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.

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.

MeSH terms

  • 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*
  • RNA-Binding Proteins
  • Repressor Proteins / metabolism
  • Two-Hybrid System Techniques*

Substances

  • ANP32A protein, human
  • AXIN1 protein, human
  • Axin Protein
  • CRMP1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Proteins
  • RNA-Binding Proteins
  • Repressor Proteins