Nitric oxide-cGMP signaling pathway module

Nitric oxide activates soluble guanylate cyclase to raise cGMP, engaging PRKG and cyclic nucleotide phosphodiesterases that control vascular smooth muscle tone and other cGMP-dependent outputs.

MODULE:nitric_oxide_cgmp_signalingDRAFTSignaling Pathwaymodules/nitric_oxide_cgmp_signaling.yaml
nitric oxide-cGMP-mediated signalingGO:0038060
file:modules/nitric_oxide_cgmp_signaling-deep-research-falcon.md
Nitric oxide-cGMP 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:0038060
nitric oxide-cGMP-mediated signaling
The module is grounded in the GO biological process term for nitric oxide-cGMP-mediated signaling.
PANTHER:PTN000453956
PAINT node PTN000453956 for NOS3
Local PAINT IBD node in PTHR43410 with propagated terms F:GO:0016491; PAINT date 20260529.
PANTHER:PTN001066032
PAINT node PTN001066032 for NOS3
Local PAINT IBD node in PTHR43410 with propagated terms C:GO:0005886, F:GO:0004517, P:GO:0006527; PAINT date 20230603.
PANTHER:PTN002322100
PAINT node PTN002322100 for NOS3
Local PAINT IBD node in PTHR43410 with propagated terms P:GO:0006809; PAINT date 20240528.

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
5Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • nitric_oxide_cgmp_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
PDE5A O76074 ✗ — —
NOS3 P29474 ✗ — —
GUCY1A1 Q02108 ✗ — —
GUCY1B1 Q02153 ✗ — —
PRKG1 Q13976 ✗ — —

Details

Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
Nitric oxide-cGMP signaling pathwaySignaling Pathwaynitric_oxide_cgmp_signaling
nitric oxide-cGMP-mediated signalingGO:0038060
Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

The initiating event promotes soluble guanylate cyclase activation.
Soluble guanylate cyclase activation leads to cgmp effector and termination.
Part 1: nitric oxide production
Nitric oxide productionRegulatory Stepnitric_oxide_production

NOS3 produces nitric oxide in endothelial signaling contexts.

Annotons

Endothelial nitric-oxide synthase
nos3_endothelial_nitric_oxide_synthase
Participant: Family: Endothelial nitric-oxide synthase family/ortholog group
Family:
Endothelial nitric-oxide synthase family/ortholog groupPANTHER:PTHR43410
Representative Members: NOS3UniProtKB:P29474

Curated exemplar for the endothelial nitric-oxide synthase role in nitric oxide-cGMP-mediated signaling.

Part 2: soluble guanylate cyclase activation
Soluble guanylate cyclase activationRegulatory Stepsoluble_guanylate_cyclase_activation

NO activates GUCY1A1/GUCY1B1 soluble guanylate cyclase to generate cGMP.

Annotons

Soluble guanylate cyclase alpha subunit
gucy1a1_soluble_guanylate_cyclase_alpha_subunit
Participant: Gene Product: GUCY1A1
Gene Product:
GUCY1A1UniProtKB:Q02108

Curated exemplar for the soluble guanylate cyclase alpha subunit role in nitric oxide-cGMP-mediated signaling.

Soluble guanylate cyclase beta subunit
gucy1b1_soluble_guanylate_cyclase_beta_subunit
Participant: Gene Product: GUCY1B1
Gene Product:
GUCY1B1UniProtKB:Q02153

Curated exemplar for the soluble guanylate cyclase beta subunit role in nitric oxide-cGMP-mediated signaling.

Part 3: cgmp effector and termination
cGMP effector and terminationRegulatory Stepcgmp_effector_and_termination

PRKG1 senses cGMP while PDE5A limits cGMP signal duration.

Annotons

cGMP-dependent protein kinase
prkg1_cgmp_dependent_protein_kinase
Participant: Gene Product: PRKG1
Gene Product:
PRKG1UniProtKB:Q13976

Curated exemplar for the cgmp-dependent protein kinase role in nitric oxide-cGMP-mediated signaling.

cGMP phosphodiesterase
pde5a_cgmp_phosphodiesterase
Participant: Gene Product: PDE5A
Gene Product:
PDE5AUniProtKB:O76074

Curated exemplar for the cgmp phosphodiesterase role in nitric oxide-cGMP-mediated signaling.