Protein Interaction Network
Protein Interaction Networks
Protein interaction networks are used to see what proteins interact with a protein of interest. These networks are often complex with a multitude of interactions between the target protein and other proteins, as well as interactions between proteins within the network. These webs can be used to see not only protein interactions, but also to see what processes that protein may affect or be involved in [1].
The HFE Protein Interaction Network
The image to the left shows an interaction network for HFE created using STRING. All of the proteins involved with iron homeostasis have been grouped in the upper left hand corner. The two proteins on the periphery, FURIN and B2M, are not involved directly in iron homeostasis. This is discussed more in the analysis below.
|
Analysis
Many of the proteins found in the iron homeostasis cluster are not surprising. TFR2 and related proteins such as TFRC and TF have been found to interact with HFE [2,3,4]. These interactions are very important for HFE's role in iron uptake regulation. HAMP is responsible for controlling the production of hepcidin which is a protein that controls the presence of ferroportins, which allow for the transport of iron from the intestine to the blood [2,3]. HFE has been shown to play a role in the regulation of the transcription of hepcidin from HAMP (see the Protein page).
One of the proteins, B2M, although not directly involved with iron homeostasis is involved with class I major histocompatibility complex (MHC). It makes sense that this protein is part of the HFE interaction network because the HFE protein has a structure similar to other class I MHCs. However, it is interesting to note that although its structure is similar, HFE has not been shown to participate in antigen presentation, which is the role of B2M [5]. Perhaps B2M is listed in this interaction network because HFE is an MHC-like protein, and this database pulled in this B2M protein due to this structural similarity.
Another protein, FURIN, could not be clustered in with the other iron homeostasis proteins. This protein is a member of a proprotein convertase family, meaning that is processes latent precursor proteins into their active forms [6]. I was slightly baffled to find this protein in this network because I have not found any evidence in the course of my research that HFE is cleaved in any way to make it active. However, I did see that one of the GO (gene ontology) terms for FURIN is the plasma membrane, which is where HFE is found [6]. Perhaps HFE is indeed cleaved by FURIN in order to become active. This would be an interesting subject for future research to characterize the HFE protein.
One of the proteins, B2M, although not directly involved with iron homeostasis is involved with class I major histocompatibility complex (MHC). It makes sense that this protein is part of the HFE interaction network because the HFE protein has a structure similar to other class I MHCs. However, it is interesting to note that although its structure is similar, HFE has not been shown to participate in antigen presentation, which is the role of B2M [5]. Perhaps B2M is listed in this interaction network because HFE is an MHC-like protein, and this database pulled in this B2M protein due to this structural similarity.
Another protein, FURIN, could not be clustered in with the other iron homeostasis proteins. This protein is a member of a proprotein convertase family, meaning that is processes latent precursor proteins into their active forms [6]. I was slightly baffled to find this protein in this network because I have not found any evidence in the course of my research that HFE is cleaved in any way to make it active. However, I did see that one of the GO (gene ontology) terms for FURIN is the plasma membrane, which is where HFE is found [6]. Perhaps HFE is indeed cleaved by FURIN in order to become active. This would be an interesting subject for future research to characterize the HFE protein.
References
1. Pellegrini, M., Haynor, D., and Johnson, J.M. (2004). Protein interaction networks. Expert Review Proteomics, 1(2), 89-99.
2. Gao, J., Chen, J., Kramer, M., Tsukamoto, H., Zhang, A., Enns, C.A. (2009). Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metabolism, 9: 217-227. doi: 10.1016/j.cmet.2009.01.010
3. Goswami, T., Andrews, N.C. (2006). Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. Journal of Biological Chemistry, 281: 28494-28498. doi: 10.1074/jbc.C600197200
4. Swinkles, D.W., Fleming, R.E. (2011). Novel observations in hereditary hemochromatosis: potential implications for clinical strategies. Haematologica, 96(4): 485-488. doi:10.3324/haematol.2011.042036
5. Bacon, B.R., Adams, P.C., Kowdley, K.V., Powell, L.W., Tavill, A.S. (2011). Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology, 54(1), 328-43. doi: 10.1002/hep.24330
6. Gene Cards - FURIN gene: http://www.genecards.org/cgi-bin/carddisp.pl?gene=FURIN
7. STRING: http://string-db.org/
2. Gao, J., Chen, J., Kramer, M., Tsukamoto, H., Zhang, A., Enns, C.A. (2009). Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metabolism, 9: 217-227. doi: 10.1016/j.cmet.2009.01.010
3. Goswami, T., Andrews, N.C. (2006). Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. Journal of Biological Chemistry, 281: 28494-28498. doi: 10.1074/jbc.C600197200
4. Swinkles, D.W., Fleming, R.E. (2011). Novel observations in hereditary hemochromatosis: potential implications for clinical strategies. Haematologica, 96(4): 485-488. doi:10.3324/haematol.2011.042036
5. Bacon, B.R., Adams, P.C., Kowdley, K.V., Powell, L.W., Tavill, A.S. (2011). Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology, 54(1), 328-43. doi: 10.1002/hep.24330
6. Gene Cards - FURIN gene: http://www.genecards.org/cgi-bin/carddisp.pl?gene=FURIN
7. STRING: http://string-db.org/