Based on the information I've gathered, let me now provide a comprehensive review of the GO-CAM model "627d95ee00000044":
Review of GO-CAM Model: 627d95ee00000044¶
Model Overview¶
Title: 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process (Mouse)
Taxon: NCBITaxon:10090 (Mouse)
Status: Production
Source: Derived from gomodel:R-HSA-174362
Model Description¶
This GO-CAM model represents the 3'-phosphoadenosine 5'-phosphosulfate (PAPS) biosynthetic and transport processes in mice. PAPS is an essential high-energy sulfate donor required for sulfation of carbohydrates, proteins, and other molecules. The model includes both PAPS synthesis activities and PAPS transport activities, depicting how sulfate is incorporated into metabolic pathways.
Key Components of the Model¶
The model includes: 1. PAPS biosynthesis enzymes (Papss1 and Papss2) 2. Sulfate transporters at the plasma membrane (Slc26a1 and Slc26a2) 3. PAPS transporters at the Golgi membrane (Slc35b2 and Slc35b3)
Molecular Activities Depicted:¶
- Sulfate adenylyltransferase (ATP) activity (GO:0004781)
- Adenylylsulfate kinase activity (GO:0004020)
- Sulfate transmembrane transporter activity (GO:0015116)
- 3'-phosphoadenosine 5'-phosphosulfate transmembrane transporter activity (GO:0046964)
Anatomical Contexts:¶
- Cytosol (GO:0005829)
- Plasma membrane (GO:0005886)
- Golgi membrane (GO:0000139)
Pathway Flow Analysis¶
The model accurately represents the PAPS biosynthesis pathway with the following logical flow:
- Extracellular sulfate is transported into the cell by sulfate transmembrane transporters (Slc26a1 and Slc26a2) at the plasma membrane
- In the cytosol, Papss1 and Papss2 proteins perform both sulfate adenylyltransferase and adenylylsulfate kinase activities
- The synthesized PAPS is then transported into the Golgi lumen by PAPS transporters (Slc35b2 and Slc35b3)
The causal relationships are represented using the 'provides input for' (RO:0002413) relation, showing how the activities flow from one to another in the pathway.
Evidence Assessment¶
The model is well-supported by experimental evidence from multiple publications, including direct assays (ECO:0000314) and mutant phenotype evidence (ECO:0000315). Key references include: - PMID:7493984 (adenylyltransferase activity evidence) - PMID:9545271 (adenylyltransferase activity evidence) - PMID:20011239 (PAPS transporter evidence) - PMID:15703192 (sulfate transporter evidence) - PMID:20160351 (sulfate transporter evidence)
Evidence for localization in some cases is based on sequence orthology (ECO:0000266), which is appropriate when direct evidence is not available for the mouse proteins.
Quality Control Assessment¶
Model Strengths:¶
- Accurate representation of the PAPS biosynthetic pathway
- Clear causal relationships between activities
- Good use of evidence codes
- Proper cellular component annotations
- Biologically plausible connections between activities
Areas for Improvement:¶
-
Dual Function Representation: Both Papss1 and Papss2 have dual enzymatic functions (adenylyltransferase and kinase activities). While this is represented in the model by having separate activities for each function, there could be more clarity about how these functions are sequentially related within the same protein.
-
Complex Representation: It's not clear if any of these activities occur as part of a protein complex. Based on the "How to annotate complexes in GO-CAM" document, if these activities occur in complexes, the model should either identify the specific subunit carrying the activity or use a GO complex term if the specific subunit is unknown.
-
Process Context: While the individual activities are part of the 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process (GO:0050428), it would be helpful to place this process in a broader biological context (e.g., its role in sulfation of specific biomolecules).
Conclusion¶
The model gomodel:627d95ee00000044 is a high-quality representation of the PAPS biosynthetic pathway in mouse. It correctly depicts the flow of sulfate from extracellular uptake through intracellular conversion to PAPS and its transport to the Golgi where it serves as a sulfate donor.
The model follows GO-CAM best practices regarding activity representation, causal relationships, and evidence attribution. The few minor improvements suggested above would make the model even more informative, particularly in helping users understand the relationship between the dual activities of the Papss proteins and the broader biological context of PAPS biosynthesis.
Overall, this is a biologically accurate and well-constructed GO-CAM model that effectively captures the key aspects of PAPS biosynthesis and transport.