Death receptor apoptotic signaling pathway module

Death ligands activate death-domain receptors and FADD-containing DISC complexes, bringing initiator caspase-8 into proximity to trigger extrinsic apoptotic protease cascades.

MODULE:death_receptor_apoptotic_signalingDRAFTSignaling Pathwaymodules/death_receptor_apoptotic_signaling.yaml
extrinsic apoptotic signaling pathway via death domain receptorsGO:0008625
file:modules/death_receptor_apoptotic_signaling-deep-research-falcon.md
Death receptor apoptotic signaling pathway Falcon module review
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.
GO:0008625
extrinsic apoptotic signaling pathway via death domain receptors
The module is grounded in the GO biological process term for extrinsic apoptotic signaling pathway via death domain receptors.
PANTHER:PTN000047947
PAINT node PTN000047947 for CASP8
Local PAINT IBD node in PTHR10454 with propagated terms C:GO:0005737, F:GO:0004197, P:GO:0006915; PAINT date 20260528.
PANTHER:PTN002930098
PAINT node PTN002930098 for TNFRSF1A
Local PAINT IBD node in PTHR46861 with propagated terms C:GO:0043235, C:GO:0045121, F:GO:0005031, F:GO:0043120; PAINT date 20260530.

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.

4Nodes
3Parts
0Variant Sets
0Variants
6Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • death_receptor_apoptotic_signaling-deep-research-falcon.md (falcon)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (2/5 grounded genes reviewed)

0 complete review(s) · 2 with deep research · 3 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
FAS P25445 ✓ 95/96 ✓
FASLG P48023 ✗ — —
FADD Q13158 ✗ — —
CASP8 Q14790 ✗ — —
TNFRSF1A P19438 ✓ 133/134 ✓

Details

Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
Death receptor apoptotic signaling pathwaySignaling Pathwaydeath_receptor_apoptotic_signaling
extrinsic apoptotic signaling pathway via death domain receptorsGO:0008625
Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

The initiating event promotes disc assembly.
DISC adaptor assembly leads to extrinsic caspase activation.
Part 1: death receptor ligation
Death receptor ligationRegulatory Stepdeath_receptor_ligation

FAS ligand engages FAS death receptor complexes.

Annotons

FAS ligand
faslg_fas_ligand
Participant: Gene Product: FASLG
Gene Product:
FASLGUniProtKB:P48023

Curated exemplar for the fas ligand role in extrinsic apoptotic signaling pathway via death domain receptors.

FAS death receptor
fas_fas_death_receptor
Participant: Gene Product: FAS
Gene Product:
FASUniProtKB:P25445

Curated exemplar for the fas death receptor role in extrinsic apoptotic signaling pathway via death domain receptors.

Part 2: disc assembly
DISC adaptor assemblyRegulatory Stepdisc_adaptor_assembly

FADD bridges death receptors to initiator caspase recruitment.

Annotons

FADD adaptor
fadd_fadd_adaptor
Participant: Gene Product: FADD
Gene Product:
FADDUniProtKB:Q13158

Curated exemplar for the fadd adaptor role in extrinsic apoptotic signaling pathway via death domain receptors.

Caspase-8 initiator
casp8_caspase_8_initiator
Participant: Family: Caspase-8 initiator family/ortholog group
Family:
Caspase-8 initiator family/ortholog groupPANTHER:PTHR10454
Representative Members: CASP8UniProtKB:Q14790

Curated exemplar for the caspase-8 initiator role in extrinsic apoptotic signaling pathway via death domain receptors.

Part 3: extrinsic caspase activation
Extrinsic caspase activationRegulatory Stepextrinsic_caspase_activation

Caspase-8 activation initiates downstream apoptotic execution programs.

Annotons

Caspase-8 initiator protease
casp8_caspase_8_initiator_protease
Participant: Family: Caspase-8 initiator protease family/ortholog group
Family:
Caspase-8 initiator protease family/ortholog groupPANTHER:PTHR10454
Representative Members: CASP8UniProtKB:Q14790

Curated exemplar for the caspase-8 initiator protease role in extrinsic apoptotic signaling pathway via death domain receptors.

Death-domain receptor context
tnfrsf1a_death_domain_receptor_context
Participant: Family: Death-domain receptor context family/ortholog group
Family:
Death-domain receptor context family/ortholog groupPANTHER:PTHR46861
Representative Members: TNFRSF1AUniProtKB:P19438

Curated exemplar for the death-domain receptor context role in extrinsic apoptotic signaling pathway via death domain receptors.