Tnfrsf1a encodes mouse TNF receptor 1 (p55/CD120a), a type I transmembrane TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. TNFR1 binds TNF/lymphotoxin-alpha and initiates TNF-mediated signaling, especially canonical NF-kappaB/inflammatory signaling and extrinsic apoptotic signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043235 receptor complex | IBA GO_REF:0000033 | MODIFY | Summary: receptor complex captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than tumor necrosis factor receptor superfamily complex for this gene. Replace with tumor necrosis factor receptor superfamily complex to align the annotation with the reviewed evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002930098 SUPPORTS TRANSFER TNFR1-clade node in PTHR46861. The WITH/FROM names a single donor, which is not a weakness: an IBD placed on one well-characterised human gene at a clade node is a phylogenetic judgement about where the property arose, and the target sits squarely inside that clade. Checked in the ontology: GO:0002947 is a descendant of GO:0043235, so the replacement refines the annotation to the receptor superfamily actually involved without changing the claim. UniProtKB:P19438 Β· TNFRSF1A SUPPORTS TRANSFER Human TNFRSF1A (TNF receptor superfamily member 1A), the target's direct ortholog and the sole seed. A type-I membrane receptor with an extracellular ligand-binding region and an intracellular death domain that assembles trimeric receptor complexes - exactly what GO:0002947 names. Proposed replacements: tumor necrosis factor receptor superfamily complex Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0006954 inflammatory response | IBA GO_REF:0000033 | ACCEPT | Summary: inflammatory response is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes TNFR1 Complex I signaling as driving inflammatory and survival gene expression through NF-kappaB and MAPK pathways. |
| GO:0045121 membrane raft | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: membrane raft is supported in an ADAM17 shedding/trafficking context, but is not the core TNFR1 receptor function. Reason: Lipid-raft partitioning is relevant to regulated shedding of TNFR1 substrates, while core Tnfrsf1a biology is TNF binding, NF-kappaB signaling, and death-domain apoptotic signaling. Supporting Evidence: PMID:17010968 metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Golgi membrane is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: plasma membrane is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as a type I transmembrane receptor that initiates signaling at the plasma membrane. |
| GO:0006693 prostaglandin metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: prostaglandin metabolic process is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0006954 inflammatory response | IEA GO_REF:0000002 | ACCEPT | Summary: inflammatory response is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IEA evidence (GO_REF:0000002). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes TNFR1 Complex I signaling as driving inflammatory and survival gene expression through NF-kappaB and MAPK pathways. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: signal transduction captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than tumor necrosis factor-mediated signaling pathway for this gene. Replace with tumor necrosis factor-mediated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: tumor necrosis factor-mediated signaling pathway Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: regulation of gene expression is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000117 | MODIFY | Summary: positive regulation of apoptotic process captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than extrinsic apoptotic signaling pathway via death domain receptors for this gene. Replace it with the death-domain receptor term to align the annotation with TNFR1 biology. Proposed replacements: extrinsic apoptotic signaling pathway via death domain receptors Supporting Evidence: UniProt:P25118 FADD recruits caspase-8 to the activated receptor, and the resulting death-inducing signaling complex performs caspase-8 proteolytic activation to initiate the caspase cascade mediating apoptosis. |
| GO:0050793 regulation of developmental process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: regulation of developmental process is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0051241 negative regulation of multicellular organismal process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: negative regulation of multicellular organismal process is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0005515 protein binding | IPI PMID:15102471 Bioinformatics and cellular signaling. | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:16680093 Tumour necrosis factor receptor 1 mediates endoplasmic retic... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:18022363 IAP antagonists target cIAP1 to induce TNFalpha-dependent ap... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:18719121 Beyond tumor necrosis factor receptor: TRADD signaling in to... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:26649818 Phosphorylation and linear ubiquitin direct A20 inhibition o... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IEA GO_REF:0000107 | REMOVE | Summary: cell surface receptor signaling pathway via JAK-STAT is not supported as an appropriate annotation for Tnfrsf1a after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Tnfrsf1a biology. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0043120 tumor necrosis factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: tumor necrosis factor binding is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon states that TNFR1 binds trimeric TNF and transduces extracellular TNF binding into intracellular signaling. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | ACCEPT | Summary: positive regulation of canonical NF-kappaB signal transduction is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon describes Complex I assembly after TNF binding, with ubiquitin scaffolds recruiting TAK1/TABs and the IKK complex to activate NF-kappaB. |
