Protein palmitoylation is the post-translational attachment of fatty acids, most commonly palmitate (C16 : 0), onto a cysteine residue of a protein. This reaction is catalysed by a family of integral membrane proteins, the zDHHC protein acyltransferases (PATs), so-called due to the presence of an invariant Asp–His–His–Cys (DHHC) cysteine-rich domain harbouring the catalytic centre of the enzyme. Conserved throughout eukaryotes, the zDHHC PATs are encoded by multigene families and mediate palmitoylation of thousands of protein substrates. In humans, a number of zDHHC proteins are associated with human diseases, including intellectual disability, Huntington's disease, schizophrenia and cancer. Key to understanding the physiological and pathophysiological importance of individual zDHHC proteins is the identification of their protein substrates. Here, we will describe the approaches and challenges in assigning substrates for individual zDHHCs, highlighting key mechanisms that underlie substrate recruitment.

蛋白质棕榈酰化是脂肪酸（最常见的是棕榈酸酯（C16：0））在蛋白质的半胱氨酸残基上的翻译后连接。该反应由一个完整的膜蛋白家族催化，即 zDHHC 蛋白酰基转移酶 (PATs)，之所以如此命名，是因为存在一个不变的 Asp–His–His–Cys (DHHC) 富含半胱氨酸的结构域，该结构域具有催化中心的催化中心。酶。zDHHC PAT 在整个真核生物中都是保守的，由多基因家族编码并介导数千种蛋白质底物的棕榈酰化。在人类中，许多 zDHHC 蛋白与人类疾病有关，包括智力残疾、亨廷顿病、精神分裂症和癌症。了解单个 zDHHC 蛋白的生理和病理生理重要性的关键是识别它们的蛋白质底物。