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Based on my review of the GO-CAM model and related documents, here's my evaluation of the model:

Review of GO-CAM Model: gomodel:617b481400000793

Model Summary

Title: KAT5 autoacetylation and deacetylation by HDAC3 and SIRT1 (Human)
Taxon: Human (NCBITaxon:9606)
Status: Production
Link: https://bioregistry.io/go.model:617b481400000793

Model Contents

This GO-CAM model represents the regulatory mechanism of KAT5 (Histone acetyltransferase KAT5/TIP60) involving autoacetylation and deacetylation by HDAC3 and SIRT1. The model includes:

  1. KAT5 autoacetylation: KAT5 (UniProtKB:Q92993) has peptide-lysine-N-acetyltransferase activity (GO:0061733) that directly positively regulates its own histone acetyltransferase activity (GO:0004402)

  2. KAT5 deacetylation by HDAC3: HDAC3 (UniProtKB:O15379) has protein lysine deacetylase activity (GO:0033558) that directly negatively regulates KAT5's peptide-lysine-N-acetyltransferase activity

  3. KAT5 deacetylation by SIRT1: SIRT1 (UniProtKB:Q96EB6) has NAD-dependent protein lysine deacetylase activity (GO:0034979) that directly negatively regulates KAT5's peptide-lysine-N-acetyltransferase activity

  4. Biological context: All activities are part of DNA repair-dependent chromatin remodeling (GO:0140861)

Scientific Accuracy

The model accurately represents the biological process described in the literature. According to the referenced papers (PMID:25301942 and PMID:20100829), KAT5 undergoes autoacetylation which enhances its activity, while both HDAC3 and SIRT1 can deacetylate KAT5, reducing its activity. The subcellular location (nucleus) is correctly specified for the relevant activities.

GO-CAM Structure Assessment

Strengths:

  1. Proper use of causal relationships: The model correctly uses "directly positively regulates" (RO:0002629) and "directly negatively regulates" (RO:0002630) to connect the activities.

  2. Appropriate molecular functions: The model uses specific molecular functions for each protein:

  3. KAT5: peptide-lysine-N-acetyltransferase activity (GO:0061733) and histone acetyltransferase activity (GO:0004402)
  4. HDAC3: protein lysine deacetylase activity (GO:0033558)

  5. SIRT1: NAD-dependent protein lysine deacetylase activity (GO:0034979)

  6. Clear biological context: All activities are properly situated within DNA repair-dependent chromatin remodeling (GO:0140861)

  7. Evidence and references: Each activity has appropriate evidence codes (ECO:0000314 - direct assay evidence used in manual assertion) with corresponding literature references.

Areas for Improvement:

  1. Missing evidence for one causal association: The causal association between HDAC3's protein lysine deacetylase activity and KAT5's peptide-lysine-N-acetyltransferase activity lacks evidence codes and references. This should be added for completeness.

  2. Protein complex representation: While not necessarily an issue in this case, the model doesn't explicitly represent KAT5 as part of any complexes it might function in. According to UniProt records, KAT5 is part of the NuA4 histone acetyltransferase complex, but since the model focuses on KAT5 regulation rather than its downstream targets, this representation is acceptable.

Recommendations

  1. Add evidence for HDAC3's regulatory relationship: Add appropriate evidence codes and references for the causal association between HDAC3's deacetylase activity and KAT5's acetyltransferase activity.

  2. Consider expanding the model: While the current model is coherent and focused, it could potentially be expanded to include:

  3. The specific lysine residues on KAT5 that are acetylated/deacetylated (e.g., Lys-104, Lys-120, Lys-148, Lys-150, Lys-187, and Lys-189 as mentioned in the UniProt entry)

  4. Downstream effects of KAT5 acetylation/deacetylation on its target proteins or biological processes

  5. Consistency check: Verify that the temporal relationships in the model are accurate - autoacetylation occurs first, followed by its effect on KAT5's acetyltransferase activity, which can be regulated by HDAC3 and SIRT1's deacetylase activities.

Overall Assessment

This is a high-quality GO-CAM model that effectively represents the regulatory mechanism of KAT5 through autoacetylation and deacetylation by HDAC3 and SIRT1. The model adheres to GO-CAM annotation guidelines, uses appropriate terms and relationships, and is supported by literature evidence. With the minor addition of evidence for one causal association, the model would be complete and ready for continued use in production.