Ubiquitin Binds to and Regulates a Subset of SH3 Domains

Svetoslava D. Stamenova, Michael E. French, Yuan He, Smitha A. Francis, Zachary B. Kramer, Linda Hicke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


SH3 domains are modules of 50-70 amino acids that promote interactions among proteins, often participating in the assembly of large dynamic complexes. These domains bind to peptide ligands, which usually contain a core Pro-X-X-Pro (PXXP) sequence. Here we identify a class of SH3 domains that bind to ubiquitin. The yeast endocytic protein Sla1, as well as the mammalian proteins CIN85 and amphiphysin, carry ubiquitin-binding SH3 domains. Ubiquitin and peptide ligands bind to the same hydrophobic groove on the SH3 domain surface, and ubiquitin and a PXXP-containing protein fragment compete for binding to SH3 domains. We conclude that a subset of SH3 domains constitutes a distinct type of ubiquitin-binding domain and that ubiquitin binding can negatively regulate interaction of SH3 domains with canonical proline-rich ligands.

Original languageEnglish (US)
Pages (from-to)273-284
Number of pages12
JournalMolecular cell
Issue number2
StatePublished - Jan 26 2007



ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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