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Review of GO-CAM Model gomodel:613aae0000000579

Model Overview

This model (GO-CAM ID: gomodel:613aae0000000579) titled "SP-ANN-TPPP" represents interactions between various S100 calcium-binding proteins (S100B, S100A6, S100A2) and the Tubulin Polymerization Promoting Protein (TPPP/p25), focusing on their role in regulating microtubule dynamics and organization.

Biological Content Assessment

The model represents a regulatory pathway where multiple S100 proteins (S100B, S100A6, and S100A2) interact with TPPP/p25 to inhibit its dimerization activity, which in turn affects microtubule nucleation. The model includes:

  1. Three S100 proteins (S100B, S100A6, S100A2) with protein binding activity (GO:0005515)
  2. TPPP/p25 with protein dimerization activity (GO:0046983) and microtubule nucleator activity (GO:0140490)
  3. Causal relationships where S100 proteins negatively regulate (RO:0002630, "directly negatively regulates") TPPP's dimerization activity
  4. TPPP's dimerization activity positively regulates (RO:0002629, "directly positively regulates") its own microtubule nucleator activity
  5. The microtubule nucleator activity occurs in the Golgi apparatus (GO:0005794)

This pathway accurately represents the findings from the literature, particularly from the 2021 paper by Doi et al. (PMID: 33831707) which demonstrated that S100 proteins regulate TPPP activity by inhibiting its dimerization.

Evidence Assessment

The model cites appropriate evidence for its assertions:

  • TPPP's protein dimerization activity: ECO:0000314 (direct assay) from PMID:22484033
  • TPPP's microtubule nucleator activity: ECO:0000314 (direct assay) from PMID:31522887
  • S100 proteins' inhibition of TPPP dimerization: ECO:0000314 (direct assay) from PMID:33831707
  • TPPP's dimerization promoting microtubule nucleation: ECO:0000314 (direct assay) from PMID:22484033

The evidence aligns with current scientific understanding:

  1. Olah et al. (2012) demonstrated that TPPP forms dimers that promote microtubule assembly
  2. Fu et al. (2019) showed that TPPP acts as a microtubule nucleator at Golgi outposts
  3. Doi et al. (2021) established that S100 proteins (S100B, S100A6, S100A2) directly bind to TPPP and inhibit its dimerization

GO-CAM Best Practices Assessment

The model generally follows GO-CAM best practices:

  1. Correct causal relationships: The model appropriately uses "directly negatively regulates" (RO:0002630) for inhibitory relationships and "directly positively regulates" (RO:0002629) for activating relationships.

  2. Proper molecular function annotation: The model correctly annotates TPPP with protein dimerization activity (GO:0046983) and microtubule nucleator activity (GO:0140490), and S100 proteins with protein binding activity (GO:0005515).

  3. Cellular location specification: The model includes location information for the microtubule nucleator activity (Golgi apparatus).

  4. Evidence provenance: All assertions include appropriate evidence codes and references.

  5. Complex representation: According to the GO-CAM best practices document on complexes, when specific subunits carrying the activity are known, the activities are represented by the specific proteins. This model follows this guideline by showing TPPP's specific activities rather than using a generic complex term.

Suggestions for Improvement

While the model generally follows best practices, a few minor improvements could be made:

  1. More specific protein binding terms for S100 proteins: Instead of the general GO:0005515 (protein binding), more specific terms like "S100 protein binding" or "calcium-dependent protein binding" could better describe the molecular function.

  2. Include calcium as a cofactor: Since the regulation by S100 proteins is calcium-dependent, this information could be included in the model.

  3. Include additional downstream effects: The model could be expanded to show how TPPP's microtubule nucleation activity affects cellular processes like myelination, which is discussed in the Fu et al. (2019) paper.

  4. Additional evidence for location: While the Golgi apparatus location is appropriate based on Fu et al. (2019), adding this specific reference for this assertion would strengthen the model.

Conclusion

This GO-CAM model accurately represents the regulation of TPPP's microtubule nucleator activity by S100 proteins through inhibition of TPPP dimerization. The biological content is consistent with current literature, the evidence is appropriate, and the model follows GO-CAM best practices. Minor improvements could enhance its specificity and completeness, but overall, this is a well-constructed model that effectively captures this regulatory pathway.