| GO:0043235 receptor complex | IEA GO_REF:0000107 | MODIFY | Summary: receptor complex captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than tumor necrosis factor receptor superfamily complex for this gene. Replace with tumor necrosis factor receptor superfamily complex to align the annotation with the reviewed evidence. Proposed replacements: tumor necrosis factor receptor superfamily complex Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0045121 membrane raft | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: membrane raft is supported in an ADAM17 shedding/trafficking context, but is not the core TNFR1 receptor function. Reason: Lipid-raft partitioning is relevant to regulated shedding of TNFR1 substrates, while core Tnfrsf1a biology is TNF binding, NF-kappaB signaling, and death-domain apoptotic signaling. Supporting Evidence: PMID:17010968 metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: positive regulation of transcription by RNA polymerase II is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0050728 negative regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of inflammatory response is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0071260 cellular response to mechanical stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: cellular response to mechanical stimulus is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0072659 protein localization to plasma membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: protein localization to plasma membrane describes TNFR1 membrane placement/trafficking context, not an active localization function of Tnfrsf1a. Reason: TNFR1 is a type I plasma-membrane receptor and cargo of localization/trafficking processes, but the gene product is not the localization machinery; keep this marked as over-annotated relative to ligand binding and TNF receptor signaling. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:1903140 regulation of establishment of endothelial barrier | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: regulation of establishment of endothelial barrier is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0032991 protein-containing complex | ISO GO_REF:0000096 | MODIFY | Summary: protein-containing complex captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than tumor necrosis factor receptor superfamily complex for this gene. Replace with tumor necrosis factor receptor superfamily complex to align the annotation with the reviewed evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS TRANSFER Rat TNFR1 supports receptor-complex biology, but GO:0032991 is a generic parent of the TNF receptor superfamily complex term used for mouse. Proposed replacements: tumor necrosis factor receptor superfamily complex Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0002947 tumor necrosis factor receptor superfamily complex | ISO GO_REF:0000119 | ACCEPT | Summary: tumor necrosis factor receptor superfamily complex is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0005886 plasma membrane | ISO GO_REF:0000119 | ACCEPT | Summary: plasma membrane is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as a type I transmembrane receptor that initiates signaling at the plasma membrane. |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: identical protein binding is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: UniProt:P25118 Binding of TNF to the extracellular domain leads to homotrimerization, and aggregated death domains provide the interface for TRADD recruitment. |
| GO:0000139 Golgi membrane | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Golgi membrane is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0002020 protease binding | ISO GO_REF:0000096 | UNDECIDED | Summary: protease binding is not directly established by the reviewed mouse TNFR1 evidence. Reason: UniProt supports FADD-mediated recruitment and activation of caspase-8 in the death-inducing signaling complex, but that does not by itself establish direct TNFR1-protease binding. Propagation Review Root cause: UNRESOLVED Sources checked: RGD:621237 Β· rat Tnfrsf1a UNRESOLVED Rat evidence links TNFR1 to downstream caspase activation, but direct TNFR1-protease binding was not established from the reviewed mouse evidence. |
| GO:0005031 tumor necrosis factor receptor activity | ISO GO_REF:0000096 | ACCEPT | Summary: tumor necrosis factor receptor activity is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFRSF1A/TNFR1 as a broadly expressed cell-surface TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. |
| GO:0005031 tumor necrosis factor receptor activity | ISO GO_REF:0000119 | ACCEPT | Summary: tumor necrosis factor receptor activity is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFRSF1A/TNFR1 as a broadly expressed cell-surface TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | ISO GO_REF:0000119 | REMOVE | Summary: cell surface receptor signaling pathway via JAK-STAT is not supported as an appropriate annotation for Tnfrsf1a after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Tnfrsf1a biology. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P19438 Β· human TNFRSF1A SOURCE WEAK OR INFERRED Human TNFRSF1A supports TNF receptor signaling, but the propagated JAK-STAT pathway assertion is outside the curated TNFR1 model. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0009986 cell surface | ISO GO_REF:0000119 | ACCEPT | Summary: cell surface is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as initiating signaling at the cell surface/plasma membrane after trimeric TNF engagement. |
