Signal transducer and activator of transcription 3 (Stat3) is a latent cytoplasmic transcription factor of the STAT family (N-terminal, coiled-coil, DNA-binding, linker, SH2 and transactivation domains). Binding of cytokines of the gp130 family (IL-6, IL-11, LIF, OSM, CNTF), IL-10, IL-23, leptin and several growth factors to their receptors activates receptor-associated JAK kinases, which phosphorylate Stat3 on Tyr705; phosphorylated Stat3 dimerises through reciprocal SH2-phosphotyrosine contacts, accumulates in the nucleus and binds GAS-type and IL-6 response elements to activate RNA polymerase II transcription of target genes, with Ser727 phosphorylation and acetylation enhancing activity. In rat it was purified from acute-phase liver nuclei bound to the IL-6 response element of the alpha2-macroglobulin gene, and drives acute-phase, cardioprotective (alphaB-crystallin, with NFAT), prosurvival (survivin) and proliferative (cyclin D1) gene programmes. Non-nuclear pools have been described in the mitochondrial inner membrane, where STAT3 supports respiratory function, and in the postsynaptic density, where it is required for NMDA receptor-dependent long-term depression independently of transcription.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IEA GO_REF:0000107 | ACCEPT | Summary: Stat3 binds chromatin at target promoters after activation. Reason: Activated STAT3 occupies cis-regulatory regions in chromatin; ChIP in rat CA1 shows promoter occupancy. Location on chromatin follows directly from its core sequence-specific DNA-binding TF activity. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. file:rat/Stat3/Stat3-uniprot.txt interaction promotes STAT3 recruitment to chromatin and T-helper Th17 cell differentiation |
| GO:0000785 chromatin | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 binds chromatin at target promoters after activation. Reason: Activated STAT3 occupies cis-regulatory regions in chromatin; ChIP in rat CA1 shows promoter occupancy. Location on chromatin follows directly from its core sequence-specific DNA-binding TF activity. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. file:rat/Stat3/Stat3-uniprot.txt interaction promotes STAT3 recruitment to chromatin and T-helper Th17 cell differentiation |
| GO:0000785 chromatin | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 binds chromatin at target promoters after activation. Reason: Activated STAT3 occupies cis-regulatory regions in chromatin; ChIP in rat CA1 shows promoter occupancy. Location on chromatin follows directly from its core sequence-specific DNA-binding TF activity. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. file:rat/Stat3/Stat3-uniprot.txt interaction promotes STAT3 recruitment to chromatin and T-helper Th17 cell differentiation |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | MODIFY | Summary: Stat3 binds transcription cis-regulatory regions; the Pol II-specific sequence-specific term is better supported. Reason: Correct but general. Stat3 binds GAS/IL-6 response elements in Pol II promoters (alpha2-macroglobulin, CryAB, survivin); the more specific descendant GO:0000978, already carried by this gene (IBA), is preferred. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0000976 transcription cis-regulatory region binding | ISO GO_REF:0000121 | MODIFY | Summary: Stat3 binds transcription cis-regulatory regions; the Pol II-specific sequence-specific term is better supported. Reason: Correct but general. Stat3 binds GAS/IL-6 response elements in Pol II promoters (alpha2-macroglobulin, CryAB, survivin); the more specific descendant GO:0000978, already carried by this gene (IBA), is preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0000976 transcription cis-regulatory region binding | ISO GO_REF:0000121 | MODIFY | Summary: Stat3 binds transcription cis-regulatory regions; the Pol II-specific sequence-specific term is better supported. Reason: Correct but general. Stat3 binds GAS/IL-6 response elements in Pol II promoters (alpha2-macroglobulin, CryAB, survivin); the more specific descendant GO:0000978, already carried by this gene (IBA), is preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0000976 transcription cis-regulatory region binding | ISS GO_REF:0000024 | MODIFY | Summary: Stat3 binds transcription cis-regulatory regions; the Pol II-specific sequence-specific term is better supported. Reason: Correct but general. Stat3 binds GAS/IL-6 response elements in Pol II promoters (alpha2-macroglobulin, CryAB, survivin); the more specific descendant GO:0000978, already carried by this gene (IBA), is preferred. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Core: sequence-specific binding to cis-regulatory elements of Pol II-transcribed genes. Reason: Stat3 was purified from rat liver nuclei by DNA-affinity chromatography on the IL-6 response element and binds promoter elements of acute-phase and cardioprotective genes. IBA is sound: the STAT family node carries this activity throughout. Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Core: sequence-specific binding to cis-regulatory elements of Pol II-transcribed genes. Reason: Stat3 was purified from rat liver nuclei by DNA-affinity chromatography on the IL-6 response element and binds promoter elements of acute-phase and cardioprotective genes. IBA is sound: the STAT family node carries this activity throughout. Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: Core: sequence-specific binding to cis-regulatory elements of Pol II-transcribed genes. Reason: Stat3 was purified from rat liver nuclei by DNA-affinity chromatography on the IL-6 response element and binds promoter elements of acute-phase and cardioprotective genes. IBA is sound: the STAT family node carries this activity throughout. Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: Core: sequence-specific binding to cis-regulatory elements of Pol II-transcribed genes. Reason: Stat3 was purified from rat liver nuclei by DNA-affinity chromatography on the IL-6 response element and binds promoter elements of acute-phase and cardioprotective genes. IBA is sound: the STAT family node carries this activity throughout. Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Core: Stat3 is a Pol II-specific DNA-binding transcription factor. Reason: STAT family DNA-binding transcription factor; the IBA node and rat experimental data (acute-phase genes, CryAB, survivin) agree. Retained at this level because STAT3 also represses some targets; the activator descendant GO:0001228 is also accepted. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Belongs to the transcription factor STAT family. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Core: Stat3 is a Pol II-specific DNA-binding transcription factor. Reason: STAT family DNA-binding transcription factor; the IBA node and rat experimental data (acute-phase genes, CryAB, survivin) agree. Retained at this level because STAT3 also represses some targets; the activator descendant GO:0001228 is also accepted. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Belongs to the transcription factor STAT family. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: Core: Stat3 is a Pol II-specific DNA-binding transcription factor. Reason: STAT family DNA-binding transcription factor; the IBA node and rat experimental data (acute-phase genes, CryAB, survivin) agree. Retained at this level because STAT3 also represses some targets; the activator descendant GO:0001228 is also accepted. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Belongs to the transcription factor STAT family. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: Core: Stat3 is a Pol II-specific DNA-binding transcription factor. Reason: STAT family DNA-binding transcription factor; the IBA node and rat experimental data (acute-phase genes, CryAB, survivin) agree. Retained at this level because STAT3 also represses some targets; the activator descendant GO:0001228 is also accepted. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Belongs to the transcription factor STAT family. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: Core: Stat3 is a Pol II-specific DNA-binding transcription factor. Reason: STAT family DNA-binding transcription factor; the IBA node and rat experimental data (acute-phase genes, CryAB, survivin) agree. Retained at this level because STAT3 also represses some targets; the activator descendant GO:0001228 is also accepted. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt Belongs to the transcription factor STAT family. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Core: Stat3 is a transcriptional activator of Pol II target genes. Reason: Activated Stat3 drives transcription of acute-phase, cardioprotective (CryAB) and prosurvival (survivin) genes in rat tissues. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. file:rat/Stat3/Stat3-uniprot.txt binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: Core: Stat3 is a transcriptional activator of Pol II target genes. Reason: Activated Stat3 drives transcription of acute-phase, cardioprotective (CryAB) and prosurvival (survivin) genes in rat tissues. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. file:rat/Stat3/Stat3-uniprot.txt binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0001659 temperature homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 contributes to temperature homeostasis via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0001659 temperature homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 contributes to temperature homeostasis via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0001666 response to hypoxia | IEP PMID:38602915 IL-6/gp130 signaling in CD4(+) T cells drives the pathogenes... | KEEP AS NON CORE | Summary: STAT3 phosphorylation in CD4+ cells in hypoxia-induced pulmonary hypertension. Reason: Expression/activation evidence (IEP) only; non-core. Supporting Evidence: PMID:38602915 Phosphorylation of STAT3 in CD4+ cells was also observed around the vascular lesions in the lungs of the SuHx rat |
| GO:0001754 eye photoreceptor cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Eye photoreceptor cell differentiation (mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0001754 eye photoreceptor cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Eye photoreceptor cell differentiation (mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0001817 regulation of cytokine production | IEA GO_REF:0000117 | MODIFY | Summary: Regulation of cytokine production is general. Reason: Specific cytokine-production terms are carried by the gene (IL-6, IL-10). Proposed replacements: positive regulation of interleukin-6 production positive regulation of interleukin-10 production Supporting Evidence: PMID:29702085 TNF-Ξ±-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IΞΊB-NFΞΊB and JAK-STAT3 pathways. |
| GO:0002317 plasma cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 required for plasma cell differentiation (mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0002931 response to ischemia | IMP PMID:23884942 Survivin Is a transcriptional target of STAT3 critical to es... | KEEP AS NON CORE | Summary: Stat3 is activated by and required for protection after cerebral ischemia. Reason: In rat CA1, ischemia activates STAT3 and STAT3 knockdown abolishes estradiol neuroprotection; non-core. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. PMID:23884942 we show that STAT3 is critical to estradiol neuroprotection, as evidenced by the ability of STAT3 inhibitor peptide and STAT3 shRNA delivered directly into the CA1 of living animals to abolish neuroprotection. |
| GO:0003677 DNA binding | IDA PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat li... | MODIFY | Summary: Stat3 binds the IL-6 response element of the rat alpha2-macroglobulin gene. Reason: DNA-affinity purification on the IL-6 response element shows sequence-specific Pol II cis-regulatory binding; refine to GO:0000978. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:8530402 Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | MODIFY | Summary: DNA binding is correct but uninformative. Reason: Stat3 binds DNA in a sequence-specific manner at Pol II cis-regulatory elements (IL-6 response element). Replace with GO:0000978, already accepted for this gene. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0003677 DNA binding | ISO GO_REF:0000121 | MODIFY | Summary: DNA binding is correct but uninformative. Reason: Stat3 binds DNA in a sequence-specific manner at Pol II cis-regulatory elements (IL-6 response element). Replace with GO:0000978, already accepted for this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0003677 DNA binding | ISS GO_REF:0000024 | MODIFY | Summary: DNA binding is correct but uninformative. Reason: Stat3 binds DNA in a sequence-specific manner at Pol II cis-regulatory elements (IL-6 response element). Replace with GO:0000978, already accepted for this gene. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: DNA-binding transcription factor activity is correct but the Pol II-specific activator term is better supported. Reason: Stat3 is a Pol II-specific transcriptional activator; refine to GO:0001228 (a descendant), already carried by the gene. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:8530402 Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 |
| GO:0003700 DNA-binding transcription factor activity | ISO GO_REF:0000121 | MODIFY | Summary: DNA-binding transcription factor activity is correct but the Pol II-specific activator term is better supported. Reason: Stat3 is a Pol II-specific transcriptional activator; refine to GO:0001228 (a descendant), already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:8530402 Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 |
