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Based on all the information I've gathered, I'll now review the GO-CAM model gomodel:6690711d00002607.

Review of GO-CAM Model gomodel:6690711d00002607

Model Summary

Title: "ANG tRNA ribonuclease activity inhibits translation in response to stress (Human)" Taxon: Human (NCBITaxon:9606) Status: Production

Model Content Overview

This model describes how angiogenin (ANG) acts to inhibit translation in response to stress in human cells. The model includes interactions between: 1. Angiogenin (ANG, UniProtKB:P03950) 2. Plexin-B2 (PLXNB2, UniProtKB:O15031) 3. Cytosolic large ribosomal subunit (GO:0022625)

The model captures how ANG produces tRNA-derived stress-induced small RNAs (tiRNAs) in response to stress, which inhibit translation, and how this activity is regulated.

Detailed Model Assessment

1. Proteins and Molecular Functions:

Angiogenin (UniProtKB:P03950):

  • Activities in the model:
  • tRNA-specific ribonuclease activity (GO:0004549)
  • Receptor ligand activity (GO:0048018)
  • Appropriately annotated: Yes, based on the literature evidence. ANG has dual functions: it can act as a ligand for its receptor and cleaves tRNAs when activated.

Plexin-B2 (UniProtKB:O15031):

  • Activities in the model:
  • Signaling receptor activity (GO:0038023)
  • Ribonuclease inhibitor activity (GO:0008428)
  • Appropriately annotated: Yes, based on the literature provided. Plexin-B2 acts as a receptor for ANG and is involved in mediating ANG endocytosis and translocation.

Cytosolic large ribosomal subunit (GO:0022625):

  • Activities in the model:
  • Structural constituent of ribosome (GO:0003735)
  • Ribonuclease inhibitor activity (GO:0008428)
  • Appropriately annotated: Generally yes, but with a potential issue discussed below.

2. Biological Processes:

The model connects the molecular functions to the appropriate biological processes: - Negative regulation of translation in response to stress (GO:0032055) - Receptor-mediated endocytosis (GO:0006898) - Signal transduction (GO:0007165) - Cytoplasmic translation (GO:0002181) - Cellular response to stress (GO:0033554)

These process annotations accurately reflect the biology depicted in the model.

3. Cellular Components:

The cellular locations are well annotated: - Plasma membrane (GO:0005886) for PLXNB2 - Cytoplasm (GO:0005737) for ANG - Cytosol (GO:0005829) for ribosomal activity and inhibitor activity - Extracellular space (GO:0005615) for ANG's receptor ligand activity

4. Causal Relationships:

The causal relationships in the model appear to be correctly depicted: 1. ANG's receptor ligand activity positively regulates PLXNB2's signaling receptor activity (RO:0002304) 2. PLXNB2's signaling receptor activity positively regulates ribonuclease inhibitor activity (RO:0002629) 3. Ribonuclease inhibitor activity positively regulates ANG's tRNA ribonuclease activity (RO:0002629) 4. ANG's tRNA ribonuclease activity negatively regulates ribosomal structural activity (RO:0002630)

These relationships accurately represent the chain of events from ANG binding to PLXNB2 to the eventual inhibition of translation.

Issues and Recommendations

1. Protein Complex Representation and Activity Attribution:

According to the "How to annotate complexes in GO-CAM" guidelines, when the specific subunit carrying an activity is not known, the GO term for the complex should be used. In this model, the ribonuclease inhibitor activity (GO:0008428) is attributed to the cytosolic large ribosomal subunit (GO:0022625), which is appropriate based on the findings in the literature.

However, the recent paper (PMID:38718836) provides evidence that the ribosome actually activates ANG by refolding its C-terminal tail rather than acting as a ribonuclease inhibitor. The model currently depicts the ribosome as having ribonuclease inhibitor activity, which seems to contradict this finding.

Recommendation: Consider revising the model to reflect the latest research showing that the ribosome activates ANG rather than inhibiting it. This would involve changing the molecular function attribution and possibly the causal relationships.

2. Complex Members:

The model represents the cytosolic large ribosomal subunit (GO:0022625) but does not specify any members of this complex. While not strictly required, it would be helpful to include at least some key ribosomal proteins if they are directly involved in the interaction with ANG.

Recommendation: Consider adding specific ribosomal proteins that interact with ANG if this information is available from the literature.

3. Evidence and References:

The model uses appropriate evidence codes (ECO:0000314 - direct assay evidence used in manual assertion) and references recent relevant literature (PMID:38718836, PMID:29100074, PMID:23843625, PMID:12533544). The evidence appears to be well-connected to the assertions in the model.

Conclusion

The GO-CAM model gomodel:6690711d00002607 is generally well-constructed and accurately represents the current understanding of how ANG inhibits translation in response to stress through its tRNA ribonuclease activity. The model follows most GO-CAM best practices regarding representation of molecular functions, biological processes, cellular components, and causal relationships.

The main issue is the potential misrepresentation of the ribosome's role in ANG activation based on the most recent research. Updating this aspect would make the model more accurate according to current knowledge.

The model is parsimonious and includes the key components and relationships necessary to understand the pathway, making it accessible to human interpretation.