Deciphering a global network of functionally associated post‐translational modifications

• DOI: 10.1038/msb.2012.31
• Publication Date: 2012-07-17T15:56:23Z
• Authors: Pablo Minguez; Luca Parca; Francesca Diella; Daniel R Mende; Runjun Kumar; Manuela Helmer‐Ci...; Anne‐Claude Gavin; Vera van Noort; Peer Bork
• Keywords: Proteomics; Medicine (General); QH301-705.5; Article; Evolution, Molecular; Mice; proteomics; R5-920; protein regulation; Animals; Humans; post‐translational modifications; Biology (General); PTM code; Phylogeny; Settore BIO/11 - BIOLOGIA MOLECOLARE; Systems Biology; PTM crosstalk; Proteins; 006; Macaca mulatta; Rats; Cardiovascular and Metabolic Diseases; Cattle; Chickens; Protein Processing, Post-Translational

Various post-translational modifications (PTMs) fine-tune the functions of almost all eukaryotic proteins, and co-regulation of different types of PTMs has been shown within and between a number of proteins. Aiming at a more global view of the interplay between PTM types, we collected modifications for 13 frequent PTM types in 8 eukaryotes, compared their speed of evolution and developed a method for measuring PTM co-evolution within proteins based on the co-occurrence of sites across eukaryotes. As many sites are still to be discovered, this is a considerable underestimate, yet, assuming that most co-evolving PTMs are functionally associated, we found that PTM types are vastly interconnected, forming a global network that comprise in human alone >50,000 residues in about 6000 proteins. We predict substantial PTM type interplay in secreted and membrane-associated proteins and in the context of particular protein domains and short-linear motifs. The global network of co-evolving PTM types implies a complex and intertwined post-translational regulation landscape that is likely to regulate multiple functional states of many if not all eukaryotic proteins.