| GO:0003700 DNA-binding transcription factor activity | ISO GO_REF:0000121 | MODIFY | Summary: DNA-binding transcription factor activity is correct but the Pol II-specific activator term is better supported. Reason: Stat3 is a Pol II-specific transcriptional activator; refine to GO:0001228 (a descendant), already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:8530402 Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 |
| GO:0003700 DNA-binding transcription factor activity | ISS GO_REF:0000024 | MODIFY | Summary: DNA-binding transcription factor activity is correct but the Pol II-specific activator term is better supported. Reason: Stat3 is a Pol II-specific transcriptional activator; refine to GO:0001228 (a descendant), already carried by the gene. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:8530402 Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 |
| GO:0003700 DNA-binding transcription factor activity | ISS GO_REF:0000024 | MODIFY | Summary: DNA-binding transcription factor activity is correct but the Pol II-specific activator term is better supported. Reason: Stat3 is a Pol II-specific transcriptional activator; refine to GO:0001228 (a descendant), already carried by the gene. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:8530402 Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat li... | MODIFY | Summary: Stat3 identified as a transcription factor binding IL-6 response elements. Reason: Refine to the Pol II-specific activator term GO:0001228. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0003723 RNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RNA binding, transferred from mouse/human STAT3 reports of RNA interactions. Reason: STAT3 has been reported to bind lncRNAs and pri-miRNAs in mouse/human cells; this is peripheral to its role as a DNA-binding transcription factor and not shown for rat. |
| GO:0003723 RNA binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: RNA binding, transferred from mouse/human STAT3 reports of RNA interactions. Reason: STAT3 has been reported to bind lncRNAs and pri-miRNAs in mouse/human cells; this is peripheral to its role as a DNA-binding transcription factor and not shown for rat. |
| GO:0004879 nuclear receptor activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: STAT3 is not a ligand-regulated nuclear receptor. Reason: Nuclear receptor activity denotes a transcription factor directly regulated by binding of a small-molecule ligand (steroid/thyroid hormone type). STAT3 is activated by receptor-associated tyrosine kinases (JAKs) after cytokine binding at the cell surface, not by binding a ligand itself. The term over-reaches the evidence; the TF activity is captured by GO:0000981/GO:0001228. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0004879 nuclear receptor activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: STAT3 is not a ligand-regulated nuclear receptor. Reason: Nuclear receptor activity denotes a transcription factor directly regulated by binding of a small-molecule ligand (steroid/thyroid hormone type). STAT3 is activated by receptor-associated tyrosine kinases (JAKs) after cytokine binding at the cell surface, not by binding a ligand itself. The term over-reaches the evidence; the TF activity is captured by GO:0000981/GO:0001228. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; STAT3 is not a ligand-regulated nuclear receptor; activation is by receptor-associated JAKs. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stat3 is recruited to activated cytokine receptors. Reason: STAT3 docks via its SH2 domain on phosphotyrosine motifs of diverse cytokine receptors (gp130, IL23R, leptin receptor, CCR5 associations reported in rat). The binding is part of the activation mechanism but no single descendant covers the set of receptors; kept as non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Interacts with IL23R in presence of IL23. PMID:14674010 The association of STAT-1 and STAT-3 with CCR5 on days 18 and 21 correlated with JAK-1 phosphorylation and binding on day 18. |
| GO:0005102 signaling receptor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stat3 is recruited to activated cytokine receptors. Reason: STAT3 docks via its SH2 domain on phosphotyrosine motifs of diverse cytokine receptors (gp130, IL23R, leptin receptor, CCR5 associations reported in rat). The binding is part of the activation mechanism but no single descendant covers the set of receptors; kept as non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Interacts with IL23R in presence of IL23. PMID:14674010 The association of STAT-1 and STAT-3 with CCR5 on days 18 and 21 correlated with JAK-1 phosphorylation and binding on day 18. |
| GO:0005515 protein binding | IPI PMID:16055727 Signal regulatory protein alpha ligation induces macrophage ... | REMOVE | Summary: Co-IP of STAT3 with Rac1 in macrophages (SIRPalpha signalling). Reason: Per the protein-binding policy, bare GO:0005515 is uninformative; the Rac1-STAT3 co-IP is not disputed but establishes no more specific MF. Supporting Evidence: PMID:16055727 Upon SIRPΞ± activation, we observed the presence of STAT3 in immunoprecipitates of Rac1. |
| GO:0005515 protein binding | IPI PMID:17954917 ephrinB1 signals from the cell surface to the nucleus by rec... | REMOVE | Summary: STAT3 associates with ephrinB1 in a phosphorylation-dependent manner. Reason: Per the protein-binding policy, bare GO:0005515 is uninformative; the interaction (with Xenopus ephrinB1) is not disputed. Supporting Evidence: PMID:17954917 signal transducer and activator of transcription 3 (STAT3) can interact with ephrinB1 in a phosphorylation-dependent manner |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Stat3 accumulates in the nucleus upon activation, where it acts. Reason: Shown in rat cardiomyocytes (EN-1-induced nuclear translocation) and rat CA1 nuclear fractions; the site of its core transcriptional activity. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005634 nucleus | IDA PMID:19538478 Cross-talk between calcineurin/NFAT and Jak/STAT signalling ... | ACCEPT | Summary: EN-1 induced STAT3 nuclear translocation in rat cardiomyocytes. Reason: Direct evidence; core location. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. |
| GO:0005634 nucleus | IDA PMID:23884942 Survivin Is a transcriptional target of STAT3 critical to es... | ACCEPT | Summary: Nuclear STAT3 increases in rat CA1 after ischemia/estradiol. Reason: Direct fractionation evidence. Supporting Evidence: PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Stat3 accumulates in the nucleus upon activation, where it acts. Reason: Shown in rat cardiomyocytes (EN-1-induced nuclear translocation) and rat CA1 nuclear fractions; the site of its core transcriptional activity. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 accumulates in the nucleus upon activation, where it acts. Reason: Shown in rat cardiomyocytes (EN-1-induced nuclear translocation) and rat CA1 nuclear fractions; the site of its core transcriptional activity. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 accumulates in the nucleus upon activation, where it acts. Reason: Shown in rat cardiomyocytes (EN-1-induced nuclear translocation) and rat CA1 nuclear fractions; the site of its core transcriptional activity. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 accumulates in the nucleus upon activation, where it acts. Reason: Shown in rat cardiomyocytes (EN-1-induced nuclear translocation) and rat CA1 nuclear fractions; the site of its core transcriptional activity. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 accumulates in the nucleus upon activation, where it acts. Reason: Shown in rat cardiomyocytes (EN-1-induced nuclear translocation) and rat CA1 nuclear fractions; the site of its core transcriptional activity. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Stat3 accumulates in the nucleus upon activation, where it acts. Reason: Shown in rat cardiomyocytes (EN-1-induced nuclear translocation) and rat CA1 nuclear fractions; the site of its core transcriptional activity. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005654 nucleoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Nucleoplasm: activated STAT3 is nucleoplasmic. Reason: Consistent with nuclear localisation and chromatin binding. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleoplasm: activated STAT3 is nucleoplasmic. Reason: Consistent with nuclear localisation and chromatin binding. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000107 | MODIFY | Summary: Transcription regulator complex is correct but the Pol II-specific complex term is better. Reason: STAT3 dimers and the STAT3-NFATC3-NFATC4 promoter-binding complex regulate Pol II genes; refine to GO:0090575, already carried. Proposed replacements: RNA polymerase II transcription regulator complex Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4 PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0005667 transcription regulator complex | ISO GO_REF:0000121 | MODIFY | Summary: Transcription regulator complex is correct but the Pol II-specific complex term is better. Reason: STAT3 dimers and the STAT3-NFATC3-NFATC4 promoter-binding complex regulate Pol II genes; refine to GO:0090575, already carried. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: RNA polymerase II transcription regulator complex Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4 PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0005667 transcription regulator complex | ISO GO_REF:0000121 | MODIFY | Summary: Transcription regulator complex is correct but the Pol II-specific complex term is better. Reason: STAT3 dimers and the STAT3-NFATC3-NFATC4 promoter-binding complex regulate Pol II genes; refine to GO:0090575, already carried. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: RNA polymerase II transcription regulator complex Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4 PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0005737 cytoplasm | EXP PMID:19538478 Cross-talk between calcineurin/NFAT and Jak/STAT signalling ... | ACCEPT | Summary: STAT3 is cytoplasmic in unstimulated cardiomyocytes. Reason: Direct evidence; latent pool. Supporting Evidence: PMID:19538478 AG490 was also effective in blocking the nuclear translocation of NFAT and STAT3 in cardiomyocytes treated with En-1. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Latent Stat3 resides in the cytoplasm before activation. Reason: Shown in rat cardiomyocytes and CA1; the cytoplasm is where latent STAT3 is recruited to receptors and phosphorylated. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. file:rat/Stat3/Stat3-uniprot.txt Shuttles between the nucleus and the cytoplasm. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Latent Stat3 resides in the cytoplasm before activation. Reason: Shown in rat cardiomyocytes and CA1; the cytoplasm is where latent STAT3 is recruited to receptors and phosphorylated. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. file:rat/Stat3/Stat3-uniprot.txt Shuttles between the nucleus and the cytoplasm. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Latent Stat3 resides in the cytoplasm before activation. Reason: Shown in rat cardiomyocytes and CA1; the cytoplasm is where latent STAT3 is recruited to receptors and phosphorylated. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. file:rat/Stat3/Stat3-uniprot.txt Shuttles between the nucleus and the cytoplasm. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Latent Stat3 resides in the cytoplasm before activation. Reason: Shown in rat cardiomyocytes and CA1; the cytoplasm is where latent STAT3 is recruited to receptors and phosphorylated. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. file:rat/Stat3/Stat3-uniprot.txt Shuttles between the nucleus and the cytoplasm. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Latent Stat3 resides in the cytoplasm before activation. Reason: Shown in rat cardiomyocytes and CA1; the cytoplasm is where latent STAT3 is recruited to receptors and phosphorylated. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. file:rat/Stat3/Stat3-uniprot.txt Shuttles between the nucleus and the cytoplasm. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Latent Stat3 resides in the cytoplasm before activation. Reason: Shown in rat cardiomyocytes and CA1; the cytoplasm is where latent STAT3 is recruited to receptors and phosphorylated. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. file:rat/Stat3/Stat3-uniprot.txt Shuttles between the nucleus and the cytoplasm. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Latent Stat3 resides in the cytoplasm before activation. Reason: Shown in rat cardiomyocytes and CA1; the cytoplasm is where latent STAT3 is recruited to receptors and phosphorylated. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. file:rat/Stat3/Stat3-uniprot.txt Shuttles between the nucleus and the cytoplasm. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:23271731 The import of the transcription factor STAT3 into mitochondr... | KEEP AS NON CORE | Summary: A pool of STAT3 resides in the mitochondrial inner membrane. Reason: Import assays show mitochondrial STAT3 associates with the inner membrane via GRIM-19 and complex I. Real but non-canonical; peripheral to core TF function. Supporting Evidence: PMID:23271731 In this report we show that mitochondrial-localized STAT3 resides in the inner mitochondrial membrane. |
