ArticlePLoS genetics2011
NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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117 citing papers in PubMed, 191 citations in OpenAlex.
- Top-Down versus Bottom-Up Proteomics in Highly Sensitive LC-MS-Based Profiling of Limited Samples.Analytical chemistry · 2026Article
- N-terminal acetylation controls multiple functional aspects of the influenza A virus ribonuclease PA-X.Journal of virology · 2026Article
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- Understanding brain calcification via N-terminal acetylation at the Golgi apparatus.Brain : a journal of neurology · 2025Review
- NAA10 (N-Alpha-Acetyltransferase 10): A Multifunctional Regulator in Development, Disease, and Cancer.Cells · 2025Review
- Proximal partners of the organellar N-terminal acetyltransferase NAA60: insights into Golgi structure and transmembrane protein topology.Open biology · 2025Article
- Illuminating the impact of N-terminal acetylation: from protein to physiology.Nature communications · 2025Review
- Naa80 is required for actin N-terminal acetylation and normal hearing in zebrafish.Life science alliance · 2024Article
- N-terminal acetylation of Set1-COMPASS fine-tunes H3K4 methylation patterns.Science advances · 2024Article
- N-terminal cysteine acetylation and oxidation patterns may define protein stability.Nature communications · 2024Article
- Genome-Wide Identification and Characterization of miRNAs and Natural Antisense Transcripts Show the Complexity of Gene Regulatory Networks for Secondary Metabolism inInternational journal of molecular sciences · 2024Article
- Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis.The EMBO journal · 2024Article
- Biallelic NAA60 variants with impaired n-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications.Nature communications · 2024Article
- N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity.Nature communications · 2023Article
- The Post-Translational Modifications of Human Salivary Peptides and Proteins Evidenced by Top-Down Platforms.International journal of molecular sciences · 2023Review
- Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import.PLoS genetics · 2023Article
- Impact of Protein NLife (Basel, Switzerland) · 2023Review
- N-terminal acetylation can stabilize proteins independent of their ubiquitination.Scientific reports · 2023Article
- An N-acetyltransferase required for EsxA N-terminal protein acetylation and virulence in Mycobacterium marinum.bioRxiv : the preprint server for biology · 2023Article
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57 more citing papers are in PubMed but not listed here.
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8 authors at 4 institutions in 3 countries.
Funding
Abstract
N-terminal acetylation (N-Ac) is a highly abundant eukaryotic protein modification. Proteomics revealed a significant increase in the occurrence of N-Ac from lower to higher eukaryotes, but evidence explaining the underlying molecular mechanism(s) is currently lacking. We first analysed protein N-termini and their acetylation degrees, suggesting that evolution of substrates is not a major cause for the evolutionary shift in N-Ac. Further, we investigated the presence of putative N-terminal acetyltransferases (NATs) in higher eukaryotes. The purified recombinant human and Drosophila homologues of a novel NAT candidate was subjected to in vitro peptide library acetylation assays. This provided evidence for its NAT activity targeting Met-Lys- and other Met-starting protein N-termini, and the enzyme was termed Naa60p and its activity NatF. Its in vivo activity was investigated by ectopically expressing human Naa60p in yeast followed by N-terminal COFRADIC analyses. hNaa60p acetylated distinct Met-starting yeast protein N-termini and increased general acetylation levels, thereby altering yeast in vivo acetylation patterns towards those of higher eukaryotes. Further, its activity in human cells was verified by overexpression and knockdown of hNAA60 followed by N-terminal COFRADIC. NatF's cellular impact was demonstrated in Drosophila cells where NAA60 knockdown induced chromosomal segregation defects. In summary, our study revealed a novel major protein modifier contributing to the evolution of N-Ac, redundancy among NATs, and an essential regulator of normal chromosome segregation. With the characterization of NatF, the co-translational N-Ac machinery appears complete since all the major substrate groups in eukaryotes are accounted for.
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