id: MODULE:death_receptor_apoptotic_signaling title: Death receptor apoptotic signaling pathway module description: Death ligands activate death-domain receptors and FADD-containing DISC complexes, bringing initiator caspase-8 into proximity to trigger extrinsic apoptotic protease cascades, exemplified by FASLG-FAS (CD95) signaling. status: DRAFT evidence: - source_id: file:modules/death_receptor_apoptotic_signaling-deep-research-falcon.md title: Death receptor apoptotic signaling pathway Falcon module review statement: >- Falcon/Edison module review generated 2026-06-28 is linked as supporting evidence for module boundaries, core mechanism, variation, constraints, and failure modes; open questions in that report require manual review before promotion to curated knowledge gaps. - source_id: GO:0008625 title: extrinsic apoptotic signaling pathway via death domain receptors statement: The module is grounded in the GO biological process term for extrinsic apoptotic signaling pathway via death domain receptors. - source_id: GO:0036337 title: Fas signaling pathway statement: >- The core FASLG-FAS-FADD-CASP8 arm of this module represents the Fas (CD95) signaling pathway (GO:0036337, is_a GO:0008625), matching production GO-CAM 663d668500001551. - source_id: file:interpro/panther/PTHR11471/PTHR11471-review.yaml title: PANTHER family PTHR11471 review (TNF superfamily cytokines) statement: >- Curated PANTHER family review for PTHR11471 scopes GO:0005125 (cytokine activity) family-wide (PTN000895255) and scopes GO:0036337 (Fas signaling pathway) and GO:0008625 (extrinsic apoptotic signaling pathway via death domain receptors) to the FASLG subfamily PTHR11471:SF33 (PTN002607446). - source_id: file:genes/human/FASLG/FASLG-ai-review.yaml title: Human FASLG AI gene review statement: >- Curated human FASLG review supports cytokine activity (GO:0005125), death receptor binding (GO:0005123), Fas signaling pathway (GO:0036337), and extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625) at the external side of the plasma membrane and in the extracellular region. - source_id: file:genes/human/FAS/FAS-ai-review.yaml title: Human FAS AI gene review statement: >- Curated human FAS review supports tumor necrosis factor receptor activity (GO:0005031), Fas signaling pathway (GO:0036337), and extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625) in the CD95 DISC at the plasma membrane. - source_id: file:genes/human/FADD/FADD-ai-review.yaml title: Human FADD AI gene review statement: >- Curated human FADD review supports protein-macromolecule adaptor activity (GO:0030674) and caspase binding (GO:0089720) in the death-inducing signaling complex (GO:0031264, GO:0031265) during extrinsic apoptotic signaling (GO:0008625, GO:0036337). - source_id: PANTHER:PTN000895255 title: PAINT node PTN000895255 for PTHR11471 TNF family root statement: >- Local PAINT IBD node in PTHR11471 with propagated terms C:GO:0005576, F:GO:0005125, P:GO:0007166, P:GO:0043123, P:GO:2001238; PAINT date 20260528. - source_id: PANTHER:PTN002607446 title: PAINT node PTN002607446 for FASLG (PTHR11471:SF33) statement: >- Local PAINT IBD node in PTHR11471 with propagated term P:GO:0008625; PAINT date 20260528. - source_id: PANTHER:PTN002930185 title: PAINT node PTN002930185 for FAS (PTHR46874:SF1) statement: >- Local PAINT IBD node in PTHR46874 with propagated terms C:GO:0009897, C:GO:0031265, C:GO:0045121, F:GO:0005031, P:GO:0006924, P:GO:0032872, P:GO:0043066, P:GO:0097049, P:GO:0097527; PAINT date 20241121. - source_id: PANTHER:PTN008354262 title: PAINT node PTN008354262 for FADD (PTHR15077:SF10) statement: >- Local PAINT IBD node in PTHR15077 with propagated terms C:GO:0031265, F:GO:0005123, F:GO:0089720, P:GO:0045089, P:GO:0097191; PAINT date 20231109. - source_id: PANTHER:PTN000047947 title: PAINT node PTN000047947 for CASP8 