| GO:0005829 cytosol | IDA PMID:23884942 Survivin Is a transcriptional target of STAT3 critical to es... | ACCEPT | Summary: Cytoplasmic STAT3 in rat CA1 fractions. Reason: Direct fractionation evidence. Supporting Evidence: PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Latent Stat3 is cytosolic. Reason: Unphosphorylated STAT3 is a soluble cytosolic protein that shuttles to the nucleus; consistent with rat CA1 cytoplasmic fractionation. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: Latent Stat3 is cytosolic. Reason: Unphosphorylated STAT3 is a soluble cytosolic protein that shuttles to the nucleus; consistent with rat CA1 cytoplasmic fractionation. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005829 cytosol | TAS Reactome:R-RNO-198717 | ACCEPT | Summary: Latent Stat3 is cytosolic. Reason: Unphosphorylated STAT3 is a soluble cytosolic protein that shuttles to the nucleus; consistent with rat CA1 cytoplasmic fractionation. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Predominantly present in the cytoplasm without stimuli. PMID:23884942 STAT3 abundance and phosphorylation status were assessed in the cytoplasmic and nuclear fractions of CA1 at times after ischemia. |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 is transiently recruited to activated receptors at the plasma membrane. Reason: Recruitment to receptor phosphotyrosines is transient and part of activation; not a resident membrane location. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 is transiently recruited to activated receptors at the plasma membrane. Reason: Recruitment to receptor phosphotyrosines is transient and part of activation; not a resident membrane location. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | MODIFY | Summary: Regulation of DNA-templated transcription: the Pol II-positive term is better. Reason: STAT3 is principally a Pol II activator; refine to GO:0045944. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0006355 regulation of DNA-templated transcription | ISO GO_REF:0000121 | MODIFY | Summary: Regulation of DNA-templated transcription: the Pol II-positive term is better. Reason: STAT3 is principally a Pol II activator; refine to GO:0045944. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0006355 regulation of DNA-templated transcription | ISS GO_REF:0000024 | MODIFY | Summary: Regulation of DNA-templated transcription: the Pol II-positive term is better. Reason: STAT3 is principally a Pol II activator; refine to GO:0045944. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: STAT3 regulates transcription by RNA polymerase II. Reason: IBA from the STAT family node; retained at this level as STAT3 both activates and, at some targets, represses Pol II genes. The positive descendant GO:0045944 is also accepted. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0006357 regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: STAT3 regulates transcription by RNA polymerase II. Reason: IBA from the STAT family node; retained at this level as STAT3 both activates and, at some targets, represses Pol II genes. The positive descendant GO:0045944 is also accepted. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0006366 transcription by RNA polymerase II | ISO GO_REF:0000121 | MODIFY | Summary: STAT3 regulates, rather than performs, Pol II transcription. Reason: A sequence-specific TF should be annotated to regulation of transcription; replace with GO:0045944. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term names the process executed by the Pol II machinery, whereas STAT3 regulates it. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0006606 protein import into nucleus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: STAT3 is a cargo of nuclear import, not part of the import machinery. Reason: Activated STAT3 is imported via importin-alpha (KPNA4/5); STAT3 is the substrate of import rather than an effector of the process. Over-annotation. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0006606 protein import into nucleus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: STAT3 is a cargo of nuclear import, not part of the import machinery. Reason: Activated STAT3 is imported via importin-alpha (KPNA4/5); STAT3 is the substrate of import rather than an effector of the process. Over-annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; STAT3 is the cargo of importin-mediated import, not an effector of it. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0006606 protein import into nucleus | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: STAT3 is a cargo of nuclear import, not part of the import machinery. Reason: Activated STAT3 is imported via importin-alpha (KPNA4/5); STAT3 is the substrate of import rather than an effector of the process. Over-annotation. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Translocated into the nucleus upon tyrosine phosphorylation and dimerization |
| GO:0006952 defense response | IBA GO_REF:0000033 | MODIFY | Summary: Defense response is general; acute-phase response is the supported descendant. Reason: The IBA STAT-family node asserts a defense role; for STAT3 the best-supported specific form is the IL-6-driven acute-phase response (GO:0006953). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000927860 STAT-family PAINT node; STAT3 lies inside the clade; node placement not re-examined here; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: acute-phase response Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. |
| GO:0006953 acute-phase response | IEP PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat li... | ACCEPT | Summary: Stat3 mediates the hepatic acute-phase response. Reason: Stat3 was purified from rat liver nuclei late in an acute-phase response bound to the IL-6 response element of an acute-phase gene; this is the classic physiological context of STAT3 in rat. Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. |
| GO:0006954 inflammatory response | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: STAT3 participates in inflammatory responses. Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0006954 inflammatory response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 participates in inflammatory responses. Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0006954 inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 participates in inflammatory responses. Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0007165 signal transduction | IEA GO_REF:0000120 | MODIFY | Summary: Signal transduction is correct but uninformative. Reason: STAT3 is a signal transducer in JAK-STAT signalling; refine to GO:0007259. Proposed replacements: cell surface receptor signaling pathway via JAK-STAT Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: STAT3 is not a component of TGF-beta receptor (SMAD) signalling. Reason: TGF-beta and IL-6/STAT3 cooperate in Th17 differentiation, but STAT3 does not transduce the TGF-beta receptor signal; the annotation likely reflects pathway cross-talk. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: STAT3 is not a component of TGF-beta receptor (SMAD) signalling. Reason: TGF-beta and IL-6/STAT3 cooperate in Th17 differentiation, but STAT3 does not transduce the TGF-beta receptor signal; the annotation likely reflects pathway cross-talk. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; STAT3 cooperates with TGF-beta in Th17 differentiation but does not transduce the TGF-beta receptor signal. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | ACCEPT | Summary: Core: Stat3 is the signal transducer of JAK-STAT receptor signalling. Reason: Stat3 is tyrosine-phosphorylated by receptor-associated JAKs, dimerises and translocates to the nucleus to activate target genes; this is its defining role, supported in rat by IL-6/acute-phase studies. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IEA GO_REF:0000107 | ACCEPT | Summary: Core: Stat3 is the signal transducer of JAK-STAT receptor signalling. Reason: Stat3 is tyrosine-phosphorylated by receptor-associated JAKs, dimerises and translocates to the nucleus to activate target genes; this is its defining role, supported in rat by IL-6/acute-phase studies. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | ISO GO_REF:0000121 | ACCEPT | Summary: Core: Stat3 is the signal transducer of JAK-STAT receptor signalling. Reason: Stat3 is tyrosine-phosphorylated by receptor-associated JAKs, dimerises and translocates to the nucleus to activate target genes; this is its defining role, supported in rat by IL-6/acute-phase studies. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | TAS PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat li... | ACCEPT | Summary: Stat3 activated in rat liver during the IL-6-driven acute phase. Reason: Classic JAK-STAT context in rat liver; core. Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0008283 cell population proliferation | ISO GO_REF:0000121 | MODIFY | Summary: STAT3 promotes, rather than executes, cell proliferation. Reason: Refine to positive regulation (GO:0008284), supported in rat satellite cells and NSCs. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; STAT3 regulates proliferation rather than executing it. Proposed replacements: positive regulation of cell population proliferation Supporting Evidence: PMID:23869758 IL-6 induced dose-dependent increase in satellite cell proliferation by activating the JAK2/STAT3/cyclin D1 pathway. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:23608221 Multiple signaling pathways mediate ghrelin-induced prolifer... | KEEP AS NON CORE | Summary: Stat3 mediates ghrelin- and IL-6-induced proliferation in rat cells. Reason: Inhibitor evidence in rat hippocampal NSCs and satellite cells; context-specific consequence of STAT3 target-gene (cyclin D1) induction. Non-core. Supporting Evidence: PMID:23608221 pretreatment of cells with specific inhibitors of MEK/ERK1/2, phosphatidylinositol-3-kinase (PI3K)/Akt, mTOR, and Jak2/STAT3 attenuated ghrelin-induced cell proliferation PMID:23869758 IL-6 induced dose-dependent increase in satellite cell proliferation by activating the JAK2/STAT3/cyclin D1 pathway. |
| GO:0008285 negative regulation of cell population proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 can inhibit proliferation in some contexts. Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0010467 gene expression | ISO GO_REF:0000121 | MODIFY | Summary: STAT3 regulates gene expression rather than executing it. Reason: Gene expression as a process is carried out by the transcription/translation machinery; STAT3's role is positive regulation of Pol II transcription. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; gene expression is executed by the transcription/translation machinery; STAT3 regulates it. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0010467 gene expression | ISO GO_REF:0000121 | MODIFY | Summary: STAT3 regulates gene expression rather than executing it. Reason: Gene expression as a process is carried out by the transcription/translation machinery; STAT3's role is positive regulation of Pol II transcription. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; gene expression is executed by the transcription/translation machinery; STAT3 regulates it. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0010507 negative regulation of autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytoplasmic STAT3 represses autophagy via PKR. Reason: Non-canonical cytoplasmic role (mouse/human); non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity |
| GO:0010507 negative regulation of autophagy | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cytoplasmic STAT3 represses autophagy via PKR. Reason: Non-canonical cytoplasmic role (mouse/human); non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity |
| GO:0010575 positive regulation of vascular endothelial growth factor production | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 acts upstream of VEGF production. Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: STAT3 positively regulates expression of target genes. Reason: True; the more precise GO:0045944 is accepted. Kept as non-core summary term. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 positively regulates expression of target genes. Reason: True; the more precise GO:0045944 is accepted. Kept as non-core summary term. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 positively regulates expression of target genes. Reason: True; the more precise GO:0045944 is accepted. Kept as non-core summary term. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 can repress some target genes. Reason: Context-dependent repressive effects (transferred from mouse/human); non-core. |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 can repress some target genes. Reason: Context-dependent repressive effects (transferred from mouse/human); non-core. |
| GO:0010730 negative regulation of hydrogen peroxide biosynthetic process | IMP PMID:23590160 The STAT3 inhibitor stattic impairs cardiomyocyte mitochondr... | KEEP AS NON CORE | Summary: Mitochondrial STAT3 restrains ROS (H2O2) formation. Reason: Stattic dose-dependently increased H2O2 formation in rat cardiac mitochondria. Pharmacological, non-core. Supporting Evidence: PMID:23590160 Stattic dose-dependently increased mitochondrial ROS formation |
| GO:0014069 postsynaptic density | IDA PMID:10891587 Occurrence of a transcription factor, signal transducer and ... | KEEP AS NON CORE | Summary: Stat3 is enriched in the rat brain PSD fraction and by immuno-EM. Reason: Direct evidence for a synaptic pool (both IDA and IEP rows); non-core location. Supporting Evidence: PMID:10891587 The occurrence of Stat3 in the synaptic site, especially in the PSD, was confirmed by immunoelectron microscopic examination. |
