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646ff70100000391 Canonical mTORC1 signaling Human

Now I need to check the GO term definition directly. Let me look at the model in more detail.

Based on my review of the GO-CAM model "Canonical mTORC1 signaling (Human)" with ID gomodel:646ff70100000391, I'll provide a comprehensive assessment:

Model Overview:

This model represents the canonical mTORC1 (mammalian Target Of Rapamycin Complex 1) signaling pathway in human cells. It describes how various proteins and complexes interact to regulate mTOR kinase activity, which ultimately controls protein synthesis and translation through multiple downstream effectors.

Model Structure Review:

Strengths:

  1. Biological accuracy: The model captures the key components of the canonical mTORC1 pathway, including the Ragulator complex, Rag GTPases, RHEB, mTOR, and downstream effectors (RPS6KB1/2, EIF4EBP1, RPS6).

  2. Correct cellular localization: Activities are properly localized to the lysosomal membrane (GO:0005765) where mTORC1 signaling occurs.

  3. Proper causality: The causal relationships between activities are well-represented using appropriate predicates (mostly RO:0002629 "directly positively regulates").

  4. Appropriate evidence: Each activity and causal relationship is supported by scientific literature references (PMIDs).

  5. Complete pathway representation: The model covers upstream activators (Ragulator complex, Rag GTPases, RHEB) through downstream effectors (RPS6KB1/2, EIF4EBP1) to the final outcome (translation regulation).

Areas for Improvement:

  1. Complex annotation: The Ragulator complex (GO:0071986) is correctly used when the specific subunit carrying the guanyl-nucleotide exchange factor activity is unknown. However, the model does not specify the members of this complex. According to the complex annotation guidelines, members can be indicated.

  2. RPTOR annotation: RPTOR (Q8N122) has "enzyme-substrate adaptor activity" (GO:0140767) and positively regulates mTOR (P42345) kinase activity. This aligns with its known function as a regulatory-associated protein of mTOR that serves as a scaffold. However, based on adaptor activity guidelines, it might be beneficial to specify what specific molecules it is bringing together using "has input" relations.

  3. Representation of EIF4E: While EIF4EBP1 (Q13541) is included with its translation repressor activity, the model doesn't explicitly show how mTOR-mediated phosphorylation of EIF4EBP1 relieves inhibition of EIF4E (P06730). EIF4E is listed in the objects but not as an active participant.

  4. Nutrient sensing upstream: While the model includes the lysosomal-based activation of mTORC1, it could potentially include more details about how amino acid levels are sensed and signal to the Rag GTPases.

Consistency with GO-CAM Best Practices:

  1. The model follows the GO-CAM practice of representing activities connected by causal relationships.
  2. Each activity is properly contextualized with molecular function, biological process, and cellular component.
  3. Evidence is provided for each assertion.
  4. Complex usage follows the guidelines in "How to annotate complexes in GO-CAM" document.
  5. Adaptor protein annotation generally follows the "Molecular adaptor activity" guidelines.

Recommendations:

  1. Consider explicitly representing the members of the Ragulator complex.
  2. Add "has input" relationships for adaptor activities to clearly indicate which molecules are being brought together.
  3. Consider adding EIF4E as an active participant to complete the translation initiation regulation part of the pathway.
  4. Perhaps expand the model to include upstream nutrient sensing mechanisms.
  5. Consider adding a brief description or comments that explain the overall biological significance of this pathway.

Summary:

Overall, this is a well-constructed GO-CAM model that accurately represents the canonical mTORC1 signaling pathway in humans. It captures the key molecular activities and their causal relationships, with proper evidence and cellular context. The model successfully demonstrates how mTOR kinase activation leads to the regulation of protein synthesis through multiple downstream effectors. With a few minor enhancements as suggested, this model would be even more comprehensive and informative.

The model can be accessed at: https://bioregistry.io/go.model:646ff70100000391