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Now I'm going to analyze the GO-CAM model based on the information I've gathered. First, let me check if there are any relevant documents on how to annotate molecular carrier activity, since this appears to be an important part of the model.

GO-CAM Model Review: gomodel:613aae0000000341

Model Overview

GO-CAM model 613aae0000000341 represents "cobalamin transport 2, distribution to tissues (Mouse)" in mouse (Mus musculus, NCBITaxon:10090). This model describes the process of cobalamin (vitamin B12) transport from the intestine to tissues through the bloodstream via cobalamin-binding proteins.

Key Components

The model includes four main proteins and their activities:

  1. Abcc1/MRP1 (MGI:MGI:102676) - Enables ABC-type vitamin B12 transporter activity (GO:0015420)
  2. Tcn2 (MGI:MGI:98534) - Enables both:
  3. Molecular carrier activity (GO:0140104)
  4. Cargo receptor ligand activity (GO:0140355)
  5. Cobalamin binding (GO:0031419)
  6. Cd320 (MGI:MGI:1860083) - Enables cargo receptor activity (GO:0038024)

Model Structure and Causal Flow

The model represents a sequential process of cobalamin transport with the following causal associations:

  1. Abcc1/MRP1 with ABC-type vitamin B12 transporter activity (GO:0015420) in the basal plasma membrane (GO:0009925) provides input for Tcn2's molecular carrier activity (GO:0140104) in extracellular space (GO:0005615).

  2. Tcn2 with molecular carrier activity (GO:0140104) in extracellular space (GO:0005615) directly positively regulates Tcn2's cargo receptor ligand activity (GO:0140355) on the external side of plasma membrane (GO:0009897).

  3. Tcn2 with cargo receptor ligand activity (GO:0140355) on the external side of plasma membrane (GO:0009897) directly positively regulates Cd320's cargo receptor activity (GO:0038024) on the plasma membrane (GO:0005886).

  4. The molecular carrier activity of Tcn2 includes a nested activity of cobalamin binding (GO:0031419), connected through a BFO:0000051 relation (has_part).

Evidence

The model is supported by several published studies: - PMID:19897579 - Identification of MRP1/ABCC1 as the transporter responsible for cellular export of cobalamin - PMID:23430977 - Transcobalamin receptor (Cd320) knockout mouse study - PMID:21655200 - Mouse transcobalamin features compared to human transcobalamin and haptocorrin - PMID:237480 - Transport of vitamin B12 into mouse leukemia cells

QC Assessment

Strengths

  1. Biological accuracy: The model correctly represents the current understanding of cobalamin transport in mice, especially regarding:
  2. The role of MRP1/ABCC1 in exporting cobalamin from cells
  3. Tcn2 as the primary cobalamin binding protein in mouse (unlike humans who have both transcobalamin and haptocorrin)

  4. Cd320 as the receptor for Tcn2-cobalamin complex

  5. Causal flow: The model has appropriate directional flow showing how cobalamin moves from cells to extracellular space and then is taken up by other cells.

  6. Cell locations: Each activity is properly annotated with the appropriate cellular location.

  7. Evidence base: All activities are supported by experimental evidence from mouse studies.

Issues/Suggestions for Improvement

  1. Molecular carrier activity representation: According to the "Molecular_carrier_activity" guidelines, the relation between a transported molecule (cobalamin) and its carrier (Tcn2) should be "has input" and "has output". While the model properly represents Tcn2's cobalamin binding activity as part of its molecular carrier activity, it might benefit from explicitly representing the cobalamin molecule as input and output.

  2. Complete pathway representation: The model starts with the export of cobalamin from cells (via MRP1) but doesn't represent the initial uptake of dietary cobalamin. Consider expanding the model to include the intestinal absorption of cobalamin.

  3. Part_of biological process annotation: All activities are appropriately annotated as part_of the cobalamin transport process (GO:0015889), which is correct.

Conclusion

Overall, GO-CAM model 613aae0000000341 is a well-constructed representation of cobalamin transport in mice. It accurately captures the molecular mechanisms of how cobalamin is exported from cells, bound by transcobalamin (Tcn2) in the extracellular space, and subsequently taken up by other cells through the Cd320 receptor.

The model effectively integrates information from several primary research papers and correctly represents the differences between mouse and human cobalamin transport (particularly that mice have Tcn2 but no haptocorrin). The causal connections between activities create a coherent biological story.

The only minor suggestion would be to consider explicitly representing the cobalamin molecule as input and output in the carrier activity, as recommended in the molecular carrier activity guidelines. However, this doesn't detract from the overall quality and accuracy of the model.