Skip to content

5fce9b7300001590 SPModule PGLYRP1 HSP701A

Now I'll review the GO-CAM model with ID gomodel:5fce9b7300001590 based on the information obtained. This model appears to focus on the interactions between HSPA1A (Heat shock 70 kDa protein 1A), HSPBP1 (HSP70-binding protein 1), PGLYRP1 (Peptidoglycan recognition protein 1), and TNFRSF1A (Tumor necrosis factor receptor superfamily member 1A).

GO-CAM Model Review: gomodel:5fce9b7300001590 (SPModule-PGLYRP1/HSP701A)

Summary of Model Components:

This GO-CAM model represents molecular interactions between heat shock proteins and their regulatory partners, particularly focusing on HSPA1A (HSP70) and its interactions with HSPBP1 and PGLYRP1, ultimately affecting TNFRSF1A signaling.

Activities and Causal Associations:

  1. HSPA1A (P0DMV8) has "receptor ligand activity" (GO:0048018) that occurs in "extracellular space" (GO:0005615)

  2. This activity directly positively regulates (RO:0002629) TNFRSF1A's "tumor necrosis factor receptor activity" (GO:0005031)

  3. HSPBP1 (Q9NZL4) has "molecular sequestering activity" (GO:0140313) that occurs in "extracellular space" (GO:0005615)

  4. This activity directly negatively regulates (RO:0002630) PGLYRP1's "Hsp70 protein binding" (GO:0030544)

  5. PGLYRP1 (O75594) has "Hsp70 protein binding" (GO:0030544) that occurs in "extracellular space" (GO:0005615)

  6. This activity directly positively regulates (RO:0002629) HSPA1A's "receptor ligand activity" (GO:0048018)

  7. TNFRSF1A (P19438-1) has "tumor necrosis factor receptor activity" (GO:0005031) that occurs on "cell surface" (GO:0009986)

Strengths of the Model:

  1. The model correctly represents the established interactions between these proteins based on the literature.
  2. The causal relationships between activities follow the proper direction of regulatory flow.
  3. The model uses appropriate molecular function terms for each protein and includes proper cellular component annotations.
  4. Evidence citations are properly included, with relevant PMIDs for each assertion.

Areas for Improvement:

  1. Missing Mechanism Details: The model doesn't completely capture the mechanism by which HSPBP1 inhibits PGLYRP1-HSPA1A interaction as described in PMID:21247889. According to this reference, HSPBP1 protects cells against the cytotoxic action of the PGLYRP1-HSPA1A complex.

  2. Incomplete Process Context: The biological context of this regulatory module could be better represented. The literature indicates that this pathway relates to tumor cell cytotoxicity, which isn't captured in the model.

  3. Potential Missing Activities:

  4. HSPA1A's chaperone activity isn't represented, though it's central to its function

  5. TNFRSF1A's signaling activities downstream of activation could be included

  6. Complex Representation: According to the "How to annotate complexes in GO-CAM" guidelines, the PGLYRP1-HSPA1A complex could be more explicitly modeled since it appears to function as a unit to activate TNFRSF1A.

Biological Consistency:

The model is consistent with the literature findings that: - PGLYRP1 (Tag7) forms a complex with HSPA1A (Hsp70) - This complex can induce cytotoxic processes in tumor cells via TNFRSF1A (TNFR1) - HSPBP1 can inhibit the activity of the PGLYRP1-HSPA1A complex

Parsimony and Clarity:

The model is relatively parsimonious, focusing on the core interactions without unnecessary complexity. However, the biological context and downstream effects could be more clearly represented to help users understand the functional significance of these interactions.

Recommendations for Improvement:

  1. Consider adding the PGLYRP1-HSPA1A complex as a distinct entity or clarifying their joint action
  2. Include the biological context (tumor cell cytotoxicity) as part of the model
  3. Add potential downstream effects of TNFRSF1A activation
  4. Consider including HSPA1A's chaperone activity which may be relevant to the overall mechanism

Overall Assessment:

This GO-CAM model provides a valid representation of the molecular interactions between HSPA1A, HSPBP1, PGLYRP1, and TNFRSF1A. It captures the core regulatory relationships described in the literature, though it could be enhanced by including more mechanistic details and biological context. The model uses appropriate GO terms and relationship types to represent the causal flow of activities, making it a useful resource for understanding this signaling module.