TNFSF10, also called TRAIL or Apo2L, is a type II transmembrane TNF-family cytokine that can remain at the cell surface or be released as a soluble extracellular ligand. Its extracellular TNF-homology domain forms homotrimers that bind TNFRSF10A/DR4 and TNFRSF10B/DR5 death receptors, as well as TNFRSF10C/D decoy receptors, to initiate FADD- and CASP8-dependent TRAIL-activated extrinsic apoptotic signaling. TRAIL receptor engagement can also produce contextual NF-kappaB outputs and immune-cell regulatory effects, while the zinc site and identical subunit binding are structural features of the trimeric ligand.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005102 signaling receptor binding | IEA GO_REF:0000117 | MODIFY | Summary: TRAIL is an extracellular TNF-family ligand for TNFRSF10A/DR4 and TNFRSF10B/DR5; the seeded term is a broad receptor-binding parent. Reason: Use tumor necrosis factor receptor binding to capture the TNFRSF10 receptor-ligand activity supported by the original Apo2L/TRAIL discovery papers and later DR4/DR5 structural work. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:8663110 Apo-2L may serve as an extracellular signal PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005102 signaling receptor binding | TAS PMID:8663110 Induction of apoptosis by Apo-2 ligand, a new member of the ... | MODIFY | Summary: TRAIL is an extracellular TNF-family ligand for TNFRSF10A/DR4 and TNFRSF10B/DR5; the seeded term is a broad receptor-binding parent. Reason: Use tumor necrosis factor receptor binding to capture the TNFRSF10 receptor-ligand activity supported by the original Apo2L/TRAIL discovery papers and later DR4/DR5 structural work. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:8663110 Apo-2L may serve as an extracellular signal PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005102 signaling receptor binding | TAS PMID:8777713 Identification and characterization of a new member of the T... | MODIFY | Summary: TRAIL is an extracellular TNF-family ligand for TNFRSF10A/DR4 and TNFRSF10B/DR5; the seeded term is a broad receptor-binding parent. Reason: Use tumor necrosis factor receptor binding to capture the TNFRSF10 receptor-ligand activity supported by the original Apo2L/TRAIL discovery papers and later DR4/DR5 structural work. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:8663110 Apo-2L may serve as an extracellular signal PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005125 cytokine activity | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT node assigns cytokine activity to metazoan TNF-family ligands, including experimentally supported TNFSF10/TRAIL. Reason: Cytokine activity is the molecular-function term used for the TNFSF10 nodes in the production TRAIL/TRAILR1 and TRAIL/TRAILR2 GO-CAMs and is coherent for a TNF-family death-receptor ligand. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005125 cytokine activity | IDA PMID:21146232 Plasma cytokine concentrations associated with HIV/hepatitis... | ACCEPT | Summary: TNFSF10 is a TNF-family cytokine, although PMID:21146232 itself is a plasma cytokine measurement panel rather than a receptor-activation assay. Reason: The term is correct for TNFSF10; the GOA reference mainly supports the soluble extracellular pool, while the original soluble Apo2L/TRAIL apoptosis assay and receptor-complex structures establish the activity. Supporting Evidence: PMID:21146232 measure chemokine and cytokine levels using an xMAP multiplexed bead array immunoassay PMID:8663110 Soluble Apo-2L induces extensive apoptosis PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005164 tumor necrosis factor receptor binding | IEA GO_REF:0000002 | ACCEPT | Summary: The InterPro TNF-family signature maps TNFSF10 to tumor necrosis factor receptor binding. Reason: TNFSF10 binds the TNFRSF10A/DR4 and TNFRSF10B/DR5 death receptors and TNFRSF10C/D decoy receptors through its extracellular TNF-homology domain. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:10549288 Triggering cell death: the crystal structure of Apo2L/TRAIL ... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:19427028 Cullin3-based polyubiquitination and p62-dependent aggregati... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:19427028 Cullin3-based polyubiquitination and p62-dependent aggregati... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:19427028 Cullin3-based polyubiquitination and p62-dependent aggregati... | REMOVE | Summary: CUL3 acts intracellularly on caspase-8 after death receptor ligation and is not a direct extracellular TNFSF10 receptor. Reason: The CUL3 biology belongs to DISC-associated caspase-8 ubiquitylation downstream of ligand-bound receptors, so a direct TNFSF10 protein-binding molecular function is not supported. |
