This page was produced as an assignment for Genetics 677, an undergraduate course at UW - Madison.
Protein Interactions and Networks
Proteins often act within in a large web of interconnected other proteins, and the PAH protein is no exception. Metabolic proteins can be particularly interconnected, as the product from one protein can change the current state of the cell, which can affect the expression of numerous other proteins, which can further alter the state of the cell, and so on. In terms of the PAH protein, we would expect that its activity would not only affect the synthesis and functioning of other proteins in which phenylalanine is a main component, but we would expect it to have an affect on proteins downstream of phenylalanine breakdown as well. Namely this includes proteins that use large amounts of tyrosine.
The image below was generated using the String Database, which generates protein interaction networks. The different colored lines represent the different interactions. Of most relevance here are the green lines, which indicates that the proteins share the same "neighborhood," and the black lines, which indicates that the proteins are co-expressed, or expressed at the same time [1].
The image below was generated using the String Database, which generates protein interaction networks. The different colored lines represent the different interactions. Of most relevance here are the green lines, which indicates that the proteins share the same "neighborhood," and the black lines, which indicates that the proteins are co-expressed, or expressed at the same time [1].
This interaction network indicates that the PAH gene is "in the same neighborhood" and is co-expressed with PCBD1, PCBD1, and QDPR. These three proteins are all involved in making BH4, PAH's cofactor in the catabolic process. Also co-expressed is the protein tyrosinase, which is important in the processing of tyrosine into dopamine and melanin. This can be considered intuitive as tyrosine processing is in some ways dependent on phenylalanine breakdown. The rest of the proteins PAH is linked to (such as GOT1 and GOT2, PRDX6, and TAT) are involved in general amino acid catabolism and breakdown [1]. In general, PAH doesn't have the absolute largest protein network, however, the things that it is connected to are deeply rooted, far-reaching processes within the body that have the potential to have a lot of effects.
References
1. Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, Doerks T, Julien P, Roth A, Simonovic M, Bork P, von Mering C.STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res. 2009 Jan;37(Database issue):D412-6. doi: 10.1093/nar/gkn760. Epub 2008 Oct 21. PubMed PMID: 18940858; PubMed Central PMCID: PMC2686466.