A human protein-protein interaction network: a resource for annotating the proteome


  • U. Stelzl
  • U. Worm
  • M. Lalowski
  • C. Haenig
  • F.H. Brembeck
  • H. Goehler
  • M. Stroedicke
  • M. Zenkner
  • A. Schoenherr
  • S. Koeppen
  • J. Timm
  • S. Mintzlaff
  • C. Abraham
  • N. Bock
  • S. Kietzmann
  • A. Goedde
  • E. Toksoez
  • A. Droege
  • S. Krobitsch
  • B. Korn
  • W. Birchmeier
  • H. Lehrach
  • E.E. Wanker


  • Cell


  • Cell 122 (6): 957-968


  • Protein-protein interaction maps provide a valuable framework for a better understanding of the functional organization of the proteome. To detect interacting pairs of human proteins systematically, a protein matrix of 4456 baits and 5632 preys was screened by automated yeast two-hybrid (Y2H) interaction mating. We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. Independent pull-down and co-immunoprecipitation assays validated the overall quality of the Y2H interactions. Using topological and GO criteria, a scoring system was developed to define 911 high-confidence interactions among 401 proteins. Furthermore, the network was searched for interactions linking uncharacterized gene products and human disease proteins to regulatory cellular pathways. Two novel Axin-1 interactions were validated experimentally, characterizing ANP32A and CRMP1 as modulators of Wnt signaling. Systematic human protein interaction screens can lead to a more comprehensive understanding of protein function and cellular processes.