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

  • Cell. 2005 Sep 23;122(6):957-68. doi: 10.1016/j.cell.2005.08.029.
Ulrich Stelzl  1 ,  Uwe Worm ,  Maciej Lalowski ,  Christian Haenig ,  Felix H Brembeck ,  Heike Goehler ,  Martin Stroedicke ,  Martina Zenkner ,  Anke Schoenherr ,  Susanne Koeppen ,  Jan Timm ,  Sascha Mintzlaff ,  Claudia Abraham ,  Nicole Bock ,  Silvia Kietzmann ,  Astrid Goedde ,  Engin Toksöz ,  Anja Droege ,  Sylvia Krobitsch ,  Bernhard Korn ,  Walter Birchmeier ,  Hans Lehrach ,  Erich E Wanker
Affiliations
  • 1. Max Delbrueck Center for Molecular Medicine, 13092 Berlin-Buch, Germany.
PMID: 16169070 DOI: 10.1016/j.cell.2005.08.029
Abstract

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.