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Based on my review of the model, the proteins involved, and the relevant best practices, I can now provide a comprehensive review of GO-CAM model gomodel:67086be200001601.

Review of GO-CAM Model: gomodel:67086be200001601

Model Overview

Title: Fertilization complex allows sperm-egg recognition during fertilization. (Human)
Taxon: Human (NCBITaxon:9606)
Status: Production

Summary

This model describes the molecular functions and interactions involved in sperm-egg recognition during fertilization in humans. The model involves four key proteins: 1. IZUMO1 (UniProtKB:Q8IYV9) - Sperm protein with receptor ligand activity 2. IZUMO1R/JUNO (UniProtKB:A6ND01) - Egg protein with signaling receptor activity 3. SPACA6 (UniProtKB:W5XKT8) - Sperm protein with protein-macromolecule adaptor activity 4. TMEM81 (UniProtKB:Q6P7N7) - Sperm protein with protein-macromolecule adaptor activity

All activities are part of the biological process of sperm-egg recognition (GO:0035036) and occur at the plasma membrane (GO:0005886).

Strengths of the Model

  1. Recent Evidence Base: The model is well-supported by a recent publication (PMID:39423812, 2024) that demonstrates the formation of a conserved fertilization complex involving IZUMO1, SPACA6, and TMEM81.

  2. Appropriate Molecular Functions: The molecular functions assigned to each protein appear accurate:

  3. IZUMO1 as receptor ligand (GO:0048018)
  4. IZUMO1R/JUNO as signaling receptor (GO:0038023)

  5. SPACA6 and TMEM81 as protein-macromolecule adaptors (GO:0030674)

  6. Correct Causal Relationships: The model correctly shows SPACA6 and TMEM81 directly positively regulating (RO:0002629) IZUMO1's receptor ligand activity, followed by IZUMO1 directly positively regulating IZUMO1R/JUNO's signaling receptor activity.

  7. Consistent Cellular Location: All activities appropriately occur at the plasma membrane (GO:0005886).

Areas for Improvement

  1. Complex Representation: Based on the "How to annotate complexes in GO-CAM" guidelines, since the model is representing a complex (IZUMO1, SPACA6, and TMEM81), it may be appropriate to consider if a GO complex ID could be used. However, since the individual roles of each protein are well-defined and supported by evidence, the current representation with individual proteins is also valid.

  2. Biological Completeness: While the model accurately represents the interaction between the sperm proteins and the egg receptor, it could be expanded to show the downstream effects following receptor activation. According to the UniProt entry for IZUMO1R/JUNO, the receptor is rapidly cleaved following fertilization to block polyspermy. This could be represented as a downstream event.

  3. Evidence Codes: The model correctly uses ECO:0000250 (sequence similarity evidence) with references to mouse orthologs for some interactions, and ECO:0000314 (direct assay evidence) with the PMID reference for others. This is appropriate based on the available evidence.

  4. MAIA/FCRL3 Consideration: Recent evidence (PMID:36070373) suggests that in humans, FCRL3/MAIA replaces IZUMO1R/JUNO as the IZUMO1 receptor after initial sperm-egg adhesion. This subsequent interaction could potentially be included in an expanded version of the model to provide a more complete picture of the fertilization process in humans.

Conclusion

The GO-CAM model gomodel:67086be200001601 is well-constructed and accurately represents current knowledge about the sperm-egg recognition process during human fertilization. The model is appropriately parsimonious while capturing the key molecular functions and causal relationships involved in this process. It is supported by recent scientific evidence, particularly PMID:39423812, which provides direct experimental evidence for the interactions represented.

The model correctly applies GO-CAM best practices regarding the representation of complex interactions and is consistent with what is known about the proteins involved based on their UniProt entries. The causal relationships between the proteins accurately reflect the molecular mechanisms described in the literature.

In summary, this model is of high quality and provides a clear, evidence-supported representation of the sperm-egg recognition process in humans.