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Based on my review of the provided GO-CAM model (gomodel:5fadbcf000002236) and associated references, I'll provide a comprehensive assessment of this model.

GO-CAM Model Review: "dCMP catabolic process (Mouse)"

Model ID: gomodel:5fadbcf000002236
Title: dCMP catabolic process (Mouse)
Taxon: NCBITaxon:10090 (Mouse)
Status: Production

Overview

This GO-CAM model represents the dCMP (deoxycytidine monophosphate) catabolic pathway in mouse, showing the sequence of enzymatic activities that lead to the breakdown of dCMP. The model connects multiple gene products and their molecular functions in a causal chain, representing the flow of metabolites through this catabolic pathway.

Model Structure Analysis

Key Components and Activities

The model consists of 7 activities, each performed by a different mouse protein:

  1. Cda (MGI:MGI:1919519) - Cytidine deaminase activity (GO:0019239)
  2. Input: 2'-deoxycytidine (CHEBI:15698)
  3. Part of dCMP catabolic process (GO:0006249)

  4. Occurs in cytosol (GO:0005829)

  5. Upp1 (MGI:MGI:1097668) - Deoxyuridine phosphorylase activity (GO:0047847)

  6. Part of dCMP catabolic process (GO:0006249)

  7. Occurs in cytosol (GO:0005829)

  8. Dpyd (MGI:MGI:2139667) - Dihydropyrimidine dehydrogenase (NADP+) activity (GO:0017113)

  9. Part of dCMP catabolic process (GO:0006249)

  10. Occurs in cytosol (GO:0005829)

  11. Nt5c3 (MGI:MGI:1927186) - 5'-nucleotidase activity (GO:0008253)

  12. Part of dCMP catabolic process (GO:0006249)

  13. Occurs in cytosol (GO:0005829)

  14. Nt5c (MGI:MGI:1354954) - 5'-nucleotidase activity (GO:0008253)

  15. Part of dCMP catabolic process (GO:0006249)

  16. Occurs in cytosol (GO:0005829)

  17. Dpys (MGI:MGI:1928679) - Dihydropyrimidinase activity (GO:0004157)

  18. Part of dCMP catabolic process (GO:0006249)

  19. Occurs in cytosol (GO:0005829)

  20. Upp2 (MGI:MGI:1923904) - Deoxyuridine phosphorylase activity (GO:0047847)

  21. Part of dCMP catabolic process (GO:0006249)

  22. Occurs in cytosol (GO:0005829)

  23. Upb1 (MGI:MGI:2143535) - Beta-ureidopropionase activity (GO:0003837)

  24. Occurs in cytosol (GO:0005829)

Causal Connections

The model shows the following causal relationships (all using RO:0002413 "provides input for"):

  1. Cytidine deaminase (Cda) → Deoxyuridine phosphorylase (Upp1)
  2. Cytidine deaminase (Cda) → Deoxyuridine phosphorylase (Upp2)
  3. Deoxyuridine phosphorylase (Upp1) → Dihydropyrimidine dehydrogenase (Dpyd)
  4. Deoxyuridine phosphorylase (Upp2) → Dihydropyrimidine dehydrogenase (Dpyd)
  5. Dihydropyrimidine dehydrogenase (Dpyd) → Dihydropyrimidinase (Dpys)
  6. Dihydropyrimidinase (Dpys) → Beta-ureidopropionase (Upb1)
  7. 5'-nucleotidase (Nt5c3) → Cytidine deaminase (Cda)
  8. 5'-nucleotidase (Nt5c) → Cytidine deaminase (Cda)

Literature Support

The model is well-supported by literature evidence with multiple references for most activities and causal connections:

  • Cytidine deaminase (Cda) function is supported by PMID:7923172, demonstrating that this enzyme can deaminate 2'-deoxycytidine
  • The role of Upp1/Upp2 (uridine phosphorylases) in nucleoside metabolism is supported by PMID:12849978, which specifically identified UPP2 as a novel uridine phosphorylase with broad substrate specificity
  • The overall pathway structure is supported by references including PMID:7744869, PMID:5472365, and PMID:6301357

Evaluation

Strengths

  1. Biological Accuracy: The model correctly represents the dCMP catabolic pathway with appropriate enzymes and their activities. The UniProt entries for human cytidine deaminase (P32320) and uridine phosphorylase 2 (O95045) confirm that the activities and substrates represented in the model are accurate.

  2. Pathway Completeness: The model captures the complete catabolic pathway from dCMP to final breakdown products, with each step represented by the appropriate enzyme activity.

  3. Evidence and References: The model incorporates appropriate literature evidence for each assertion, with multiple references provided for key activities and causal connections.

  4. Correct Causal Relationships: The causal connections use the appropriate predicate (RO:0002413 "provides input for") to show metabolic flow through the pathway.

  5. Proper Cellular Context: All activities are correctly localized to the cytosol, which is the appropriate cellular compartment for these enzymes.

  6. Parallel Pathways: The model correctly represents alternative paths in the pathway, showing that both Upp1 and Upp2 can act on the product of Cda, with both ultimately feeding into Dpyd.

Minor Issues

  1. Part_of Annotations: All molecular activities are annotated as part of the dCMP catabolic process (GO:0006249), which is appropriate. However, Upb1 does not have this annotation, which would be expected for consistency.

  2. Input/Output Specification: While Cda has an explicit has_input annotation for 2'-deoxycytidine (CHEBI:15698), the inputs and outputs for other enzymes in the pathway are not explicitly stated, though they can be inferred from the causal connections and the known activities of the enzymes.

Recommendations

Overall, this is a well-constructed GO-CAM model that accurately represents the dCMP catabolic pathway in mouse. My recommendations for minor improvements include:

  1. Add a part_of annotation to Upb1 to indicate it is part of the dCMP catabolic process (GO:0006249), consistent with other enzymes in the pathway.

  2. Consider adding explicit has_input and has_output annotations for each enzyme to make the metabolic flow more transparent, though this is not strictly necessary as the enzyme activities and causal connections already imply these relationships.

  3. The model appropriately uses orthology evidence in some cases (ECO:0000266), which is suitable when direct evidence for mouse proteins is limited. This approach is consistent with GO-CAM best practices.

Conclusion

The GO-CAM model for the dCMP catabolic process in mouse (gomodel:5fadbcf000002236) is biologically accurate, well-supported by evidence, and properly structured according to GO-CAM best practices. The model provides a clear representation of the metabolic pathway and the causal relationships between the enzymatic activities involved. It effectively combines experimental evidence from multiple sources to build a comprehensive representation of this biological process.