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Now that I have gathered all the necessary information, I'll provide a comprehensive review of the GO-CAM model with ID 63d320cd00000399.

Review of GO-CAM Model: 63d320cd00000399

Basic Information

  • Model ID: gomodel:63d320cd00000399
  • Title: "Negative regulation of the AIM2 inflammasome by Ifi202 (Mouse)"
  • Taxon: Mouse (NCBITaxon:10090)
  • Status: Production

Model Overview

This GO-CAM model describes the mechanism by which Ifi202 (p202) negatively regulates the AIM2 inflammasome in mice. The model captures the molecular interactions between Ifi202 and Aim2, and how these interactions prevent AIM2 inflammasome complex assembly.

Key Components and Molecular Activities

The model includes five key molecular activities:

  1. Ifi202a double-stranded DNA binding activity (GO:0003690) enabled by Ifi202a (MGI:MGI:1347080)
  2. Part of negative regulation of AIM2 inflammasome complex assembly (GO:0140972)

  3. Causally upstream of (negatively regulates) Aim2's DNA binding activity

  4. Ifi202a molecular adaptor activity (GO:0060090) enabled by Ifi202a (MGI:MGI:1347080)

  5. Part of negative regulation of AIM2 inflammasome complex assembly (GO:0140972)

  6. Causally upstream of (negatively regulates) Aim2's signaling adaptor activity

  7. Aim2 double-stranded DNA binding activity (GO:0003690) enabled by Aim2 (MGI:MGI:2686159)

  8. Occurs in cytoplasm (GO:0005737)
  9. Part of AIM2 inflammasome complex assembly (GO:0140970)

  10. Causally upstream of (positively regulates) Aim2's pattern recognition receptor activity

  11. Aim2 pattern recognition receptor activity (GO:0038187) enabled by Aim2 (MGI:MGI:2686159)

  12. Occurs in cytoplasm (GO:0005737)
  13. Part of AIM2 inflammasome complex assembly (GO:0140970)

  14. Causally upstream of (positively regulates) Aim2's signaling adaptor activity

  15. Aim2 signaling adaptor activity (GO:0035591) enabled by Aim2 (MGI:MGI:2686159)

  16. Occurs in cytoplasm (GO:0005737)
  17. Part of AIM2 inflammasome complex assembly (GO:0140970)

Evidence and References

The model is supported by several published studies, primarily: - PMID:23850291 - Primary reference describing the molecular mechanism of p202-mediated inhibition of AIM2 inflammasome - PMID:23567559 - Describes the structural basis for termination of AIM2-mediated signaling by p202 - PMID:19158679 - Provides evidence for cytoplasmic localization of the AIM2 inflammasome complex

Review Findings

Biological Accuracy

  1. Molecular mechanism representation: The model accurately represents the key findings from the literature showing that Ifi202a (p202) inhibits AIM2 inflammasome assembly through two complementary mechanisms:
  2. Direct binding to double-stranded DNA (competing with AIM2)

  3. Direct interaction with AIM2 via its HIN domain, which prevents proper clustering of AIM2 and recruitment of ASC

  4. Cellular localization: The model correctly indicates that AIM2 inflammasome assembly occurs in the cytoplasm.

  5. Causal relationships: The causal relationships in the model correctly show how Ifi202a activities negatively regulate AIM2 activities, preventing inflammasome assembly.

GO-CAM Best Practices

  1. Activity representation: The model follows GO-CAM best practices by:
  2. Appropriately representing the molecular functions of both proteins
  3. Connecting activities with causal relationships (RO:0002630 "directly negatively regulates" and RO:0002629 "directly positively regulates")

  4. Including proper cellular locations

  5. Complex annotation: The model follows the recommendations from the "How to annotate complexes in GO-CAM" document. Since the activities of specific subunits (Ifi202a and Aim2) are known, the activities are represented by the specific proteins carrying the activities rather than using a complex ID.

  6. Evidence coding: Each activity and relationship is properly supported with evidence codes (ECO:0000314 "direct assay evidence used in manual assertion") and appropriate PMID references.

Areas for Improvement

  1. Additional context: The model could potentially include more context about the downstream effects of AIM2 inflammasome inhibition, such as reduced caspase-1 activation and IL-1β/IL-18 processing.

  2. ASC recruitment: The model does not explicitly represent the recruitment of ASC (PYCARD/Asc) to the AIM2 inflammasome, which is a key step in inflammasome assembly and is blocked by Ifi202a. Including this would provide a more complete picture of the mechanism.

  3. Tetrameric structure of Ifi202a: The model doesn't capture the tetrameric structure of Ifi202a that was highlighted in PMID:23850291 as important for its function in inhibiting AIM2. This structural feature enhances its ability to bind DNA with higher affinity than AIM2.

Conclusion

The GO-CAM model 63d320cd00000399 accurately represents the current scientific understanding of how Ifi202a negatively regulates AIM2 inflammasome assembly in mice. It captures the key molecular activities and their causal relationships based on published evidence. The model follows GO-CAM best practices for complex annotation and causality representation.

The model effectively illustrates an important species-specific regulatory mechanism, as p202 is present in mice but not humans, providing insight into different inflammatory response regulation between species.

While there are a few areas where additional context could enhance the model, overall it represents a high-quality GO-CAM model of this important regulatory pathway.