TNF-mediated signaling pathway module

TNF binding to TNF receptor complexes nucleates TRADD, RIPK, and TRAF signaling assemblies that balance NF-kappaB activation, inflammatory gene expression, survival, and death decisions.

MODULE:tnf_signalingDRAFTSignaling Pathwaymodules/tnf_signaling.yaml
tumor necrosis factor-mediated signaling pathwayGO:0033209
file:modules/tnf_signaling-deep-research-falcon.md
TNF-mediated 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:0033209
tumor necrosis factor-mediated signaling pathway
The module is grounded in the GO biological process term for tumor necrosis factor-mediated signaling pathway.
PANTHER:PTN000585372
PAINT node PTN000585372 for RIPK1
Local PAINT IBD node in PTHR44329 with propagated terms P:GO:0097527; PAINT date 20240725.
PANTHER:PTN000805648
PAINT node PTN000805648 for TRAF2
Local PAINT IBD node in PTHR10131 with propagated terms P:GO:0043122; PAINT date 20260528.
PANTHER:PTN000805720
PAINT node PTN000805720 for TRAF2
Local PAINT IBD node in PTHR10131 with propagated terms F:GO:0005164, P:GO:0033209; PAINT date 20231108.
PANTHER:PTN001908418
PAINT node PTN001908418 for RIPK1
Local PAINT IBD node in PTHR44329 with propagated terms F:GO:0004674, P:GO:0007165; PAINT date 20260530.
PANTHER:PTN002562154
PAINT node PTN002562154 for TRAF2
Local PAINT IBD node in PTHR10131 with propagated terms C:GO:1990604, F:GO:0004842, P:GO:0043123; PAINT date 20241119.
PANTHER:PTN002892787
PAINT node PTN002892787 for RIPK1
Local PAINT IBD node in PTHR44329 with propagated terms C:GO:0005737; PAINT date 20260530.
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.
PANTHER:PTN008301857
PAINT node PTN008301857 for TRAF2
Local PAINT IBD node in PTHR10131 with propagated terms P:GO:0007166; PAINT date 20250411.
PANTHER:PTN008938480
PAINT node PTN008938480 for TRAF2
Local PAINT IBD node in PTHR10131 with propagated terms C:GO:0005737; PAINT date 20260528.

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
7Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • tnf_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 (1/5 grounded genes reviewed)

0 complete review(s) · 1 with deep research · 4 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
TNF P01375 ✗ — —
TRAF2 Q12933 ✗ — —
RIPK1 Q13546 ✗ — —
TRADD Q15628 ✗ — —
TNFRSF1A P19438 ✓ 133/134 ✓

Details

Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
TNF-mediated signaling pathwaySignaling Pathwaytnf_signaling
tumor necrosis factor-mediated signaling pathwayGO:0033209
Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

The initiating event promotes tnfr adaptor complex.
TNFR adaptor complex assembly leads to tnf inflammatory output.
Part 1: tnf receptor ligation
TNF engages TNFR1Regulatory Steptnf_engages_tnfr1

TNF ligand activates TNFRSF1A/TNFR1 receptor signaling complexes.

Annotons

TNF ligand
tnf_tnf_ligand
Participant: Gene Product: TNF
Gene Product:
TNFUniProtKB:P01375

Curated exemplar for the tnf ligand role in tumor necrosis factor-mediated signaling pathway.

TNFR1 receptor
tnfrsf1a_tnfr1_receptor
Participant: Family: TNFR1 receptor family/ortholog group
Family:
TNFR1 receptor family/ortholog groupPANTHER:PTHR46861
Representative Members: TNFRSF1AUniProtKB:P19438

Curated exemplar for the tnfr1 receptor role in tumor necrosis factor-mediated signaling pathway.

Part 2: tnfr adaptor complex
TNFR adaptor complex assemblyRegulatory Steptnfr_adaptor_complex_assembly

TRADD, RIPK1, and TRAF2 assemble proximal TNFR signaling complexes.

Annotons

TRADD adaptor
tradd_tradd_adaptor
Participant: Gene Product: TRADD
Gene Product:
TRADDUniProtKB:Q15628

Curated exemplar for the tradd adaptor role in tumor necrosis factor-mediated signaling pathway.

RIPK1 kinase/scaffold
ripk1_ripk1_kinase_scaffold
Participant: Family: RIPK1 kinase/scaffold family/ortholog group
Family:
RIPK1 kinase/scaffold family/ortholog groupPANTHER:PTHR44329
Representative Members: RIPK1UniProtKB:Q13546

Curated exemplar for the ripk1 kinase/scaffold role in tumor necrosis factor-mediated signaling pathway.

TRAF2 adaptor
traf2_traf2_adaptor
Participant: Family: TRAF2 adaptor family/ortholog group
Family:
TRAF2 adaptor family/ortholog groupPANTHER:PTHR10131
Representative Members: TRAF2UniProtKB:Q12933

Curated exemplar for the traf2 adaptor role in tumor necrosis factor-mediated signaling pathway.

Part 3: tnf inflammatory output
NF-kappaB and inflammatory outputRegulatory Stepnf_kappab_and_inflammatory_output

TRAF and RIPK signaling relays TNF input to NF-kappaB and inflammatory programs.

Annotons

TRAF2 signal relay
traf2_traf2_signal_relay
Participant: Family: TRAF2 signal relay family/ortholog group
Family:
TRAF2 signal relay family/ortholog groupPANTHER:PTHR10131
Representative Members: TRAF2UniProtKB:Q12933

Curated exemplar for the traf2 signal relay role in tumor necrosis factor-mediated signaling pathway.

TNFR1 pathway context
tnfrsf1a_tnfr1_pathway_context
Participant: Family: TNFR1 pathway context family/ortholog group
Family:
TNFR1 pathway context family/ortholog groupPANTHER:PTHR46861
Representative Members: TNFRSF1AUniProtKB:P19438

Curated exemplar for the tnfr1 pathway context role in tumor necrosis factor-mediated signaling pathway.