This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is a protein interaction network?
Protein interaction networks show how proteins regulate and affect, and are regulated and affected by, other proteins. The many interactions proteins experience are fundamental to the basic operations of any cellular organism. By analyzing protein interactions techniques for effecting these proteins can be informed and designed. (1)
ABCA4 protein interaction network
This ABCA4 protein interaction network was made via STRING.
Figure 1: Protein interaction network of ABCA4. The red oval includes proteins that are responsible for visual perception, the blue for retinal homeostasis, and the green for retinol metabolism. Grey lines show interactions, and colored lines show known modes of action.
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The ABCA4 protein interaction network is mainly related to visual perception. This makes sense considering the ABCA4 negative phenotype of vision loss. ABCA4's role in retinal homeostasis makes sense as well, considering that the main damage in ABCA4 negative cases takes place initially in the retina. Considering that retinol is the main chemical that builds up in ABCA4 negative phenotypes the interactions with proteins involved in retinol metabolism is not out of place. Something that is noticeable here though is the lack of any real knowledge about modes of interaction, how these proteins regulate and involve themselves with each other. (2)
Discussion
While certain direct functions are known about the proteins making up ABCA4's protein interaction network, there are few interactions that are currently understood between them. There is no known mode of interaction between ABCA4 and retinol metabolism proteins, which compose nearly a third of the direct interaction involved with ABCA4. Considering the role retinol plays in Stargardt disease ABCA4 negative phenotypes, there would be much to gain from understanding how these proteins are involved together. (2)
References
1. Szklarczyk, D., Franceschini, A., Wyder, S., Forslund, K., Heller, D., Huerta-Cepas, J., … von Mering, C. (2014). STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Research, 43(D1), D447–D452. https://doi.org/10.1093/nar/gku1003
2. Beharry, S., Zhong, M., & Molday, R. S. (2004). N-Retinylidene-phosphatidylethanolamine Is the Preferred Retinoid Substrate for the Photoreceptor-specific ABC Transporter ABCA4 (ABCR). Journal of Biological Chemistry, 279(52), 53972–53979. https://doi.org/10.1074/jbc.m405216200
2. Beharry, S., Zhong, M., & Molday, R. S. (2004). N-Retinylidene-phosphatidylethanolamine Is the Preferred Retinoid Substrate for the Photoreceptor-specific ABC Transporter ABCA4 (ABCR). Journal of Biological Chemistry, 279(52), 53972–53979. https://doi.org/10.1074/jbc.m405216200