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. 2008 Jan;36(Database issue):D695-9.
doi: 10.1093/nar/gkm902. Epub 2007 Nov 2.

NetworKIN: a resource for exploring cellular phosphorylation networks

Rune Linding  1 , Lars Juhl Jensen, Adrian Pasculescu, Marina Olhovsky, Karen Colwill, Peer Bork, Michael B Yaffe, Tony Pawson
Affiliations

NetworKIN: a resource for exploring cellular phosphorylation networks

Rune Linding et al. Nucleic Acids Res. 2008 Jan.

Abstract

Protein kinases control cellular responses by phosphorylating specific substrates. Recent proteome-wide mapping of protein phosphorylation sites by mass spectrometry has discovered thousands of in vivo sites. Systematically assigning all 518 human kinases to all these sites is a challenging problem. The NetworKIN database (http://networkin.info) integrates consensus substrate motifs with context modelling for improved prediction of cellular kinase-substrate relations. Based on the latest human phosphoproteome from the Phospho.ELM and PhosphoSite databases, the resource offers insight into phosphorylation-modulated interaction networks. Here, we describe how NetworKIN can be used for both global and targeted molecular studies. Via the web interface users can query the database of precomputed kinase-substrate relations or obtain predictions on novel phosphoproteins. The database currently contains a predicted phosphorylation network with 20,224 site-specific interactions involving 3978 phosphoproteins and 73 human kinases from 20 families.

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Figures

Figure 1.
Figure 1.
Overview of the NetworKIN resource. NetworKIN starts from a set of known in vivo phosphorylation sites, which are obtained and kept synchronized with the Phospho.ELM and PhosphoSite databases to facilitate reciprocal database cross-links. We first compare these phosphorylation sites to consensus sequence motifs from the Scansite and NetPhosK resources in order to predict possible kinase families responsible for the phosphorylation. Second, we capture the kinase and substrate context using a probabilistic functional association network from the string database (12). The resulting site-specific kinase–substrate interaction network is stored in a SQL database, which is accessible via a web interface.
Figure 2.
Figure 2.
Using NetworKIN. A researcher is interested in the 53BP1 tumour surpressor. From the homepage of NetworKIN, this protein is chosen as the substrate protein to query the database for predictions relating any kinase to specific phosphorylation sites within 53BP1 (A). The system returns a total of 78 relations involving 12 different kinases that are predicted to phosphorylated 39 different sites, which are presented in a tabular view (B), (only the first 10 predictions are shown). These predictions can now be investigated in further detail by following either the links to the Phospho.ELM and PhosphoSite databases for curated knowledge related to the sites (C), or by following the links to the string network viewer to visualize the most probable path in the protein assocation network, which connects the kinase and the substrate (D).
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