# NAA40 (Q86UY6) research notes

## Summary
NAA40 (N-alpha-acetyltransferase 40; also NatD/Nat4/Nat11) is a highly substrate-specific N-terminal acetyltransferase that acetylates the free alpha-amino group of the N-terminal serine of histones H4 and H2A (which share an identical Ser-Gly-Arg-Gly N-terminal sequence after initiator-methionine removal), producing N-terminally acetylated H4/H2A (EC 2.3.1.257). Unlike the ribosome-associated NatA/NatB/NatC/NatE complexes, NAA40 is a monomeric enzyme with a narrow, sequence-specific selectivity restricted to these histone N-termini and recognizes the substrate independently of the bulk Nt-acetylation machinery. NAA40-mediated N-terminal acetylation of H4 influences chromatin function and crosstalk with adjacent histone marks (e.g. H4R3 methylation), and NAA40 has reported roles in transcriptional regulation, ribosomal RNA expression, cellular metabolism (including hepatic lipid metabolism), and as a negative regulator of apoptosis. NAA40 localizes mainly to the nucleus with a cytoplasmic pool.

## Core functions (from review)
- **GO:0010485 histone H4 acetyltransferase activity** — N-terminal acetyltransferase (NatD) that specifically acetylates the alpha-amino group of the N-terminal serine of histones H4 and H2A (Ser-Gly-Arg- Gly N-terminus), using acetyl-CoA, thereby writing an N-terminal histone acetyl mark that influences chromatin function and histone-mark crosstalk.
- **GO:0043998 histone H2A acetyltransferase activity** — N-terminal acetylation of histone H2A, which shares the H4 N-terminal sequence, by the same NatD active site.

## Provenance
Research and verbatim supporting quotes are recorded inline in `NAA40-ai-review.yaml` (per-annotation `supported_by` and `references` findings). This notes file summarizes the completed review; see the YAML for evidence citations.