| GO:0014069 postsynaptic density | IEP PMID:10891587 Occurrence of a transcription factor, signal transducer and ... | KEEP AS NON CORE | Summary: Stat3 is enriched in the rat brain PSD fraction and by immuno-EM. Reason: Direct evidence for a synaptic pool (both IDA and IEP rows); non-core location. Supporting Evidence: PMID:10891587 The occurrence of Stat3 in the synaptic site, especially in the PSD, was confirmed by immunoelectron microscopic examination. |
| GO:0019221 cytokine-mediated signaling pathway | IEA GO_REF:0000107 | MODIFY | Summary: Cytokine-mediated signalling is correct; specific cytokine pathways are better supported. Reason: STAT3 mediates signalling by gp130-family cytokines (IL-6, IL-11, LIF, OSM, CNTF), IL-10 and IL-23; replace with these specific descendants. Proposed replacements: interleukin-6-mediated signaling pathway interleukin-11-mediated signaling pathway leukemia inhibitory factor signaling pathway oncostatin-M-mediated signaling pathway ciliary neurotrophic factor-mediated signaling pathway interleukin-10-mediated signaling pathway interleukin-23-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. |
| GO:0019221 cytokine-mediated signaling pathway | ISO GO_REF:0000121 | MODIFY | Summary: Cytokine-mediated signalling is correct; specific cytokine pathways are better supported. Reason: STAT3 mediates signalling by gp130-family cytokines (IL-6, IL-11, LIF, OSM, CNTF), IL-10 and IL-23; replace with these specific descendants. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: interleukin-6-mediated signaling pathway interleukin-11-mediated signaling pathway leukemia inhibitory factor signaling pathway oncostatin-M-mediated signaling pathway ciliary neurotrophic factor-mediated signaling pathway interleukin-10-mediated signaling pathway interleukin-23-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. |
| GO:0019827 stem cell population maintenance | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stem cell population maintenance (LIF/STAT3 in ES cells, mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0019901 protein kinase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stat3 binds protein kinases that activate it (JAKs, BMX, FER). Reason: Binding to activating kinases is part of how STAT3 is regulated, not an activity it performs on other proteins; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Activated through tyrosine phosphorylation by BMX. |
| GO:0019901 protein kinase binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Stat3 binds protein kinases that activate it (JAKs, BMX, FER). Reason: Binding to activating kinases is part of how STAT3 is regulated, not an activity it performs on other proteins; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Activated through tyrosine phosphorylation by BMX. |
| GO:0019903 protein phosphatase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stat3 binds phosphatases (PTPN2) that inactivate it. Reason: Interaction with PTPN2 mediates STAT3 dephosphorylation and termination of signalling; a regulatory interaction, non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Interacts with PTPN2; the interaction is promoted by FAM220A and leads to STAT3 dephosphorylation |
| GO:0019903 protein phosphatase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stat3 binds phosphatases (PTPN2) that inactivate it. Reason: Interaction with PTPN2 mediates STAT3 dephosphorylation and termination of signalling; a regulatory interaction, non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Interacts with PTPN2; the interaction is promoted by FAM220A and leads to STAT3 dephosphorylation |
| GO:0030154 cell differentiation | IEA GO_REF:0000107 | MODIFY | Summary: Cell differentiation is general; specific differentiation processes are carried. Reason: STAT3-dependent differentiation outputs carried by the gene include astrocyte and Th17 differentiation. Proposed replacements: astrocyte differentiation T-helper 17 cell lineage commitment Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0030154 cell differentiation | ISO GO_REF:0000121 | MODIFY | Summary: Cell differentiation is general; specific differentiation processes are carried. Reason: STAT3-dependent differentiation outputs carried by the gene include astrocyte and Th17 differentiation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: astrocyte differentiation T-helper 17 cell lineage commitment Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0030335 positive regulation of cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of cell migration (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0030335 positive regulation of cell migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of cell migration (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0030522 intracellular receptor signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Intracellular receptor signalling does not describe STAT3 activation. Reason: STAT3 is activated downstream of cell-surface receptors, not intracellular (nuclear) receptors; the annotation appears to follow from the nuclear receptor activity mapping. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0030522 intracellular receptor signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Intracellular receptor signalling does not describe STAT3 activation. Reason: STAT3 is activated downstream of cell-surface receptors, not intracellular (nuclear) receptors; the annotation appears to follow from the nuclear receptor activity mapping. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; STAT3 acts downstream of cell-surface, not intracellular, receptors. Supporting Evidence: PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0030968 endoplasmic reticulum unfolded protein response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 in ER unfolded protein response (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0031490 chromatin DNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stat3 binds DNA within chromatin. Reason: Accurate description of how activated STAT3 engages promoter DNA in chromatin; overlaps the core sequence-specific DNA-binding activity and is kept as non-core. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0031490 chromatin DNA binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stat3 binds DNA within chromatin. Reason: Accurate description of how activated STAT3 engages promoter DNA in chromatin; overlaps the core sequence-specific DNA-binding activity and is kept as non-core. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0031490 chromatin DNA binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Stat3 binds DNA within chromatin. Reason: Accurate description of how activated STAT3 engages promoter DNA in chromatin; overlaps the core sequence-specific DNA-binding activity and is kept as non-core. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0031730 CCR5 chemokine receptor binding | IPI PMID:14674010 Chemokine receptor expression and in vivo signaling pathways... | KEEP AS NON CORE | Summary: Stat3 co-immunoprecipitates with CCR5 in arthritic rat joints. Reason: Rat adjuvant-induced arthritis study shows STAT3 association with CCR5 in joint tissue by co-IP. Plausibly reflects receptor docking during chemokine-induced JAK-STAT activation; context-specific and indirect (co-IP from tissue), so non-core. Supporting Evidence: PMID:14674010 The association of STAT-1 and STAT-3 with CCR5 on days 18 and 21 correlated with JAK-1 phosphorylation and binding on day 18. |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stat3 is activated in responses to estradiol. Reason: Estradiol enhances STAT3 activation in rat CA1; non-core. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0032355 response to estradiol | IEP PMID:17916759 Protective effects of estradiol on ethanol-induced bone loss... | KEEP AS NON CORE | Summary: Stat3 is activated in responses to estradiol. Reason: Estradiol enhances STAT3 activation in rat CA1; non-core. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0032355 response to estradiol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stat3 is activated in responses to estradiol. Reason: Estradiol enhances STAT3 activation in rat CA1; non-core. Supporting Evidence: PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. |
| GO:0032731 positive regulation of interleukin-1 beta production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 positively regulates IL-1beta production (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0032731 positive regulation of interleukin-1 beta production | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 positively regulates IL-1beta production (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0032733 positive regulation of interleukin-10 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 positively regulates IL-10 production (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0032733 positive regulation of interleukin-10 production | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 positively regulates IL-10 production (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0032755 positive regulation of interleukin-6 production | IGI PMID:29702085 TNF-Ξ±-sensitive brain pericytes activate microglia by releas... | KEEP AS NON CORE | Summary: STAT3 contributes to TNF-induced IL-6 release from rat brain pericytes. Reason: Pharmacological inhibition study in rat pericytes (IGI with NF-kB pathway); acts upstream, non-core. Supporting Evidence: PMID:29702085 TNF-Ξ±-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IΞΊB-NFΞΊB and JAK-STAT3 pathways. |
| GO:0032757 positive regulation of interleukin-8 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 positively regulates IL-8 production (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0032757 positive regulation of interleukin-8 production | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 positively regulates IL-8 production (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 positively regulates TNF production (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0032760 positive regulation of tumor necrosis factor production | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 positively regulates TNF production (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0032870 cellular response to hormone stimulus | IEA GO_REF:0000107 | MODIFY | Summary: Cellular response to hormone stimulus is general. Reason: The specific hormone pathways in which STAT3 transduces signal are leptin and growth hormone receptor signalling, both carried by the gene. Proposed replacements: leptin-mediated signaling pathway growth hormone receptor signaling pathway via JAK-STAT Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0032870 cellular response to hormone stimulus | ISO GO_REF:0000121 | MODIFY | Summary: Cellular response to hormone stimulus is general. Reason: The specific hormone pathways in which STAT3 transduces signal are leptin and growth hormone receptor signalling, both carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: leptin-mediated signaling pathway growth hormone receptor signaling pathway via JAK-STAT Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0033210 leptin-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: STAT3 is the principal transducer of leptin receptor (LepRb) signalling. Reason: Leptin effects on melanocortin production and energy homeostasis are mediated by STAT3 (mouse/human, transferred by ISO/ISS/IBA). Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0033210 leptin-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: STAT3 is the principal transducer of leptin receptor (LepRb) signalling. Reason: Leptin effects on melanocortin production and energy homeostasis are mediated by STAT3 (mouse/human, transferred by ISO/ISS/IBA). Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0033210 leptin-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: STAT3 is the principal transducer of leptin receptor (LepRb) signalling. Reason: Leptin effects on melanocortin production and energy homeostasis are mediated by STAT3 (mouse/human, transferred by ISO/ISS/IBA). Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0033210 leptin-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: STAT3 is the principal transducer of leptin receptor (LepRb) signalling. Reason: Leptin effects on melanocortin production and energy homeostasis are mediated by STAT3 (mouse/human, transferred by ISO/ISS/IBA). Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0033210 leptin-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: STAT3 is the principal transducer of leptin receptor (LepRb) signalling. Reason: Leptin effects on melanocortin production and energy homeostasis are mediated by STAT3 (mouse/human, transferred by ISO/ISS/IBA). Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0033210 leptin-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: STAT3 is the principal transducer of leptin receptor (LepRb) signalling. Reason: Leptin effects on melanocortin production and energy homeostasis are mediated by STAT3 (mouse/human, transferred by ISO/ISS/IBA). Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0034097 response to cytokine | IDA PMID:18270592 Prevention of hypovolemic circulatory collapse by IL-6 activ... | MODIFY | Summary: Response to cytokine: Stat3 is activated by IL-6 in rat heart. Reason: The cited rat study shows IL-6-activated cardiac Stat3 mediates protection; refine to the specific pathway GO:0070102 (descendant). Proposed replacements: interleukin-6-mediated signaling pathway Supporting Evidence: PMID:18270592 Pre-treatment of rats with a selective inhibitor of Stat3, T40214, reduced the IL-6-mediated increase in cardiac Stat3 activity |
