Nodal signaling pathway module

Nodal/TGF-beta family ligands use EGF-CFC co-receptors and activin-class receptors to activate SMAD2/3 transcriptional programs for embryonic axis formation and cell-fate decisions.

MODULE:nodal_signalingDRAFTSignaling Pathwaymodules/nodal_signaling.yaml

nodal signaling pathwayGO:0038092

file:modules/nodal_signaling-deep-research-falcon.md

Nodal 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:0038092

nodal signaling pathway

The module is grounded in the GO biological process term for nodal signaling pathway.

PANTHER:PTN000218063

PAINT node PTN000218063 for NODAL

Local PAINT IBD node in PTHR11848 with propagated terms C:GO:0005576, F:GO:0005125, P:GO:0007178; PAINT date 20260528.

PANTHER:PTN000746990

PAINT node PTN000746990 for NODAL

Local PAINT IBD node in PTHR11848 with propagated terms P:GO:0030154, P:GO:0038092; PAINT date 20250902.

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

nodal_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 (1/7 grounded genes reviewed)

1 complete review(s) · 1 with deep research · 6 missing review · 0 reviewed but lacking deep research

Gene	Review	Complete	Deep research
CRIPTO P13385	✗	—	—
ACVR1B P36896	✗	—	—
SMAD4 Q13485	✗	—	—
ACVR2B Q13705	✗	—	—
SMAD2 Q15796	✗	—	—
NODAL Q96S42	✗	—	—
SMAD3 P84022	✓	✓	✓

Tree

Nodal signaling pathwaySignaling Pathwaynodal_signaling

Parts
1. 1. nodal coreceptor engagement
2. Nodal coreceptor engagementRegulatory Stepnodal_coreceptor_engagement
  
  Annotons
  - Nodal ligand Family: Nodal ligand family/ortholog group
  - CRIPTO co-receptor Gene Product: CRIPTO
3. 2. nodal receptor activation
4. Nodal receptor activationRegulatory Stepnodal_receptor_activation
  
  Annotons
  - ACVR1B type I receptor Gene Product: ACVR1B
  - ACVR2B type II receptor Gene Product: ACVR2B
5. 3. nodal smad output
6. Nodal SMAD outputRegulatory Stepnodal_smad_output
  
  Annotons
  - SMAD2 transcriptional effector Gene Product: SMAD2
  - SMAD3 transcriptional effector Gene Product: SMAD3
  - SMAD4 common mediator Gene Product: SMAD4

Details

Context

metazoaNCBITaxon:33208

plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Nodal signaling pathwaySignaling Pathwaynodal_signaling

nodal signaling pathwayGO:0038092

Context

metazoaNCBITaxon:33208

plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

nodal_coreceptor_engagement -> nodal_receptor_activation Causes

The initiating event promotes nodal receptor activation.

nodal_receptor_activation -> nodal_smad_output Causes

Nodal receptor activation leads to nodal smad output.

Part 1: nodal coreceptor engagement

Nodal coreceptor engagementRegulatory Stepnodal_coreceptor_engagement

NODAL ligand and CRIPTO co-receptor promote activin receptor complex signaling.

Annotons

Nodal ligand

nodal_nodal_ligand

Participant: Family: Nodal ligand family/ortholog group

Family:

Nodal ligand family/ortholog groupPANTHER:PTHR11848

Representative Members: NODALUniProtKB:Q96S42

Curated exemplar for the nodal ligand role in nodal signaling pathway.

CRIPTO co-receptor

cripto_cripto_co_receptor

Participant: Gene Product: CRIPTO

Gene Product:

CRIPTOUniProtKB:P13385

Curated exemplar for the cripto co-receptor role in nodal signaling pathway.

Part 2: nodal receptor activation

Nodal receptor activationRegulatory Stepnodal_receptor_activation

ACVR1B and ACVR2B receptor chains relay Nodal ligand input.

Annotons

ACVR1B type I receptor

acvr1b_acvr1b_type_i_receptor

Participant: Gene Product: ACVR1B

Gene Product:

ACVR1BUniProtKB:P36896

Curated exemplar for the acvr1b type i receptor role in nodal signaling pathway.

ACVR2B type II receptor

acvr2b_acvr2b_type_ii_receptor

Participant: Gene Product: ACVR2B

Gene Product:

ACVR2BUniProtKB:Q13705

Curated exemplar for the acvr2b type ii receptor role in nodal signaling pathway.

Part 3: nodal smad output

Nodal SMAD outputRegulatory Stepnodal_smad_output

SMAD2/3 and SMAD4 mediate Nodal-dependent transcriptional control.

Annotons

SMAD2 transcriptional effector

smad2_smad2_transcriptional_effector

Participant: Gene Product: SMAD2

Gene Product:

SMAD2UniProtKB:Q15796

Curated exemplar for the smad2 transcriptional effector role in nodal signaling pathway.

SMAD3 transcriptional effector

smad3_smad3_transcriptional_effector

Participant: Gene Product: SMAD3

Gene Product:

SMAD3UniProtKB:P84022

Curated exemplar for the smad3 transcriptional effector role in nodal signaling pathway.

SMAD4 common mediator

smad4_smad4_common_mediator

Participant: Gene Product: SMAD4

Gene Product:

SMAD4UniProtKB:Q13485

Curated exemplar for the smad4 common mediator role in nodal signaling pathway.