title: Systematic analysis of human kinase genes: a large number of genes and alternative splicing events result in functional and structural diversity.
abstract: BACKGROUND
  Protein kinases are a well defined family of proteins, characterized by the presence of a common kinase catalytic domain and playing a significant role in many important cellular processes, such as proliferation, maintenance of cell shape, apoptosis. In many members of the family, additional non-kinase domains contribute further specialization, resulting in subcellular localization, protein binding and regulation of activity, among others. About 500 genes encode members of the kinase family in the human genome, and although many of them represent well known genes, a larger number of genes code for proteins of more recent identification, or for unknown proteins identified as kinase only after computational studies.
  
  
  RESULTS
  A systematic in silico study performed on the human genome, led to the identification of 5 genes, on chromosome 1, 11, 13, 15 and 16 respectively, and 1 pseudogene on chromosome X; some of these genes are reported as kinases from NCBI but are absent in other databases, such as KinBase. Comparative analysis of 483 gene regions and subsequent computational analysis, aimed at identifying unannotated exons, indicates that a large number of kinase may code for alternately spliced forms or be incorrectly annotated. An InterProScan automated analysis was performed to study domain distribution and combination in the various families. At the same time, other structural features were also added to the annotation process, including the putative presence of transmembrane alpha helices, and the cystein propensity to participate into a disulfide bridge.
  
  
  CONCLUSIONS
  The predicted human kinome was extended by identifying both additional genes and potential splice variants, resulting in a varied panorama where functionality may be searched at the gene and protein level. Structural analysis of kinase proteins domains as defined in multiple sources together with transmembrane alpha helices and signal peptide prediction provides hints to function assignment. The results of the human kinome analysis are collected in the KinWeb database, available for browsing and searching over the internet, where all results from the comparative analysis and the gene structure annotation are made available, alongside the domain information. Kinases may be searched by domain combinations and the relative genes may be viewed in a graphic browser at various level of magnification up to gene organization on the full chromosome set.
authors.affiliation: Biomedical Technologies Institute (ITB), National Research Council, Milan, Italy. luciano.milanesi@itb.cnr.it
authors.forename: Luciano
authors.initials: L
authors.lastname: Milanesi
authors.forename: Mauro
authors.initials: M
authors.lastname: Petrillo
authors.forename: Leandra
authors.initials: L
authors.lastname: Sepe
authors.forename: Angelo
authors.initials: A
authors.lastname: Boccia
authors.forename: Nunzio
authors.initials: N
authors.lastname: D'Agostino
authors.forename: Myriam
authors.initials: M
authors.lastname: Passamano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Nardo
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tasco
authors.forename: Rita
authors.initials: R
authors.lastname: Casadio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paolella
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D030562:Databases, Protein; D004220:Disulfides; D005091:Exons; D015971:Gene Expression Regulation, Enzymologic; D014644:Genetic Variation; D016678:Genome; D006801:Humans; D020407:Internet; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D010770:Phosphotransferases / Q000235:genetics*; D017434:Protein Structure, Tertiary; D020543:Proteome; D017421:Sequence Analysis; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D004220:Disulfides; D020543:Proteome; D010770:Phosphotransferases