The small ubiquitin-like modifier-1 (SUMO-1) consensus sequence mediates Ubc9 binding and is essential for SUMO-1 modification

J Biol Chem. 2001 Jun 15;276(24):21664-9. doi: 10.1074/jbc.M100006200. Epub 2001 Mar 19.

Abstract

SUMO-1 is an ubiquitin-related protein that is covalently conjugated to a diverse assortment of proteins. The consequences of SUMO-1 modification include the regulation of protein-protein interactions, protein-DNA interactions, and protein subcellular localization. At present, very little is understood about the specific mechanisms that govern the recognition of proteins as substrates for SUMO-1 modification. However, many of the proteins that are modified by SUMO-1 interact directly with the SUMO-1 conjugating enzyme, Ubc9. These interactions suggest that Ubc9 binding may play an important role in substrate recognition as well as in substrate modification. The SUMO-1 consensus sequence (SUMO-1-CS) is a motif of conserved residues surrounding the modified lysine residue of most SUMO-1 substrates. This motif conforms to the sequence "PsiKXE," where Psi is a large hydrophobic residue, K is the lysine to which SUMO-1 is conjugated, X is any amino acid, and E is glutamic acid. In this study, we demonstrate that the SUMO-1-CS is a major determinant of Ubc9 binding and SUMO-1 modification. Mutating residues in the SUMO-1-CS abolishes both Ubc9 binding and substrate modification. These findings have important implications for how SUMO-1 substrates are recognized and for how SUMO-1 is ultimately transferred to specific lysine residues on these substrates.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Consensus Sequence
  • Conserved Sequence
  • DNA, Complementary
  • Humans
  • Ligases / chemistry
  • Ligases / metabolism
  • Liver / metabolism
  • Plasmids
  • Protein Binding
  • Protein Biosynthesis
  • Rabbits
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Reticulocytes / metabolism
  • SUMO-1 Protein
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Ubiquitin-Conjugating Enzymes*
  • Ubiquitins / chemistry*
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*

Substances

  • DNA, Complementary
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • SUMO-1 Protein
  • Ubiquitins
  • Ubiquitin-Conjugating Enzymes
  • Ligases
  • ubiquitin-conjugating enzyme UBC9