Towards a systematic map of the functional role of protein phosphorylation

摘要: Abstract Phosphorylation is a critical post-translational modification involved in the regulation of almost all cellular processes. However, less than 5% thousands recently discovered phosphorylation sites have known function. Here, we devised chemical genetic approach to study functional relevance S. cerevisiae. We generated 474 phospho-deficient mutants that, along with gene deletion library, were screened for fitness 102 conditions. Of these, 42% exhibited growth phenotypes, suggesting these phosphosites are likely functional. inferred their function based on similarity profiles that deletions, and validated subset by thermal proteome profiling lipidomics. While some phosphomutants showed loss-of-function higher fraction phenotypes not seen corresponding suggestive gain-of-function effect. For conserved humans, severity yeast indicative human relevance. This provides roadmap functionally characterizing systematic manner.