Kinome-wide identification of phosphorylation networks in eukaryotic proteomes

Bioinformatics
Luca ParcaManuela Helmer-Citterich

Abstract

Signaling and metabolic pathways are finely regulated by a network of protein phosphorylation events. Unraveling the nature of this intricate network, composed of kinases, target proteins and their interactions, is therefore of crucial importance. Although thousands of kinase-specific phosphorylations (KsP) have been annotated in model organisms their kinase-target network is far from being complete, with less studied organisms lagging behind. In this work, we achieved an automated and accurate identification of kinase domains, inferring the residues that most likely contribute to peptide specificity. We integrated this information with the target peptides of known human KsP to predict kinase-specific interactions in other eukaryotes through a deep neural network, outperforming similar methods. We analyzed the differential conservation of kinase specificity among eukaryotes revealing the high conservation of the specificity of tyrosine kinases. With this approach we discovered 1590 novel KsP of potential clinical relevance in the human proteome. http://akid.bio.uniroma2.it. Supplementary data are available at Bioinformatics online.

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Citations

Oct 5, 2019·Nucleic Acids Research·UNKNOWN PDBe-KB consortium
Nov 11, 2021·Nucleic Acids Research·UNKNOWN PDBe-KB consortium

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Software Mentioned

TimeTree
GOSemSim
AKID
hmmer
Polyphen
PhosphoGRID
iGPS
ROCR
PhosphoSitePlus
Ensembl

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