title: Large-scale analysis of the evolutionary histories of phosphorylation motifs in the human genome.
abstract: BACKGROUND
  Protein phosphorylation is a post-translational modification that is essential for a wide range of eukaryotic physiological processes, such as transcription, cytoskeletal regulation, cell metabolism, and signal transduction. Although more than 200,000 phosphorylation sites have been reported in the human genome, the physiological roles of most remain unknown. In this study, we provide some useful datasets for the assessment of functional phosphorylation signaling using a comparative genome analysis of phosphorylation motifs.
  
  
  RESULTS
  We described the evolutionary patterns of conservation of these and comparative genomic data for 93,101 phosphosites and 1,003,756 potential phosphosites in human phosphomotifs, using 178 phosphomotifs identified in a previous study that occupied 69% of known phosphosites in public databases. Comparative genomic analyses were performed using genomes from nine species from yeast to humans. Here we provide an overview of the evolutionary patterns of phosphomotif acquisition and indicate the dependence on motif structures. Using the data from our previous study, we describe the interaction networks of phosphoproteins, identify the kinase substrates associated with phosphoproteins, and perform gene ontology enrichment analyses. In addition, we show how this dataset can help to elucidate the function of phosphomotifs.
  
  
  CONCLUSIONS
  Our characterizations of motif structures and assessments of evolutionary conservation of phosphosites reveal physiological roles of unreported phosphosites. Thus, interactions between protein groups that share motifs are likely to be helpful for inferring kinase-substrate interaction networks. Our computational methods can be used to elucidate the relationships between phosphorylation signaling and cellular functions.
authors.affiliation: Department of Pathology I, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293 Japan ; Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-0058 Japan.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Yoshizaki
authors.affiliation: Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510 Japan.
authors.forename: Shujiro
authors.initials: S
authors.lastname: Okuda
mesh_terms: D020816:Amino Acid Motifs; D017124:Conserved Sequence; D019143:Evolution, Molecular; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D060066:Protein Interaction Maps; D011499:Protein Processing, Post-Translational
chemical_list: D010750:Phosphoproteins
keywords: Comparative evolutionary analysis; Kinase; Phosphorylation motif