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6205c24300000330 Microtubule polyglutamylation regulation Human

Now that I've gathered information about the model, let me review gomodel:6205c24300000330 - "Microtubule polyglutamylation regulation (Human)".

GO-CAM Review for gomodel:6205c24300000330

Model Overview

This GO-CAM model represents the regulation of microtubule polyglutamylation in humans. The model shows various molecular interactions involved in microtubule polymerization, stabilization, and post-translational modifications, particularly focusing on polyglutamylation.

Biological Content Accuracy

The model accurately represents the tubulin polyglutamylation pathway based on current scientific understanding:

  1. The model includes key players in the regulation of tubulin polyglutamylation, including:
  2. TTLL1 (O95922) - Tubulin-glutamic acid ligase activity
  3. MAP4 (P27816) - Microtubule-associated protein involved in stabilization
  4. MARK4 (Q96L34) - Protein serine/threonine kinase that regulates MAP4 through phosphorylation
  5. TPGS1 (Q6ZTW0) and TPGS2 (Q68CL5) - Molecular adaptor proteins in the tubulin polyglutamylase complex
  6. LRRC49 (Q8IUZ0-4) - Adaptor protein in the tubulin polyglutamylase complex

  7. PCM1 (Q15154) - Involved in scaffold activity in the centriolar satellite

  8. The evidence for these interactions is well-documented in the literature, particularly in the Wang et al. (2022) paper (PMIDs: 34782749 and 34040253) which describe the molecular mechanisms of how MARK4 regulates microtubule polyglutamylation by controlling MAP4 phosphorylation.

Model Structure and Connectivity

The model correctly represents causal connections between activities using appropriate relations:

  1. The regulatory relationships are represented with causal predicates:
  2. RO:0002629 (directly positively regulates) for positive regulation

  3. RO:0002630 (directly negatively regulates) for negative regulation

  4. Key pathway connections:

  5. MARK4 (Q96L34) phosphorylates MAP4 (P27816), negatively regulating its microtubule stabilizing activity
  6. TTLL1 (O95922) has tubulin-glutamic acid ligase activity, which negatively regulates microtubule stabilization
  7. PCM1 (Q15154) acts as a molecular scaffold, recruiting various adaptor proteins
  8. Adaptor proteins (TPGS1, TPGS2, LRRC49) all positively regulate TTLL1's activity

Quality Control Review

  1. Evidence and Citations:
  2. The model is well-supported with evidence from appropriate experimental sources
  3. The primary references (PMIDs: 34782749, 34040253, 10791892) provide solid experimental evidence for the claimed relationships

  4. Evidence codes are correctly used (ECO:0000314 for direct assay, ECO:0000250 for sequence similarity evidence)

  5. Cellular Locations:

  6. Appropriate cellular locations are specified for each activity

  7. Most activities occur on microtubules (GO:0005874) or at the centrosome/centriolar satellite (GO:0034451)

  8. GO Term Usage:

  9. The molecular function terms are appropriate for each protein:

    • GO:0070740 (tubulin-glutamic acid ligase activity) for TTLL1
    • GO:0140778 (microtubule stabilizing activity) for MAP4
    • GO:0004674 (protein serine/threonine kinase activity) for MARK4
    • GO:0030674 (protein-macromolecule adaptor activity) for the adaptor proteins

  10. Biological Processes:

  11. The model correctly connects activities to appropriate biological processes:
    • GO:0000226 (microtubule cytoskeleton organization)
    • GO:0046785 (microtubule polymerization)
    • GO:0140706 (protein-containing complex localization to centriolar satellite)
    • GO:0061635 (regulation of protein complex stability)
    • GO:1902850 (microtubule cytoskeleton organization involved in mitosis)

Minor Issues to Address

  1. Evidence Documentation:
  2. Some causal associations lack specific evidence instances (such as in the connections from Q9H6J7 to Q8IUZ0-4 and Q68CL5)

  3. These should be supported with the same evidence as other similar relationships in the model

  4. Complex Representation:

  5. According to the GO-CAM document on representing complexes, the model uses the correct approach by representing individual subunits with known activities rather than using a complex ID
  6. This is appropriate since the tubulin polyglutamylase complex members have distinct molecular functions

Overall Assessment

The GO-CAM model "Microtubule polyglutamylation regulation (Human)" (gomodel:6205c24300000330) is a high-quality representation of the current understanding of microtubule polyglutamylation regulation. It accurately captures the molecular mechanisms described in recent literature, particularly the roles of MARK4 in regulating MAP4 activity and the subsequent effects on microtubule polyglutamylation via TTLL1.

The model follows GO-CAM best practices by: 1. Using appropriate molecular function terms 2. Correctly specifying cellular locations 3. Linking activities to biological processes 4. Using appropriate causal relations between activities 5. Providing solid experimental evidence for most relationships

The minor issues noted (some missing evidence annotations) don't significantly impact the overall quality of the model.

This model successfully represents a complex regulatory pathway in a clear and parsable format, making it valuable for researchers interested in microtubule regulation, post-translational modifications, and cytoskeletal organization.