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623d156d00000029 Glycogen biosynthetic process Mouse

Based on my review of the GO-CAM model "Glycogen biosynthetic process (Mouse)" (gomodel:623d156d00000029) and the supporting information, here's my detailed assessment:

GO-CAM Model Review

Overview

This model represents the glycogen biosynthetic process in mice, showing the sequential enzymatic activities involved in glycogen synthesis from glucose phosphates through to glycogen polymer formation. The model includes 10 activities connected in a pathway-like structure with appropriate causal relationships.

Strengths

  1. Correct Biological Process Representation: The model accurately captures the glycogen biosynthetic process (GO:0005978) with the appropriate enzymes in their correct sequence.

  2. Well-Documented Evidence: Each activity is supported by experimental evidence with appropriate ECO codes and references to primary literature.

  3. Correct Causal Relationships: The model uses appropriate causal relationships (RO:0002413 "provides input for") to connect sequential enzymatic activities in the pathway.

  4. Appropriate Cellular Location: Most activities are correctly annotated to occur in the cytosol (GO:0005829), which is appropriate for glycogen synthesis.

  5. Complete Pathway Coverage: The model covers the entire glycogen synthesis pathway from glucose-1-phosphate to glycogen, including the regulatory proteins.

Areas for Improvement

  1. Complex Representation: According to the complex annotation guidelines, the model correctly represents individual protein activities rather than complexes. However, there's no representation of the GYS1-GYG1 complex mentioned in the UniProt entry for GYS1, which indicates that "each GYS1 protomer binds to one GYG1 subunit (via GYG1 C-terminus)." This interaction could be represented more explicitly.

  2. Evidence Parity: Some activities have more extensive evidence documentation than others. For example, some PGM activities (Pgm1, Pgm2) have multiple evidence sources, while others have fewer.

  3. Regulatory Mechanisms: While the model includes EPM2A (laforin) and NHLRC1 (malin) which are involved in the regulation of glycogen metabolism, the regulatory relationship between these proteins could be more explicitly modeled. The malin-laforin complex is known to regulate glycogen synthesis through the ubiquitination of glycogen-associated proteins.

  4. Post-translational Modifications: The UniProt entries for several proteins in the pathway (especially GYS1) indicate extensive regulation by phosphorylation, which affects enzyme activity. These regulatory relationships are not captured in the model.

Specific Comments on Key Components

  1. Phosphoglucomutase (PGM1/PGM2): Correctly represented as converting glucose-1-phosphate in the initial steps of the pathway.

  2. UTP:glucose-1-phosphate uridylyltransferase (UGP2): Appropriately shown catalyzing the synthesis of UDP-glucose.

  3. Glycogenin (GYG1): Correctly represented as initiating glycogen synthesis with its glucosyltransferase activity.

  4. Glycogen synthase (GYS1/GYS2): Both isoforms are included appropriately.

  5. 1,4-alpha-glucan branching enzyme (GBE1): Correctly shown adding branch points to the growing glycogen molecule.

  6. Regulatory proteins (PPP1R3C, EPM2A, NHLRC1): The model includes these important regulatory components. PPP1R3C (protein phosphatase 1 regulatory subunit 3C) is correctly shown as a molecular adaptor positively regulating glycogen synthase activity.

Conclusion

This GO-CAM model is scientifically accurate and well-constructed, representing the glycogen biosynthetic process in mice with appropriate molecular functions, cellular locations, and causal relationships. The model is consistent with current understanding of glycogen biosynthesis as described in the literature and UniProt entries.

Minor improvements could include more explicit representation of protein complexes and regulatory relationships, particularly involving post-translational modifications and the malin-laforin complex. However, these are refinements rather than corrections to an already solid model.

The model has been properly maintained with appropriate automated updates (noted in the comments: RO:0002213 replaced by RO:0002629 and GO:0102752 replaced by GO:0003844).

Overall, this is a high-quality GO-CAM model that effectively represents glycogen biosynthesis in mice.