Based on my examination of gomodel:6197061700002397, I'll now conduct a thorough review of this GO-CAM model to assess its accuracy, consistency with GO-CAM best practices, and biological validity.

Review of gomodel:6197061700002397: Fatty acid transport by CD36 via LYN-mediated endocytosis (Human)¶

Overview¶

This model represents the fatty acid transport mechanism involving CD36 in human cells. The model shows that CD36 acts as a cargo receptor at the plasma membrane, which then initiates a signaling cascade through the LYN tyrosine kinase, ultimately involving palmitoylation regulation by ZDHHC5 and LYPLA1 proteins.

Consistency with GO-CAM Best Practices¶

Complex Annotation¶

The model correctly handles the annotation of the proteins involved in the pathway rather than using a complex ID, as the specific roles of each protein are well-defined based on the reference (PMID:32958780). This aligns with the guidance in "How to annotate complexes in GO-CAM", where individual activities are assigned to specific proteins when their roles are known.

Causal Relationships¶

The causal relationships in the model use appropriate relationship predicates: - "RO:0002629" (directly positively regulates) from CD36 to LYN - "RO:0002630" (directly negatively regulates) from LYN to ZDHHC5 - "RO:0002418" (provides input for) from ZDHHC5 to LYPLA1

These directional relationships correctly capture the flow of the pathway as described in the literature.

Subcellular Localization¶

All proteins are appropriately annotated with their subcellular locations at the plasma membrane (GO:0005886), which is consistent with the biological process of membrane transport.

Biological Process Association¶

All activities are correctly associated with the biological process "fatty acid transport" (GO:0015908), providing proper context for the molecular functions.

Biological Content Accuracy¶

CD36 Function¶

The model correctly represents CD36 (UniProtKB:P16671) with the molecular function "cargo receptor activity" (GO:0038024). According to the UniProt entry and the cited reference, CD36 functions as a cargo receptor for fatty acids, which is accurately captured in the model.

LYN Kinase Function¶

LYN (UniProtKB:P07948) is correctly annotated with "protein tyrosine kinase activity" (GO:0004713). According to PMID:32958780, LYN phosphorylates ZDHHC5 at Tyr91, inactivating it, which is accurately represented by the negative regulation relationship.

ZDHHC5 Function¶

ZDHHC5 (UniProtKB:Q9C0B5) is annotated with "palmitoyltransferase activity" (GO:0016409). This is consistent with its known function in palmitoylating CD36, which is essential for CD36's localization to the plasma membrane.

LYPLA1 Function¶

LYPLA1 (UniProtKB:O75608) is annotated with "palmitoyl-(protein) hydrolase activity" (GO:0008474), which correctly represents its role in depalmitoylating CD36, allowing for its internalization.

Evidence and References¶

All activities and relationships are supported by evidence from the same publication (PMID:32958780), which provides a comprehensive study of this pathway. The evidence code used (ECO:0000314 - direct assay evidence used in manual assertion) is appropriate for the experimental evidence presented in the paper.

Integration with Pathway Knowledge¶

The model accurately captures the dynamic process of fatty acid uptake as described in PMID:32958780: 1. CD36 binds fatty acids and activates LYN kinase 2. LYN phosphorylates ZDHHC5, inactivating it 3. Inactivation of ZDHHC5 leads to depalmitoylation of CD36 by LYPLA1 4. Depalmitoylated CD36 undergoes endocytosis, bringing fatty acids into the cell

This process is elegantly captured with the appropriate molecular functions and causal relationships.

Suggested Improvements¶

Additional Context: While not necessary, the model could potentially benefit from including additional downstream events mentioned in the paper, such as the recruitment of SYK kinase by depalmitoylated CD36, which further facilitates endocytosis.
Complex Integration: Although each protein's individual role is well-represented, the model could optionally indicate the interaction of CD36 with caveolin structures as described in the paper, which mentions that "CD36 is primarily localized in the caveolae structures".

Conclusion¶

This GO-CAM model (gomodel:6197061700002397) is a well-constructed representation of fatty acid transport by CD36 via LYN-mediated endocytosis. It accurately captures the molecular functions, subcellular localizations, and causal relationships between the components as described in the primary literature. The model adheres to GO-CAM best practices and provides a clear representation of this important biological process.

The model shows a high level of biological accuracy and adherence to GO-CAM curation standards. It elegantly captures a complex regulatory mechanism involving post-translational modifications (phosphorylation and palmitoylation) in the regulation of membrane protein trafficking and fatty acid transport.