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Let me review the GO-CAM model with ID gomodel:66c7d41500000715 based on the information I've retrieved and the GO-CAM best practices.

GO-CAM Review: gomodel:66c7d41500000715

Model Overview

Title: "CLEC12A acts as an inhibitor of neutrophil activation (Human)"

Taxon: Human (NCBITaxon:9606)

Status: Production

Model Structure and Content

This GO-CAM describes how CLEC12A (also known as MICL, Myeloid Inhibitory C-type Lectin-like receptor) functions as an inhibitory receptor to regulate neutrophil activation through a signaling cascade involving several key proteins. The model includes the following activities and their causal relationships:

  1. CLEC12A (Q5QGZ9) - Functions as a transmembrane signaling receptor (GO:0004888) at the plasma membrane (GO:0005886), participating in negative regulation of neutrophil activation (GO:1902564)

  2. SRC (P12931) - Exhibits protein tyrosine kinase activity (GO:0004713) in the negative regulation of neutrophil activation pathway, acts upstream of PTPN6 and PTPN11 through causal relationship (RO:0012010 - "causally upstream of, positive effect")

  3. PTPN6/SHP-1 (P29350) - Shows protein tyrosine phosphatase activity (GO:0004725) in the negative regulation of neutrophil activation process, acts to directly negatively regulate (RO:0002630) SYK activity

  4. PTPN11/SHP-2 (Q06124) - Exhibits protein tyrosine phosphatase activity (GO:0004725) in the negative regulation of neutrophil activation process, and like PTPN6, also directly negatively regulates (RO:0002630) SYK activity

  5. SYK (P43405) - Displays protein tyrosine kinase activity (GO:0004713) in neutrophil activation involved in immune response (GO:0002283)

Assessment of the Model

Biological Accuracy

The model accurately represents the current understanding of CLEC12A's role in neutrophil regulation as supported by literature:

  1. The PMID:34234773 paper clearly establishes CLEC12A as an inhibitory receptor that negatively regulates neutrophil activation through pathways involving SRC and phosphatases

  2. PMID:33782605 provides evidence for SYK's role in neutrophil activation in immune responses

  3. PMID:39143217 further validates CLEC12A's role as a transmembrane signaling receptor that regulates neutrophil activation

The model correctly depicts the cascade where CLEC12A engagement leads to SRC activation, which then activates the phosphatases PTPN6 and PTPN11, which in turn negatively regulate SYK, a key kinase involved in neutrophil activation.

GO-CAM Best Practices Compliance

The model adheres to GO-CAM best practices:

  1. Proper use of evidence codes: The model uses appropriate evidence codes for each assertion (ECO:0000314 for direct assay evidence, ECO:0000315 for mutant phenotype evidence)

  2. Appropriate causal relationships: The causal relationships use proper predicates (RO:0012010 for "causally upstream of, positive effect" and RO:0002630 for "directly negatively regulates")

  3. Cellular locations: When relevant, cellular locations are specified (plasma membrane for CLEC12A)

  4. Biological process context: Each molecular function is appropriately situated within a biological process context

  5. Protein annotation: Proteins are identified by UniProtKB accessions, which is the correct practice

Completeness and Parsimony

The model is both:

  1. Complete: It captures the key players and relationships in this specific inhibitory pathway

  2. Parsimonious: It includes the essential components without unnecessary complexity

Recommendations for Improvement

While the model is of high quality, a few potential enhancements could be considered:

  1. Additional contextual information: The model could potentially include more specific details about when and how CLEC12A is activated, such as its interaction with NETs (neutrophil extracellular traps) as mentioned in PMID:39143217

  2. Connection to downstream effects: The model could be expanded to show downstream effects of inhibited neutrophil activation

Conclusion

GO-CAM model gomodel:66c7d41500000715 is a high-quality representation of CLEC12A's role as an inhibitor of neutrophil activation. It accurately captures the molecular interactions, causal relationships, and biological context based on current literature. The model adheres to GO-CAM best practices and effectively conveys how this inhibitory pathway functions in human neutrophils.

The model effectively communicates the signaling cascade from the inhibitory receptor CLEC12A to the downstream effector SYK, showing how phosphatases PTPN6 and PTPN11 mediate this inhibitory signal. This provides valuable insight into mechanisms regulating neutrophil activation, which is critical for immune homeostasis and preventing excessive inflammation.