Deciphering a global network of functionally associated post-translational modifications.
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.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Pablo
P
Minguez
Luca
L
Parca
Francesca
F
Diella
Daniel R
DR
Mende
Runjun
R
Kumar
Manuela
M
Helmer-Citterich
Anne-Claude
AC
Gavin
Vera
V
van Noort
Peer
P
Bork
D000818:Animals; D002417:Cattle; D002645:Chickens; D019143:Evolution, Molecular; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D010802:Phylogeny; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D049490:Systems Biology / Q000379:methods
D011506:Proteins