Fig 1.
Palmitoylation and detection methods.
(a) Palmitoylation involves the reversible addition of long-chain fatty acids (FA) to cysteine residues via thioester bonds. (b) The ABE and Acyl-RAC assays use N-ethylmaleimide (NEM) to block free cysteines and hydroxylamine (HAM) to remove palmitate. The Acyl-RAC assay uses thiopropyl-sepharose beads that covalently react with the free cysteines, allowing enrichment and elution, using β-mercaptoethanol (β-ME), of palmitoyl-proteins and detection by MS. Following HAM treatment in the ABE assay free cysteines are labeled using Biotin-HPDP, allowing streptavidin-sepharose enrichment for MS. (c) The bioorthogonal-labeling assay uses alkyne-FA analogues followed by click chemistry to covalently link alkynyl-palmitate with biotin, allowing enrichment of palmitoyl-proteins for MS.
Table 1.
Published mammalian palmitoylomes.
Fig 2.
Hierarchical clustering of 15 published palmitoylomes.
The gene list of each palmitoyl proteome were subjected to hierarchical clustering using R. Studies that used ABE, bioorthogonal labeling (CLICK) or Acyl-RAC (ARAC) assays are in black, blue, and green font, respectively. Studies that used neuronal sample sources are outlined with black boxes. Bootstrap values are only shown for significant clusters.
Fig 3.
Gene Ontology biological process enrichments among the curated palmitoylome.
The top 15 GO biological process enrichments that obtained a FDR<0.001 and a FE≥2 plotted by-log (FDR). The FE is displayed to the right of each bar.
Fig 4.
Pathway map enrichments of the curated palmitoylome and enrichment of synaptic proteins for palmitoylated proteins.
(a) The 14 pathway map enrichments that obtained a FDR < 0.001 and FE ≥ 2 plotted by-log (FDR). The FE is displayed to the right of each bar. Venn diagram of genes in the compendium and the synaptic gene list from SynSysNet is shown in (b). The overlap between proteins from neuronal sources versus non-neuronal sources is shown in a Venn diagram in (c).
Fig 5.
Biomarker-based disease-association enrichments of the curated palmitoylome.
(a) The top 15 biomarker-based disease-association enrichments that obtained a FDR < 0.001 and a FE ≥ 2 plotted by–log (FDR). The FE is displayed to the right of each bar. All of the 40 statistically significant biomarker-based disease-association enrichments of the compendium were broadly classified and are displayed in (b). GI = Gastrointestinal. Other = those diseases that do not fit into any other category.
Table 2.
Disease-causing mutations of known or putatively palmitoylated cysteins in diseases and disorders of the nervous system.