title: Status of large-scale analysis of post-translational modifications by mass spectrometry.
abstract: Cellular function can be controlled through the gene expression program, but often protein post-translational modifications (PTMs) provide a more precise and elegant mechanism. Key functional roles of specific modification events--for instance, during the cell cycle--have been known for decades, but only in the past 10 years has mass-spectrometry-(MS)-based proteomics begun to reveal the true extent of the PTM universe. In this overview for the special PTM issue of Molecular and Cellular Proteomics, we take stock of where MS-based proteomics stands in the large-scale analysis of protein modifications. For many PTMs, including phosphorylation, ubiquitination, glycosylation, and acetylation, tens of thousands of sites can now be confidently identified and localized in the sequence of the protein. The quantification of PTM levels between different cellular states is likewise established, with label-free methods showing particular promise. It is also becoming possible to determine the absolute occupancy or stoichiometry of PTM sites on a large scale. Powerful software for the bioinformatic analysis of thousands of PTM sites has been developed. However, a complete inventory of sites has not been established for any PTM, and this situation will persist into the foreseeable future. Furthermore, although PTM coverage by MS-based methods is impressive, it still needs to be improved, especially in tissues and in clinically relevant systems. The central challenge for the field is to develop streamlined methods for determining biological functions for the myriad of modifications now known to exist.
authors.affiliation: Department of Proteomics, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark;
authors.forename: Jesper V
authors.initials: JV
authors.lastname: Olsen
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D000107:Acetylation; D019295:Computational Biology; D005786:Gene Expression Regulation; D015894:Genome, Human; D006031:Glycosylation; D006801:Humans; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods / Q000592:standards*; D008745:Methylation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D012984:Software; D054875:Ubiquitination