NAA20

Molecular characteristics

N-terminal acetyltransferases (NATs) are enzymes able to transfer an acetyl group to an N-terminal residue of a protein, in an irreversible process known as N-terminal (Nt) acetylation. Nt-acetylation plays a crucial role in protein functioning, impacting protein-protein interactions, correct subcellular localization, protein folding and turnover. About 80% of human proteins undergoes Nt-acetylation, although the global impact of this process is not entirely understood. The human NAT family includes seven known enzymes (NatA to NatF, and NatH), each of which acetylates specific N-termini substrates. Among them, NatB is a cytosolic and ribosome-associated complex consisting of the catalytic subunit NAA20 and the auxiliary subunit NAA25. It specifically acetylates protein N-terminal starting with Met-Asp, Met-Glu, Met-Asn and Met-Gln.

In vitro studies showed that the NAA20 p.Met54Val, the p.Ala80Val (Morrison et al. 2021) and the p.Leu4Pro mutations (D’Onofrio et al. 2023) were impaired in their capacity to form a NatB complex with NAA25, and in vitro acetylation assays revealed reduced catalytic activities toward different NatB substrates.