statement: Local PAINT IBD node in PTHR10454 with propagated terms C:GO:0005737, F:GO:0004197, P:GO:0006915; PAINT date 20260528. - source_id: PANTHER:PTN002930098 title: PAINT node PTN002930098 for TNFRSF1A statement: Local PAINT IBD node in PTHR46861 with propagated terms C:GO:0043235, C:GO:0045121, F:GO:0005031, F:GO:0043120; PAINT date 20260530. - source_id: PMID:7826947 title: 'Human Fas ligand: gene structure, chromosomal location and species specificity.' statement: >- Demonstrates that human Fas ligand (FASLG) is a type II membrane TNF-family protein that induces apoptosis by binding to its receptor, Fas (CD95). - source_id: PMID:9228058 title: Characterization of Fas (Apo-1, CD95)-Fas ligand interaction. statement: >- Characterizes the homotrimeric human FasL interaction with three Fas receptor molecules required for Fas-induced cytotoxicity. knowledge_gaps: - gap_statement: >- The seed module models the FASL-FAS arm but does not yet represent the TRAIL-R1 and TRAIL-R2 death-receptor variants. boundary: >- The FAS/FASLG/FADD/CASP8 chain matches production GO-CAM model 663d668500001551. TRAIL/TNFRSF10A and TRAIL/TNFRSF10B chains are present in cached production models 662af8fa00002877 and 663d668500001492 and should become alternate receptor-ligation variants rather than being collapsed into the FAS arm. gap_kind: - CURATION dark_aspect: RESIDUAL_SUBGAP status: OPEN significance: >- TRAIL-specific receptor terms and palmitoylation/context rows should be visible without broadening the FAS DISC node into a generic receptor placeholder. resolution: >- Add TRAIL-R1 and TRAIL-R2 variants grounded in the completed TNFSF10, TNFRSF10A, and TNFRSF10B reviews and in their production GO-CAM models. - gap_statement: >- TNFR1 is present only as context even though it has a distinct TNF/TRADD/RIPK1 complex-I to complex-II apoptotic arm. boundary: >- The reviewed human and mouse TNFRSF1A/Tnfrsf1a annotations support TNF receptor activity, TNF-mediated signaling, and death-domain apoptotic signaling, but TNFR1 also branches into NF-kappaB survival and necroptosis checkpoints and therefore should not be modeled as a simple FAS copy. gap_kind: - CURATION dark_aspect: RESIDUAL_SUBGAP status: OPEN significance: >- Correct TNFR1 modeling is the boundary between apoptotic death-receptor signaling and the broader TNF signaling module. resolution: >- Add a TNFR1-specific variant grounded in the mouse 64e7eefa00001233 GO-CAM plus the completed TNFRSF1A/Tnfrsf1a reviews, and connect it to TNF survival/necroptosis branches only through explicit optional context. - gap_statement: >- CFLAR and CASP10 are not yet represented at the DISC/initiator-caspase decision step. boundary: >- FADD and CASP8 are correctly modeled as the core adaptor and initiator protease, while completed CFLAR and CASP10 reviews separate c-FLIP inhibition/activation from CASP10 paralogous initiator protease biology. gap_kind: - CURATION dark_aspect: RESIDUAL_SUBGAP status: OPEN significance: >- The module needs to distinguish direct DISC recruitment from final apoptotic output and from c-FLIP-mediated restraint. resolution: >- Add CFLAR and CASP10 leaves or optional variants at DISC assembly / initiator activation, and keep effector CASP3/6/7 execution in the separate execution-phase module. notes: >- Curated compact signaling-pathway module generated from verified UniProt exemplar accessions and local PAINT IBD rows. PTN anchors are included only when the exemplar accession appears in an IBD seed row in interpro/panther; roles without local PAINT seeds remain grounded by verified UniProt exemplar accessions. Falcon integration (2026-06-28): Falcon findings are linked as evidence and family-level support. Automatically extracted open-question headings were intentionally not retained as knowledge_gap entries because they were not manually