title: Comparative conservation analysis of the human mitotic phosphoproteome.
abstract: BACKGROUND
  A key challenge in phosphoproteomic studies is to distinguish functionally relevant phosphorylation sites from potentially 'silent' phosphorylation. Considering that relevant phosphorylation sites are expected to be better conserved during evolution than overall Serine, Threonine and Tyrosine (S/ T/ Y) residues, we asked whether this can be directly demonstrated through statistic analysis, using a large experimental dataset.
  
  
  RESULTS
  Analyzing phosphoproteomic data derived from the human mitotic spindle apparatus, we found that 95.2% of 1744 phosphorylation sites are conserved in at least one of six other vertebrate species. Using a new score, termed conservation Z-score (CZ-score), we demonstrate that phosphorylation sites are significantly better conserved than other S/T/Y sites, a conclusion validated from several kinase consensus motifs. Most importantly, phosphorylation sites with experimentally verified biological functions were significantly better conserved than other phosphorylation sites, indicating that analysis utilizing evolutionary conservation may constitute a powerful basis for the development of improved phosphorylation site predictors.
  
  
  BACKGROUND
  malik@biochem.mpg.de
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Cell Biology, Max Planck Institute of Biochemistry, Martinsried D-82152, Germany. malik@biochem.mpg.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Malik
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.forename: Roman
authors.initials: R
authors.lastname: Körner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D004789:Enzyme Activation; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry*; D011485:Protein Binding; D020543:Proteome / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013045:Species Specificity
chemical_list: D020543:Proteome; D010770:Phosphotransferases