PTMcode v2: a resource for functional associations of post-translational modifications within and between proteins

Area of Science:

• Molecular Biology
• Bioinformatics
• Systems Biology

Background:

• Protein function is regulated by post-translational modifications (PTMs) and protein-protein interactions (PPIs).
• Existing databases separately catalog PTMs and PPIs, lacking a focus on their interplay.
• The regulatory role of PTMs in modulating PPIs remains under-explored.

Purpose of the Study:

• To develop methods for predicting functional associations of PTM pairs.
• To create a comprehensive resource, PTMcode v2, detailing PTMs' regulatory roles in PPIs.
• To expand PTM data accessibility for understudied organisms via ortholog propagation.

Main Methods:

• Utilized residue co-evolution and proximity to predict PTM functional associations.
• Applied prediction methods to PTMs within single proteins and between interacting proteins.
• Implemented a strategy to propagate PTM data through orthologous proteins for broader species coverage.

Main Results:

• PTMcode v2 covers 19 eukaryotic species, including over 300,000 experimentally verified PTMs.
• The resource details the post-translational regulation of >100,000 proteins and >100,000 interactions.
• Reported 8 million PTM associations regulating single proteins and over 9.4 million interplays tuning PPIs.

Conclusions:

• PTMcode v2 provides a valuable resource for understanding PTM-mediated regulation of protein interactions.
• The findings highlight the significant role of PTMs in fine-tuning protein function and cellular processes.
• The propagation strategy enhances the utility of PTMcode v2 for diverse eukaryotic proteomes.