathmin โ a mechanism demonstrated with purified recombinant proteins in vitro (PMID: 16401721) โ this would constitute a direct, non-transcriptional role in the migration machinery. Several considerations limit this argument:
The bidirectional migration phenotype is the single strongest piece of evidence for non-core classification. Core migration machinery proteins (e.g., Rac1, Cdc42, WASP, Arp2/3 complex, cofilin) consistently function in the same direction because they ARE the molecular machinery executing movement. STAT3 promotes migration in cancer and wound healing but inhibits migration in cortical neurons โ because in neurons, STAT3 activates different transcriptional targets that produce the opposite migratory effect. This is the textbook behavior of an upstream regulator, not a core machinery component.
The myeloid-specific STAT3 knockout showing "minor" impact on wound closure (PMID: 29898959) versus the keratinocyte-specific knockout showing clear migration defects (PMID: 17601706) illustrates that even the magnitude of STAT3's migration effect varies dramatically by cell type. This is another hallmark of a downstream effect mediated through different transcriptional programs.
STAT3 is the primary STAT family member implicated in migration. STAT1, STAT5A/B have distinct functions and are not prominently associated with cell migration. No organism-specific discrepancies were identified across human, mouse, and rat studies.
| Gap | What Was Checked | Why It Matters | Resolution Needed |
|---|---|---|---|
| STAT3-stathmin in NSCLC | Literature search for STAT3-stathmin in lung cancer; only transcriptional evidence found | Reference paper (PMID:31638206) is from NSCLC; stathmin mechanism not tested there | Test STAT3-stathmin co-IP in A549/H1975 NSCLC cells |
| Transcription-independent migration | No studies using transcriptionally dead STAT3 mutants in NSCLC migration | Would definitively distinguish core vs. downstream in the annotation's context | Express STAT3 DNA-binding mutants in STAT3-null NSCLC cells, measure migration |
| Quantitative contribution | Partial rescue data from PMID:16401721 only | Need to know what fraction of STAT3's migration effect is transcriptional vs. stathmin-mediated | Simultaneous measurement with WT, Y705F, DBD mutants, and stathmin-KD |
| Stathmin mechanism breadth | Demonstrated in T-cells, neurons, fibroblasts, gastric cancer; not tested in most other contexts | If context-limited, strengthens non-core; if universal, strengthens core | Systematic survey across cell types |
| Isoform-specific effects | STAT3ฮฑ vs. STAT3ฮฒ not distinguished in migration studies | STAT3ฮฒ lacks transactivation domain but may retain stathmin binding | Test isoform-specific knockdown/overexpression in migration assays |
| Wound healing mechanism | STAT3-SPRR1B transcriptional mechanism documented; stathmin role not tested | Wound healing is a physiological migration context | Test STAT3-stathmin interaction in migrating keratinocytes |
| Evolutionary conservation | Not systematically assessed | If STAT3-migration link is conserved in invertebrates, may reflect ancient core function | Compare in Drosophila STAT92E models |
The following experiments would most efficiently resolve remaining uncertainty:
Separation-of-function STAT3 mutants + migration assay (HIGHEST PRIORITY): Express in STAT3-null NSCLC cells: (a) WT STAT3, (b) STAT3-Y705F (transcriptionally impaired but retains stathmin binding), (c) STAT3-DBD mutant (cannot bind DNA), (d) STAT3 with stathmin-binding domain disrupted. Compare migration rescue. This would definitively separate the two mechanisms in the reference paper's context.
STAT3-stathmin co-IP in NSCLC cells: Test whether the stathmin mechanism is active in A549/H1975 cells. If absent, the annotation from PMID:31638206 is purely transcriptional.
Acute STAT3 degradation kinetics: Use dTAG/auxin-inducible degron STAT3 and measure migration at 2h (before transcriptional effects) vs. 24h. If acute degradation immediately impairs migration, the stathmin mechanism is active in that context.
STAT3ฮฒ isoform migration test: Express STAT3ฮฒ (lacks transactivation domain) in STAT3-null cells. If migration is partially rescued, confirms non-transcriptional contribution is sufficient.
Comparative annotation analysis: Examine how GO annotates other dual-function proteins (e.g., ฮฒ-catenin in both adhesion and Wnt transcription) for analogous core/non-core precedents.