curated. Machine-generated Falcon citations remain curation support and are not manually adjudicated here. Manual APOPTOSIS audit (2026-09-30): the FAS/FADD/CASP8 seed was checked against completed death-receptor reviews and the production FASL-FAS GO-CAM; TRAIL, TNFR1, CFLAR, and CASP10 were left as explicit expansion gaps rather than merged into the FAS arm. OUT OF SCOPE - caspase-9/APAF-1 and the apoptosome (PMID:42819741): a membership handoff routed a structural study of the human caspase-9 CARD to this module. It does not belong here. This module is grounded in GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors and models the death-ligand arm only: FASLG -> FAS -> FADD -> CASP8, with TNFRSF1A as receptor context. Caspase-9 is the initiator caspase of the *intrinsic* (mitochondrial) pathway and is activated by the APAF-1/cytochrome c apoptosome, not at a DISC; neither CASP9 (UniProtKB:P55211) nor APAF1 (UniProtKB:O14727) is a participant of this module, and the paper assays neither FAS, FADD nor CASP8 (CASP8 appears in it only as a filament-forming comparator). The correct home for apoptosome-level mechanism is modules/intrinsic_apoptotic_signaling.yaml, where CASP9 and APAF1 are already annotons and where this candidate was assessed and recorded as not modelled. Note that CASP8 and CASP9 share the PANTHER family this module selects on (PTHR10454 CASPASE), so a family-level selector could in principle sweep caspase-9 literature in here, and the shared PAINT node PTN000047947 does not separate them either - it is cited for CASP8 in this module and for CASP9 in the intrinsic module, carrying the same generic C:GO:0005737 / F:GO:0004197 / P:GO:0006915 propagation. What keeps the initiator-caspase role extrinsic is only the representative member, UniProtKB:Q14790 (CASP8); treat the family term as context, not as the role's identity. Route apoptosome, CYCS, APAF1 and CASP9 findings to the intrinsic module, and effector CASP3/6/7 findings to modules/apoptotic_execution_phase.yaml. Ligands in Signaling Pathways upgrade (2026-10-25, Tranche 4A): replaced GENE_PRODUCT selectors on FASLG, FAS, and FADD with PANTHER subfamily selectors (PTHR11471:SF33, PTHR46874:SF1, PTHR15077:SF10) anchored to local PAINT IBD nodes, added GO:0036337 (Fas signaling pathway) alongside GO:0008625, and populated function, processes, locations, and evidence on all annotons. module: id: death_receptor_apoptotic_signaling label: Death receptor apoptotic signaling pathway module_type: SIGNALING_PATHWAY concepts: - preferred_term: extrinsic apoptotic signaling pathway via death domain receptors term: id: GO:0008625 label: extrinsic apoptotic signaling pathway via death domain receptors description: Death ligands activate death-domain receptors and FADD-containing DISC complexes, bringing initiator caspase-8 into proximity to trigger extrinsic apoptotic protease cascades. - preferred_term: Fas signaling pathway term: id: GO:0036337 label: Fas signaling pathway description: >- Extrinsic apoptotic signaling pathway initiated by trimeric FASLG binding to the FAS (CD95) death receptor at the plasma membrane, recruiting FADD and procaspase-8 into the CD95 death-inducing signaling complex (DISC). context: taxa: - preferred_term: metazoa term: id: NCBITaxon:33208 label: Metazoa cellular_components: - preferred_term: extracellular region term: id: GO:0005576 label: extracellular region - preferred_term: plasma membrane term: id: GO:0005886 label: plasma membrane - preferred_term: cytosol term: id: GO:0005829 label: cytosol - preferred_term: nucleus term: id: GO:0005634 label: nucleus parts: - order: 1 role: death receptor ligation node: id: death_receptor_ligation label: Death receptor ligation module_type: REGULATORY_STEP description: FAS ligand engages FAS death receptor complexes at the cell surface. annotons: - id: faslg_fas_ligand label: FAS ligand participant: selector_type: FAMILY family: preferred_term: Fas ligand (FASLG / TNFSF6) subfamily term: id: PANTHER:PTHR11471:SF33 label: TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 6 representative_members: - preferred_term: FASLG term: id: UniProtKB:P48023 label: 'Tumor necrosis factor ligand superfamily member 6 (Apoptosis antigen ligand) (APTL) (CD95 ligand) (CD95-L) (Fas antigen ligand) (Fas ligand) (FasL) (CD antigen CD178) [Cleaved into: Tumor necrosis factor ligand superfamily member 6, membrane form; Tumor necrosis factor ligand superfamily member 6, soluble form (Receptor-binding FasL ectodomain) (Soluble Fas ligand) (sFasL); ADAM10-processed FasL form (APL); FasL intracellular domain (FasL ICD) (SPPL2A-processed FasL form) (SPA)]' ancestral_nodes: - preferred_term: PAINT node PTN000895255 for PTHR11471 TNF family root term: id: PANTHER:PTN000895255 label: PTN000895255 description: >- Local PAINT IBD node in PTHR11471 with propagated terms C:GO:0005576, F:GO:0005125, P:GO:0007166, P:GO:0043123, P:GO:2001238; PAINT date 20260528. evidence: - source_id: GO_REF:0000033 statement: IBD propagation from PAINT node PTN000895255 in PTHR11471. - preferred_term: PAINT node PTN002607446 for FASLG subfamily term: id: PANTHER:PTN002607446 label: PTN002607446 description: >- Local PAINT IBD node in PTHR11471 (PTHR11471:SF33 clade) with propagated term P:GO:0008625; PAINT date 20260528. evidence: - source_id: GO_REF:0000033 statement: IBD propagation from PAINT node PTN002607446 in PTHR11471. evidence: - source_id: file:interpro/panther/PTHR11471/PTHR11471-review.yaml title: PANTHER family PTHR11471 review statement: >- PTHR11471:SF33 (clade PTN002607446) groups vertebrate FASLG orthologs that enable cytokine activity (GO:0005125) and death receptor binding (GO:0005123) in the Fas signaling pathway (GO:0036337) and extrinsic apoptotic signaling via death domain receptors (GO:0008625). role_description: >- Homotrimeric type II transmembrane or soluble TNF-family death ligand that binds and cross-links the FAS (CD95) receptor to initiate the Fas signaling pathway and extrinsic apoptosis. function: preferred_term: cytokine activity term: id: GO:0005125 label: cytokine activity processes: - preferred_term: Fas signaling pathway term: id: GO:0036337 label: Fas signaling pathway - preferred_term: extrinsic apoptotic signaling pathway via death domain receptors term: id: GO:0008625 label: extrinsic apoptotic signaling pathway via death domain receptors locations: - preferred_term: external side of plasma membrane term: id: GO:0009897 label: external side of plasma membrane - preferred_term: extracellular region term: id: GO:0005576 label: extracellular region evidence: - source_id: file:genes/human/FASLG/FASLG-ai-review.yaml title: Human FASLG AI gene review statement: >- Curated human FASLG review supports GO:0005125 (cytokine activity), GO:0036337 (Fas signaling pathway), and GO:0008625 (extrinsic apoptotic signaling pathway via death domain receptors). - source_id: PMID:7826947 title: 'Human Fas ligand: gene structure, chromosomal location and species specificity.' statement: >- Human FasL is a type II membrane protein that induces apoptosis by binding to its receptor, Fas. gocam_associations: - model: gomodel:663d668500001551 activity: gomodel:663d668500001551/663d668500001652 title: FASL-FAS interaction leading to apoptosis (human) - id: fas_fas_death_receptor label: FAS death receptor participant: selector_type: FAMILY family: preferred_term: FAS (CD95 / TNFRSF6) death receptor subfamily term: id: PANTHER:PTHR46874:SF1 label: TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 6 representative_members: - preferred_term: FAS term: id: UniProtKB:P25445 label: Tumor necrosis factor receptor superfamily member 6 (Apo-1 antigen) (Apoptosis-mediating