Protein lipidation events are one of an essential and diverse class of post-translational modification. S-palmitoylation is the most studied form of protein lipidations, which could reversibly attach palmitate (16-carbon) to specific cysteine residues in protein substrates. The so-called “palmitoylome” comprises palmitoylated proteins encoded by approximately 10% of the genome (Spinelli et al., 2018). Aberrant palmitoylation’s dynamic circulation might affect protein localization, accumulation, secretion, stability, and function by changing membrane affinity (Dunphy and Linder, 1998; Percherancier et al., 2001; Lanyon-Hogg et al., 2017; Jiang et al., 2018). Conventionally, palmitoylation sites were mapped by mutagenesis of candidate cysteine residues. Proteomic methods of high-throughput and tandem mass spectrometry (MS) were also applied to identifying palmitoylation sites. However, these results remained to be dissected.
