This page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Protein Interaction Network
The protein interaction network of the human MSH2 protein was determined using STRING (Figure 1) [1]. The network uses an evidence view, meaning different line colors represent the types of evidence for the association. These types of evidence are color coded below, along with descriptions of the predicted functional partners (Figure 2). The human MSH2 interaction network shows that MSH2 interacts with other DNA mismatch proteins including MSH3, MSH6, and MLH1. MSH2 also interacts with EXO1, which is an exonuclease that functions to remove the DNA mismatches. Interestingly, MSH2 also interacts with BRCA1 and P53, known tumor suppressor genes. I will focus on the DNA mismatch protein interactions.
Figure 1. Protein interaction network of the human MSH2 protein determined using STRING.
Figure 2. Predicted functional partners of the human MSH2 protein based on different types of evidence.
The protein interaction network of the human MSH2 protein was then compared to the interaction networks of MSH2 model organism homologs. A few of these homolog interaction networks are shown in Figure 3. Most proteins are present in all these interactions networks. DNA mismatch proteins are circled in red in Figure 3.
Figure 3. Human MSH2 and model organism MSH2 protein networks. DNA mismatch proteins are circled in red.
Analysis
Many DNA mismatch repair proteins are found in the human MSH2 protein interaction network. Most homologs to these DNA mismatch repair proteins are found in model organisms as well. It should be noted, however, that MSH3 has not yet been described to interact with MSH2 in mice and drosophila. This has been described in S. cerevisiae, though; for that reason, S. cerevisiae may be the most appropriate model organism to study the interaction and function of human MSH2 with other proteins.