PhosphoPOINT: a comprehensive human kinase interactome and phospho-protein database

Bioinformatics. 2008 Aug 15;24(16):i14-20. doi: 10.1093/bioinformatics/btn297.

Abstract

Motivation: To fully understand how a protein kinase regulates biological processes, it is imperative to first identify its substrate(s) and interacting protein(s). However, of the 518 known human serine/threonine/tyrosine kinases, 35% of these have known substrates, while 14% of the kinases have identified substrate recognition motifs. In contrast, 85% of the kinases have protein-protein interaction (PPI) datasets, raising the possibility that we might reveal potential kinase-substrate pairs from these PPIs.

Results: PhosphoPOINT, a comprehensive human kinase interactome and phospho-protein database, is a collection of 4195 phospho-proteins with a total of 15 738 phosphorylation sites. PhosphoPOINT annotates the interactions among kinases, with their down-stream substrates and with interacting (phospho)-proteins to modulate the kinase-substrate pairs. PhosphoPOINT implements various gene expression profiles and Gene Ontology cellular component information to evaluate each kinase and their interacting (phospho)-proteins/substrates. Integration of cSNPs that cause amino acids change with the proteins with the phosphoprotein dataset reveals that 64 phosphorylation sites result in a disease phenotypes when changed; the linked phenotypes include schizophrenia and hypertension. PhosphoPOINT also provides a search function for all phospho-peptides using about 300 known kinase/phosphatase substrate/binding motifs. Altogether, PhosphoPOINT provides robust annotation for kinases, their downstream substrates and their interaction (phospho)-proteins and this should accelerate the functional characterization of kinomemediated signaling.

Availability: PhosphoPOINT can be freely accessed in http://kinase. bioinformatics.tw/.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Databases, Protein*
  • Humans
  • Information Storage and Retrieval / methods
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotransferases / chemistry
  • Phosphotransferases / metabolism*
  • Protein Binding
  • Protein Interaction Mapping / methods*
  • Proteome / chemistry
  • Proteome / metabolism*
  • User-Computer Interface

Substances

  • Phosphoproteins
  • Proteome
  • Phosphotransferases