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Now I have a better understanding of the guidelines. Let me synthesize all the information about this GO-CAM model and provide a comprehensive review.

Review of GO-CAM Model: gomodel:65288b2200001267

Model Title

"USP9X-TRIM32 modulation of IQCB1 during G2-M (Human)"

Overview

This model describes a molecular pathway involving USP9X (deubiquitinating enzyme), TRIM32 and MARCH7 (E3 ubiquitin ligases), and IQCB1/NPHP5 (a protein with adaptor activity). The model shows how these proteins interact during cilium assembly regulation within the centrosome.

Model Structure and Content

The model consists of four key activities: 1. TRIM32 (Q13049) - ubiquitin protein ligase activity (GO:0061630) 2. IQCB1 (Q15051) - protein-macromolecule adaptor activity (GO:0030674) 3. MARCHF7/MARCH7 (Q9H992) - ubiquitin protein ligase activity (GO:0061630) 4. USP9X (Q93008) - molecular sequestering activity (GO:0140313)

These activities are connected through causal relationships: - TRIM32 activity directly negatively regulates (RO:0002630) IQCB1 activity - MARCH7 activity directly negatively regulates (RO:0002630) IQCB1 activity - USP9X activity directly negatively regulates (RO:0002630) MARCH7 activity

The model shows the biological processes involved: - TRIM32 and MARCH7 are part of negative regulation of cilium assembly (GO:1902018) - IQCB1 and USP9X are part of cilium assembly (GO:0060271)

Cellular locations: - TRIM32, MARCH7, and IQCB1 occur in the centrosome (GO:0005813) - USP9X occurs in the cytoplasm (GO:0005737)

Scientific Accuracy Assessment

Based on the literature: 1. The model correctly represents that IQCB1/NPHP5 is a positive regulator of ciliogenesis (cilium assembly), as confirmed by PMID 28498859. 2. IQCB1 directly binds to USP9X (a deubiquitinating enzyme) and two E3 ubiquitin ligases (TRIM32 and MARCH7), which is consistent with the literature. 3. The model correctly captures that IQCB1 undergoes ubiquitination by TRIM32 and MARCH7, which negatively regulates its function in cilium assembly. 4. USP9X counteracts the ubiquitination of NPHP5/IQCB1 to regulate ciliogenesis, as shown in PMID 28498859. 5. The location of these activities in the centrosome is supported by the literature, as IQCB1 is localized to the ciliary transition zone and centrosome.

Compliance with GO-CAM Best Practices

  1. Molecular Function Representation:
  2. Each protein has a correctly assigned molecular function term
  3. TRIM32 and MARCH7 have E3 ubiquitin ligase activity (GO:0061630)
  4. IQCB1 is assigned protein-macromolecule adaptor activity (GO:0030674), which is appropriate

  5. USP9X is assigned molecular sequestering activity (GO:0140313) - this is a bit unusual but appears to be attempting to represent its role in counteracting ubiquitination

  6. Causal Relationships:

  7. The model uses "directly negatively regulates" (RO:0002630) consistently and appropriately to indicate the direct negative regulatory relationships between proteins

  8. This follows the guidelines for representing regulation in GO-CAM

  9. Biological Process Context:

  10. Each molecular function is appropriately placed within a biological process context

  11. The processes (negative regulation of cilium assembly and cilium assembly) accurately capture the roles of these proteins

  12. Cellular Component Context:

  13. Each activity has an appropriate cellular location
  14. The centrosome location for TRIM32, MARCH7, and IQCB1 is accurate
  15. USP9X in cytoplasm is also accurate, though it should be noted that USP9X also localizes to centrosomes according to literature

Areas for Improvement

  1. USP9X molecular function:
  2. The use of "molecular sequestering activity" (GO:0140313) for USP9X is somewhat unconventional

  3. USP9X is primarily a deubiquitinating enzyme, so "deubiquitinase activity" (GO:0101005) or "ubiquitin-specific protease activity" would be more appropriate

  4. Completeness:

  5. The model captures the core regulatory interactions but could be expanded to include more details on how this regulation affects downstream cilium assembly processes

  6. The connection to G2-M phase mentioned in the title could be made more explicit in the model

  7. Evidence:

  8. All activities have evidence from publications, which is good practice

  9. However, it would be helpful to include more specific evidence for each causal relationship

  10. Causal flow clarity:

  11. The causal flow from USP9X to MARCH7 to IQCB1 could be made clearer by possibly showing how USP9X might also directly affect IQCB1

Overall Assessment

This is a well-constructed GO-CAM model that accurately represents the biological interactions between USP9X, TRIM32, MARCH7, and IQCB1 in regulating cilium assembly. The model is consistent with the scientific literature and generally follows GO-CAM best practices.

The model effectively captures the antagonistic relationship between E3 ubiquitin ligases (TRIM32 and MARCH7) and the deubiquitinating enzyme USP9X in regulating IQCB1's role in cilium assembly. The use of appropriate molecular functions, biological processes, and cellular components creates a coherent and biologically meaningful representation.

The main recommendation would be to reconsider the molecular function assigned to USP9X to better reflect its deubiquitinating enzymatic activity rather than using the more general "molecular sequestering activity" term.