A Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome

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) intera...

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Bibliographic Details
Published in:Cell 2005-09, Vol.122 (6), p.957-968
Main Authors: Stelzl, Ulrich, Worm, Uwe, Lalowski, Maciej, Haenig, Christian, Brembeck, Felix H., Goehler, Heike, Stroedicke, Martin, Zenkner, Martina, Schoenherr, Anke, Koeppen, Susanne, Timm, Jan, Mintzlaff, Sascha, Abraham, Claudia, Bock, Nicole, Kietzmann, Silvia, Goedde, Astrid, Toksöz, Engin, Droege, Anja, Krobitsch, Sylvia, Korn, Bernhard, Birchmeier, Walter, Lehrach, Hans, Wanker, Erich E.
Format: Article
Language:English
Subjects:
Axin Protein
Databases as Topic
Humans
Intracellular Signaling Peptides and Proteins
Models, Molecular
Nerve Tissue Proteins - metabolism
Protein Binding
Proteins - genetics
Proteins - metabolism
Proteins - physiology
Proteomics - methods
Repressor Proteins - metabolism
Two-Hybrid System Techniques
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Summary: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 coimmunoprecipitation 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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2005.08.029