| GO:0005515 protein binding | IPI PMID:20097879 Identification of a novel proapoptotic function of resveratr... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:20103630 Multivalent DR5 peptides activate the TRAIL death pathway an... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:20103630 Multivalent DR5 peptides activate the TRAIL death pathway an... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:20103630 Multivalent DR5 peptides activate the TRAIL death pathway an... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:20103630 Multivalent DR5 peptides activate the TRAIL death pathway an... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:21459798 Bortezomib primes neuroblastoma cells for TRAIL-induced apop... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:21525171 Bortezomib primes glioblastoma, including glioblastoma stem ... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:21822306 Identification of a novel pro-apoptotic role of NF-ΞΊB in the... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:22266862 Histone deacetylase inhibitors sensitize glioblastoma cells ... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:23678861 Inhibition of vacuolar ATPase attenuates the TRAIL-induced a... | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: This partner-specific IntAct import reflects TNFSF10 binding to a TRAIL receptor and is better curated as TNF receptor binding than as generic protein binding. Reason: TNFSF10 receptor engagement is the informative molecular function; use GO:0005164 rather than an unqualified protein-binding edge for TNFRSF10A/B/C/D contacts. Proposed replacements: tumor necrosis factor receptor binding Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0005576 extracellular region | EXP PMID:14609566 Regulation of soluble and surface-bound TRAIL in human T cel... | ACCEPT | Summary: Human TNFSF10 is detected as a soluble extracellular protein. Reason: Soluble TRAIL measured in leukocyte cultures and plasma is consistent with an extracellular-region location for the released ectodomain. Supporting Evidence: PMID:14609566 It can be found in two forms PMID:21146232 measure chemokine and cytokine levels using an xMAP multiplexed bead array immunoassay |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: The TNF-family ligand clade acts extracellularly after secretion or display at the cell surface. Reason: The PAINT extracellular-region assertion is coherent for TNFSF10 and matches the extracellular activity nodes in the TRAIL GO-CAMs. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:14609566 It can be found in two forms |
| GO:0005576 extracellular region | IDA PMID:21146232 Plasma cytokine concentrations associated with HIV/hepatitis... | ACCEPT | Summary: Human TNFSF10 is detected as a soluble extracellular protein. Reason: Soluble TRAIL measured in leukocyte cultures and plasma is consistent with an extracellular-region location for the released ectodomain. Supporting Evidence: PMID:14609566 It can be found in two forms PMID:21146232 measure chemokine and cytokine levels using an xMAP multiplexed bead array immunoassay |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: UniProtKB-SubCell correctly propagates the secreted location of the soluble TRAIL ectodomain. Reason: TNFSF10 exists as both a type II plasma-membrane protein and a soluble extracellular ligand. Supporting Evidence: PMID:14609566 It can be found in two forms |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-139952 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-141139 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-141156 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-141316 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3371359 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3465429 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3465448 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5675456 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-75146 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-75187 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-75238 | ACCEPT | Summary: Reactome places TNFSF10 in the extracellular ligand-receptor complexes that initiate TRAIL death-receptor signaling. Reason: These TRAIL receptor events include the extracellular TNFSF10 ligand bound to TNFRSF10A or TNFRSF10B before DISC assembly. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0005886 plasma membrane | EXP PMID:14609566 Regulation of soluble and surface-bound TRAIL in human T cel... | ACCEPT | Summary: TNFSF10 is synthesized as a type II plasma-membrane protein before shedding of a soluble extracellular ligand. Reason: The plasma-membrane annotation captures the membrane-bound TRAIL precursor and cell-surface ligand pool. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:14609566 It can be found in two forms |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: TNFSF10 is synthesized as a type II plasma-membrane protein before shedding of a soluble extracellular ligand. Reason: The plasma-membrane annotation captures the membrane-bound TRAIL precursor and cell-surface ligand pool. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:14609566 It can be found in two forms |
| GO:0005886 plasma membrane | TAS PMID:8663110 Induction of apoptosis by Apo-2 ligand, a new member of the ... | ACCEPT | Summary: TNFSF10 is synthesized as a type II plasma-membrane protein before shedding of a soluble extracellular ligand. Reason: The plasma-membrane annotation captures the membrane-bound TRAIL precursor and cell-surface ligand pool. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:14609566 It can be found in two forms |
| GO:0006915 apoptotic process | TAS PMID:8663110 Induction of apoptosis by Apo-2 ligand, a new member of the ... | MODIFY | Summary: Apo2L/TRAIL triggers apoptosis through TRAIL receptors, but the seeded top-level apoptotic-process term is too broad. Reason: Use the TRAIL-specific death-receptor apoptotic signaling pathway instead of the generic apoptosis parent. Proposed replacements: TRAIL-activated apoptotic signaling pathway Supporting Evidence: PMID:8663110 Apo-2L may serve as an extracellular signal PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0006955 immune response | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: TNFSF10 has immunoregulatory ligand biology, but this InterPro immune-response projection is generic. Reason: Keep as contextual and non-core; the core curated process is the direct TRAIL-activated death-receptor apoptotic signaling pathway. Supporting Evidence: PMID:9485194 mediated by activation of caspases |
| GO:0007154 cell communication | IEA GO_REF:0000117 | MODIFY | Summary: TNFSF10 signals through TRAIL death receptors; this seeded process is an over-broad signaling ancestor. Reason: Use GO:0036462 to name the ligand-specific death-receptor pathway initiated by TNFSF10. Proposed replacements: TRAIL-activated apoptotic signaling pathway Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:9485194 mediated by activation of caspases |
| GO:0007165 signal transduction | TAS PMID:8663110 Induction of apoptosis by Apo-2 ligand, a new member of the ... | MODIFY | Summary: TNFSF10 signals through TRAIL death receptors; this seeded process is an over-broad signaling ancestor. Reason: Use GO:0036462 to name the ligand-specific death-receptor pathway initiated by TNFSF10. Proposed replacements: TRAIL-activated apoptotic signaling pathway Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:9485194 mediated by activation of caspases |
| GO:0007165 signal transduction | TAS PMID:8777713 Identification and characterization of a new member of the T... | MODIFY | Summary: TNFSF10 signals through TRAIL death receptors; this seeded process is an over-broad signaling ancestor. Reason: Use GO:0036462 to name the ligand-specific death-receptor pathway initiated by TNFSF10. Proposed replacements: TRAIL-activated apoptotic signaling pathway Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:9485194 mediated by activation of caspases |
| GO:0007166 cell surface receptor signaling pathway | IBA GO_REF:0000033 | MODIFY | Summary: TNFSF10 signals through TRAIL death receptors; this seeded process is an over-broad signaling ancestor. Reason: Use GO:0036462 to name the ligand-specific death-receptor pathway initiated by TNFSF10. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000895255 Β· TNF-family cytokine/apoptotic signaling node SUPPORTS TRANSFER The PAINT node correctly transfers TNF-family cell-surface signaling to TNFSF10, but the seeded GO term is an ancestor of the TRAIL-activated apoptotic signaling pathway. Proposed replacements: TRAIL-activated apoptotic signaling pathway Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:9485194 mediated by activation of caspases |
