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Mol Syst Biol. 2009;5:260. doi: 10.1038/msb.2009.17. Epub 2009 Apr 7.

Tissue specificity and the human protein interaction network.

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EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation, UPF, Barcelona, Spain.


A protein interaction network describes a set of physical associations that can occur between proteins. However, within any particular cell or tissue only a subset of proteins is expressed and so only a subset of interactions can occur. Integrating interaction and expression data, we analyze here this interplay between protein expression and physical interactions in humans. Proteins only expressed in restricted cell types, like recently evolved proteins, make few physical interactions. Most tissue-specific proteins do, however, bind to universally expressed proteins, and so can function by recruiting or modifying core cellular processes. Conversely, most 'housekeeping' proteins that are expressed in all cells also make highly tissue-specific protein interactions. These results suggest a model for the evolution of tissue-specific biology, and show that most, and possibly all, 'housekeeping' proteins actually have important tissue-specific molecular interactions.

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