@misc{RianoPachonKleessenNeigenfindetal.2010,
  author    = {Ria{\~n}o-Pach{\´o}n, Diego Mauricio and Kleessen, Sabrina and Neigenfind, Jost and Durek, Pawel and Weber, Elke and Engelsberger, Wolfgang R. and Walther, Dirk and Selbig, Joachim and Schulze, Waltraud X. and Kersten, Birgit},
  title     = {Proteome-wide survey of phosphorylation patterns affected by nuclear DNA polymorphisms in Arabidopsis thaliana},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1328},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43118},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431181},
  pages     = {19},
  year      = {2010},
  abstract  = {Background: Protein phosphorylation is an important post-translational modification influencing many aspects of dynamic cellular behavior. Site-specific phosphorylation of amino acid residues serine, threonine, and tyrosine can have profound effects on protein structure, activity, stability, and interaction with other biomolecules. Phosphorylation sites can be affected in diverse ways in members of any species, one such way is through single nucleotide polymorphisms (SNPs). The availability of large numbers of experimentally identified phosphorylation sites, and of natural variation datasets in Arabidopsis thaliana prompted us to analyze the effect of non-synonymous SNPs (nsSNPs) onto phosphorylation sites. Results: From the analyses of 7,178 experimentally identified phosphorylation sites we found that: (i) Proteins with multiple phosphorylation sites occur more often than expected by chance. (ii) Phosphorylation hotspots show a preference to be located outside conserved domains. (iii) nsSNPs affected experimental phosphorylation sites as much as the corresponding non-phosphorylated amino acid residues. (iv) Losses of experimental phosphorylation sites by nsSNPs were identified in 86 A. thaliana proteins, among them receptor proteins were overrepresented. These results were confirmed by similar analyses of predicted phosphorylation sites in A. thaliana. In addition, predicted threonine phosphorylation sites showed a significant enrichment of nsSNPs towards asparagines and a significant depletion of the synonymous substitution. Proteins in which predicted phosphorylation sites were affected by nsSNPs (loss and gain), were determined to be mainly receptor proteins, stress response proteins and proteins involved in nucleotide and protein binding. Proteins involved in metabolism, catalytic activity and biosynthesis were less affected. Conclusions: We analyzed more than 7,100 experimentally identified phosphorylation sites in almost 4,300 protein-coding loci in silico, thus constituting the largest phosphoproteomics dataset for A. thaliana available to date. Our findings suggest a relatively high variability in the presence or absence of phosphorylation sites between different natural accessions in receptor and other proteins involved in signal transduction. Elucidating the effect of phosphorylation sites affected by nsSNPs on adaptive responses represents an exciting research goal for the future.},
  language  = {en}
}
@misc{DurekSchudomaWeckwerthetal.2009,
  author    = {Durek, Pawel and Schudoma, Christian and Weckwerth, Wolfram and Selbig, Joachim and Walther, Dirk},
  title     = {Detection and characterization of 3D-signature phosphorylation site motifs and their contribution towards improved phosphorylation site prediction in proteins},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-45129},
  year      = {2009},
  abstract  = {Background: Phosphorylation of proteins plays a crucial role in the regulation and activation of metabolic and signaling pathways and constitutes an important target for pharmaceutical intervention. Central to the phosphorylation process is the recognition of specific target sites by protein kinases followed by the covalent attachment of phosphate groups to the amino acids serine, threonine, or tyrosine. The experimental identification as well as computational prediction of phosphorylation sites (P-sites) has proved to be a challenging problem. Computational methods have focused primarily on extracting predictive features from the local, one-dimensional sequence information surrounding phosphorylation sites. Results: We characterized the spatial context of phosphorylation sites and assessed its usability for improved phosphorylation site predictions. We identified 750 non-redundant, experimentally verified sites with three-dimensional (3D) structural information available in the protein data bank (PDB) and grouped them according to their respective kinase family. We studied the spatial distribution of amino acids around phosphorserines, phosphothreonines, and phosphotyrosines to extract signature 3D-profiles. Characteristic spatial distributions of amino acid residue types around phosphorylation sites were indeed discernable, especially when kinase-family-specific target sites were analyzed. To test the added value of using spatial information for the computational prediction of phosphorylation sites, Support Vector Machines were applied using both sequence as well as structural information. When compared to sequence-only based prediction methods, a small but consistent performance improvement was obtained when the prediction was informed by 3D-context information. Conclusion: While local one-dimensional amino acid sequence information was observed to harbor most of the discriminatory power, spatial context information was identified as relevant for the recognition of kinases and their cognate target sites and can be used for an improved prediction of phosphorylation sites. A web-based service (Phos3D) implementing the developed structurebased P-site prediction method has been made available at http://phos3d.mpimp-golm.mpg.de.},
  language  = {en}
}