| GO:0007267 cell-cell signaling | TAS PMID:8777713 Identification and characterization of a new member of the T... | MODIFY | Summary: TNFSF10 signals through TRAIL death receptors; this seeded process is an over-broad signaling ancestor. Reason: Use GO:0036462 to name the ligand-specific death-receptor pathway initiated by TNFSF10. Proposed replacements: TRAIL-activated apoptotic signaling pathway Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:9485194 mediated by activation of caspases |
| GO:0008270 zinc ion binding | IDA PMID:26457518 The structure of the death receptor 4-TNF-related apoptosis-... | KEEP AS NON CORE | Summary: TRAIL has a zinc site in the TNF-homology trimer. Reason: Zinc coordination is a supported structural property of the ligand trimer rather than a separate core effector activity. Supporting Evidence: PMID:26457518 a Zn 2+ site was found |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro membrane prediction is correct but less precise than TNFSF10 plasma-membrane localization. Reason: Use plasma membrane to capture the type II membrane TRAIL precursor. Proposed replacements: plasma membrane Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:14609566 It can be found in two forms |
| GO:0023052 signaling | IEA GO_REF:0000117 | MODIFY | Summary: TNFSF10 signals through TRAIL death receptors; this seeded process is an over-broad signaling ancestor. Reason: Use GO:0036462 to name the ligand-specific death-receptor pathway initiated by TNFSF10. Proposed replacements: TRAIL-activated apoptotic signaling pathway Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:9485194 mediated by activation of caspases |
| GO:0032813 tumor necrosis factor receptor superfamily binding | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse-to-human Compara transfer captures TNFSF10 binding to TNF-receptor-superfamily receptors. Reason: The superfamily-binding term is broad but semantically correct for TNFRSF10A/B death receptors and TNFRSF10C/D decoy receptors. Supporting Evidence: PMID:10549288 receptors, DR4 and DR5, triggers apoptosis PMID:26457518 death receptor 4 (DR4) in complex with TNF-related |
| GO:0036462 TRAIL-activated apoptotic signaling pathway | IDA PMID:9485194 TRAIL/Apo-2-ligand-induced apoptosis in human T cells. | ACCEPT | Summary: TNFSF10 directly initiates TRAIL-activated apoptotic signaling through TRAIL receptors. Reason: This is the best process term for the ligand step modeled in the TRAIL/TRAILR1 and TRAIL/TRAILR2 GO-CAMs. Supporting Evidence: PMID:9485194 mediated by activation of caspases PMID:10549288 receptors, DR4 and DR5, triggers apoptosis |
| GO:0042802 identical protein binding | IDA PMID:26457518 The structure of the death receptor 4-TNF-related apoptosis-... | KEEP AS NON CORE | Summary: TNFSF10 forms homotrimers through its TNF-homology domain. Reason: Identical protein binding describes TRAIL subunit self-association in the ligand trimer and is structural rather than a separate core signaling function. Supporting Evidence: PMID:26457518 protein forms the expected trimeric structure |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:21525171 Bortezomib primes glioblastoma, including glioblastoma stem ... | MODIFY | Summary: TRAIL treatment promotes death-receptor apoptosis, but this seeded term is broader than the extrinsic branch. Reason: Use the extrinsic-apoptotic-signaling regulation term rather than top-level positive regulation of apoptosis. Proposed replacements: positive regulation of extrinsic apoptotic signaling pathway |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: TNFSF10 can activate NF-kappaB in receptor contexts, but this output is contextual relative to DR4/DR5 apoptotic signaling. Reason: Keep as a non-core signaling output of TRAIL receptor engagement rather than centering the review on NF-kappaB. Supporting Evidence: PMID:12761501 cDNAs that activate the NF-kappaB pathway |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEP PMID:12761501 Large-scale identification and characterization of human gen... | KEEP AS NON CORE | Summary: TNFSF10 can activate NF-kappaB in receptor contexts, but this output is contextual relative to DR4/DR5 apoptotic signaling. Reason: Keep as a non-core signaling output of TRAIL receptor engagement rather than centering the review on NF-kappaB. Supporting Evidence: PMID:12761501 cDNAs that activate the NF-kappaB pathway |