| GO:0035259 obsolete nuclear glucocorticoid receptor binding | IPI PMID:20155810 Association of the glucocorticoid receptor with STAT3, C/EBP... | MODIFY | Summary: Activated GR co-immunoprecipitates with STAT3 at the rat haptoglobin HRE. Reason: Interaction with the glucocorticoid receptor (a nuclear receptor) in rat liver during the acute phase. The GOA label marks GO:0035259 obsolete; the parent GO:0016922 nuclear receptor binding captures the claim. Proposed replacements: nuclear receptor binding Supporting Evidence: PMID:20155810 Coimmunoprecipitation experiments showed that activated GR established de novo interaction with STAT3 isoforms |
| GO:0035591 signaling adaptor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Signaling adaptor activity transferred from mouse STAT3. Reason: STAT3 has been described as an adaptor coupling some receptors to PI3K signalling in other species; not shown in rat and peripheral to its TF function. |
| GO:0035591 signaling adaptor activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Signaling adaptor activity transferred from mouse STAT3. Reason: STAT3 has been described as an adaptor coupling some receptors to PI3K signalling in other species; not shown in rat and peripheral to its TF function. |
| GO:0035723 interleukin-15-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IL-15 signalling (gamma-c cytokine) also activates STAT3. Reason: Gamma-c cytokines signal predominantly via STAT5; STAT3 is a secondary transducer. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0035723 interleukin-15-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IL-15 signalling (gamma-c cytokine) also activates STAT3. Reason: Gamma-c cytokines signal predominantly via STAT5; STAT3 is a secondary transducer. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0038110 interleukin-2-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IL-2 signalling also activates STAT3. Reason: STAT5 is the main IL-2 transducer; STAT3 secondary. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0038110 interleukin-2-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IL-2 signalling also activates STAT3. Reason: STAT5 is the main IL-2 transducer; STAT3 secondary. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0038113 interleukin-9-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IL-9 signalling activates STAT3. Reason: Secondary to STAT5/STAT1; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0038113 interleukin-9-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IL-9 signalling activates STAT3. Reason: Secondary to STAT5/STAT1; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0038154 interleukin-11-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: STAT3 transduces IL-11 (gp130 family) signalling. Reason: IL-11 signals through gp130 and STAT3; STAT3 is tyrosine phosphorylated in response to IL11. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0038154 interleukin-11-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: STAT3 transduces IL-11 (gp130 family) signalling. Reason: IL-11 signals through gp130 and STAT3; STAT3 is tyrosine phosphorylated in response to IL11. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0038155 interleukin-23-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: STAT3 transduces IL-23 signalling. Reason: STAT3 interacts with IL23R in the presence of IL23 and is activated downstream. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Interacts with IL23R in presence of IL23. |
| GO:0038155 interleukin-23-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: STAT3 transduces IL-23 signalling. Reason: STAT3 interacts with IL23R in the presence of IL23 and is activated downstream. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Interacts with IL23R in presence of IL23. |
| GO:0038165 oncostatin-M-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: STAT3 transduces oncostatin-M signalling. Reason: OSM signals through gp130 to STAT3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0038165 oncostatin-M-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: STAT3 transduces oncostatin-M signalling. Reason: OSM signals through gp130 to STAT3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0040014 regulation of multicellular organism growth | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 contributes to regulation of multicellular organism growth via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0042127 regulation of cell population proliferation | IBA GO_REF:0000033 | MODIFY | Summary: Regulation of cell population proliferation: both directions are reported. Reason: Specific positive and negative descendants are carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000927860 STAT-family PAINT node; STAT3 lies inside the clade; node placement not re-examined here; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: positive regulation of cell population proliferation negative regulation of cell population proliferation Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 |
| GO:0042593 glucose homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 contributes to glucose homeostasis via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0042593 glucose homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 contributes to glucose homeostasis via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0042593 glucose homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 contributes to glucose homeostasis via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0042755 eating behavior | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 contributes to eating behavior via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0042755 eating behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 contributes to eating behavior via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0042789 mRNA transcription by RNA polymerase II | ISO GO_REF:0000121 | MODIFY | Summary: STAT3 regulates, rather than performs, mRNA transcription. Reason: Replace with GO:0045944. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term names the process executed by the Pol II machinery, whereas STAT3 regulates it. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | MODIFY | Summary: Identical protein binding: Stat3 homodimerises. Reason: Correct but general; the relevant self-association is dimerisation of tyrosine-phosphorylated STAT3 via reciprocal SH2-pTyr contacts. Refine to GO:0042803 (is_a descendant) already carried by the gene. Proposed replacements: protein homodimerization activity Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | MODIFY | Summary: Identical protein binding: Stat3 homodimerises. Reason: Correct but general; the relevant self-association is dimerisation of tyrosine-phosphorylated STAT3 via reciprocal SH2-pTyr contacts. Refine to GO:0042803 (is_a descendant) already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: protein homodimerization activity Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | MODIFY | Summary: Identical protein binding: Stat3 homodimerises. Reason: Correct but general; the relevant self-association is dimerisation of tyrosine-phosphorylated STAT3 via reciprocal SH2-pTyr contacts. Refine to GO:0042803 (is_a descendant) already carried by the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: protein homodimerization activity Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: Stat3 forms homodimers upon tyrosine phosphorylation, required for DNA binding. Reason: Dimerisation is an intrinsic step of the STAT activation mechanism, required for nuclear accumulation and DNA binding. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0042803 protein homodimerization activity | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 forms homodimers upon tyrosine phosphorylation, required for DNA binding. Reason: Dimerisation is an intrinsic step of the STAT activation mechanism, required for nuclear accumulation and DNA binding. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0042803 protein homodimerization activity | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 forms homodimers upon tyrosine phosphorylation, required for DNA binding. Reason: Dimerisation is an intrinsic step of the STAT activation mechanism, required for nuclear accumulation and DNA binding. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | ACCEPT | Summary: Stat3 forms homodimers upon tyrosine phosphorylation, required for DNA binding. Reason: Dimerisation is an intrinsic step of the STAT activation mechanism, required for nuclear accumulation and DNA binding. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | ACCEPT | Summary: Stat3 forms homodimers upon tyrosine phosphorylation, required for DNA binding. Reason: Dimerisation is an intrinsic step of the STAT activation mechanism, required for nuclear accumulation and DNA binding. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). PMID:19450559 This association causes JAKs to phosphorylate STATs at distinct tyrosine residues, allowing the bound STATs to be released from the receptor and undergo homo- or heterodimersation |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000117 | MODIFY | Summary: Regulation of NF-kB signalling: both directions are reported. Reason: STAT3 positively or negatively modulates canonical NF-kB signalling depending on context; specific descendants are carried. Proposed replacements: positive regulation of canonical NF-kappaB signal transduction negative regulation of canonical NF-kappaB signal transduction Supporting Evidence: PMID:29702085 TNF-Ξ±-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IΞΊB-NFΞΊB and JAK-STAT3 pathways. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IGI PMID:29702085 TNF-Ξ±-sensitive brain pericytes activate microglia by releas... | KEEP AS NON CORE | Summary: STAT3 cooperates with NF-kB in rat pericytes. Reason: Inhibitor-based rat pericyte study shows cooperation of IkB-NFkB and JAK-STAT3 pathways; non-core. Supporting Evidence: PMID:29702085 TNF-Ξ±-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IΞΊB-NFΞΊB and JAK-STAT3 pathways. |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 can restrain NF-kB signalling (from mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0043434 response to peptide hormone | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Stat3 responds to peptide hormones (prolactin, leptin, GH). Reason: Rat islet study shows prolactin increases STAT3 expression/serine phosphorylation and STAT3-dependent SERCA2 expression; leptin/GH pathways are not descendants of this term in the current GO build. Non-core. Supporting Evidence: PMID:17911393 The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. |
| GO:0043434 response to peptide hormone | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Stat3 responds to peptide hormones (prolactin, leptin, GH). Reason: Rat islet study shows prolactin increases STAT3 expression/serine phosphorylation and STAT3-dependent SERCA2 expression; leptin/GH pathways are not descendants of this term in the current GO build. Non-core. Supporting Evidence: PMID:17911393 The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. |
| GO:0043434 response to peptide hormone | IEP PMID:17911393 Signal transducer and activator of transcription 3-regulated... | KEEP AS NON CORE | Summary: Stat3 responds to peptide hormones (prolactin, leptin, GH). Reason: Rat islet study shows prolactin increases STAT3 expression/serine phosphorylation and STAT3-dependent SERCA2 expression; leptin/GH pathways are not descendants of this term in the current GO build. Non-core. Supporting Evidence: PMID:17911393 The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 cross-talk with PI3K/AKT signalling. Reason: Reported in mouse (adaptor role); in rat, ghrelin-induced NSC proliferation uses PI3K/Akt and STAT3 as parallel pathways. Non-core. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 cross-talk with PI3K/AKT signalling. Reason: Reported in mouse (adaptor role); in rat, ghrelin-induced NSC proliferation uses PI3K/Akt and STAT3 as parallel pathways. Non-core. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 cross-talk with PI3K/AKT signalling. Reason: Reported in mouse (adaptor role); in rat, ghrelin-induced NSC proliferation uses PI3K/Akt and STAT3 as parallel pathways. Non-core. |
| GO:0043524 negative regulation of neuron apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 protects neurons from apoptosis. Reason: Consistent with rat CA1 estradiol neuroprotection requiring STAT3-dependent survivin transcription; non-core consequence. Supporting Evidence: PMID:23884942 we show that STAT3 is critical to estradiol neuroprotection, as evidenced by the ability of STAT3 inhibitor peptide and STAT3 shRNA delivered directly into the CA1 of living animals to abolish neuroprotection. |
| GO:0043524 negative regulation of neuron apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 protects neurons from apoptosis. Reason: Consistent with rat CA1 estradiol neuroprotection requiring STAT3-dependent survivin transcription; non-core consequence. Supporting Evidence: PMID:23884942 we show that STAT3 is critical to estradiol neuroprotection, as evidenced by the ability of STAT3 inhibitor peptide and STAT3 shRNA delivered directly into the CA1 of living animals to abolish neuroprotection. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:16648019 Peptide YY attenuates STAT1 and STAT3 activation induced by ... | MODIFY | Summary: STAT3 DNA-binding activity increased by TNF-alpha in rat acinar AR42J cells. Reason: Protein/DNA array and EMSA show sequence-specific STAT-element binding; refine to Pol II cis-regulatory binding GO:0000978. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:16648019 TNF-alpha substantially upregulated STAT1 and STAT3 (two-fold or greater); PYY downregulated their binding activity to control levels. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000117 | MODIFY | Summary: Sequence-specific DNA binding: the Pol II cis-regulatory term is more precise. Reason: STAT3 binds GAS/IL-6 response elements in Pol II promoters; refine to GO:0000978, accepted for this gene. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0043565 sequence-specific DNA binding | ISO GO_REF:0000121 | MODIFY | Summary: Sequence-specific DNA binding: the Pol II cis-regulatory term is more precise. Reason: STAT3 binds GAS/IL-6 response elements in Pol II promoters; refine to GO:0000978, accepted for this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. |