| GO:0009986 cell surface | ISO GO_REF:0000096 | ACCEPT | Summary: cell surface is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as initiating signaling at the cell surface/plasma membrane after trimeric TNF engagement. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: positive regulation of gene expression is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET Rat evidence may support pathway-induced transcriptional changes, but a generic gene-expression parent overstates the direct receptor role in mouse. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: negative regulation of gene expression is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET Rat evidence may support pathway-induced transcriptional changes, but a generic gene-expression parent overstates the direct receptor role in mouse. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0030424 axon | ISO GO_REF:0000096 | REMOVE | Summary: axon is not supported as an appropriate annotation for Tnfrsf1a after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Tnfrsf1a biology. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET The rat source may reflect a neuronal context, but the reviewed mouse model does not place TNFR1 as an axonal resident gene product. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0032715 negative regulation of interleukin-6 production | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: negative regulation of interleukin-6 production is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET Rat inflammatory cytokine production phenotypes are downstream context for TNFR1, not the direct receptor activity or core mouse pathway assertion. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0032760 positive regulation of tumor necrosis factor production | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: positive regulation of tumor necrosis factor production is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET Rat inflammatory cytokine production phenotypes are downstream context for TNFR1, not the direct receptor activity or core mouse pathway assertion. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: tumor necrosis factor-mediated signaling pathway is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes canonical TNF-TNFR1 signaling through receptor-proximal Complex I and cytosolic death complexes. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | ISO GO_REF:0000096 | ACCEPT | Summary: tumor necrosis factor-mediated signaling pathway is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes canonical TNF-TNFR1 signaling through receptor-proximal Complex I and cytosolic death complexes. |
| GO:0038061 non-canonical NF-kappaB signal transduction | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: non-canonical NF-kappaB signal transduction is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P19438 Β· human TNFRSF1A SUPPORTS SOURCE BUT NOT TARGET Human TNFRSF1A supports canonical TNF receptor signaling, but a non-canonical NF-kappaB term is too specific for the conserved TNFR1 role. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0042307 positive regulation of protein import into nucleus | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: positive regulation of protein import into nucleus is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET Rat evidence may report downstream nuclear import during TNFR1 signaling, but the receptor is not the protein-import machinery. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0042981 regulation of apoptotic process | ISO GO_REF:0000096 | MODIFY | Summary: regulation of apoptotic process captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than extrinsic apoptotic signaling pathway via death domain receptors for this gene. Replace it with the death-domain receptor term to align the annotation with TNFR1 biology. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS TRANSFER Rat TNFR1 supports apoptotic signaling, but the broad regulatory parent should be narrowed to the death-domain receptor pathway for mouse. Proposed replacements: extrinsic apoptotic signaling pathway via death domain receptors Supporting Evidence: UniProt:P25118 FADD recruits caspase-8 to the activated receptor, and the resulting death-inducing signaling complex performs caspase-8 proteolytic activation to initiate the caspase cascade mediating apoptosis. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: negative regulation of apoptotic process is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET Rat evidence may reflect NF-kappaB survival signaling downstream of TNFR1, but the direct death-domain receptor role is pro-apoptotic signaling. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0043120 tumor necrosis factor binding | ISO GO_REF:0000096 | ACCEPT | Summary: tumor necrosis factor binding is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon states that TNFR1 binds trimeric TNF and transduces extracellular TNF binding into intracellular signaling. |
| GO:0043120 tumor necrosis factor binding | ISO GO_REF:0000119 | ACCEPT | Summary: tumor necrosis factor binding is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon states that TNFR1 binds trimeric TNF and transduces extracellular TNF binding into intracellular signaling. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | ISO GO_REF:0000119 | ACCEPT | Summary: positive regulation of canonical NF-kappaB signal transduction is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon describes Complex I assembly after TNF binding, with ubiquitin scaffolds recruiting TAK1/TABs and the IKK complex to activate NF-kappaB. |
