Protein lysine four‐carbon acylations in health and disease

Abstract Lysine acylation, a type of posttranslational protein modification sensitive to cellular metabolic states, influences the functions of target proteins involved in diverse cellular processes. Particularly, lysine butyrylation, crotonylation, β‐hydroxybutyrylation, and 2‐hydroxyisobutyrylation, four types of four‐carbon acylations, are modulated by intracellular concentrations of their respective acyl‐CoAs and sensitive to alterations of nutrient metabolism induced by cellular and/or environmental signals. In this review, we discussed the metabolic pathways producing these four‐carbon acyl‐CoAs, the regulation of lysine acylation and deacylation, and the functions of individual lysine acylation.