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60ad85f700002694 de novo AMP biosynthetic process Mouse

Now, I'll review the model in detail:

GO-CAM Model Review: "de novo AMP biosynthetic process (Mouse)"

Model ID: gomodel:60ad85f700002694

General Overview

This model represents the 'de novo' AMP biosynthetic process in mouse (taxon: NCBITaxon:10090). It was sourced from gomodel:R-HSA-73817 and is currently in production status.

Structure Analysis

The model depicts a linear pathway of the de novo AMP biosynthesis process (GO:0044208) with multiple enzymatic activities connected by causal relations using the "provides input for" (RO:0002413) predicate. The pathway flows through the following activities in sequence:

  1. Ppat (MGI:MGI:2387203) - amidophosphoribosyltransferase activity (GO:0004044)
  2. Gart (MGI:MGI:95654) with multiple functions:
  3. phosphoribosylamine-glycine ligase activity (GO:0004637)
  4. phosphoribosylglycinamide formyltransferase activity (GO:0004644)
  5. phosphoribosylformylglycinamidine cyclo-ligase activity (GO:0004641)
  6. Pfas (MGI:MGI:2684864) - phosphoribosylformylglycinamidine synthase activity (GO:0004642)
  7. Paics (MGI:MGI:1914304) with two functions:
  8. phosphoribosylaminoimidazole carboxylase activity (GO:0004638)
  9. phosphoribosylaminoimidazolesuccinocarboxamide synthase activity (GO:0004639)
  10. Adsl (MGI:MGI:103202) with two functions:
  11. (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido) succinate lyase activity (GO:0070626)
  12. N6-(1,2-dicarboxyethyl)AMP AMP-lyase activity (GO:0004018)
  13. Atic (MGI:MGI:1351352) with two functions:
  14. phosphoribosylaminoimidazolecarboxamide formyltransferase activity (GO:0004643)
  15. IMP cyclohydrolase activity (GO:0003937)
  16. Adss2 (MGI:MGI:87948) - adenylosuccinate synthase activity (GO:0004019)

Evidence Assessment

  • The model uses various evidence codes, predominantly:
  • ECO:0000266 (sequence orthology evidence)
  • ECO:0000314 (direct assay evidence)
  • ECO:0000315 (mutant phenotype evidence)
  • The evidence is supported by appropriate references to scientific literature (PMIDs)
  • There are appropriate "with" references to UniProtKB entries for orthology evidence

Cellular Location

  • Some activities (those of Gart protein) are annotated as occurring in the cytosol (GO:0005829)
  • Other activities lack cellular location annotation

Strengths of the Model

  1. The model clearly represents the sequential nature of the AMP biosynthetic pathway
  2. Each activity is appropriately connected to the biological process (GO:0044208)
  3. Appropriate molecular function terms are used for each enzyme
  4. Evidence is well documented with appropriate references

Improvement Opportunities

  1. Cellular location annotation: Only Gart activities have cellular location (GO:0005829). For consistency and completeness, all activities should have cellular location annotations.

  2. Causal chain completion: The final activity (Adss2 with GO:0004018) doesn't have any outgoing causal associations. This makes the pathway appear incomplete.

  3. GART multifunctionality representation: The Gart protein (MGI:MGI:95654) is represented with three separate activities. According to the complexes document, if these are activities of a single protein, they should be properly linked to show how they relate to each other within the pathway.

  4. Evidence consistency: While most activities have multiple evidence entries, some (like GO:0004018) have fewer. Strengthening the evidence base for these activities would improve the model.

  5. Missing substrates and products: The model focuses on the enzymatic activities but doesn't explicitly represent the small molecule substrates and products of each reaction, which would make the model more informative.

Biological Accuracy

The represented pathway follows the established steps of de novo AMP biosynthesis, with the appropriate enzymes and activities. The evidence provided supports the biological accuracy of the model.

Conclusion

This GO-CAM model provides a good representation of the de novo AMP biosynthetic process in mouse with a clear sequential pathway of enzymatic activities. The main recommendations for improvement are to complete the cellular location annotations for all activities, ensure the causal chain is complete through to the final product, and consider adding the molecular substrates and products to make the model more informative about the actual biochemical transformations occurring in the pathway.