surface antigen FAS) (FASLG receptor) (CD antigen CD95) ancestral_nodes: - preferred_term: PAINT node PTN002930185 for FAS term: id: PANTHER:PTN002930185 label: PTN002930185 description: >- Local PAINT IBD node in PTHR46874 with propagated terms C:GO:0009897, C:GO:0031265, C:GO:0045121, F:GO:0005031, P:GO:0006924, P:GO:0032872, P:GO:0043066, P:GO:0097049, P:GO:0097527; PAINT date 20241121. evidence: - source_id: GO_REF:0000033 statement: IBD propagation from PAINT node PTN002930185 in PTHR46874. role_description: >- Type I transmembrane TNF-receptor-superfamily death receptor that binds homotrimeric FASLG and recruits FADD via its cytosolic death domain to nucleate the CD95 DISC. function: preferred_term: tumor necrosis factor receptor activity term: id: GO:0005031 label: tumor necrosis factor receptor activity processes: - preferred_term: Fas signaling pathway term: id: GO:0036337 label: Fas signaling pathway - preferred_term: extrinsic apoptotic signaling pathway via death domain receptors term: id: GO:0008625 label: extrinsic apoptotic signaling pathway via death domain receptors locations: - preferred_term: plasma membrane term: id: GO:0005886 label: plasma membrane - preferred_term: membrane raft term: id: GO:0045121 label: membrane raft evidence: - source_id: file:genes/human/FAS/FAS-ai-review.yaml title: Human FAS AI gene review statement: >- Curated human FAS review supports GO:0005031 (tumor necrosis factor receptor activity), GO:0036337 (Fas signaling pathway), and GO:0008625 (extrinsic apoptotic signaling pathway via death domain receptors). - source_id: PMID:9228058 title: Characterization of Fas (Apo-1, CD95)-Fas ligand interaction. statement: >- The death-inducing receptor Fas is activated when cross-linked by the type II membrane protein Fas ligand (FasL). gocam_associations: - model: gomodel:663d668500001551 activity: gomodel:663d668500001551/663d668500001647 title: FASL-FAS interaction leading to apoptosis (human) - order: 2 role: disc assembly node: id: disc_adaptor_assembly label: DISC adaptor assembly module_type: REGULATORY_STEP description: FADD bridges death receptors to initiator caspase recruitment. annotons: - id: fadd_fadd_adaptor label: FADD adaptor participant: selector_type: FAMILY family: preferred_term: FADD death-domain adaptor subfamily term: id: PANTHER:PTHR15077:SF10 label: FAS-ASSOCIATED DEATH DOMAIN PROTEIN representative_members: - preferred_term: FADD term: id: UniProtKB:Q13158 label: FAS-associated death domain protein (FAS-associating death domain-containing protein) (Growth-inhibiting gene 3 protein) (Mediator of receptor induced toxicity) ancestral_nodes: - preferred_term: PAINT node PTN008354262 for FADD term: id: PANTHER:PTN008354262 label: PTN008354262 description: >- Local PAINT IBD node in PTHR15077 with propagated terms C:GO:0031265, F:GO:0005123, F:GO:0089720, P:GO:0045089, P:GO:0097191; PAINT date 20231109. evidence: - source_id: GO_REF:0000033 statement: IBD propagation from PAINT node PTN008354262 in PTHR15077. role_description: >- Bipartite death-domain / death-effector-domain adaptor that binds activated FAS via its C-terminal DD and recruits procaspase-8 via its N-terminal DED within the CD95 DISC. function: preferred_term: protein-macromolecule adaptor activity term: id: GO:0030674 label: protein-macromolecule adaptor activity processes: - preferred_term: Fas signaling pathway term: id: GO:0036337 label: Fas signaling pathway - preferred_term: extrinsic apoptotic signaling pathway via death domain receptors term: id: GO:0008625 label: extrinsic apoptotic signaling pathway via death domain receptors locations: - preferred_term: cytoplasmic side of plasma membrane term: id: GO:0009898 label: cytoplasmic side of plasma membrane - preferred_term: cytosol term: id: GO:0005829 label: cytosol evidence: - source_id: