N‐terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects

Abstract

The vast majority of eukaryotic proteins are N‐terminally modified by one or more processing enzymes. Enzymes acting on the very first amino acid of a polypeptide include different peptidases, transferases, and ligases. Methionine aminopeptidases excise the initiator methionine leaving the nascent polypeptide with a newly exposed amino acid that may be further modified. N‐terminal acetyl‐, methyl‐, myristoyl‐, and palmitoyltransferases may attach an acetyl, methyl, myristoyl, or palmitoyl group, respectively, to the α‐amino group of the target protein N‐terminus. With the action of ubiquitin ligases, one or several ubiquitin molecules are transferred, and hence, constitute the N‐terminal modification. Modifications at protein N‐termini represent an important contribution to proteomic diversity and complexity, and are essential for protein regulation and cellular signaling. Consequently, dysregulation of the N‐terminal modifying enzymes is implicated in human diseases. We here review the different protein N‐terminal modifications occurring co‐ or post‐translationally with emphasis on the responsible enzymes and their substrate specificities.

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Cited by papers we hold 2

• Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications · 2023
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• Spotlight on protein N-terminal acetylation · 2018
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