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5fadbcf000001101 SPModule IFIH1 MAVS

Now that I have all the necessary information, I can review the GO-CAM model gomodel:5fadbcf000001101 titled "SPModule IFIH1-MAVS".

GO-CAM Review for gomodel:5fadbcf000001101 (SPModule IFIH1-MAVS)

Overview of the Model

The model gomodel:5fadbcf000001101 describes interactions between: - IFIH1 (MDA5, UniProtKB:Q9BYX4) - MAVS (UniProtKB:Q7Z434) - PPP1CA (PP1-alpha, UniProtKB:P62136)

The model represents pathways involved in antiviral innate immune signaling, specifically how these proteins work together in virus sensing and signal transduction.

Model Structure Analysis

The model consists of five activities:

  1. IFIH1 pattern recognition receptor activity (GO:0038187)
  2. Enabled by IFIH1/MDA5 (Q9BYX4)

  3. Provides input for PPP1CA phosphatase activity

  4. PPP1CA phosphatase activity (GO:0016791)

  5. Enabled by PPP1CA (P62136)
  6. Occurs in cytoplasm (GO:0005737)

  7. Directly positively regulates IFIH1 identical protein binding activity

  8. IFIH1 identical protein binding activity (GO:0042802)

  9. Enabled by IFIH1/MDA5 (Q9BYX4)
  10. Has input ATP (CHEBI:15422)
  11. Occurs in cytoplasm (GO:0005737)

  12. Directly positively regulates MAVS identical protein binding activity

  13. MAVS identical protein binding activity (GO:0042802)

  14. Enabled by MAVS (Q7Z434)
  15. Occurs in mitochondrial outer membrane (GO:0005741)

  16. Directly positively regulates MAVS signaling adaptor activity

  17. MAVS signaling adaptor activity (GO:0035591)

  18. Enabled by MAVS (Q7Z434)
  19. Occurs in mitochondrial outer membrane (GO:0005741)

Strengths of the Model

  1. The model correctly represents the core components of the MDA5-MAVS signaling pathway.
  2. The model uses appropriate causal relationships between activities.
  3. The model correctly places the activities in their appropriate cellular compartments.
  4. The model includes the role of PPP1CA (PP1-alpha) in dephosphorylating MDA5, which is supported by the literature.
  5. The evidence cited for the activities is appropriate and well-documented with PMID references.

Issues and Recommendations

  1. Missing Interaction Details:
  2. The model doesn't explicitly show that PPP1CA dephosphorylates MDA5 at Ser-88, which is a key regulatory mechanism according to the PMID:23499489 paper.

  3. Recommendation: Consider adding this detail by including a has_output relationship from the PPP1CA activity.

  4. Missing ATP Hydrolysis Step:

  5. According to the literature, IFIH1/MDA5 has ATP hydrolysis activity, which is important for its function.

  6. Recommendation: Consider representing this more explicitly with GO:0016887 (ATP hydrolysis activity) instead of just showing ATP as an input.

  7. Missing Other Key Components:

  8. The model doesn't represent the role of viral dsRNA as an input for IFIH1/MDA5.

  9. Recommendation: Add CHEBI:67208 (double-stranded RNA) as an input for the IFIH1 pattern recognition receptor activity.

  10. Incomplete Representation of MAVS Signaling:

  11. The downstream effects of MAVS activation (activation of TBK1, IKK, IRF3, NF-κB) are not shown.

  12. Recommendation: Consider extending the model to include these downstream effects.

  13. Missing Molecular Adaptor Function:

  14. According to the annotation guidelines, MAVS functions as a molecular adaptor bringing together proteins, but this is not explicitly represented.

  15. Recommendation: Consider using GO:0060090 (molecular adaptor activity) or adding inputs that MAVS brings together.

  16. IFIH1 Identical Protein Binding:

  17. The model correctly represents that IFIH1 forms oligomers (identical protein binding), but doesn't fully capture that this oligomerization is a result of dephosphorylation.
  18. Recommendation: Consider adding more detail about how dephosphorylation enables oligomerization.

Consistency with GO-CAM Best Practices

  1. Complex Representation:

  2. The model follows GO-CAM guidelines for representing activities carried out by specific proteins rather than complexes, which is appropriate since the individual activities of each protein are known.

  3. Causal Relationships:

  4. The model appropriately uses "directly positively regulates" (RO:0002629) to show regulation between activities.

  5. The use of "provides input for" (RO:0002413) between IFIH1 pattern recognition and PPP1CA activity is appropriate.

  6. Subcellular Localization:

  7. The model correctly represents the subcellular locations: IFIH1 and PPP1CA in cytoplasm, and MAVS at the mitochondrial outer membrane.

  8. Evidence and Provenance:

  9. The model includes appropriate evidence codes and PMID references for most activities.

Overall Assessment

The GO-CAM model represents the core MDA5-MAVS signaling pathway and includes the important role of PPP1CA in regulating MDA5 activity. The model is consistent with GO-CAM best practices and is supported by scientific literature.

The model would benefit from some additional details about the mechanism of MDA5 activation (dephosphorylation at Ser-88, viral RNA binding) and more explicit representation of the downstream effects of MAVS activation. These additions would make the model more comprehensive and better aligned with the current understanding of this signaling pathway.

Despite these minor issues, the model provides a useful representation of this important antiviral signaling pathway.