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Now that I have a better understanding of the model and the relevant best practices, let me conduct a comprehensive review of this GO-CAM model.

Review of GO-CAM Model: gomodel:5fce9b7300001742 (Strap in alternative splicing-mouse)

Model Overview

This GO-CAM model (gomodel:5fce9b7300001742) describes the role of STRAP (Serine-threonine kinase receptor-associated protein, MGI:MGI:1329037) in mouse alternative splicing and its effect on retinoic acid signaling pathways via transcription factors.

Biological Content Assessment

The model contains several key components: 1. STRAP protein (MGI:MGI:1329037) with multiple molecular functions: - U2 snRNP binding (GO:1990447) - mRNA binding (GO:0003729) - An unspecified molecular function (GO:0003674) that negatively regulates transcription factors

  1. Transcription factors:
  2. KLF9 (Klf9 Mmus, MGI:MGI:1333856) - DNA-binding transcription factor activity

  3. SP1 (Sp1 Mmus, MGI:MGI:98372) - DNA-binding transcription factor activity

  4. Downstream target:

  5. CYP26A1 (Cyp26a1 Mmus, MGI:MGI:1096359) - retinoic acid 4-hydroxylase activity

Strengths of the Model

  1. The model is well-supported by experimental evidence, citing relevant PMIDs (29781215, 33230114, 9250660).
  2. The model correctly connects the molecular functions of STRAP to biological processes (alternative mRNA splicing, protein-RNA complex assembly).
  3. The causal relationships between STRAP's activities and downstream transcription factors are clear, using appropriate relationship predicates (RO:0002630 - directly negatively regulates).
  4. The flow from transcription factors to the downstream target (CYP26A1) is logically consistent, using appropriate positive regulation relationships (RO:0002629 - directly positively regulates).

Issues and Recommendations

1. Incomplete Molecular Function Annotation

STRAP is annotated with one unspecified molecular function (GO:0003674). According to best practices, generic molecular function terms should be avoided when more specific functions are known.

Recommendation: Replace GO:0003674 with a more specific molecular function term that explains how STRAP negatively regulates transcription factors. Based on literature, this could be related to its scaffolding function or protein binding activity.

2. Missing Biological Context

The model includes individual molecular functions but doesn't fully capture the larger biological context of how STRAP affects retinoic acid signaling in development.

Recommendation: Add a higher-level biological process that connects these activities to embryonic stem cell differentiation or neural development, which is mentioned in the paper (PMID:29781215).

3. Complex Representation

If STRAP functions as part of the SMN complex (as suggested by UniProt information found in search), this aspect is not represented in the model.

Recommendation: According to "How to annotate complexes in GO-CAM" document, if STRAP is part of a complex where its activity is known, the complex should be represented properly. Consider adding this information if supported by the evidence.

4. Transcription Factor Annotation

The transcription factors (KLF9 and SP1) are connected directly to the retinoic acid 4-hydroxylase activity, but according to the DNA-binding transcription factor annotation guidelines, there should be a specification of whether these are activators or repressors.

Recommendation: Use more specific terms for the transcription factor activities: - DNA-binding transcription activator activity (GO:0001228) instead of the generic GO:0003700, if they are activators - DNA-binding transcription repressor activity (GO:0001227) if they are repressors

5. Spatial Context

While one STRAP activity occurs in the nucleus (GO:0005634), other activities lack cellular location.

Recommendation: Add cellular component annotations for all activities where the location is known.

Conclusion

The GO-CAM model (5fce9b7300001742) provides a good representation of STRAP's roles in alternative splicing and regulation of retinoic acid metabolism in mouse. The model correctly uses appropriate causal relationships to represent the regulatory pathways.

With the suggested improvements, particularly specifying the molecular function of STRAP that regulates transcription factors and using more specific terms for transcription factor activities, the model would better adhere to GO-CAM best practices and provide a more complete representation of the underlying biology.

The model is scientifically accurate according to the cited literature, but could benefit from additional context to improve its utility for users trying to understand the role of STRAP in development and retinoic acid signaling.