A landscape analysis of human SUMOylation: A comprehensive meta-analysis of publicly available datasets

SUMOylation is an important but understudied post-translational modification (PTM) linked to diverse physiological and pathological processes. Various laboratories have developed protocols for identifying SUMOylation target sites using SUMO enrichment followed by mass spectrometry. As part of the PTMeXchange consortium, our group has developed tools and statistical approaches for robust PTM meta-analysis. Here, we present a comprehensive human SUMOylation reference “build,” encompassing 35,721 sites on 6,146 proteins classified into three confidence tiers. SUMOylated lysines were enriched in intrinsically disordered regions and underrepresented in tightly packed structures. Sites frequently colocalized with proximal phosphosites and were enriched for disease-associated genetic variants. Motif analysis revealed canonical, inverted, and novel motifs that connect SUMOylation to processes such as chromatin remodeling, histone modification, and mRNA processing. To support widespread use, for example, in training artificial intelligence algorithms, the build has been deposited in multiple resources to support different user groups - PRIDE, UniProtKB, and PeptideAtlas.