| GO:0045569 TRAIL binding | IEA GO_REF:0000107 | MODIFY | Summary: The Ensembl-transferred TRAIL-binding assertion is oriented toward receptors, while this row is on the TRAIL ligand itself. Reason: For TNFSF10, the supported self-interaction is trimerization of identical TRAIL subunits. Proposed replacements: identical protein binding Supporting Evidence: PMID:26457518 protein forms the expected trimeric structure |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: TNFSF10 was detected by high-throughput mass spectrometry in a human parotid-saliva exosome fraction. Reason: The exosome localization is plausible but peripheral to the receptor-ligand activity of TNFSF10. Supporting Evidence: PMID:19199708 491 proteins in the exosome fraction of human parotid saliva |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | IDA PMID:22266862 Histone deacetylase inhibitors sensitize glioblastoma cells ... | MARK AS OVER ANNOTATED | Summary: Cytochrome-c release is a downstream mitochondrial amplification event in sensitized glioblastoma cells after TRAIL receptor activation. Reason: TNFSF10 can trigger upstream caspase-8/BID signaling, but cytochrome-c release itself is executed by the BAX/BAK mitochondrial pathway rather than by TRAIL. |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: TNFSF10 is a direct upstream ligand that positively drives extrinsic apoptotic signaling through TRAIL receptors. Reason: This term is correct for the TNFSF10 ligand step; the more specific TRAIL-activated apoptotic signaling pathway row captures the same core route with receptor specificity. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:9485194 mediated by activation of caspases |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IDA PMID:20097879 Identification of a novel proapoptotic function of resveratr... | ACCEPT | Summary: TNFSF10 is a direct upstream ligand that positively drives extrinsic apoptotic signaling through TRAIL receptors. Reason: This term is correct for the TNFSF10 ligand step; the more specific TRAIL-activated apoptotic signaling pathway row captures the same core route with receptor specificity. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:9485194 mediated by activation of caspases |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IDA PMID:21525171 Bortezomib primes glioblastoma, including glioblastoma stem ... | ACCEPT | Summary: TNFSF10 is a direct upstream ligand that positively drives extrinsic apoptotic signaling through TRAIL receptors. Reason: This term is correct for the TNFSF10 ligand step; the more specific TRAIL-activated apoptotic signaling pathway row captures the same core route with receptor specificity. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:9485194 mediated by activation of caspases |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IDA PMID:22266862 Histone deacetylase inhibitors sensitize glioblastoma cells ... | ACCEPT | Summary: TNFSF10 is a direct upstream ligand that positively drives extrinsic apoptotic signaling through TRAIL receptors. Reason: This term is correct for the TNFSF10 ligand step; the more specific TRAIL-activated apoptotic signaling pathway row captures the same core route with receptor specificity. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:9485194 mediated by activation of caspases |
| GO:2001238 positive regulation of extrinsic apoptotic signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: TNFSF10 is a direct upstream ligand that positively drives extrinsic apoptotic signaling through TRAIL receptors. Reason: This term is correct for the TNFSF10 ligand step; the more specific TRAIL-activated apoptotic signaling pathway row captures the same core route with receptor specificity. Supporting Evidence: PMID:8777713 Both full-length cell surface expressed TRAIL PMID:9485194 mediated by activation of caspases |
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Download this section (compressed HTML)Q: Should GO add a more precise TRAIL receptor binding child that names TNFSF10 binding to TNFRSF10A/TNFRSF10B and distinguishes the signaling death receptors from TNFRSF10C/TNFRSF10D decoy binding?
Q: Should Reactome-to-GOA export attach TNFSF10 extracellular-region rows only to ligand-receptor events, rather than to downstream CFLAR/CASP8 events that are part of the TRAIL pathway but no longer contain the ligand as an acting molecule?
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