N-terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects.
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.
Department of Molecular Biology, University of Bergen, Bergen, Norway.
Sylvia
S
Varland
Department of Molecular Biology, University of Bergen, Bergen, Norway.|Department of Surgery, Haukeland University Hospital, Bergen, Norway.
Camilla
C
Osberg
Department of Molecular Biology, University of Bergen, Bergen, Norway.|Department of Surgery, Haukeland University Hospital, Bergen, Norway.
Thomas
T
Arnesen
D000107:Acetylation; D000818:Animals; D006801:Humans; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D040901:Proteomics; D013379:Substrate Specificity
D011506:Proteins
Acetylation; Cell biology; N-terminal; Protein modification; Substrate specificity; α-amino group