Extreme multifunctional proteins identified from a human protein interaction network

Nat Commun. 2015 Jun 9;6:7412. doi: 10.1038/ncomms8412.


Moonlighting proteins are a subclass of multifunctional proteins whose functions are unrelated. Although they may play important roles in cells, there has been no large-scale method to identify them, nor any effort to characterize them as a group. Here, we propose the first method for the identification of 'extreme multifunctional' proteins from an interactome as a first step to characterize moonlighting proteins. By combining network topological information with protein annotations, we identify 430 extreme multifunctional proteins (3% of the human interactome). We show that the candidates form a distinct sub-group of proteins, characterized by specific features, which form a signature of extreme multifunctionality. Overall, extreme multifunctional proteins are enriched in linear motifs and less intrinsically disordered than network hubs. We also provide MoonDB, a database containing information on all the candidates identified in the analysis and a set of manually curated human moonlighting proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Protein
  • Humans
  • Protein Binding
  • Proteome*


  • Proteome