A Landscape Analysis of Human SUMOylation

Area of Science:

• Biochemistry
• Proteomics
• Molecular Biology

Background:

• SUMOylation, a post-translational modification (PTM), plays crucial roles in physiological and pathological processes but remains understudied.
• Advances in mass spectrometry (MS) and enrichment strategies enable large-scale mapping of SUMOylation sites.

Purpose of the Study:

• To construct a comprehensive, high-confidence reference set of human SUMOylation sites by reanalyzing publicly available MS-based datasets.
• To characterize the features of SUMOylation sites, including their location, associated motifs, and relationship with other PTMs and disease variants.

Main Methods:

• Reanalysis of public MS-based SUMOylation datasets.
• Integration of database searching (Trans-Proteomic Pipeline) and statistical analysis for false localization rate (FLR) estimation.
• Classification of SUMOylated lysine sites into confidence tiers and comparison with non-SUMOylated lysines.

Main Results:

• The Human SUMO Build contains 35,721 SUMOylation sites across 6,146 proteins with <5% FLR.
• SUMOylated lysines are enriched in intrinsically disordered regions and near phosphosites, and associated with disease variants.
• Identified canonical, inverted, and novel SUMOylation motifs and found overlap with ubiquitination sites, particularly at disease-associated positions.

Conclusions:

• The Human SUMO Build provides a valuable resource for understanding SUMOylation.
• SUMOylation site characteristics and co-occurrence with ubiquitination offer insights into regulatory mechanisms and disease associations.
• The data is publicly available to facilitate further research and predictive modeling.