A compact TGF-beta/SMAD signaling module. A dimeric TGF-beta family ligand binds type II and type I serine/threonine kinase receptors, the type II receptor activates the type I receptor, the type I receptor phosphorylates receptor-regulated SMADs, and SMAD complexes accumulate in the nucleus to regulate transcription. The module is grounded in GO:0007179. TGFB1 is anchored to PAINT TGF-beta-family nodes; receptors and SMADs are included as curated UniProt exemplars without PTN ancestry where local seed rows were not available.
All recommended fields populated.
✗ none found
No MODULE:tgfb_smad_signaling deep-research report alongside the module YAML.
✓ 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.
1 gene-function check(s) reflected in core functions · 0 conflict(s) · 1 evidence or coverage gap(s) (3 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| tgfb_ligand | TGFB1 UniProtKB:P01137 Family Representative |
cytokine activity GO:0005125 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| tgfb_receptors | PROTEIN_COMPLEX Gene |
transmembrane receptor protein serine/threonine kinase activity GO:0004675 |
Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews. |
| tgfb_ligand | TGF-beta family ligands PANTHER:PTHR11848 Family |
cytokine activity GO:0005125 |
Family Review Missing
No supported structured family review is available for PANTHER:PTHR11848. |
1 complete review(s) · 1 with deep research · 2 missing review · 3 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| TGFBR1 P36897 | ✗ | — | — |
| TGFBR2 P37173 | ✗ | — | — |
| SMAD2 Q15796 | ✓ | 283/284 | ✗ |
| SMAD3 P84022 | ✓ | 333/349 | ✓ |
| SMAD4 Q13485 | ✓ | 422/428 | ✗ |
| TGFB1 P01137 | ✓ | ✓ | ✗ |
Mature dimeric TGF-beta ligand assembles a heterotetrameric receptor complex containing type II and type I receptor serine/threonine kinases.
Extracellular dimeric ligand that nucleates receptor complex formation.
Ligand-assembled kinase complex that activates SMAD2/3.
Activated TGFBR1 phosphorylates the C-terminal SSXS motif of SMAD2 and SMAD3, licensing complex formation with SMAD4.
Direct type I receptor substrates and signal carriers.
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. 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
Phosphorylated SMAD2/3 bind SMAD4 and partner transcription factors, accumulate in the nucleus, and regulate TGF-beta target genes.
Co-SMAD that forms nuclear complexes with phosphorylated receptor-regulated SMADs.