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.
Nuclear entry step (2026-11-10): SMAD2/3-SMAD4 nuclear import is now an explicit step, included by module_ref to karyopherin_nuclear_protein_import. No cached production GO-CAM models Nodal signaling, so no GO-CAM activities are pinned yet. 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.
All recommended fields populated.
✓ present
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.
No functional claims were checked. This does not establish consistency with gene or family reviews.
0 complete review(s) · 1 with deep research · 3 missing review · 3 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| ACVR1B P36896 | ✓ | 79/81 | ✗ |
| CRIPTO P13385 | ✗ | — | — |
| ACVR2B Q13705 | ✗ | — | — |
| NODAL Q96S42 | ✗ | — | — |
| SMAD2 Q15796 | ✓ | 283/284 | ✗ |
| SMAD3 P84022 | ✓ | 333/349 | ✓ |
| SMAD4 Q13485 | ✓ | 422/428 | ✗ |
NODAL ligand and CRIPTO co-receptor promote activin receptor complex signaling.
Curated exemplar for the nodal ligand role in nodal signaling pathway.
Curated exemplar for the cripto co-receptor role in nodal signaling pathway.
ACVR1B and ACVR2B receptor chains relay Nodal ligand input.
Curated exemplar for the acvr1b type i receptor role in nodal signaling pathway.
Curated exemplar for the acvr2b type ii receptor role in nodal signaling pathway.
Receptor-phosphorylated SMAD2/3, with SMAD4, enter the nucleus through the karyopherin import cycle, included here by reference. Activated SMAD3 binds importin-beta1 directly through its N-terminal domain and is released by RanGTP; SMAD2 cannot bind importin-beta1 because of its exon-3 insert, and both depend on importin-7/8. This is the step that GO-CAM models compress into a single edge from the plasma-membrane type I receptor to a nuclear SMAD transcription factor activity (see projects/GOCAM_COMPARTMENTS.md).
Realized by module
karyopherin_nuclear_protein_import
SMAD2/3 and SMAD4 mediate Nodal-dependent transcriptional control.
Curated exemplar for the smad2 transcriptional effector role in nodal signaling pathway.
Curated exemplar for the smad3 transcriptional effector role in nodal signaling pathway.
Curated exemplar for the smad4 common mediator role in nodal signaling pathway.