Preferred SH3 domain partners of ADAM metalloproteases include shared and ADAM-specific SH3 interactions

PLoS One. 2015 Mar 31;10(3):e0121301. doi: 10.1371/journal.pone.0121301. eCollection 2015.


A disintegrin and metalloproteinases (ADAMs) constitute a protein family essential for extracellular signaling and regulation of cell adhesion. Catalytic activity of ADAMs and their predicted potential for Src-homology 3 (SH3) domain binding show a strong correlation. Here we present a comprehensive characterization of SH3 binding capacity and preferences of the catalytically active ADAMs 8, 9, 10, 12, 15, 17, and 19. Our results revealed several novel interactions, and also confirmed many previously reported ones. Many of the identified SH3 interaction partners were shared by several ADAMs, whereas some were ADAM-specific. Most of the ADAM-interacting SH3 proteins were adapter proteins or kinases, typically associated with sorting and endocytosis. Novel SH3 interactions revealed in this study include TOCA1 and CIP4 as preferred partners of ADAM8, and RIMBP1 as a partner of ADAM19. Our results suggest that common as well as distinct mechanisms are involved in regulation and execution of ADAM signaling, and provide a useful framework for addressing the pathways that connect ADAMs to normal and aberrant cell behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism*
  • Carrier Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Protein Binding
  • Sorting Nexins / metabolism
  • src Homology Domains*


  • Carrier Proteins
  • FNBP1L protein, human
  • SNX33 protein, human
  • Sorting Nexins
  • ADAM Proteins

Grant support

This study was supported by grants to IK from The Jenny and Antti Wihuri Foundation and to KS from the Academy of Finland, Helsinki University Central Hospital Research Council, Biocentrum Helsinki, and the Sigrid Juselius Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.