| GO:0043525 positive regulation of neuron apoptotic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: positive regulation of neuron apoptotic process is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0044877 protein-containing complex binding | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: protein-containing complex binding is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET Rat evidence may contain TNFR1 signaling-complex interactions, but generic protein-complex binding conflates the receptor with an uninformative binding activity. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0045121 membrane raft | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: membrane raft is supported in an ADAM17 shedding/trafficking context, but is not the core TNFR1 receptor function. Reason: Lipid-raft partitioning is relevant to regulated shedding of TNFR1 substrates, while core Tnfrsf1a biology is TNF binding, NF-kappaB signaling, and death-domain apoptotic signaling. Supporting Evidence: PMID:17010968 metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts. |
| GO:0045766 positive regulation of angiogenesis | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: positive regulation of angiogenesis is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: RGD:621237 Β· rat Tnfrsf1a SUPPORTS SOURCE BUT NOT TARGET Angiogenesis is a downstream tissue response to TNFR1 signaling, not a core receptor function to transfer as a direct mouse annotation. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: positive regulation of transcription by RNA polymerase II is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P19438 Β· human TNFRSF1A SUPPORTS SOURCE BUT NOT TARGET Human TNFRSF1A supports NF-kappaB and inflammatory transcription downstream of TNF, but this term is a broad transcriptional output rather than the receptor function itself. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0050728 negative regulation of inflammatory response | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: negative regulation of inflammatory response is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0072659 protein localization to plasma membrane | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: protein localization to plasma membrane describes TNFR1 membrane placement/trafficking context, not an active localization function of Tnfrsf1a. Reason: TNFR1 is a type I plasma-membrane receptor and cargo of localization/trafficking processes, but the gene product is not the localization machinery; keep this marked as over-annotated relative to ligand binding and TNF receptor signaling. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P19438 Β· human TNFRSF1A SUPPORTS SOURCE BUT NOT TARGET Human TNFRSF1A supports plasma-membrane receptor localization, but TNFR1 is cargo rather than localization machinery. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0097190 apoptotic signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: apoptotic signaling pathway is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Apoptosis and death-domain signaling: UniProt notes that FADD recruits caspase-8 to the activated receptor and that the receptor complex activates apoptosis and NF-kappaB signaling. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon describes TNFR1-driven apoptosis through FADD/caspase-8-containing Complex II and necroptotic alternatives when caspase-8 is inactive. |
| GO:1903140 regulation of establishment of endothelial barrier | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: regulation of establishment of endothelial barrier is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P19438 Β· human TNFRSF1A SUPPORTS SOURCE BUT NOT TARGET Human endothelial-barrier data represent a vascular response downstream of TNFR1, not the core mouse receptor activity. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0005031 tumor necrosis factor receptor activity | IGI PMID:14985352 Role of FAN in tumor necrosis factor-alpha and lipopolysacch... | ACCEPT | Summary: tumor necrosis factor receptor activity is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IGI evidence (PMID:14985352). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFRSF1A/TNFR1 as a broadly expressed cell-surface TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. |
| GO:0005886 plasma membrane | ISO PMID:12391233 Interaction with factor associated with neutral sphingomyeli... | ACCEPT | Summary: plasma membrane is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by ISO evidence (PMID:12391233). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as a type I transmembrane receptor that initiates signaling at the plasma membrane. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IGI PMID:14985352 Role of FAN in tumor necrosis factor-alpha and lipopolysacch... | ACCEPT | Summary: tumor necrosis factor-mediated signaling pathway is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IGI evidence (PMID:14985352). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes canonical TNF-TNFR1 signaling through receptor-proximal Complex I and cytosolic death complexes. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | TAS PMID:29053143 MOMP, cell suicide as a BCL-2 family business. | ACCEPT | Summary: extrinsic apoptotic signaling pathway via death domain receptors is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by TAS evidence (PMID:29053143). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Apoptosis and death-domain signaling: UniProt notes that FADD recruits caspase-8 to the activated receptor and that the receptor complex activates apoptosis and NF-kappaB signaling. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon describes TNFR1 Complex II with FADD and caspase-8 as the route to extrinsic apoptosis when checkpoint control fails. |
| GO:0005031 tumor necrosis factor receptor activity | IDA PMID:1647956 Cloning, expression and cross-linking analysis of the murine... | ACCEPT | Summary: tumor necrosis factor receptor activity is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IDA evidence (PMID:1647956). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFRSF1A/TNFR1 as a broadly expressed cell-surface TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. |