file:genes/human/FADD/FADD-ai-review.yaml title: Human FADD AI gene review statement: >- Curated human FADD review supports GO:0030674 (protein-macromolecule adaptor activity) in the death-inducing signaling complex during extrinsic apoptotic signaling via death domain receptors (GO:0008625). gocam_associations: - model: gomodel:663d668500001551 activity: gomodel:663d668500001551/663d668500001579 title: FASL-FAS interaction leading to apoptosis (human) - id: casp8_caspase_8_initiator label: Caspase-8 initiator participant: selector_type: FAMILY family: preferred_term: Caspase-8 initiator family/ortholog group term: id: PANTHER:PTHR10454 label: CASPASE representative_members: - preferred_term: CASP8 term: id: UniProtKB:Q14790 label: 'Caspase-8 (CASP-8) (EC 3.4.22.61) (Apoptotic cysteine protease) (Apoptotic protease Mch-5) (CAP4) (FADD-homologous ICE/ced-3-like protease) (FADD-like ICE) (FLICE) (ICE-like apoptotic protease 5) (MORT1-associated ced-3 homolog) (MACH) [Cleaved into: Caspase-8 subunit p18; Caspase-8 subunit p10]' ancestral_nodes: - preferred_term: PAINT node PTN000047947 for CASP8 term: id: PANTHER:PTN000047947 label: PTN000047947 description: Local PAINT IBD node in PTHR10454 with propagated terms C:GO:0005737, F:GO:0004197, P:GO:0006915; PAINT date 20260528. evidence: - source_id: GO_REF:0000033 statement: IBD propagation from PAINT node PTN000047947 in PTHR10454. evidence: - source_id: file:interpro/panther/PTHR10454/PTHR10454-deep-research-falcon.md title: PTHR10454 Falcon family review statement: >- Falcon family-level GO review: ACCEPT the current no-mapping state Use this PANTHER family as context with representative members/PTN anchors, not as blanket pathway propagation. role_description: Curated exemplar for the caspase-8 initiator role in extrinsic apoptotic signaling pathway via death domain receptors. function: preferred_term: cysteine-type endopeptidase activity term: id: GO:0004197 label: cysteine-type endopeptidase activity processes: - preferred_term: Fas signaling pathway term: id: GO:0036337 label: Fas signaling pathway - preferred_term: extrinsic apoptotic signaling pathway via death domain receptors term: id: GO:0008625 label: extrinsic apoptotic signaling pathway via death domain receptors locations: - preferred_term: cytosol term: id: GO:0005829 label: cytosol evidence: - source_id: PANTHER:PTN000047947 title: PAINT node PTN000047947 for CASP8 statement: >- Propagates GO:0004197 (cysteine-type endopeptidase activity) and GO:0006915 (apoptotic process) to CASP8 in PTHR10454. gocam_associations: - model: gomodel:663d668500001551 activity: gomodel:663d668500001551/663d668500001589 title: FASL-FAS interaction leading to apoptosis (human) - order: 3 role: extrinsic caspase activation node: id: extrinsic_caspase_activation label: Extrinsic caspase activation module_type: REGULATORY_STEP description: Caspase-8 activation initiates downstream apoptotic execution programs. annotons: - id: casp8_caspase_8_initiator_protease label: Caspase-8 initiator protease participant: selector_type: FAMILY family: preferred_term: Caspase-8 initiator protease family/ortholog group term: id: PANTHER:PTHR10454 label: CASPASE representative_members: - preferred_term: CASP8 term: id: UniProtKB:Q14790 label: 'Caspase-8 (CASP-8) (EC 3.4.22.61) (Apoptotic cysteine protease) (Apoptotic protease Mch-5) (CAP4) (FADD-homologous ICE/ced-3-like protease) (FADD-like ICE) (FLICE) (ICE-like apoptotic protease 5) (MORT1-associated ced-3 homolog) (MACH) [Cleaved into: Caspase-8 subunit p18; Caspase-8 subunit p10]' ancestral_nodes: - preferred_term: PAINT node PTN000047947 for CASP8 term: id: PANTHER:PTN000047947 label: PTN000047947 description: Local PAINT IBD node in PTHR10454 with propagated terms C:GO:0005737, F:GO:0004197, P:GO:0006915; PAINT date 20260528. evidence: - source_id: GO_REF:0000033 