analysis of the nuclear localization of Naa15 revealed discrepant results. Function Naa15, together with its catalytic subunit Naa10, constitutes the evolutionarily conserved NatA (Nα-acetyltransferase A) complex, which acetylates the α-amino group of the first amino acid residue of proteins starting with small side chains like serine, glycine, alanine, threonine and cysteine, after the initiator methionine has been cleaved by methionine aminopeptidases. Both Naa15 and Naa16 interact with the ribosome in yeast (via the ribosomal proteins, uL23 and uL29), humans and rat, thereby linking the NatA/Naa10 to the ribosome and facilitating co-translational acetylation of nascent polypeptide chains as they emerges from the exit tunnel. Furthermore, Naa15 might act as a scaffold for other factors, including the chaperone like protein HYPK (Huntingtin Interacting Protein K) and Naa50, the catalytic acetyltransferase subunit of NatE In S. cerevisiae, NAA15Δ and NAA10Δ knockout cells exhibit the same phenotype, and biochemical data indicate that uncomplexed Naa15 is unstable and gets degraded. Therefore, Naa15 function has been closely linked to the acetyltransferase activity of Naa10 as part of the NatA complex. NatA may also regulate co-translational protein folding and protein targeting to the endoplasmic reticulum, possibly through competition with SRP and NAC for the same ribosomal binding sites or through yet unknown interference with other ribosome-associated protein biogenesis factors, such as the MetAPs, the chaperones Hsp70/Hsp40, SRP and NAC, which act on newly synthesized proteins as soon as they emerge from the ribosome exit tunnel. However, the exact mechanism of such action is obscure. Apart from this, Naa15 has been linked to many cellular processes, including the maintenance of a healthy retina, endothelial cell permeability, tumor progression, generation and differentiation of neurons apoptosis and transcriptional regulation; however, it is not well understood whether these are NatA-independent or -dependent functions of Naa15. Disease Two damaging de novo NAA15 mutations were reported by exome sequencing in parent-offspring trios with congenital heart disease. Patient 1 harbors a frameshift mutation (p. Lys335fs) and displays heterotaxy (dextrocardia, total anomalous pulmonary venous return, left superior vena cava, hypoplastic TV, double outlet right ventricle, hypoplastic RV, D-transposition of the great arteries, pulmonic stenosis) and hydronephrosis, asplenia, malrotation and abnormal neuro-development, the second patient harbors a nonsense mutation (p.S761X) and displays conotruncal defects (tetralogy of Fallot, single left coronary artery). Notes References Further reading Human proteins