| GO:0005886 plasma membrane | IDA PMID:1647956 Cloning, expression and cross-linking analysis of the murine... | ACCEPT | Summary: plasma membrane is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IDA evidence (PMID:1647956). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as a type I transmembrane receptor that initiates signaling at the plasma membrane. |
| GO:1900119 positive regulation of execution phase of apoptosis | IMP PMID:10678933 Tumor necrosis factor receptor p55-deficient mice respond to... | ACCEPT | Summary: positive regulation of execution phase of apoptosis is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IMP evidence (PMID:10678933). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Apoptosis and death-domain signaling: UniProt notes that FADD recruits caspase-8 to the activated receptor and that the receptor complex activates apoptosis and NF-kappaB signaling. |
| GO:1900119 positive regulation of execution phase of apoptosis | IGI PMID:10702415 Prevention of hepatic apoptosis and embryonic lethality in R... | ACCEPT | Summary: positive regulation of execution phase of apoptosis is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IGI evidence (PMID:10702415). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Apoptosis and death-domain signaling: UniProt notes that FADD recruits caspase-8 to the activated receptor and that the receptor complex activates apoptosis and NF-kappaB signaling. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | TAS PMID:30755793 Tumour necrosis factor signalling in health and disease. | ACCEPT | Summary: tumor necrosis factor-mediated signaling pathway is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by TAS evidence (PMID:30755793). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes canonical TNF-TNFR1 signaling through receptor-proximal Complex I and cytosolic death complexes. |
| GO:0038023 signaling receptor activity | IDA PMID:1647956 Cloning, expression and cross-linking analysis of the murine... | MODIFY | Summary: signaling receptor activity captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than tumor necrosis factor receptor activity for this gene. Replace with tumor necrosis factor receptor activity to align the annotation with the reviewed evidence. Proposed replacements: tumor necrosis factor receptor activity Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IMP PMID:7525730 Differential responses of fibroblasts from wild-type and TNF... | ACCEPT | Summary: positive regulation of canonical NF-kappaB signal transduction is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IMP evidence (PMID:7525730). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon describes Complex I assembly after TNF binding, with ubiquitin scaffolds recruiting TAK1/TABs and the IKK complex to activate NF-kappaB. |
| GO:0006915 apoptotic process | IMP PMID:17884256 TNF is a key mediator of septic encephalopathy acting throug... | KEEP AS NON CORE | Summary: apoptotic process is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Apoptosis and death-domain signaling: UniProt notes that FADD recruits caspase-8 to the activated receptor and that the receptor complex activates apoptosis and NF-kappaB signaling. |
| GO:0009986 cell surface | IDA PMID:17884256 TNF is a key mediator of septic encephalopathy acting throug... | ACCEPT | Summary: cell surface is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IDA evidence (PMID:17884256). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as initiating signaling at the cell surface/plasma membrane after trimeric TNF engagement. |
| GO:0010467 gene expression | IMP PMID:17884256 TNF is a key mediator of septic encephalopathy acting throug... | MARK AS OVER ANNOTATED | Summary: gene expression is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IMP PMID:17884256 TNF is a key mediator of septic encephalopathy acting throug... | ACCEPT | Summary: tumor necrosis factor-mediated signaling pathway is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IMP evidence (PMID:17884256). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes canonical TNF-TNFR1 signaling through receptor-proximal Complex I and cytosolic death complexes. |
| GO:0048143 astrocyte activation | IMP PMID:17884256 TNF is a key mediator of septic encephalopathy acting throug... | KEEP AS NON CORE | Summary: astrocyte activation is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0060856 establishment of blood-brain barrier | IMP PMID:17884256 TNF is a key mediator of septic encephalopathy acting throug... | KEEP AS NON CORE | Summary: establishment of blood-brain barrier is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0071222 cellular response to lipopolysaccharide | IMP PMID:17884256 TNF is a key mediator of septic encephalopathy acting throug... | KEEP AS NON CORE | Summary: cellular response to lipopolysaccharide is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway | IGI PMID:25220458 ΞΊB-Ras proteins regulate both NF-ΞΊB-dependent inflammation a... | KEEP AS NON CORE | Summary: regulation of tumor necrosis factor-mediated signaling pathway is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0003176 aortic valve development | IGI PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: aortic valve development is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0003177 pulmonary valve development | IGI PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: pulmonary valve development is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0003332 negative regulation of extracellular matrix constituent secretion | IGI PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: negative regulation of extracellular matrix constituent secretion is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0010614 negative regulation of cardiac muscle hypertrophy | IGI PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: negative regulation of cardiac muscle hypertrophy is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:1902339 positive regulation of apoptotic process involved in morphogenesis | IGI PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: positive regulation of apoptotic process involved in morphogenesis is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0005515 protein binding | IPI PMID:11374864 Hepatitis C virus core protein potentiates TNF-alpha-induced... