A comprehensive compilation of SUMO proteomics

Key Points Small ubiquitin-like modifier (SUMO)ylation is a ubiquitin-like post-translational modification that is technically challenging to study by mass spectrometry-based proteomics, owing to low modification stoichiometry and incompatibility with standard mass spectrometry approaches. Over the past decade, several methods were developed to allow the identification of sumoylated proteins. Recently, novel methods were established that enable the identification of site-specific sumoylation, leading to the identification of thousands of modified Lys residues. We have compiled and evaluated data of sumoylated proteins and sites from 22 proteomic studies and generated the most comprehensive sumoylation database to date. The most abundantly sumoylated proteins are some of the most functionally interconnected proteins, indicating that sumoylation preferentially targets specific pathways and protein complexes and acts as a group modifier. The regulation of the SUMO signal is more complex than previously appreciated, owing to the post-translational modification of SUMO family members by phosphorylation, acetylation and ubiquitylation. With the availability of increasingly potent proteomic methods and equipment, our understanding of sumoylation and its functions can now be developed to match that of ubiquitylation, acetylation and phosphorylation. Analysis of the available human small ubiquitin-like modifier (SUMO) proteomics data provided evidence for the sumoylation of thousands of proteins and residues, and clustered the sumoylated proteins into functional networks. Sumoylation is a frequent modification, occurring mostly on nuclear proteins, with functions including transcription, mRNA processing and the DNA-damage response. Small ubiquitin-like modifiers (SUMOs) are essential for the regulation of several cellular processes and are potential therapeutic targets owing to their involvement in diseases such as cancer and Alzheimer disease. In the past decade, we have witnessed a rapid expansion of proteomic approaches for identifying sumoylated proteins, with recent advances in detecting site-specific sumoylation. In this Analysis, we combined all human SUMO proteomics data currently available into one cohesive database. We provide proteomic evidence for sumoylation of 3,617 proteins at 7,327 sumoylation sites, and insight into SUMO group modification by clustering the sumoylated proteins into functional networks. The data support sumoylation being a frequent