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Now that I have the essential information, I'll conduct a comprehensive review of the GO-CAM model gomodel:663d668500003232, which is titled "TGFB3-mediated signaling pathway (Human)".

Review of GO-CAM Model: TGFB3-mediated signaling pathway (Human)

Model Overview

This GO-CAM model (https://bioregistry.io/go.model:663d668500003232) represents the TGF-beta 3 signaling pathway in humans, focusing on the canonical pathway from ligand binding through receptor activation to transcriptional regulation. The model shows four key proteins and their interactions:

  1. TGFB3 (UniProtKB:P10600) - transforming growth factor beta 3, acting as a cytokine
  2. TGFBR2 (UniProtKB:P37173) - TGF-beta receptor type 2
  3. TGFBR1 (UniProtKB:P36897) - TGF-beta receptor type 1
  4. SMAD2 (UniProtKB:Q15796) - transcription factor activated by the pathway

Model Evaluation

Biological Content Accuracy

The model correctly represents the canonical TGF-beta signaling pathway: - TGFB3 acts as a cytokine (GO:0005125) in the extracellular space - TGFB3 activates TGFBR2 via direct positive regulation (RO:0002629) - TGFBR2 activates TGFBR1 via direct positive regulation (RO:0002629) - TGFBR1 activates SMAD2, which then acts as a transcription factor (GO:0003700) in the nucleus

All molecular activities in the model are supported by literature evidence, and the components are present in the correct cellular locations.

Causal Connections

The causal connections are correctly represented: - The direction of signaling flows appropriately from extracellular TGFB3 → TGFBR2 → TGFBR1 → SMAD2 - The predicate "directly positively regulates" (RO:0002629) is used appropriately for these direct activation events, following GO-CAM guidelines

Consistency with GO-CAM Guidelines

Looking at the model against the guidelines for signaling receptor activity:

  1. Ligand (TGFB3):
  2. ✓ Correct MF: Has cytokine activity (GO:0005125), which is a child of receptor ligand activity
  3. ✓ Correct location: In extracellular space (GO:0005615)
  4. ✓ Correct process: Part of TGF-beta receptor signaling pathway (GO:0007179)

  5. ✓ Correct relation to receptor: Directly positively regulates its receptor

  6. Signaling receptor (TGFBR2):

  7. ✓ Correct MF: Has TGF-beta receptor type II activity (GO:0005026)
  8. ✓ Correct location: Occurs in plasma membrane (GO:0005886)
  9. ✓ Correct process: Part of TGF-beta receptor signaling pathway (GO:0007179)

  10. ✓ Correct relation: Directly positively regulates its target (TGFBR1)

  11. Type I receptor (TGFBR1):

  12. ✓ Correct MF: Has TGF-beta receptor type I activity (GO:0005025)
  13. ✓ Correct location: Occurs in plasma membrane (GO:0005886)
  14. ✓ Correct process: Part of TGF-beta receptor signaling pathway (GO:0007179)

  15. ✓ Correct relation: Directly positively regulates its target (SMAD2)

  16. Transcription Factor (SMAD2):

  17. ✓ Correct MF: Has DNA-binding transcription factor activity (GO:0003700)
  18. ✓ Correct location: Occurs in nucleus (GO:0005634)
  19. ✓ Correct process: Part of TGF-beta receptor signaling pathway (GO:0007179)

Evidence Quality

The model uses appropriate evidences: - Most assertions use direct assay evidence (ECO:0000314) - The cytokine activity for TGFB3 uses biological aspect of ancestor evidence (ECO:0000318) - Each assertion is backed by relevant PMIDs or GO_REF IDs - The model shows good evidence coverage across all assertions

Recommendations for Improvement

While the model is generally well-constructed, there are a few improvements that could be made:

  1. Downstream effects of SMAD2: The model could be extended to show what genes SMAD2 regulates. Currently, SMAD2 is shown as a transcription factor but has no outputs, leaving the pathway incomplete.

  2. SMAD2/SMAD4 complex: According to the literature, SMAD2 typically forms a complex with SMAD4 to regulate transcription. This is not represented in the current model.

  3. Feedback mechanisms: The model could include negative feedback loops that regulate TGF-beta signaling (such as inhibitory SMADs or other regulatory proteins).

  4. Phosphorylation status: The model doesn't capture the important phosphorylation of SMAD2 by TGFBR1, which is a key regulatory mechanism for this pathway.

Conclusion

This GO-CAM model (gomodel:663d668500003232) is a well-constructed representation of the TGF-beta 3 signaling pathway that follows GO-CAM best practices. The activities are properly connected and supported by evidence. It provides a parsimonious and clear representation of the canonical pathway.

The model could be extended to show downstream effects of SMAD2 activation and include regulatory mechanisms, but as a focused representation of the core signaling pathway, it meets quality standards and is biologically accurate.