Molecular characterization of propionyllysines in non-histone proteins

Mol Cell Proteomics. 2009 Jan;8(1):45-52. doi: 10.1074/mcp.M800224-MCP200. Epub 2008 Aug 26.


Lysine propionylation and butyrylation are protein modifications that were recently identified in histones. The molecular components involved in the two protein modification pathways are unknown, hindering further functional studies. Here we report identification of the first three in vivo non-histone protein substrates of lysine propionylation in eukaryotic cells: p53, p300, and CREB-binding protein. We used mass spectrometry to map lysine propionylation sites within these three proteins. We also identified the first two in vivo eukaryotic lysine propionyltransferases, p300 and CREB-binding protein, and the first eukaryotic depropionylase, Sirt1. p300 was able to perform autopropionylation on lysine residues in cells. Our results suggest that lysine propionylation, like lysine acetylation, is a dynamic and regulatory post-translational modification. Based on these observations, it appears that some enzymes are common to the lysine propionylation and lysine acetylation regulatory pathways. Our studies therefore identified first several important players in lysine propionylation pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyltransferases / metabolism
  • Amino Acid Sequence
  • Biocatalysis
  • CREB-Binding Protein / chemistry
  • CREB-Binding Protein / metabolism*
  • Cell Line
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism*
  • Mass Spectrometry
  • Molecular Sequence Data
  • Protein Processing, Post-Translational*
  • Sirtuins / metabolism
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism*
  • p300-CBP Transcription Factors / chemistry
  • p300-CBP Transcription Factors / metabolism*


  • Histones
  • Tumor Suppressor Protein p53
  • Acyltransferases
  • CREB-Binding Protein
  • p300-CBP Transcription Factors
  • Sirtuins
  • Lysine