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65c57c3400002539 The CRL5 ASB11 complex mediates ubiquitination and degradation of DIRAS2 Human

Based on all this information, I'm now ready to review the GO-CAM model gomodel:65c57c3400002539 titled "The CRL5(ASB11) complex mediates ubiquitination and degradation of DIRAS2 (Human)."

GO-CAM Review: gomodel:65c57c3400002539

Overview

This model represents the cullin-RING E3 ubiquitin-protein ligase complex 5 containing ASB11 (CRL5-ASB11) that mediates the ubiquitination and subsequent degradation of DIRAS2, a small GTPase. The model is based primarily on findings from a recent 2024 publication (PMID:38574733) along with background information from an earlier paper (PMID:12194967).

Components and Structure

The model consists of 4 activities connected in a cascade:

  1. CUL5 (Q93034) - acts as a scaffold protein with "ubiquitin ligase complex scaffold activity" (GO:0160072)
  2. ASB11 (Q8WXH4) - acts as the substrate recognition component with "ubiquitin-like ligase-substrate adaptor activity" (GO:1990756)
  3. RNF7/RBX2 (Q9UBF6) - has "ubiquitin protein ligase activity" (GO:0061630)
  4. DIRAS2 (Q96HU8) - the substrate protein with "GTPase activity" (GO:0003924)

Causal Relationships

The model correctly represents the flow of activity: - CUL5 directly positively regulates (RO:0002629) ASB11's adaptor activity - ASB11 provides input for (RO:0002413) RNF7's ligase activity - RNF7 directly negatively regulates (RO:0002630) DIRAS2's GTPase activity

Biological Process Annotations

All three components of the CRL5 complex (CUL5, ASB11, RNF7) are annotated to the same biological process: "protein K11-linked ubiquitination" (GO:0070979), which is accurate based on the reference paper showing K11-linked ubiquitin chains on DIRAS2.

DIRAS2 is annotated to "signal transduction" (GO:0007165) and located at the "plasma membrane" (GO:0005886), both of which are consistent with its function.

Evidence and References

All activities and causal relationships are appropriately supported by the PMID:38574733 reference with "direct assay evidence" (ECO:0000314). The DIRAS2 GTPase activity and location are supported by PMID:12194967, which is appropriate.

Evaluation

Strengths:

  1. The model correctly follows the GO-CAM guidelines for annotating E3 ubiquitin ligase complexes.
  2. The molecular activities assigned to each protein are accurate.
  3. The causal relationships properly reflect the mechanism of the CRL5-ASB11 complex activity on DIRAS2.
  4. Evidence codes and references are appropriately used.
  5. The biological processes are accurately represented.

Minor suggestions for improvement:

  1. Consider adding "proteasome-mediated ubiquitin-dependent protein catabolic process" (GO:0043161) as an additional biological process that this ubiquitination is part of, as recommended in the E3 ubiquitin ligase annotation guidelines.
  2. The model could be enhanced by including information about the regulatory role of UBE2F mentioned in the paper (PMID:38574733), as it is described as a key part of the axis in the paper's title.
  3. Consider adding information about the biological consequences of DIRAS2 degradation in pancreatic cancer, which is the main focus of the paper.

Conclusion

The GO-CAM model gomodel:65c57c3400002539 accurately represents the CRL5(ASB11) complex-mediated ubiquitination and degradation of DIRAS2. It follows the appropriate GO-CAM best practices for annotating E3 ubiquitin ligase complexes. The model is well-supported by evidence and correctly shows the functional relationships between the components.

The model is parsimonious, focusing on the core mechanism of DIRAS2 ubiquitination, though it could be extended in the future to include the broader biological context described in the reference paper related to pancreatic cancer and the regulatory role of UBE2F.

Overall, the model is of high quality and meets GO-CAM standards.