Post-translational modification (PTM) plays an important role in regulating the functions of
proteins. PTMs of multiple residues on one protein may work together to determine a
functional outcome, which is known as PTM cross-talk. Identification of PTM cross-talks is an
emerging theme in proteomics and has elicited great interest, but their properties remain to
be systematically characterized. To this end, we collected 193 PTM cross-talk pairs in 77
human proteins from the literature and then tested location preference and co-evolution at …

Motivation Protein post-translational modifications (PTMs) regulate a wide range of cellular
protein functions. Many PTM sites from the same (intra) or different (inter) proteins often
cooperate with each other to perform a function, which is defined as PTM cross-talk. PTM
cross-talk within proteins attracted great attentions in the past a few years. However, the inter-
protein PTM cross-talk is largely under studied due to its large protein pair space and lack of
a gold standard dataset, even though the PTM interplay between proteins is a key element …