Skip to content

Based on all the information collected, I'll now review the GO-CAM model:

Review of GO-CAM Model gomodel:666b894f00000196

Model Overview

The model titled "CD93/Multimerin-2/β1 integrin complex function in angiogenesis (Human)" represents the molecular interactions between three key proteins:

  1. MMRN2 (Multimerin-2) - An extracellular matrix protein with receptor ligand activity
  2. CD93 - A C-type lectin domain receptor with signaling receptor activity
  3. ITGB1 (Integrin β1) - A coreceptor that functions in angiogenesis

The model depicts how these proteins interact in the context of angiogenesis in humans, showing causal relationships between their molecular functions.

Scientific Content Assessment

The scientific basis for this model is well-supported by current literature. Recent studies, particularly by Khan et al. (2017), have established that Multimerin-2 (MMRN2) is a ligand for CD93, which is a member of the group 14 family of C-type lectins. These interactions have been shown to be important in angiogenesis.

The model shows MMRN2 located in the extracellular space (GO:0005615) with receptor ligand activity (GO:0048018), which is consistent with its known function as a secreted ECM protein. CD93 is shown on the plasma membrane (GO:0005886) with signaling receptor activity (GO:0038023), which aligns with its established role. ITGB1 is also correctly placed on the plasma membrane with coreceptor activity (GO:0015026).

The causal relationships showing MMRN2 directly positively regulating (RO:0002629) CD93, and CD93 directly positively regulating ITGB1 are supported by the literature. Evidence from the Khan et al. study demonstrates that MMRN2 binds to CD93, and these proteins are both involved in angiogenesis (GO:0001525). Additional evidence suggests ITGB1 functions in this pathway.

Model Structure and GO-CAM Standards

The model follows GO-CAM standards for representing molecular activities and causal relationships:

  1. Each activity is correctly enabled by a single gene product
  2. Activities are appropriately localized to cellular compartments
  3. Activities are placed in the context of the biological process of angiogenesis
  4. Causal relationships are represented with the correct predicates (RO:0002629 - directly positively regulates)

However, there is a duplication in the model that needs to be corrected:

  • MMRN2's receptor ligand activity (gomodel:666b894f00000196/666b894f00000197) has two identical causal associations to CD93's signaling receptor activity (gomodel:666b894f00000196/666b894f00000204) using the same predicate (RO:0002629). This is redundant and one of these relationships should be removed.

Supporting Evidence

The model cites appropriate evidence codes and literature references:

  • ECO:0000314 (direct assay evidence used in manual assertion) is used with various PMIDs
  • Key references include PMID:28671670, which establishes the MMRN2-CD93 interaction
  • Other citations (PMID:11559704, PMID:31138217, etc.) provide supporting evidence for cellular locations and participation in angiogenesis

The reference PMID:23125415 provides evidence for ITGB1's coreceptor activity, which is consistent with findings about integrin β1 functions.

Recommendations for Improvement

  1. Remove the duplicate causal relationship: There are two identical causal associations from MMRN2 to CD93, one of which should be removed.

  2. Consider representing the complex: Since the document "How to annotate complexes in GO-CAM" suggests representing complexes when multiple proteins function together, the curator might consider explicitly modeling the CD93/MMRN2/ITGB1 complex if evidence suggests they function as a unit.

  3. Add more molecular detail if available: If there is evidence for specific signaling events downstream of CD93 activation by MMRN2, these could enrich the model.

  4. Evidence for the second causal relationship: The causal association between CD93 and ITGB1 has an empty evidence field in one case. This should be filled with appropriate evidence codes and references.

Conclusion

The GO-CAM model "CD93/Multimerin-2/β1 integrin complex function in angiogenesis (Human)" represents a scientifically accurate pathway based on current literature. It correctly depicts the roles of MMRN2, CD93, and ITGB1 in angiogenesis, with appropriate molecular functions, cellular locations, and causal relationships.

With minor corrections (removing the duplicate causal relationship and adding missing evidence), this model will provide a valuable representation of how these three proteins interact in angiogenesis. Overall, the model is well-constructed and follows GO-CAM best practices.