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0050729 positive regulation of inflammatory response | IMP PMID:24211183 Tumor necrosis factor receptor signaling in keratinocytes tr... | KEEP AS NON CORE | Summary: positive regulation of inflammatory response is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0005515 protein binding | IPI PMID:17702576 Optineurin negatively regulates TNFalpha- induced NF-kappaB ... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0043235 receptor complex | ISO PMID:23382219 Structural basis for endosomal trafficking of diverse transm... | MODIFY | Summary: receptor complex captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than tumor necrosis factor receptor superfamily complex for this gene. Replace with tumor necrosis factor receptor superfamily complex to align the annotation with the reviewed evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P19438 Β· human TNFRSF1A SUPPORTS TRANSFER Human TNFR1 supports receptor-complex biology, but GO:0043235 is a generic parent of the TNF receptor superfamily complex term used for mouse. Proposed replacements: tumor necrosis factor receptor superfamily complex Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0005515 protein binding | IPI PMID:19641494 Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IMP PMID:17242187 p85alpha acts as a novel signal transducer for mediation of ... | MARK AS OVER ANNOTATED | Summary: intrinsic apoptotic signaling pathway in response to DNA damage is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Apoptosis and death-domain signaling: UniProt notes that FADD recruits caspase-8 to the activated receptor and that the receptor complex activates apoptosis and NF-kappaB signaling. |
| GO:0000139 Golgi membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Golgi membrane is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0005515 protein binding | IPI PMID:20826683 Tumor necrosis factor-alpha (TNF-alpha) regulates shedding o... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0009986 cell surface | IDA PMID:21410936 Signal pathways in astrocytes activated by cross-talk betwee... | ACCEPT | Summary: cell surface is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IDA evidence (PMID:21410936). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as initiating signaling at the cell surface/plasma membrane after trimeric TNF engagement. |
| GO:0042742 defense response to bacterium | IMP PMID:9324362 Listeriosis in p47(phox-/-) and TRp55-/- mice: protection de... | KEEP AS NON CORE | Summary: defense response to bacterium is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0045121 membrane raft | IDA PMID:17010968 The shedding activity of ADAM17 is sequestered in lipid raft... | KEEP AS NON CORE | Summary: membrane raft is supported in an ADAM17 shedding/trafficking context, but is not the core TNFR1 receptor function. Reason: Lipid-raft partitioning is relevant to regulated shedding of TNFR1 substrates, while core Tnfrsf1a biology is TNF binding, NF-kappaB signaling, and death-domain apoptotic signaling. Supporting Evidence: PMID:17010968 metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts. |
| GO:0005031 tumor necrosis factor receptor activity | IPI PMID:1645445 Molecular cloning and expression of the type 1 and type 2 mu... | ACCEPT | Summary: tumor necrosis factor receptor activity is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IPI evidence (PMID:1645445). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFRSF1A/TNFR1 as a broadly expressed cell-surface TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. |
| GO:0005031 tumor necrosis factor receptor activity | IMP PMID:11588035 Roles of tumor necrosis factor-alpha receptor subtypes in th... | ACCEPT | Summary: tumor necrosis factor receptor activity is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IMP evidence (PMID:11588035). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFRSF1A/TNFR1 as a broadly expressed cell-surface TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. |
| GO:0019221 cytokine-mediated signaling pathway | IMP PMID:11588035 Roles of tumor necrosis factor-alpha receptor subtypes in th... | MODIFY | Summary: cytokine-mediated signaling pathway captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than tumor necrosis factor-mediated signaling pathway for this gene. Replace with tumor necrosis factor-mediated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: tumor necrosis factor-mediated signaling pathway Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:11588035 Roles of tumor necrosis factor-alpha receptor subtypes in th... | MARK AS OVER ANNOTATED | Summary: positive regulation of transcription by RNA polymerase II is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0050729 positive regulation of inflammatory response | IMP PMID:11588035 Roles of tumor necrosis factor-alpha receptor subtypes in th... | KEEP AS NON CORE | Summary: positive regulation of inflammatory response is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0006954 inflammatory response | IMP PMID:9551933 TNF receptor-deficient mice reveal divergent roles for p55 a... | ACCEPT | Summary: inflammatory response is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IMP evidence (PMID:9551933). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes TNFR1 Complex I signaling as driving inflammatory and survival gene expression through NF-kappaB and MAPK pathways. |
