TY - JOUR T1 - The functional landscape of the human phosphoproteome JF - bioRxiv DO - 10.1101/541656 SP - 541656 AU - David Ochoa AU - Andrew F. Jarnuczak AU - Maja Gehre AU - Margaret Soucheray AU - Askar A. Kleefeldt AU - Cristina Viéitez AU - Anthony Hill AU - Luz Garcia-Alonso AU - Danielle L. Swaney AU - Juan Antonio Vizcaíno AU - Kyung-Min Noh AU - Pedro Beltrao Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/02/05/541656.abstract N2 - Protein phosphorylation is a key post-translational modification regulating protein function in almost all cellular processes. While tens of thousands of phosphorylation sites have been identified in human cells to date, the extent and functional importance of the phosphoproteome remains largely unknown. Here, we have analyzed 6,801 publicly available phospho-enriched mass spectrometry proteomics experiments, creating a state-of-the-art phosphoproteome containing 119,809 human phosphosites. To prioritize functional sites, 59 features indicative of proteomic, structural, regulatory or evolutionary relevance were integrated into a single functional score using machine learning. We demonstrate how this prioritization identifies regulatory phosphosites across different molecular mechanisms and pinpoint genetic susceptibilities at a genomic scale. Several novel regulatory phosphosites were experimentally validated including a role in neuronal differentiation for phosphosites present in the SWI/SNF SMARCC2 complex member. The scored reference phosphoproteome and its annotations identify the most relevant phosphorylations for a given process or disease addressing a major bottleneck in cell signaling studies. ER -