An organellar nα-acetyltransferase, naa60, acetylates cytosolic N termini of transmembrane proteins and maintains Golgi integrity

Cell Rep. 2015 Mar 3;10(8):1362-74. doi: 10.1016/j.celrep.2015.01.053. Epub 2015 Feb 26.


N-terminal acetylation is a major and vital protein modification catalyzed by N-terminal acetyltransferases (NATs). NatF, or Nα-acetyltransferase 60 (Naa60), was recently identified as a NAT in multicellular eukaryotes. Here, we find that Naa60 differs from all other known NATs by its Golgi localization. A new membrane topology assay named PROMPT and a selective membrane permeabilization assay established that Naa60 faces the cytosolic side of intracellular membranes. An Nt-acetylome analysis of NAA60-knockdown cells revealed that Naa60, as opposed to other NATs, specifically acetylates transmembrane proteins and has a preference for N termini facing the cytosol. Moreover, NAA60 knockdown causes Golgi fragmentation, indicating an important role in the maintenance of the Golgi's structural integrity. This work identifies a NAT associated with membranous compartments and establishes N-terminal acetylation as a common modification among transmembrane proteins, a thus-far poorly characterized part of the N-terminal acetylome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Cell Membrane / metabolism
  • Cytosol / metabolism
  • Golgi Apparatus / metabolism*
  • Golgi Apparatus / pathology
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism*
  • N-Terminal Acetyltransferase F / antagonists & inhibitors
  • N-Terminal Acetyltransferase F / genetics
  • N-Terminal Acetyltransferase F / metabolism*
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Substrate Specificity


  • Membrane Proteins
  • NAA60 protein, human
  • RNA, Small Interfering
  • N-Terminal Acetyltransferase F