| GO:0007166 cell surface receptor signaling pathway | IMP PMID:9551933 TNF receptor-deficient mice reveal divergent roles for p55 a... | MODIFY | Summary: cell surface receptor signaling pathway captures the right general biology for Tnfrsf1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than tumor necrosis factor-mediated signaling pathway for this gene. Replace with tumor necrosis factor-mediated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: tumor necrosis factor-mediated signaling pathway Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." |
| GO:0006693 prostaglandin metabolic process | TAS PMID:8387893 Mice deficient for the 55 kd tumor necrosis factor receptor ... | MARK AS OVER ANNOTATED | Summary: prostaglandin metabolic process is related to reported Tnfrsf1a biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Curation judgment: TNFR1 is not primarily a JAK-STAT receptor, and generic signal transduction, gene expression, developmental process, extracellular matrix secretion, and mechanical-stimulus terms are downstream or context-specific. |
| GO:0006952 defense response | IMP PMID:8387893 Mice deficient for the 55 kd tumor necrosis factor receptor ... | KEEP AS NON CORE | Summary: defense response is supported for Tnfrsf1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Tnfrsf1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0005031 tumor necrosis factor receptor activity | TAS PMID:9551933 TNF receptor-deficient mice reveal divergent roles for p55 a... | ACCEPT | Summary: tumor necrosis factor receptor activity is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by TAS evidence (PMID:9551933). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFRSF1A/TNFR1 as a broadly expressed cell-surface TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. |
| GO:0005031 tumor necrosis factor receptor activity | TAS PMID:9843922 The locus of tumor necrosis factor-alpha action in lung infl... | ACCEPT | Summary: tumor necrosis factor receptor activity is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by TAS evidence (PMID:9843922). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFRSF1A/TNFR1 as a broadly expressed cell-surface TNF receptor with extracellular cysteine-rich ligand-binding domains and an intracellular death domain. |
| GO:0005886 plasma membrane | TAS PMID:9551933 TNF receptor-deficient mice reveal divergent roles for p55 a... | ACCEPT | Summary: plasma membrane is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by TAS evidence (PMID:9551933). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon identifies TNFR1 as a type I transmembrane receptor that initiates signaling at the plasma membrane. |
| GO:0006954 inflammatory response | IMP PMID:9843922 The locus of tumor necrosis factor-alpha action in lung infl... | ACCEPT | Summary: inflammatory response is biologically consistent with the curated synthesis for Tnfrsf1a and is supported by IMP evidence (PMID:9843922). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." file:mouse/Tnfrsf1a/Tnfrsf1a-deep-research-falcon.md Falcon summarizes TNFR1 Complex I signaling as driving inflammatory and survival gene expression through NF-kappaB and MAPK pathways. |
| GO:0005031 tumor necrosis factor receptor activity | IPI PMID:1645445 Molecular cloning and expression of the type 1 and type 2 mu... | ACCEPT | Summary: tumor necrosis factor receptor activity is a direct molecular function of Tnfrsf1a. Reason: Mouse Tnfrsf1a encodes TNFR1, a type I membrane receptor for TNF-family ligands; Goodwin et al. directly characterized recombinant murine TNF receptors with TNF-alpha and TNF-beta binding properties matching their human orthologs. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." |
| GO:0005515 protein binding | IPI PMID:11374864 Hepatitis C virus core protein potentiates TNF-alpha-induced... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:11374864 Hepatitis C virus core protein potentiates TNF-alpha-induced... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:16680093 Tumour necrosis factor receptor 1 mediates endoplasmic retic... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:17702576 Optineurin negatively regulates TNFalpha- induced NF-kappaB ... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:17702576 Optineurin negatively regulates TNFalpha- induced NF-kappaB ... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0005515 protein binding | IPI PMID:26649818 Phosphorylation and linear ubiquitin direct A20 inhibition o... | REMOVE | Summary: protein binding is an uninformative generic molecular-function term for a TNFR1 pathway interaction. Reason: The interaction may be real and relevant to receptor-proximal TNFR1 signaling, but GO:0005515 does not say whether TNFR1 is acting as a receptor, binding TNF, recruiting an adaptor, or being regulated by the partner. Retain the specific TNF receptor, TNF binding, complex, and pathway annotations instead. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Protein-interaction curation: Several IPI annotations to protein binding reflect specific pathway interactors such as ERN1, TRADD/RIPK1-associated proteins, cIAP/A20 pathway proteins, FAN/RACK1, or shedding regulators. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: tumor necrosis factor-mediated signaling pathway captures the canonical pathway output of TNFR1. Reason: TNFR1 binds extracellular TNF and nucleates receptor-proximal signaling complexes that activate NF-kappaB and related TNF-mediated outputs, so the transferred TNF-mediated signaling annotation should be retained. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." |
| GO:0002947 tumor necrosis factor receptor superfamily complex | IEA GO_REF:0000107 | ACCEPT | Summary: tumor necrosis factor receptor superfamily complex is the appropriate receptor-complex term for TNFR1. Reason: TNFR1 is a type I membrane receptor that forms ligand-bound receptor complexes through its extracellular region and signals through its cytoplasmic death domain; GO:0002947 captures this receptor-superfamily complex more specifically than generic receptor complex terms. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Membrane and complex localization: UniProt describes TNFRSF1A as a type I membrane protein with extracellular ligand-binding and intracellular death-domain regions. |