Ensure the following core-function annotations exist for STAT3:
- MF: DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)
- BP: JAK-STAT signaling pathway (GO:0007259)
- BP: Cytokine-mediated signaling pathway (GO:0019221)
| PMID | Title (abbreviated) | Role in Assessment |
|---|---|---|
| 31638206 | miR-4500 suppresses NSCLC by regulating STAT3 | Reference paper โ IMP evidence for migration annotation; classic indirect design |
| 23623921 | STAT3 mediates TGF-ฮฒ1-induced TWIST1 and invasion | Establishes transcriptional mechanism for migration via ChIP |
| 25653024 | STAT3 cooperates with Twist for EMT in HCC | Confirms transcriptional pathway to migration via reporter assay |
| 22907754 | KLF4 role in neurogenesis and radial migration | Critical โ shows STAT3 INHIBITS migration in neurons; clinches bidirectionality |
| 16401721 | Stat3 regulates MTs by antagonizing stathmin | Seminal stathmin interaction paper; strongest competing evidence |
| 19251695 | STAT3-stathmin in migrating T-cells | Confirms stathmin mechanism in T-cell migration |
| PMID | Title (abbreviated) | Role in Assessment |
|---|---|---|
| 30254684 | STAT3-inducible mouse ESCs | STAT3 KO lethality at E6.5โE7.5 confirms transcriptional essentiality |
| 28170160 | Inducible model to silence Stat3 | Core TF function characterization |
| 17601706 | Stat3 in skin biology | Keratinocyte-specific KO shows in vivo migration defect |
| 29898959 | Myeloid STAT3 antifibrotic repair | Cell-type specificity of wound healing role (minor effect) |
| 33305182 | STAT3 inhibitor OPB-51602 | Non-transcriptional STAT3 role is mitochondrial, not cytoskeletal |
| 27978828 | Integrin-FAK and mitochondrial STAT3 | S727 non-transcriptional function is mitochondrial |
| 31837949 | PRECSIT promotes cSCC via STAT3/MMPs | STAT3 โ MMP transcriptional axis for invasion |
| 30442941 | PLOD3 promotes lung metastasis via STAT3 | STAT3 โ MMP-2/9 in lung cancer metastasis |
| 30361813 | Paeoniflorin inhibits gastric CAF migration | IL-6/STAT3/MMP paracrine migration cascade |
| 23109669 | STAT3 in pmn motoneuron disease | STAT3-stathmin interaction in axon maintenance |
| 23333463 | STAT3/Skp2/p27/p21 in gastric cancer motility | Dual mechanisms: cytoskeletal + transcriptional |
| 39300285 | SPRR1B+ keratinocytes in wound healing | STAT3 โ SPRR1B transcriptional mechanism for keratinocyte migration |
| 39473261 | STAT3 in CRC pathogenesis | Review listing migration among many STAT3 downstream activities |
| 16835434 | Touched and moved by STAT3 | Commentary on stathmin mechanism |
Literature bias toward cancer. The vast majority of STAT3-migration studies are in cancer cell lines, which have numerous dysregulated pathways that may amplify or distort STAT3's contribution to migration. Normal physiological contexts (wound healing, immune cell trafficking) are less well-studied.
Incomplete mechanism dissection. Most studies use total STAT3 knockdown/knockout, which eliminates both transcriptional and non-transcriptional functions simultaneously. No study directly compares the quantitative contribution of each mechanism in the same cell system.
Reference paper limitations. PMID:31638206 is a cancer cell line study focused on miR-4500 as an anti-cancer mechanism, with migration as one of several measured phenotypes. It was not designed to address the core vs. non-core question.
Stathmin mechanism under-explored. The STAT3-stathmin interaction, first published in 2006, has relatively few follow-up studies (~6) compared to the transcriptional migration literature (~14+). This asymmetry may partly reflect publication bias rather than biological importance.
No separation-of-function experiments in NSCLC. The definitive experiment (transcriptionally dead STAT3 mutant in NSCLC migration assay) has not been performed. Our classification relies on the convergence of indirect evidence.
Species considerations. Most evidence is from mouse conditional knockouts and human cancer cell lines. Evolutionary conservation of the stathmin mechanism has not been systematically assessed.
Report generated from 5 iterations of systematic investigation, reviewing 73 papers across PubMed, UniProt, and GO databases. Investigation covered transcriptional mechanisms, non-transcriptional stathmin interaction, bidirectional migration effects, conditional knockout phenotypes, and GO annotation landscape analysis. Last updated: 2026-06-07.
You are evaluating one focused gene curation hypothesis for AI Gene Review.
This is not a general gene overview. Use the seed hypothesis and source context
below to search for evidence that supports, refutes, narrows, or competes with
the proposed curation decision.
