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

Affiliation

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.

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