| GO:0005031 tumor necrosis factor receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: tumor necrosis factor receptor activity is a direct molecular function of Tnfrsf1a. Reason: Mouse Tnfrsf1a encodes TNFR1, a type I membrane receptor for TNF-family ligands; Goodwin et al. directly characterized recombinant murine TNF receptors with TNF-alpha and TNF-beta binding properties matching their human orthologs. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." |
| GO:0005031 tumor necrosis factor receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: tumor necrosis factor receptor activity is a direct molecular function of Tnfrsf1a. Reason: Mouse Tnfrsf1a encodes TNFR1, a type I membrane receptor for TNF-family ligands; Goodwin et al. directly characterized recombinant murine TNF receptors with TNF-alpha and TNF-beta binding properties matching their human orthologs. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." |
| GO:0005576 extracellular region | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: extracellular region reflects the shed TNFR1 ectodomain and is peripheral to the membrane receptor function. Reason: Full-length TNFR1 is primarily a single-pass membrane receptor, while TNFR1 can also be cleaved from the surface as a soluble ectodomain. Retain this broad extracellular localization as non-core so it does not obscure the plasma-membrane receptor activity. Supporting Evidence: PMID:17010968 metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts |
| GO:0005576 extracellular region | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: extracellular region reflects the shed TNFR1 ectodomain and is peripheral to the membrane receptor function. Reason: Full-length TNFR1 is primarily a single-pass membrane receptor, while TNFR1 can also be cleaved from the surface as a soluble ectodomain. Retain this broad extracellular localization as non-core so it does not obscure the plasma-membrane receptor activity. Supporting Evidence: PMID:17010968 metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts |
| GO:0005576 extracellular region | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: extracellular region reflects the shed TNFR1 ectodomain and is peripheral to the membrane receptor function. Reason: Full-length TNFR1 is primarily a single-pass membrane receptor, while TNFR1 can also be cleaved from the surface as a soluble ectodomain. Retain this broad extracellular localization as non-core so it does not obscure the plasma-membrane receptor activity. Supporting Evidence: PMID:17010968 metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000117 | MODIFY | Summary: response to lipopolysaccharide is broader than the supported cellular LPS-response context for TNFR1. Reason: TNFR1 acts in TNF-dependent inflammatory signaling downstream of LPS exposure, but GO:0032496 is broader than the cellular LPS-response term already supported for mouse Tnfrsf1a. Replace it with GO:0071222 and retain that LPS response as non-core relative to direct TNF receptor activity. Proposed replacements: cellular response to lipopolysaccharide Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Inflammation and host defense phenotypes: p55 and p75 receptor knockouts reveal that "The majority of biologic responses classically attributed to TNF are mediated by p55." |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: tumor necrosis factor-mediated signaling pathway captures the canonical pathway output of TNFR1. Reason: TNFR1 binds extracellular TNF and nucleates receptor-proximal signaling complexes that activate NF-kappaB and related TNF-mediated outputs, so the transferred TNF-mediated signaling annotation should be retained. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md NF-kappaB and inflammatory signaling: TNF-R55-deficient fibroblasts show loss of major TNF-induced functions, including "NF-kappa B activation." |
| GO:0043120 tumor necrosis factor binding | IBA GO_REF:0000033 | ACCEPT | Summary: tumor necrosis factor binding is a direct TNFR1 molecular function. Reason: The PAINT assertion follows the TNFR1 clade and is consistent with direct mouse and human evidence that TNFRSF1A binds TNF-family ligands. Supporting Evidence: file:mouse/Tnfrsf1a/Tnfrsf1a-notes.md Mouse TNF binding/receptor evidence: Goodwin et al. cloned murine TNF receptor type 1 and reported that the "ligand-binding characteristics of the recombinant murine receptors mirror those of the human homologs." |
| GO:0071396 cellular response to lipid | IEA GO_REF:0000117 | MODIFY | Summary: cellular response to lipid is a broad ARBA parent of the supported LPS-response context. Reason: GO places GO:0071222 cellular response to lipopolysaccharide under GO:0071396 cellular response to lipid. Tnfrsf1a evidence supports TNFR1-dependent inflammatory brain responses after LPS challenge, so the generic lipid-response parent should be narrowed to the LPS child and retained as non-core relative to direct TNF receptor activity. Proposed replacements: cellular response to lipopolysaccharide Supporting Evidence: PMID:17884256 Following LPS administration TNFR1(-/-) mice had less caspase-dependent apoptosis in brain cells and fewer neutrophils infiltrating the brain |
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Experiment: Quantify TNF-induced Complex I and Complex II assembly, NF-kappaB activation, caspase-8 activation, and cell death in Tnfrsf1a-null cells rescued with ligand-binding or death-domain mutants.
Hypothesis: TNFR1 pathway choice depends on assembly of distinct receptor-proximal complexes that separate NF-kappaB signaling from apoptotic signaling.
Type: receptor complex signaling assay
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