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Based on the information I have collected, I'll now review the GO-CAM model "gomodel:62b4ffe300005623" titled "HHV1-US3 inhibition of host TCR signaling via LAT (Human-Herpesvirus)".

Review of GO-CAM Model 62b4ffe300005623

Model Overview

Title: HHV1-US3 inhibition of host TCR signaling via LAT (Human-Herpesvirus)
Model ID: gomodel:62b4ffe300005623
Taxon: Human (NCBITaxon:9606)
Status: Production

Model Description

This model represents how Herpes Simplex Virus 1 (HHV-1) protein US3 inhibits host T cell receptor (TCR) signaling by interfering with the function of the Linker for Activation of T cells (LAT) protein. The model shows a mechanism where viral US3 protein uses protein sequestering activity to inhibit LAT signaling receptor complex adaptor activity, thereby disrupting the T cell receptor signaling pathway.

Components of the Model

Proteins and Activities

  1. HHV-1 US3 protein (UniProtKB:P04413)
  2. Activity: Protein sequestering activity (GO:0140311)
  3. Location: Host cell cytoplasm (GO:0030430)
  4. Part of: Symbiont-mediated suppression of host T-cell mediated immune response (GO:0052085)

  5. Evidence: ECO:0000314, PMID:25907557

  6. LAT protein (UniProtKB:O43561)

  7. Activity: Signaling receptor complex adaptor activity (GO:0030159)
  8. Location: Plasma membrane (GO:0005886)
  9. Part of: T cell receptor signaling pathway (GO:0050852)

  10. Evidence: ECO:0000314, PMID:9489702; ECO:0000314, PMID:9729044; ECO:0000314, PMID:25907557

  11. ZAP70 protein (UniProtKB:P43403)

  12. Activity: Protein tyrosine kinase activity (GO:0004713)
  13. Location: Cytoplasm (GO:0005737)
  14. Part of: T cell receptor signaling pathway (GO:0050852)

  15. Evidence: ECO:0000314, PMID:15292186; ECO:0000304, PMID:12359715; ECO:0000314, PMID:9489702

  16. TRAF6 protein (UniProtKB:Q9Y4K3)

  17. Activity: Ubiquitin protein ligase activity (GO:0061630)
  18. Location: Cytoplasm (GO:0005737)
  19. Part of: T cell receptor signaling pathway (GO:0050852)
  20. Evidence: ECO:0000314, PMID:23514740; ECO:0000314, PMID:22851693

Causal Relationships

  1. HHV-1 US3 protein directly negatively regulates (RO:0002630) LAT's signaling receptor complex adaptor activity
  2. ZAP70 directly positively regulates (RO:0002629) LAT's signaling receptor complex adaptor activity
  3. LAT directly positively regulates (RO:0002629) TRAF6's ubiquitin protein ligase activity

Evaluation of the Model

Strengths

  1. Biological Accuracy: The model correctly represents the mechanism described in PMID:25907557, where HHV-1 US3 protein inhibits T cell signaling by interfering with LAT activation via TRAF6.

  2. Appropriate Use of GO Terms: The molecular functions, cellular components, and biological processes are appropriately assigned to each protein based on their known roles.

  3. Appropriate Causal Relationships: The causal relationships use the correct relation ontology terms (RO:0002629 for positive regulation, RO:0002630 for negative regulation).

  4. Evidence Support: All assertions in the model are supported by specific literature references with appropriate evidence codes.

Issues Found

  1. Missing Target Input for Sequestering Activity: According to the "Protein sequestering activity" guidelines, the protein that acts as a sequesterer should have a "has input" relation to its target. In this model, there is no explicit "has input" relationship between US3 and LAT.

  2. Incomplete Representation of TRAF6-LAT Mechanism: Based on PMID:25907557 and UniProt entries, US3 prevents LAT and TRAF6 interaction, but the model doesn't fully show this mechanistic detail. The paper suggests US3 confines LAT activation via TRAF6, indicating US3 may prevent TRAF6-mediated ubiquitination of LAT.

  3. ZAP70-LAT Relationship Evidence Needs Clarification: The model correctly shows ZAP70 positively regulating LAT, but the evidence cited (PMID:15292186) appears to focus on ZAP70 kinase structure rather than specifically on LAT phosphorylation. While ZAP70 is known to phosphorylate LAT (as confirmed in PMID:9489702), the evidence citation could be more specific.

  4. Lack of Molecular Details: The model doesn't capture some mechanistic details, such as the phosphorylation of LAT by ZAP70 or the ubiquitination of LAT by TRAF6.

Recommendations

  1. Add "has input" Relation: Add a "has input" relation from US3's protein sequestering activity to LAT to properly represent the sequestering mechanism as per GO-CAM guidelines.

  2. Clarify Mechanism: Consider clarifying that US3 prevents the interaction between TRAF6 and LAT, disrupting LAT ubiquitination by TRAF6. This could be done by adding additional details or comments to the model.

  3. Review Evidence Citations: Review the evidence citation for the ZAP70-LAT relationship and consider citing PMID:9489702 as the primary evidence for this relationship.

  4. Consider Adding Molecular Details: If appropriate based on available evidence, consider adding more molecular details such as:

  5. Phosphorylation of LAT by ZAP70 at specific sites

  6. Ubiquitination of LAT by TRAF6 (with Lys-63-linked polyubiquitin chains)

  7. Add Contextual Information: Consider adding a comment or description to the model that explains the viral evasion strategy, highlighting how this disruption of TCR signaling benefits the virus by suppressing host immune responses.

Conclusion

The model "HHV1-US3 inhibition of host TCR signaling via LAT" provides a clear representation of how HHV-1 US3 protein inhibits T cell receptor signaling by interfering with LAT function. The model correctly uses GO and relation ontology terms and is supported by appropriate evidence. With a few minor improvements as suggested above, the model would provide an even more complete and accurate representation of this host-pathogen interaction mechanism.