Lysine-targeting specificity in ubiquitin and ubiquitin-like modification pathways

Nat Struct Mol Biol. 2014 Apr;21(4):308-16. doi: 10.1038/nsmb.2792.


Ubiquitin and ubiquitin-like modifications are central to virtually all cellular signaling pathways. They occur primarily on lysine residues of target proteins and stimulate a large number of downstream signals. The diversity of these signals depends on the type, location and dynamics of the modification, but the role of the exact site of modification and the selectivity for specific lysines are poorly understood. Here we review the current literature on lysine specificity in these modifications, and we highlight the known signaling mechanisms and the open questions that pose future challenges to ubiquitin research.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Lysine / chemistry
  • Lysine / metabolism*
  • Models, Biological*
  • Signal Transduction
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Small Ubiquitin-Related Modifier Proteins / physiology
  • Substrate Specificity
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitin-Protein Ligases / physiology*
  • Ubiquitination


  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Lysine