statement: IBD propagation from PAINT node PTN000047947 in PTHR10454. evidence: - source_id: file:interpro/panther/PTHR10454/PTHR10454-deep-research-falcon.md title: PTHR10454 Falcon family review statement: >- Falcon family-level GO review: ACCEPT the current no-mapping state Use this PANTHER family as context with representative members/PTN anchors, not as blanket pathway propagation. role_description: Curated exemplar for the caspase-8 initiator protease role in extrinsic apoptotic signaling pathway via death domain receptors. function: preferred_term: cysteine-type endopeptidase activity term: id: GO:0004197 label: cysteine-type endopeptidase activity processes: - preferred_term: Fas signaling pathway term: id: GO:0036337 label: Fas signaling pathway - preferred_term: extrinsic apoptotic signaling pathway via death domain receptors term: id: GO:0008625 label: extrinsic apoptotic signaling pathway via death domain receptors locations: - preferred_term: cytosol term: id: GO:0005829 label: cytosol evidence: - source_id: PANTHER:PTN000047947 title: PAINT node PTN000047947 for CASP8 statement: >- Propagates GO:0004197 (cysteine-type endopeptidase activity) and GO:0006915 (apoptotic process) to CASP8 in PTHR10454. - id: tnfrsf1a_death_domain_receptor_context label: Death-domain receptor context participant: selector_type: FAMILY family: preferred_term: Death-domain receptor context family/ortholog group term: id: PANTHER:PTHR46861 label: TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 1A representative_members: - preferred_term: TNFRSF1A term: id: UniProtKB:P19438 label: 'Tumor necrosis factor receptor superfamily member 1A (Tumor necrosis factor receptor 1) (TNF-R1) (Tumor necrosis factor receptor type I) (TNF-RI) (TNFR-I) (p55) (p60) (CD antigen CD120a) [Cleaved into: Tumor necrosis factor receptor superfamily member 1A, membrane form; Tumor necrosis factor-binding protein 1 (TBPI)]' ancestral_nodes: - preferred_term: PAINT node PTN002930098 for TNFRSF1A term: id: PANTHER:PTN002930098 label: PTN002930098 description: Local PAINT IBD node in PTHR46861 with propagated terms C:GO:0043235, C:GO:0045121, F:GO:0005031, F:GO:0043120; PAINT date 20260530. evidence: - source_id: GO_REF:0000033 statement: IBD propagation from PAINT node PTN002930098 in PTHR46861. evidence: - source_id: file:interpro/panther/PTHR46861/PTHR46861-deep-research-falcon.md title: PTHR46861 Falcon family review statement: >- Falcon family-level GO review: PTHR46861 is a narrow, functionally homogeneous TNFRSF1A ortholog family whose current no-mapping state is treated as under-annotated. Use the family report as candidate support for TNFR1-specific terms after manual confirmation, while grounding this module role in representative members/PTN anchors. role_description: Curated exemplar for the death-domain receptor context role in extrinsic apoptotic signaling pathway via death domain receptors. function: preferred_term: tumor necrosis factor receptor activity term: id: GO:0005031 label: tumor necrosis factor receptor activity processes: - preferred_term: extrinsic apoptotic signaling pathway via death domain receptors term: id: GO:0008625 label: extrinsic apoptotic signaling pathway via death domain receptors locations: - preferred_term: plasma membrane term: id: GO:0005886 label: plasma membrane evidence: - source_id: PANTHER:PTN002930098 title: PAINT node PTN002930098 for TNFRSF1A statement: >- Propagates GO:0005031 (tumor necrosis factor receptor activity) to TNFRSF1A in PTHR46861. connections: - source: death_receptor_ligation target: disc_adaptor_assembly connection_type: CAUSES description: The initiating event promotes disc assembly. - source: disc_adaptor_assembly target: extrinsic_caspase_activation connection_type: CAUSES description: DISC adaptor assembly leads to extrinsic caspase activation.