| GO:0044320 cellular response to leptin stimulus | IEA GO_REF:0000107 | MODIFY | Summary: Cellular response to leptin stimulus: the specific pathway term is preferred. Reason: STAT3 participates in leptin receptor signalling (GO:0033210, part_of this term, already accepted). Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0044320 cellular response to leptin stimulus | ISO GO_REF:0000121 | MODIFY | Summary: Cellular response to leptin stimulus: the specific pathway term is preferred. Reason: STAT3 participates in leptin receptor signalling (GO:0033210, part_of this term, already accepted). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0044320 cellular response to leptin stimulus | ISS GO_REF:0000024 | MODIFY | Summary: Cellular response to leptin stimulus: the specific pathway term is preferred. Reason: STAT3 participates in leptin receptor signalling (GO:0033210, part_of this term, already accepted). Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0044321 response to leptin | IEA GO_REF:0000107 | MODIFY | Summary: Response to leptin: the specific pathway term is preferred. Reason: STAT3 participates in leptin receptor signalling (GO:0033210, a descendant, already accepted). Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0044321 response to leptin | ISO GO_REF:0000121 | MODIFY | Summary: Response to leptin: the specific pathway term is preferred. Reason: STAT3 participates in leptin receptor signalling (GO:0033210, a descendant, already accepted). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0044321 response to leptin | ISO GO_REF:0000121 | MODIFY | Summary: Response to leptin: the specific pathway term is preferred. Reason: STAT3 participates in leptin receptor signalling (GO:0033210, a descendant, already accepted). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0044321 response to leptin | ISS GO_REF:0000024 | MODIFY | Summary: Response to leptin: the specific pathway term is preferred. Reason: STAT3 participates in leptin receptor signalling (GO:0033210, a descendant, already accepted). Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0044321 response to leptin | ISS GO_REF:0000024 | MODIFY | Summary: Response to leptin: the specific pathway term is preferred. Reason: STAT3 participates in leptin receptor signalling (GO:0033210, a descendant, already accepted). Proposed replacements: leptin-mediated signaling pathway Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0045471 response to ethanol | IEP PMID:17916759 Protective effects of estradiol on ethanol-induced bone loss... | KEEP AS NON CORE | Summary: STAT3 activation in ethanol-treated osteoblasts. Reason: IEP; non-core. Supporting Evidence: PMID:17916759 signal-regulated kinase (ERK) and activation of signal transducer and activator of transcription 3, resulting in increased gene expression of RANKL. |
| GO:0045648 positive regulation of erythrocyte differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of erythrocyte differentiation (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0045648 positive regulation of erythrocyte differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of erythrocyte differentiation (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0045648 positive regulation of erythrocyte differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of erythrocyte differentiation (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0045747 positive regulation of Notch signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of Notch signalling (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0045747 positive regulation of Notch signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of Notch signalling (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0045766 positive regulation of angiogenesis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of angiogenesis (e.g. VEGF induction). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0045820 negative regulation of glycolysis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of glycolysis (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000120 | MODIFY | Summary: Positive regulation of DNA-templated transcription: the Pol II-specific term is better. Reason: STAT3 targets are Pol II genes; refine to GO:0045944 (descendant), already carried. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000121 | MODIFY | Summary: Positive regulation of DNA-templated transcription: the Pol II-specific term is better. Reason: STAT3 targets are Pol II genes; refine to GO:0045944 (descendant), already carried. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000121 | MODIFY | Summary: Positive regulation of DNA-templated transcription: the Pol II-specific term is better. Reason: STAT3 targets are Pol II genes; refine to GO:0045944 (descendant), already carried. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000121 | MODIFY | Summary: Positive regulation of DNA-templated transcription: the Pol II-specific term is better. Reason: STAT3 targets are Pol II genes; refine to GO:0045944 (descendant), already carried. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | MODIFY | Summary: Positive regulation of DNA-templated transcription: the Pol II-specific term is better. Reason: STAT3 targets are Pol II genes; refine to GO:0045944 (descendant), already carried. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:19538478 Cross-talk between calcineurin/NFAT and Jak/STAT signalling ... | ACCEPT | Summary: STAT3 with NFAT activates CryAB transcription in rat cardiomyocytes. Reason: Core activator function shown in rat cardiomyocytes. Supporting Evidence: PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene file:rat/Stat3/Stat3-uniprot.txt binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Core: STAT3 positively regulates transcription by RNA polymerase II. Reason: Rat cardiomyocyte (CryAB) and CA1 (survivin) studies show STAT3-dependent transcription of target genes. Supporting Evidence: PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. file:rat/Stat3/Stat3-uniprot.txt binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Core: STAT3 positively regulates transcription by RNA polymerase II. Reason: Rat cardiomyocyte (CryAB) and CA1 (survivin) studies show STAT3-dependent transcription of target genes. Supporting Evidence: PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. file:rat/Stat3/Stat3-uniprot.txt binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Core: STAT3 positively regulates transcription by RNA polymerase II. Reason: Rat cardiomyocyte (CryAB) and CA1 (survivin) studies show STAT3-dependent transcription of target genes. Supporting Evidence: PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. file:rat/Stat3/Stat3-uniprot.txt binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Core: STAT3 positively regulates transcription by RNA polymerase II. Reason: Rat cardiomyocyte (CryAB) and CA1 (survivin) studies show STAT3-dependent transcription of target genes. Supporting Evidence: PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene PMID:23884942 Ischemia promotes activation of STAT3 signaling, association of STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein expression of prosurvival proteins in the selectively vulnerable CA1. file:rat/Stat3/Stat3-uniprot.txt binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes |
| GO:0046902 regulation of mitochondrial membrane permeability | IMP PMID:23590160 The STAT3 inhibitor stattic impairs cardiomyocyte mitochondr... | KEEP AS NON CORE | Summary: Mitochondrial STAT3 affects MPTP opening. Reason: Stattic sensitised rat cardiac mitochondria to calcium-induced MPTP opening; non-core. Supporting Evidence: PMID:23590160 inhibition of mitochondrial STAT3 by Stattic impacts on mitochondrial ATP production and MPTP opening through enhanced ROS formation |
| GO:0046983 protein dimerization activity | ISO GO_REF:0000121 | MODIFY | Summary: Protein dimerization activity is correct but general. Reason: STAT3 forms homodimers (and heterodimers with STAT1). The homodimerization descendant GO:0042803 is already carried and accepted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:103038 Β· Stat3 Mouse Stat3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: protein homodimerization activity Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). |
| GO:0046983 protein dimerization activity | ISS GO_REF:0000024 | MODIFY | Summary: Protein dimerization activity is correct but general. Reason: STAT3 forms homodimers (and heterodimers with STAT1). The homodimerization descendant GO:0042803 is already carried and accepted. Proposed replacements: protein homodimerization activity Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Forms a homodimer or a heterodimer with a related family member (at least STAT1). |
| GO:0048708 astrocyte differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 drives astrocyte differentiation (gp130/CNTF-LIF). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0048708 astrocyte differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 drives astrocyte differentiation (gp130/CNTF-LIF). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0048861 leukemia inhibitory factor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: STAT3 transduces LIF (gp130 family) signalling. Reason: LIF signals through LIFR/gp130 to STAT3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0048861 leukemia inhibitory factor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: STAT3 transduces LIF (gp130 family) signalling. Reason: LIF signals through LIFR/gp130 to STAT3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0050728 negative regulation of inflammatory response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 limits inflammation (IL-10 signalling). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0050729 positive regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 promotes inflammation in some contexts (IL-6, Th17). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0050729 positive regulation of inflammatory response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 promotes inflammation in some contexts (IL-6, Th17). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0050766 positive regulation of phagocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of phagocytosis (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0050766 positive regulation of phagocytosis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of phagocytosis (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0050804 modulation of chemical synaptic transmission | EXP PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | MODIFY | Summary: Stat3 is required for NMDAR-dependent hippocampal LTD. Reason: The cited rat study shows a specific role in long-term synaptic depression (GO:0060292, is_a descendant via regulation of synaptic plasticity). Proposed replacements: long-term synaptic depression Supporting Evidence: PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0050804 modulation of chemical synaptic transmission | IDA PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | MODIFY | Summary: Stat3 is required for NMDAR-dependent hippocampal LTD. Reason: The cited rat study shows a specific role in long-term synaptic depression (GO:0060292, is_a descendant via regulation of synaptic plasticity). Proposed replacements: long-term synaptic depression Supporting Evidence: PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0050804 modulation of chemical synaptic transmission | IMP PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | MODIFY | Summary: Stat3 is required for NMDAR-dependent hippocampal LTD. Reason: The cited rat study shows a specific role in long-term synaptic depression (GO:0060292, is_a descendant via regulation of synaptic plasticity). Proposed replacements: long-term synaptic depression Supporting Evidence: PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0051240 positive regulation of multicellular organismal process | IEA GO_REF:0000117 | MODIFY | Summary: Positive regulation of multicellular organismal process is an uninformative grouping term. Reason: Replace with the specific supported process, positive regulation of angiogenesis. Proposed replacements: positive regulation of angiogenesis |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 regulates the cell cycle by inducing G1/S genes (CCND1). Reason: Non-core consequence of transcriptional activity. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 |
| GO:0051726 regulation of cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 regulates the cell cycle by inducing G1/S genes (CCND1). Reason: Non-core consequence of transcriptional activity. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 |
| GO:0051726 regulation of cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 regulates the cell cycle by inducing G1/S genes (CCND1). Reason: Non-core consequence of transcriptional activity. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 |
