title: Deciphering kinase-substrate relationships by analysis of domain-specific phosphorylation network.
abstract: BACKGROUND
  In silico prediction of site-specific kinase-substrate relationships (ssKSRs) is crucial for deciphering phosphorylation networks by linking kinomes to phosphoproteomes. However, currently available predictors for ssKSRs give rise to a large number of false-positive results because they use only a short sequence stretch around phosphosite as determinants of kinase specificity and do not consider the biological context of kinase-substrate recognition.
  
  
  RESULTS
  Based on the analysis of domain-specific kinase-substrate relationships, we have constructed a domain-level phosphorylation network that implicitly incorporates various contextual factors. It reveals preferential phosphorylation of specific domains by certain kinases. These novel correlations have been implemented in PhosNetConstruct, an automated program for predicting target kinases for a substrate protein. PhosNetConstruct distinguishes cognate kinase-substrate pairs from a large number of non-cognate combinations. Benchmarking on independent datasets using various statistical measures demonstrates the superior performance of PhosNetConstruct over ssKSR-based predictors.
  
  
  METHODS
  PhosNetConstruct is freely available at http://www.nii.ac.in/phosnetconstruct.html.
authors.affiliation: Bioinformatics Centre, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Nikhil Prakash
authors.initials: NP
authors.lastname: Damle
authors.affiliation: Bioinformatics Centre, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Debasisa
authors.initials: D
authors.lastname: Mohanty
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000145:classification / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D012984:Software
chemical_list: D010750:Phosphoproteins; D011494:Protein Kinases