NAA10

NAA10, also known as N-acetyltransferase 10 and ARD1, is a human gene that encodes the catalytic subunit of the NatA N-terminal acetyltransferase complex. The NatA complex in humans consists of the catalytic subunit NAA10 and the auxiliary subunit NAA15. This enzyme acetylates the N-termini of many nascent polypeptides as they emerge from the ribosome, typically after removal of the initiator methionine when the second residue is small. N-terminal acetylation by NatA influences protein stability, localization, and interactions, and is a widespread, co-translationally applied modification in eukaryotes.

Genetics and structure: NAA10 is located on the X chromosome (Xq28) and is broadly expressed across tissues. In humans, multiple NAA10 isoforms arise from alternative splicing, contributing to tissue- and development-stage-specific expression. The NatA complex activity can be modulated by other factors, including the regulatory protein HYPK, which can influence substrate selection and catalytic efficiency.

Clinical significance: Mutations in NAA10 are associated with a spectrum of NAA10-related disorders. Ogden syndrome is a severe X-linked condition caused by a de novo missense mutation, notably p.Ser37Pro (S37P), which impairs NatA activity and is linked to early lethality in infancy. Additional NAA10 variants have been reported in individuals with intellectual disability, developmental delay, microcephaly, autism spectrum disorders, and congenital heart defects. The full phenotypic range and mechanisms by which NAA10 variants cause disease are subjects of ongoing research.

Notes: As the catalytic heart of NatA, NAA10 is essential for the broad N-terminal acetylation landscape in human cells, and disruptions can affect proteome stability and cellular pathways dependent on properly acetylated proteins.