A proline-90 residue unique to SUMO-4 prevents maturation and sumoylation

Biochem Biophys Res Commun. 2005 Nov 18;337(2):517-20. doi: 10.1016/j.bbrc.2005.09.090. Epub 2005 Sep 22.


Four small ubiquitin-related modifier (SUMO) genes have been identified in humans. However, little is known about the basic biology of SUMO-4. Here, we report that SUMO-4 differs from SUMO-1, -2, and -3 in that the maturation process of SUMO-4 to active form containing C-terminal di-glycine residues is inhibited by a unique proline residue located at position 90 (Pro-90). Although, both the hydrolase and isopeptidase activities of SUMO peptidases are significantly diminished by Pro-90 as compared to Gln-90 (glutamine) in mutated SUMO genes, only the defective hydrolase activity appears to be biologically relevant. Native SUMO-4, thus, appears to be unable to form covalent isopeptide bonds with substrates. A biological role of SUMO-4, through non-covalent interactions is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carbon-Nitrogen Lyases / metabolism
  • Cells, Cultured
  • Endopeptidases / metabolism
  • Glycine / chemistry
  • Humans
  • Hydrolases / metabolism
  • Mutation
  • Proline / chemistry*
  • Protein Binding
  • SUMO-1 Protein / chemistry
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / metabolism
  • Small Ubiquitin-Related Modifier Proteins / chemistry
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Ubiquitin / genetics
  • Ubiquitin / metabolism*


  • SUMO-1 Protein
  • SUMO4 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitin
  • Proline
  • Hydrolases
  • Endopeptidases
  • Carbon-Nitrogen Lyases
  • isopeptidase
  • Glycine