| GO:0051726 regulation of cell cycle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 regulates the cell cycle by inducing G1/S genes (CCND1). Reason: Non-core consequence of transcriptional activity. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 |
| GO:0051726 regulation of cell cycle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 regulates the cell cycle by inducing G1/S genes (CCND1). Reason: Non-core consequence of transcriptional activity. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 |
| GO:0060019 radial glial cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Radial glial cell differentiation (mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0060019 radial glial cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Radial glial cell differentiation (mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0060259 regulation of feeding behavior | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 contributes to regulation of feeding behavior via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0060259 regulation of feeding behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 contributes to regulation of feeding behavior via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0060396 growth hormone receptor signaling pathway | IEA GO_REF:0000107 | MODIFY | Summary: GH receptor signalling: the JAK-STAT-specific child is more precise. Reason: STAT3 participates via JAK-STAT; refine to GO:0060397 (descendant, carried by gene). Proposed replacements: growth hormone receptor signaling pathway via JAK-STAT Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0060396 growth hormone receptor signaling pathway | ISO GO_REF:0000121 | MODIFY | Summary: GH receptor signalling: the JAK-STAT-specific child is more precise. Reason: STAT3 participates via JAK-STAT; refine to GO:0060397 (descendant, carried by gene). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P40763 Β· STAT3 Human STAT3, 1:1 ortholog; source record not re-inspected for this review, so its status is not asserted; the transferred term is correct but less specific than the descendant this review proposes. Proposed replacements: growth hormone receptor signaling pathway via JAK-STAT Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAT3 is activated in growth hormone receptor JAK-STAT signalling. Reason: STAT5 is the dominant GH transducer; STAT3 contributes. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 is activated in growth hormone receptor JAK-STAT signalling. Reason: STAT5 is the dominant GH transducer; STAT3 contributes. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 is activated in growth hormone receptor JAK-STAT signalling. Reason: STAT5 is the dominant GH transducer; STAT3 contributes. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 is activated in growth hormone receptor JAK-STAT signalling. Reason: STAT5 is the dominant GH transducer; STAT3 contributes. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 is activated in growth hormone receptor JAK-STAT signalling. Reason: STAT5 is the dominant GH transducer; STAT3 contributes. Non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stat3 binds other Pol II-specific transcription factors. Reason: STAT3 forms heterodimers with STAT1/STAT5 and a promoter-binding complex with NFATC3/NFATC4; cooperative TF partner binding supports, but is not itself, the core activity. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4 PMID:16527988 An increased association of STAT-5B with STAT-3 occurred in response to thrombin |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stat3 binds other Pol II-specific transcription factors. Reason: STAT3 forms heterodimers with STAT1/STAT5 and a promoter-binding complex with NFATC3/NFATC4; cooperative TF partner binding supports, but is not itself, the core activity. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4 PMID:16527988 An increased association of STAT-5B with STAT-3 occurred in response to thrombin |
| GO:0070102 interleukin-6-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Core: STAT3 is the principal transducer of IL-6/gp130 signalling. Reason: In rat liver Stat3 binds IL-6 response elements during the acute phase; in rat heart and satellite cells IL-6 acts via Stat3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:23869758 IL-6 induced dose-dependent increase in satellite cell proliferation by activating the JAK2/STAT3/cyclin D1 pathway. |
| GO:0070102 interleukin-6-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Core: STAT3 is the principal transducer of IL-6/gp130 signalling. Reason: In rat liver Stat3 binds IL-6 response elements during the acute phase; in rat heart and satellite cells IL-6 acts via Stat3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:23869758 IL-6 induced dose-dependent increase in satellite cell proliferation by activating the JAK2/STAT3/cyclin D1 pathway. |
| GO:0070102 interleukin-6-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Core: STAT3 is the principal transducer of IL-6/gp130 signalling. Reason: In rat liver Stat3 binds IL-6 response elements during the acute phase; in rat heart and satellite cells IL-6 acts via Stat3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes. PMID:8530402 Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. PMID:23869758 IL-6 induced dose-dependent increase in satellite cell proliferation by activating the JAK2/STAT3/cyclin D1 pathway. |
| GO:0070120 ciliary neurotrophic factor-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: STAT3 transduces CNTF signalling. Reason: CNTF signals through gp130/LIFR to STAT3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0070120 ciliary neurotrophic factor-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: STAT3 transduces CNTF signalling. Reason: CNTF signals through gp130/LIFR to STAT3. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0070878 primary miRNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Primary miRNA binding transferred from mouse STAT3. Reason: Reported in mouse/human systems; peripheral to the core DNA-binding TF activity and not shown in rat. |
| GO:0070878 primary miRNA binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Primary miRNA binding transferred from mouse STAT3. Reason: Reported in mouse/human systems; peripheral to the core DNA-binding TF activity and not shown in rat. |
| GO:0071345 cellular response to cytokine stimulus | IDA PMID:19414010 JANEX-1, a JAK3 inhibitor, protects pancreatic islets from c... | KEEP AS NON CORE | Summary: Stat3 responds to cytokine stimulation. Reason: The IDA (abstract only) concerns IL-1beta/IFN-gamma-induced JAK/STAT activation in islets without resolving STAT3 specifically; kept at this level as non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0071345 cellular response to cytokine stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Stat3 responds to cytokine stimulation. Reason: The IDA (abstract only) concerns IL-1beta/IFN-gamma-induced JAK/STAT activation in islets without resolving STAT3 specifically; kept at this level as non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0072538 T-helper 17 type immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 is required for Th17 immune responses. Reason: STAT3 drives Th17 differentiation (mouse/human); cell-type-specific, non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0072538 T-helper 17 type immune response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 is required for Th17 immune responses. Reason: STAT3 drives Th17 differentiation (mouse/human); cell-type-specific, non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) |
| GO:0072540 T-helper 17 cell lineage commitment | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 drives T-helper 17 lineage commitment. Reason: Cell-type-specific role transferred from mouse/human; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) file:rat/Stat3/Stat3-uniprot.txt interaction promotes STAT3 recruitment to chromatin and T-helper Th17 cell differentiation |
| GO:0072540 T-helper 17 cell lineage commitment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 drives T-helper 17 lineage commitment. Reason: Cell-type-specific role transferred from mouse/human; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg) file:rat/Stat3/Stat3-uniprot.txt interaction promotes STAT3 recruitment to chromatin and T-helper Th17 cell differentiation |
| GO:0090091 positive regulation of extracellular matrix disassembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of ECM disassembly (acts upstream; transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0090575 RNA polymerase II transcription regulator complex | IBA GO_REF:0000033 | ACCEPT | Summary: Stat3 is part of Pol II transcription regulator complexes. Reason: STAT3 forms DNA-bound dimers and a ternary promoter-binding complex with NFAT factors at the CryAB alphaBE4 element in rat cardiomyocytes. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4 PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0090575 RNA polymerase II transcription regulator complex | IEA GO_REF:0000107 | ACCEPT | Summary: Stat3 is part of Pol II transcription regulator complexes. Reason: STAT3 forms DNA-bound dimers and a ternary promoter-binding complex with NFAT factors at the CryAB alphaBE4 element in rat cardiomyocytes. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4 PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0090575 RNA polymerase II transcription regulator complex | ISO GO_REF:0000121 | ACCEPT | Summary: Stat3 is part of Pol II transcription regulator complexes. Reason: STAT3 forms DNA-bound dimers and a ternary promoter-binding complex with NFAT factors at the CryAB alphaBE4 element in rat cardiomyocytes. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4 PMID:19538478 the transcription factors NFAT, Nished and STAT3 form a dynamic ternary complex and interact with the alphaBE4 promoter element of the CryAB gene |
| GO:0097009 energy homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 contributes to energy homeostasis via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0097009 energy homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT3 contributes to energy homeostasis via hypothalamic leptin signalling (mouse). Reason: Organismal phenotype of neuronal STAT3 loss in mouse, downstream of leptin receptor-STAT3 transcription; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. |
| GO:0097398 cellular response to interleukin-17 | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to IL-17 (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0097696 cell surface receptor signaling pathway via STAT | IEA GO_REF:0000107 | ACCEPT | Summary: Core: cell surface receptor signalling via STAT. Reason: Parent of the JAK-STAT term; STAT3 also transduces signals from receptor tyrosine kinases (EGFR, FGFRs). Accepted alongside GO:0007259. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0097696 cell surface receptor signaling pathway via STAT | ISO GO_REF:0000121 | ACCEPT | Summary: Core: cell surface receptor signalling via STAT. Reason: Parent of the JAK-STAT term; STAT3 also transduces signals from receptor tyrosine kinases (EGFR, FGFRs). Accepted alongside GO:0007259. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0097696 cell surface receptor signaling pathway via STAT | ISO GO_REF:0000121 | ACCEPT | Summary: Core: cell surface receptor signalling via STAT. Reason: Parent of the JAK-STAT term; STAT3 also transduces signals from receptor tyrosine kinases (EGFR, FGFRs). Accepted alongside GO:0007259. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0097696 cell surface receptor signaling pathway via STAT | ISS GO_REF:0000024 | ACCEPT | Summary: Core: cell surface receptor signalling via STAT. Reason: Parent of the JAK-STAT term; STAT3 also transduces signals from receptor tyrosine kinases (EGFR, FGFRs). Accepted alongside GO:0007259. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. file:rat/Stat3/Stat3-uniprot.txt Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and OSM. |
| GO:0098685 Schaffer collateral - CA1 synapse | EXP PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | KEEP AS NON CORE | Summary: Stat3 acts at Schaffer collateral-CA1 synapses (NMDAR-LTD). Reason: Shown in rat hippocampal slices. Location of a non-canonical, non-nuclear role. Supporting Evidence: PMID:22284190 For the initial set of experiments we used extracellular recording in acutely prepared rat hippocampal slices and stimulated two independent inputs onto the same population of neurons. PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0098685 Schaffer collateral - CA1 synapse | IDA PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | KEEP AS NON CORE | Summary: Stat3 acts at Schaffer collateral-CA1 synapses (NMDAR-LTD). Reason: Shown in rat hippocampal slices. Location of a non-canonical, non-nuclear role. Supporting Evidence: PMID:22284190 For the initial set of experiments we used extracellular recording in acutely prepared rat hippocampal slices and stimulated two independent inputs onto the same population of neurons. PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0098685 Schaffer collateral - CA1 synapse | IMP PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | KEEP AS NON CORE | Summary: Stat3 acts at Schaffer collateral-CA1 synapses (NMDAR-LTD). Reason: Shown in rat hippocampal slices. Location of a non-canonical, non-nuclear role. Supporting Evidence: PMID:22284190 For the initial set of experiments we used extracellular recording in acutely prepared rat hippocampal slices and stimulated two independent inputs onto the same population of neurons. PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0098978 glutamatergic synapse | EXP PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | KEEP AS NON CORE | Summary: Stat3 acts at glutamatergic synapses. Reason: SynGO annotation from rat hippocampal LTD study; non-core location. Supporting Evidence: PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0098978 glutamatergic synapse | IDA PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | KEEP AS NON CORE | Summary: Stat3 acts at glutamatergic synapses. Reason: SynGO annotation from rat hippocampal LTD study; non-core location. Supporting Evidence: PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0098978 glutamatergic synapse | IEP PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | KEEP AS NON CORE | Summary: Stat3 acts at glutamatergic synapses. Reason: SynGO annotation from rat hippocampal LTD study; non-core location. Supporting Evidence: PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0098978 glutamatergic synapse | IMP PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | KEEP AS NON CORE | Summary: Stat3 acts at glutamatergic synapses. Reason: SynGO annotation from rat hippocampal LTD study; non-core location. Supporting Evidence: PMID:22284190 Thus, pharmacological inhibition or knockdown of STAT3 also blocks the induction of NMDAR-LTD. |