The existing STAT3 GO annotation to positive regulation of cell migration (GO:0030335) is currently action ACCEPT and was flagged by the ASSAY_TO_FUNCTION readout class CELL_MIGRATION_INVASION. Decide whether this BP term is a CORE function of STAT3 (a primary process the gene product evolved to drive) versus a DOWNSTREAM, secondary, or context-dependent consequence of its core molecular activity that is better captured as non-core. Distinguish a 'real, documented effect' (which may not be in question) from a 'core function'. Flag rationale: ACCEPT BP call aligned to CELL_MIGRATION_INVASION; rubric default is non-core unless gene is in the machinery
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: UNDECIDED
reason: 'Real but borderline core vs non-core. STAT3''s core molecular function is signal-dependent
DNA-binding transcription factor activity (JAK-STAT); cell migration is a downstream transcriptional
consequence rather than an activity STAT3 itself performs, and STAT3 is not part of the cytoskeletal/
adhesion motility machinery. The IMP evidence (knockdown/overexpression migration phenotype) is the
classic indirect "perturb gene -> phenotype" inference. Flagged by the ASSAY_TO_FUNCTION CELL_MIGRATION_INVASION
readout class; given STAT3 is high-profile and the call is genuinely contested (oncogenic migration
driver vs downstream consequence), deferred to expert review rather than unilaterally demoted (issue
#1422; staged OpenScientist hypothesis job under STAT3-hypotheses/).'
supported_by:
- reference_id: PMID:31638206
supporting_text: Oct 11. MicroRNAโ4500 suppresses tumor progression in nonโsmall cell lung cancer
by regulating STAT3.
Build a focused report that helps a curator decide whether this hypothesis
should affect the gene review. Address the focus type directly:
Use primary literature whenever possible. Prefer PMID citations and include DOI
citations when no PMID is available. Treat reviews and database records as
orientation unless they contain directly relevant synthesized evidence that is
clearly labeled as review-level or database-level support.
Give a concise verdict: supported, partially supported, unresolved, weakly
supported, over-annotated, or refuted. Explain the reasoning and the most
important caveats.
Create a table with one row per important evidence item:
State the likely curation action as a lead requiring curator verification. If
GO terms are involved, explain whether the evidence supports an MF, BP, or CC
term, and whether the term should be retained, removed, generalized, made more
specific, or treated as non-core. Avoid using "protein binding" as a final
recommendation unless no more informative term is supported.
Describe the immediate molecular or cellular function being tested. Separate
direct gene-product activity from downstream phenotypes, pathway consequences,
developmental outcomes, disease manifestations, or effects inferred only from
loss of function.
Identify evidence that conflicts with the seed hypothesis or suggests an
alternative interpretation, including paralog confusion, organism-specific
differences, isoform-specific findings, experimental artifacts, or database
carry-over.
List explicit uncertainties that matter for curation. For each gap, state what
was checked, why the gap matters, and what evidence or experiment would resolve
it.
Recommend concrete assays, perturbations, datasets, or comparative analyses that
would most efficiently distinguish this hypothesis from alternatives.
Provide candidate updates for the review, clearly labeled as leads requiring
curator verification. Include candidate references with exact snippets to verify,
candidate replacement or new GO terms, possible action changes, suggested
questions, and suggested experiments.
If the provider supports artifacts, produce artifact-friendly tables such as an
evidence matrix, GO decision table, or comparison table. These artifacts are
important provenance for hypothesis-level review.
STAT3 encodes a transcription factor with isoforms that have distinct transcriptional activities.
| 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 |
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
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
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
Completed comprehensive systematic review of 456 existing GO annotations for human STAT3 (UniProt P40763).
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.
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
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)
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
Binds GAS elements in target gene promoters
Protein homodimerization activity (GO:0042803)
SH2-pY705 reciprocal interactions essential for activation
JAK-STAT signaling pathway (GO:0007259)
Activated by JAK kinases downstream of cytokine receptors
IL-6-mediated signaling pathway (GO:0070106)
IL-6 โ IL-6Rฮฑ/gp130 โ JAKs โ pY705-STAT3 โ dimerization โ nucleus โ transcription
Astrocyte differentiation (GO:0048708)
All annotations reference: file:human/STAT3/STAT3-deep-research-falcon.md
Key findings from deep research:
- Canonical IL-6โJAKโSTAT3 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)
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
COMPLETE - All 456 annotations systematically reviewed with specific rationales and supporting references.
/Users/cjm/repos/ai-gene-review/genes/human/STAT3/STAT3-ai-review.yaml (5140 lines)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: STAT3 acts downstream of hypothalamic leptin/JAK signalling, but as a highly pleiotropic transcription factor its link to feeding behaviour is an electronically-inferred, distal organismal output rather than a core STAT3 function.
action: KEEP_AS_NON_CORE
reason: Electronic (IEA/ISS) behavioural annotation on a pleiotropic transcription factor; distal to its core JAK-STAT signalling role; non-core.
