N-terminal acetylation has been extensively studied in yeast and humans and represents one of the most common protein modifications in eukaryotes, occurring on approximately 57% of yeast proteins and 84% human proteins 1, although it is rare in prokaryotes. Eukaryotic proteins initiate with methionine residues, which are cleaved from nascent chains if the penultimate residue has a radius of gyration of 1.29 Å or less 2. N-terminal acetylation subsequently occurs on certain of the proteins, either containing or lacking the methionine residue, as depicted in Fig. 1. The salient features of N-terminal acetylation are summarized in Table 1 and Fig. 2. Detailed reviews on the N-terminal acetyltransferases have appeared 34567, and the N-terminal acetylation status of 742 human and 616 yeast protein N-termini have been compiled 1. The wide range and diversity of substrates is due in part to the large number of different N-terminal acetylating enzymes, NatA-NatE. The sequence requirements for N-terminal acetylation vary with the N-terminal acetyltransferase. Only two amino acid residues, Met-Asn-, Met-Asp-, or Met-Glu-, are required for at least partial N-terminal acetylation by NatB 18. On the other hand, 30 to 50 specific amino acids are required for N-terminal acetylation by NatD 9. Each of the three major N-terminal acetyltransferases, NatA, NatB and NatC, contain a catalytic subunit, and one or two auxiliary subunits (Table 1). The sequence and functions of the yeast and human orthologous subunits are obviously related. A yeast ard1-Δ nat1-Δ strain was phenotypically complemented by hARD1 hNAT1, suggesting that yNatA and hNatA are similar. However, heterologous combinations, hARD1 yNAT1 and yARD1 hNAT1, were not functional in yeast, suggesting significant structural subunit differences between the species 1.

During a recent international meeting on N-terminal acetylation, it was pointed out that there is critical need to revise the gene symbols encoding the N-terminal acetyltransferases. The main reason for changing the nomenclature is so that each of the orthologous genes from different species would have the same name. Furthermore, orthologous genes were assigned not only by similarity of their sequences, but also by their action on the same set of proteins. Yeast NatA and human NatA were shown to acetylate the same set proteins by comparing a normal yeast strain with the mutant naa10-Δ naa15-ΔhNAA10 hNAA15 1.

The use of the different symbols NAT, ARD, MDM, and MAK is confusing, and does not provide useful information, especially when applied to human NATs. We believe it can be misleading to assign a gene symbol based on one phenotype of a mutant when a large number of proteins are affected, and when the mutant is pleiotropic.

Most importantly, different orthologous genes should have different names. The symbols NAT1, NAT2 and NAT3 denote human genes encoding arylamine N-acetyltransferases, which are distinct from N-terminal acetyltransferases 10. On the other hand, NCBI has designated the human homologue of the yeast NAT genes as follows: yNAT1 designated as hNARG1; yNAT3 designated as hNAT5; and yNAT5 designated as hNAT13. Also, ARD1 is used to describe the ADP-ribosylation factor domain protein 1 11.

Therefore, in this paper we have introduced a new nomenclature for protein N-terminal acetyltransferases in eukaryotes (Table 1). It is important to note that NAA (

Nα ac

The authors declare that they have no competing interests.

All authors wrote the manuscript and approved the final version.