Skip to content

Now I have enough information to review the GO-CAM model. Let me provide a comprehensive review:

Review of GO-CAM Model: gomodel:636d9ce800001222

Model Overview

Title: "DCAF12 controls MOV10 during spermatogeneis. (Human)"
Model ID: gomodel:636d9ce800001222
Taxon: Human (NCBITaxon:9606)
Status: Production

Model Content Summary

This GO-CAM model represents the mechanism by which DCAF12 (DDB1- and CUL4-associated factor 12) controls MOV10 RNA helicase during spermatogenesis in humans. The model describes a ubiquitin-dependent protein catabolic process in which:

  1. CUL4A provides scaffold activity for the CRL4-DCAF12 ubiquitin ligase complex
  2. DCAF12 acts as the substrate adaptor (recognizing the C-terminal -EL degron in MOV10)
  3. RBX1 provides ubiquitin protein ligase activity
  4. MOV10 functions as an RNA helicase that is targeted for degradation

The causal chain involves CUL4A (scaffold) → DCAF12 (substrate adaptor) → RBX1 (ligase) → MOV10 (target protein).

Scientific Correctness Assessment

The model accurately reflects the biological mechanism described in the primary literature (PMID:34065512). The paper clearly demonstrates that:

  1. DCAF12 is part of a CRL4 E3 ubiquitin ligase complex with CUL4A and RBX1
  2. This complex specifically recognizes the C-terminal glutamate-leucine (Glu-Leu) degron of MOV10
  3. The complex mediates ubiquitination of MOV10, leading to its degradation
  4. This regulation is important during spermatogenesis and T cell activation

The causal relationships and molecular activities in the model correctly represent this process.

GO-CAM Structure and Compliance Assessment

The model follows GO-CAM best practices for representing complexes. Since the functional roles of each component in the complex are known, each protein is individually represented with its specific molecular function:

  1. CUL4A (UniProtKB:Q13619): Ubiquitin ligase complex scaffold activity (GO:0160072)
  2. DCAF12 (UniProtKB:Q5T6F0): Ubiquitin-like ligase-substrate adaptor activity (GO:1990756)
  3. RBX1 (UniProtKB:P62877): Ubiquitin protein ligase activity (GO:0061630)
  4. MOV10 (UniProtKB:Q9HCE1): 5'-3' RNA helicase activity (GO:0032574)

The causal relationships (using RO terms) are appropriately modeled: - CUL4A directly positively regulates (RO:0002629) DCAF12 - DCAF12 provides input for (RO:0002413) RBX1 - RBX1 directly negatively regulates (RO:0002630) MOV10

All activities are correctly situated in biological context: - CUL4A and DCAF12 activities occur in the cytoplasm (GO:0005737) - DCAF12 activity is more specifically localized in the cytosol (GO:0005829) - All activities are part of the ubiquitin-dependent protein catabolic process via the C-end degron rule pathway (GO:0140627) - MOV10 activity is part of miRNA-mediated gene silencing by mRNA destabilization (GO:0035279)

Evidence Quality

The annotations are supported by appropriate evidence codes and literature: - Direct assay evidence (ECO:0000314) from PMID:34065512 for most relationships - Additional supporting references including PMID:29779948, PMID:31267705, and PMID:22405651 - Evidence for MOV10's RNA helicase activity comes from PMID:24726324

All contributions have clear provenance with ORCID identifiers (mainly https://orcid.org/0000-0001-8769-177X) and dates.

Recommendations for Improvement

While the model is generally well-constructed, here are a few suggestions for improvement:

  1. Missing cellular component for MOV10: MOV10's activity is currently annotated to "cellular_component" (GO:0005575), which is a placeholder term. Based on the literature, MOV10 is primarily located in the cytoplasm, and more specifically in P-bodies or cytoplasmic ribonucleoprotein granules. Adding this location would improve the model.

  2. T cell activation aspect: The model title and content focus on spermatogenesis, but the paper demonstrates that DCAF12 also controls MOV10 during T cell activation. A complementary model or extension of this model to include the T cell context would provide a more complete representation of the biology described in the paper.

  3. Connection to downstream processes: The model could be expanded to show how MOV10 degradation affects miRNA-mediated gene silencing, which is briefly described in the paper as one of the consequences of this regulatory mechanism.

Conclusion

The GO-CAM model gomodel:636d9ce800001222 is a scientifically accurate and structurally sound representation of how the CRL4-DCAF12 ubiquitin ligase complex controls MOV10 during spermatogenesis. It follows GO-CAM best practices for representing complexes by showing each component with its specific molecular function and connecting them with appropriate causal relationships. The model is well-supported by evidence from the primary literature.

The few suggested improvements would enhance the completeness of the model but don't detract significantly from its current quality. This model successfully captures the core mechanism described in the literature.