N-alpha-acetyltransferase 20 (NAA20)

N-alpha-acetyltransferase 20 (NAA20) is the catalytic subunit of the N-terminal acetyltransferase B (NatB) complex, a highly conserved enzyme responsible for co-translational N-terminal acetylation of proteins in eukaryotic cells[1][2][4]. The NatB complex is composed of the catalytic NAA20 and the auxiliary subunit NAA25, and specifically acetylates protein N-termini that retain their initial methionine followed by an acidic residue (e.g., MD-, ME-, MN-, or MQ- sequences). NatB/NAA20 acetylates approximately 20% of the human proteome, influencing protein stability, localization, and function, as well as actomyosin fiber structure and cell migration[5]. NAA20's activity is linked to disease processes, most notably hepatocellular carcinoma, where increased NAA20 expression promotes oncogenic traits by inhibiting AMPK activity and activating the mTOR signaling pathway, thereby stimulating cell proliferation and autophagy[3][6]. Structural studies have defined the substrate recognition and catalytic site of NAA20, enabling the development of specific inhibitors as molecular probes or potential therapeutics[1][2]. Loss-of-function or pathogenic variants in NAA20 can disrupt N-terminal acetylation, with possible consequences for development and proteostasis[4]. No approved drugs currently target NAA20, but synthetic inhibitors such as CoA-Ac-MDEL have been used in structural and mechanistic research[1][2].

Other names

NAA20NAT5NatB catalytic subunitNatB complex subunit NAT5dJ1002M8.1NAT3Methionine N-acetyltransferaseN-acetyltransferase 5N-terminal acetyltransferase B complex catalytic subunit NAA20N-terminal acetyltransferase B complex catalytic subunit NAT5N-acetyltransferase 3 homolog (S. cerevisiae)MRT73NAT3PNAT5P

Competitive inhibition of N-terminal acetyltransferase activity (by molecules such as CoA-Ac-MDEL, which mimic substrate peptides to block the NAA20 catalytic site)