Abstract
More than 300 different types of protein post‐translational modifications (PTMs) have been described, many of which are known to have pivotal roles in cellular physiology and disease. Nevertheless, only a handful of PTMs have been extensively investigated at the proteome level. Knowledge of protein substrates and their PTM sites is key to dissection of PTM‐mediated cellular processes. The past several years have seen a tremendous progress in developing MS‐based proteomics technologies for global PTM analysis, including numerous studies of yeast and other microbes. Modification‐specific enrichment techniques combined with advanced MS/MS methods and computational data analysis have revealed a surprisingly large extent of PTMs in proteins, including multi‐site, cooperative modifications in individual proteins. We review some of the current strategies employed for enrichment and detection of PTMs in modification‐specific proteomics.