title: The biological functions of Naa10 - From amino-terminal acetylation to human disease.
abstract: N-terminal acetylation (NTA) is one of the most abundant protein modifications known, and the N-terminal acetyltransferase (NAT) machinery is conserved throughout all Eukarya. Over the past 50 years, the function of NTA has begun to be slowly elucidated, and this includes the modulation of protein-protein interaction, protein-stability, protein function, and protein targeting to specific cellular compartments. Many of these functions have been studied in the context of Naa10/NatA; however, we are only starting to really understand the full complexity of this picture. Roughly, about 40% of all human proteins are substrates of Naa10 and the impact of this modification has only been studied for a few of them. Besides acting as a NAT in the NatA complex, recently other functions have been linked to Naa10, including post-translational NTA, lysine acetylation, and NAT/KAT-independent functions. Also, recent publications have linked mutations in Naa10 to various diseases, emphasizing the importance of Naa10 research in humans. The recent design and synthesis of the first bisubstrate inhibitors that potently and selectively inhibit the NatA/Naa10 complex, monomeric Naa10, and hNaa50 further increases the toolset to analyze Naa10 function.
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, NY, USA. Electronic address: MDoerfel@cshl.edu.
authors.forename: Max J
authors.initials: MJ
authors.lastname: Dörfel
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, NY, USA; Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA; Utah Foundation for Biomedical Research, Salt Lake City, UT, USA. Electronic address: gholsonjlyon@gmail.com.
authors.forename: Gholson J
authors.initials: GJ
authors.lastname: Lyon
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D015687:Cell Hypoxia; D004249:DNA Damage; D005786:Gene Expression Regulation; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D063209:N-Terminal Acetyltransferase A / Q000737:chemistry / Q000502:physiology*; D063213:N-Terminal Acetyltransferase E / Q000737:chemistry / Q000502:physiology*; D009369:Neoplasms / Q000201:enzymology; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary
chemical_list: D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E
keywords: Acetyltransferases; Amino-terminal acetylation; Enzymology; NAA10; NAA15; NAA50; Ogden syndrome; Proteins; Proteomics; ard1