- 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: UNDECIDED
reason: >-
Real but borderline core vs non-core. STAT3's core molecular function is
signal-dependent DNA-binding transcription factor activity (JAK-STAT);
cell migration is a downstream transcriptional consequence rather than an
activity STAT3 itself performs, and STAT3 is not part of the cytoskeletal/
adhesion motility machinery. The IMP evidence (knockdown/overexpression
migration phenotype) is the classic indirect "perturb gene -> phenotype"
inference. Flagged by the ASSAY_TO_FUNCTION CELL_MIGRATION_INVASION
readout class; given STAT3 is high-profile and the call is genuinely
contested (oncogenic migration driver vs downstream consequence), deferred
to expert review rather than unilaterally demoted (issue #1422; staged
OpenScientist hypothesis job under STAT3-hypotheses/). The OpenScientist
cited adjudication (29 refs, verified) converged on NON-CORE (retain,
not remove). Verification of its citations independently found that the
supporting reference PMID:31638206 is indexed by PubMed as a RETRACTED
publication, and surfaced a genuine non-transcriptional STAT3-stathmin
microtubule mechanism (PMID:16401721) that currently has no GO
cytoskeletal annotation - both noted for the expert (issue #1422).
supported_by:
- reference_id: PMID:31638206
supporting_text: Oct 11. MicroRNAโ4500 suppresses tumor progression in nonโsmall cell lung cancer by regulating STAT3.
- reference_id: file:human/STAT3/STAT3-hypotheses/readout-go-0030335/openscientist.md
supporting_text: >-
Verdict NON-CORE (over-annotated as core): cell migration is a real,
well-documented downstream consequence of STAT3's core transcription
factor activity (e.g. transcriptional induction of Twist1, MMPs)
rather than evidence STAT3 is part of the migration machinery;
bidirectional context-dependent effects (also GO:2001223) are the
hallmark of a transcription factor. Retain but reclassify non-core.
- 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: UNDECIDED
reason: >-
Real but borderline core vs non-core (companion IMP annotation to the
GO:0030335 call on PMID:31638206). STAT3's core is signal-dependent
DNA-binding TF activity; cell migration is a downstream transcriptional
consequence, not in the motility machinery. Flagged by ASSAY_TO_FUNCTION
(CELL_MIGRATION_INVASION); deferred to expert review rather than
unilaterally demoted. See issue #1422.
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 GTPaseโlike 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: STAT3 acts downstream of hypothalamic leptin/JAK signalling, but as a highly pleiotropic transcription factor its link to feeding behaviour is an electronically-inferred, distal organismal output rather than a core STAT3 function.
action: KEEP_AS_NON_CORE
reason: Electronic (IEA/ISS) behavioural annotation on a pleiotropic transcription factor; distal to its core JAK-STAT signalling role; non-core.
- 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: Eating-behaviour effects of STAT3 reflect its role in leptin-responsive hypothalamic transcription, a distal consequence of STAT3 signalling rather than a direct STAT3 function; evidence is ISS only.
action: KEEP_AS_NON_CORE
reason: Electronic (ISS) behavioural annotation on a pleiotropic transcription factor; non-core.
- 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: file:human/STAT3/STAT3-hypotheses/readout-go-0030335/openscientist.md
title: OpenScientist focused review โ STAT3 positive regulation of cell migration (GO:0030335) core vs downstream
findings:
- statement: Verdict NON-CORE โ migration is a real but downstream transcriptional consequence of STAT3's core transcription factor activity, not migration machinery; retain the annotation but reclassify as non-core (resolve UNDECIDED to non-core).
- statement: STAT3 drives migration mainly by transcriptionally inducing pro-migratory targets (Twist1, MMP-1/2/3/9/10/13); bidirectional context-dependent effects (it also carries GO:2001223 negative regulation of neuron migration) are the hallmark of a TF.
- statement: A genuine non-transcriptional STAT3-stathmin (STMN1) microtubule-stabilizing mechanism exists (PMID:16401721, PMID:19251695) but is context-limited and has no GO cytoskeletal annotation โ a possible evidence/annotation gap for expert review.
- statement: Citation verification (PubMed) confirmed all pivotal PMIDs are real; it also found the supporting reference PMID:31638206 is indexed as a RETRACTED publication โ a curation-relevant caveat the agent report did not flag.
- 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 GTPaseโlike 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: MicroRNAโ4500 suppresses tumor progression in nonโsmall 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: pโY705-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:pโJAK1: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:pโJAK2,pโJAK3 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:pโJAK1:IL20RB:pโSTAT3
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