| GO:0099527 postsynapse to nucleus signaling pathway | IDA PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | MARK AS OVER ANNOTATED | Summary: The cited study shows STAT3 acts in LTD independently of the nucleus. Reason: Postsynapse-to-nucleus signalling requires a signal to reach the nucleus. PMID:22284190 explicitly shows that the requirement for STAT3 in NMDAR-LTD does not involve DNA binding, transcription or the cell body, contradicting this term for the process studied. Supporting Evidence: PMID:22284190 These data collectively suggest that NMDAR-LTD can be readily induced and expressed for at least 3 hr, without the need for gene transcription and that the effects of inhibition of STAT3 are independent of an action within the nucleus. |
| GO:0099527 postsynapse to nucleus signaling pathway | IEP PMID:22284190 The Jak/STAT pathway is involved in synaptic plasticity. | MARK AS OVER ANNOTATED | Summary: The cited study shows STAT3 acts in LTD independently of the nucleus. Reason: Postsynapse-to-nucleus signalling requires a signal to reach the nucleus. PMID:22284190 explicitly shows that the requirement for STAT3 in NMDAR-LTD does not involve DNA binding, transcription or the cell body, contradicting this term for the process studied. Supporting Evidence: PMID:22284190 These data collectively suggest that NMDAR-LTD can be readily induced and expressed for at least 3 hr, without the need for gene transcription and that the effects of inhibition of STAT3 are independent of an action within the nucleus. |
| GO:0106015 negative regulation of inflammatory response to wounding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of inflammatory response to wounding (from mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0106015 negative regulation of inflammatory response to wounding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of inflammatory response to wounding (from mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0106015 negative regulation of inflammatory response to wounding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of inflammatory response to wounding (from mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:0106222 lncRNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: lncRNA binding transferred from mouse/human STAT3. Reason: STAT3 binding to specific lncRNAs (e.g. lnc-DC) has been reported in other species; peripheral and not shown in rat. |
| GO:0106222 lncRNA binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: lncRNA binding transferred from mouse/human STAT3. Reason: STAT3 binding to specific lncRNAs (e.g. lnc-DC) has been reported in other species; peripheral and not shown in rat. |
| GO:0140105 interleukin-10-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: STAT3 is the key transducer of IL-10 signalling. Reason: IL-10 anti-inflammatory signalling depends on STAT3 (from mouse/human). Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0140105 interleukin-10-mediated signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: STAT3 is the key transducer of IL-10 signalling. Reason: IL-10 anti-inflammatory signalling depends on STAT3 (from mouse/human). Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stat3 binds other DNA-binding transcription factors (STAT5B, NFAT, GR). Reason: In rat VSMC thrombin induced STAT-5B/STAT-3 association; in rat liver GR associated with STAT3. Partner-TF binding is part of combinatorial regulation; non-core. Supporting Evidence: PMID:16527988 An increased association of STAT-5B with STAT-3 occurred in response to thrombin PMID:20155810 Coimmunoprecipitation experiments showed that activated GR established de novo interaction with STAT3 isoforms |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16527988 Novel role for STAT-5B in the regulation of Hsp27-FGF-2 axis... | KEEP AS NON CORE | Summary: Stat3 binds other DNA-binding transcription factors (STAT5B, NFAT, GR). Reason: In rat VSMC thrombin induced STAT-5B/STAT-3 association; in rat liver GR associated with STAT3. Partner-TF binding is part of combinatorial regulation; non-core. Supporting Evidence: PMID:16527988 An increased association of STAT-5B with STAT-3 occurred in response to thrombin PMID:20155810 Coimmunoprecipitation experiments showed that activated GR established de novo interaction with STAT3 isoforms |
| GO:0140297 DNA-binding transcription factor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Stat3 binds other DNA-binding transcription factors (STAT5B, NFAT, GR). Reason: In rat VSMC thrombin induced STAT-5B/STAT-3 association; in rat liver GR associated with STAT3. Partner-TF binding is part of combinatorial regulation; non-core. Supporting Evidence: PMID:16527988 An increased association of STAT-5B with STAT-3 occurred in response to thrombin PMID:20155810 Coimmunoprecipitation experiments showed that activated GR established de novo interaction with STAT3 isoforms |
| GO:0140311 protein sequestering activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cytoplasmic STAT3 sequesters PKR (EIF2AK2), inhibiting autophagy. Reason: Transferred from mouse/human; a non-canonical cytoplasmic function, non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity |
| GO:0140610 RNA sequestering activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RNA sequestering activity transferred from mouse/human. Reason: Peripheral non-canonical activity; not shown in rat. |
| GO:0140610 RNA sequestering activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: RNA sequestering activity transferred from mouse/human. Reason: Peripheral non-canonical activity; not shown in rat. |
| GO:0140854 interleukin-19-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IL-19 (IL-10 family) signalling activates STAT3. Reason: Transferred from mouse/human; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:0140854 interleukin-19-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IL-19 (IL-10 family) signalling activates STAT3. Reason: Transferred from mouse/human; non-core. Supporting Evidence: file:rat/Stat3/Stat3-uniprot.txt Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. |
| GO:1900016 negative regulation of cytokine production involved in inflammatory response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of cytokine production in inflammation (from mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:1900017 positive regulation of cytokine production involved in inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of cytokine production in inflammation. Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:1900017 positive regulation of cytokine production involved in inflammatory response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of cytokine production in inflammation. Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:1900037 regulation of cellular response to hypoxia | IMP PMID:19450559 STAT3 deletion sensitizes cells to oxidative stress. | KEEP AS NON CORE | Summary: Stat3 protects rat cardiomyocytes against simulated ischemia/reperfusion. Reason: Overexpression of STAT3 protected NRVM against I/R-induced death; Y705F dominant negative enhanced death. Context-specific cytoprotective role, non-core. Supporting Evidence: PMID:19450559 Overexpression of STAT3 in primary neonatal rat ventricular myocytes (NRVM) protects against I/R-induced cell death. PMID:19450559 This data provides further evidence that a fully transcriptionally active STAT3 that requiring the 705 tyrosine phosphorylation site is necessary for its cytoprotective properties. |
| GO:1902728 positive regulation of growth factor dependent skeletal muscle satellite cell proliferation | IMP PMID:23869758 Interleukin-6-induced satellite cell proliferation is regula... | KEEP AS NON CORE | Summary: IL-6 induced rat satellite-cell proliferation via JAK2/STAT3. Reason: STAT3 inhibitor peptide blocked IL-6-induced satellite cell proliferation; context-specific, non-core. Supporting Evidence: PMID:23869758 IL-6 induced dose-dependent increase in satellite cell proliferation by activating the JAK2/STAT3/cyclin D1 pathway. |
| GO:1902895 positive regulation of miRNA transcription | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 induces transcription of some miRNA genes. Reason: E.g. miR-21 induction in mouse/human; non-core. |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 induces transcription of some miRNA genes. Reason: E.g. miR-21 induction in mouse/human; non-core. |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 induces transcription of some miRNA genes. Reason: E.g. miR-21 induction in mouse/human; non-core. |
| GO:1903578 regulation of ATP metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Regulation of ATP metabolic process: the IMP-supported specific term is carried. Reason: Mitochondrial STAT3 supports ATP production; refine to GO:2001171. Proposed replacements: positive regulation of ATP biosynthetic process Supporting Evidence: PMID:23590160 inhibition of mitochondrial STAT3 by Stattic impacts on mitochondrial ATP production and MPTP opening through enhanced ROS formation |
| GO:1905564 positive regulation of vascular endothelial cell proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of vascular endothelial cell proliferation (transferred). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:2000635 negative regulation of primary miRNA processing | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT3 negative regulation of pri-miRNA processing (from mouse/human). Reason: Non-canonical, not shown in rat; non-core. |
| GO:2000635 negative regulation of primary miRNA processing | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 negative regulation of pri-miRNA processing (from mouse/human). Reason: Non-canonical, not shown in rat; non-core. |
| GO:2000737 negative regulation of stem cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of stem cell differentiation (mouse ES cells). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:2001171 positive regulation of ATP biosynthetic process | IMP PMID:23590160 The STAT3 inhibitor stattic impairs cardiomyocyte mitochondr... | KEEP AS NON CORE | Summary: Mitochondrial STAT3 supports ATP production in rat heart mitochondria. Reason: Stattic reduced ATP production in isolated rat cardiac mitochondria; pharmacological evidence for a non-canonical mitochondrial role. Non-core. Supporting Evidence: PMID:23590160 inhibition of mitochondrial STAT3 by Stattic impacts on mitochondrial ATP production and MPTP opening through enhanced ROS formation |
| GO:2001223 negative regulation of neuron migration | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of neuron migration (mouse). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. |
| GO:2001243 negative regulation of intrinsic apoptotic signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: STAT3 inhibits intrinsic apoptosis (prosurvival gene induction). Reason: Stat3 is a pleiotropic cytokine-activated transcription factor; this process is a cell-type- or context-specific downstream consequence of its JAK-STAT transcriptional activity (largely transferred from mouse/human STAT3), not a distinct core function. Supporting Evidence: PMID:19450559 Overexpression of STAT3 in primary neonatal rat ventricular myocytes (NRVM) protects against I/R-induced cell death. |
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Download this section (compressed HTML)Q: Should GO:0099527 postsynapse to nucleus signaling pathway be retained for Stat3 when PMID:22284190 shows the STAT3 requirement in NMDAR-LTD is independent of nuclear action and transcription?
Q: Is GO:0004879 nuclear receptor activity appropriate for any STAT protein, given STATs are activated by receptor-associated kinases rather than by direct ligand binding? Which source annotation (in human/mouse) seeds the ISO/IEA propagation?
Q: What does mitochondrial STAT3 do at the inner membrane: is it a structural/regulatory component of complex I, and is any of the Stattic-based evidence independent of Stattic off-target effects?
Experiment: Genetic (not pharmacological) test of mitochondrial STAT3 in rat cardiomyocytes: rescue STAT3-deficient cells with a mitochondria-targeted, DNA-binding-dead STAT3 and measure complex I respiration, ATP production and MPTP sensitivity.
Type: genetic rescue / respirometry
Experiment: Identify the cytoplasmic/PSD targets of STAT3 during NMDAR-LTD (e.g. proximity labelling of PSD-localised STAT3 during LTD induction) to define its non-transcriptional molecular activity at synapses.
Type: proximity proteomics
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