NLR signaling pathway module

Nucleotide-binding leucine-rich-repeat receptors detect intracellular perturbations and assemble RIPK-, ASC-, or caspase-containing signaling platforms for inflammatory and antimicrobial responses.

MODULE:nlr_signalingDRAFTSignaling Pathwaymodules/nlr_signaling.yaml
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathwayGO:0035872
file:modules/nlr_signaling-deep-research-falcon.md
NLR 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:0035872
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
The module is grounded in the GO biological process term for nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway.
PANTHER:PTN001908418
PAINT node PTN001908418 for RIPK2
Local PAINT IBD node in PTHR44329 with propagated terms P:GO:0007165; PAINT date 20250904.
PANTHER:PTN002892787
PAINT node PTN002892787 for RIPK2
Local PAINT IBD node in PTHR44329 with propagated terms C:GO:0005737; PAINT date 20260530.
PANTHER:PTN002892800
PAINT node PTN002892800 for RIPK2
Local PAINT IBD node in PTHR44329 with propagated terms P:GO:0043123, P:GO:0045087; PAINT date 20210604.
PANTHER:PTN004670420
PAINT node PTN004670420 for NOD2
Local PAINT IBD node in PTHR24106 with propagated terms C:GO:0005829, F:GO:0038187, P:GO:0002221, P:GO:0032495, P:GO:0035556, P:GO:0042742, P:GO:0043123; PAINT date 20250903.
PANTHER:PTN008720308
PAINT node PTN008720308 for CASP1
Local PAINT IBD node in PTHR47901 with propagated terms F:GO:0004197, P:GO:0016485; PAINT date 20250522.
PANTHER:PTN008720309
PAINT node PTN008720309 for CASP1
Local PAINT IBD node in PTHR47901 with propagated terms C:GO:0072559, C:GO:0097169; PAINT date 20170228.
PANTHER:PTN009213768
PAINT node PTN009213768 for CASP1
Local PAINT IBD node in PTHR47901 with propagated terms P:GO:0050727; PAINT date 20250522.

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

  • nlr_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 (0/5 grounded genes reviewed)

0 complete review(s) · 0 with deep research · 5 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
RIPK2 O43353 ✗ — —
CASP1 P29466 ✗ — —
NLRP3 Q96P20 ✗ — —
NOD2 Q9HC29 ✗ — —
PYCARD Q9ULZ3 ✗ — —

Details

Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
NLR signaling pathwaySignaling Pathwaynlr_signaling
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathwayGO:0035872
Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

The initiating event promotes nlr adaptor assembly.
NLR adaptor assembly leads to inflammatory protease output.
Part 1: nlr sensor activation
NLR sensor activationRegulatory Stepnlr_sensor_activation

NOD2 and NLRP3 exemplify cytosolic NLR sensors for innate immune signaling.

Annotons

NOD2 sensor
nod2_nod2_sensor
Participant: Family: NOD2 sensor family/ortholog group
Family:
NOD2 sensor family/ortholog groupPANTHER:PTHR24106
Representative Members: NOD2UniProtKB:Q9HC29

Curated exemplar for the nod2 sensor role in nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway.

NLRP3 inflammasome sensor
nlrp3_nlrp3_inflammasome_sensor
Participant: Gene Product: NLRP3
Gene Product:
NLRP3UniProtKB:Q96P20

Curated exemplar for the nlrp3 inflammasome sensor role in nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway.

Part 2: nlr adaptor assembly
NLR adaptor assemblyRegulatory Stepnlr_adaptor_assembly

RIPK2 and ASC/PYCARD link activated NLRs to downstream signaling complexes.

Annotons

RIPK2 kinase/adaptor
ripk2_ripk2_kinase_adaptor
Participant: Family: RIPK2 kinase/adaptor family/ortholog group
Family:
RIPK2 kinase/adaptor family/ortholog groupPANTHER:PTHR44329
Representative Members: RIPK2UniProtKB:O43353

Curated exemplar for the ripk2 kinase/adaptor role in nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway.

ASC adaptor
pycard_asc_adaptor
Participant: Gene Product: PYCARD
Gene Product:
PYCARDUniProtKB:Q9ULZ3

Curated exemplar for the asc adaptor role in nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway.

Part 3: inflammatory protease output
Inflammatory protease outputRegulatory Stepinflammatory_protease_output

NLR signaling can activate caspase-1 and inflammatory cytokine maturation programs.

Annotons

Caspase-1 inflammatory protease
casp1_caspase_1_inflammatory_protease
Participant: Family: Caspase-1 inflammatory protease family/ortholog group
Family:
Caspase-1 inflammatory protease family/ortholog groupPANTHER:PTHR47901
Representative Members: CASP1UniProtKB:P29466

Curated exemplar for the caspase-1 inflammatory protease role in nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway.

RIPK2 inflammatory signal relay
ripk2_ripk2_inflammatory_signal_relay
Participant: Family: RIPK2 inflammatory signal relay family/ortholog group
Family:
RIPK2 inflammatory signal relay family/ortholog groupPANTHER:PTHR44329
Representative Members: RIPK2UniProtKB:O43353

Curated exemplar for the ripk2 inflammatory signal relay role in nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway.