The cytoplasmic FRET biosensor was generated by removing the N-terminal H2B sequence

their incorporation in the receptor molecule in select phylogenetic lineages, is informative of distinct selection pressures and can be informative of newly acquired functions through the acquisition of new ligand-binding domains. This is the case with the Trk family of receptor tyrosine kinases, which encode the neurotrophin receptors. The neurotrophin receptors are an ancient family whose function has been lost in multiple lineages and the roles of the receptors have been modified over time. Kinomer v. 1.0 also includes the manually annotated MedChemExpress Vorapaxar kinomes of the model fungi S. cerevisiae and S. pombe, and that of the unicellular fungi-like parasite Encephalitozoon cuniculi. We have recently shown that the two model fungi share $85% of their kinomes, a degree of similarity much higher than that previously reported. The kinomes of budding and fission yeasts are therefore a useful dataset for annotating the kinomes of other fungi, among which we have included species of importance in basic and medical research, and in biotechnology. The manually annotated kinomes of C. elegans, D. discoideum, D. melanogaster, H. sapiens and M. musculus, as provided in Kinbase, have also been included in the Kinomer v. 1.0 database. These will facilitate the manual annotation of other kinomes included in the database and which belong to the same taxonomic clade. The classification of a number of kinases in the kinomes of C. elegans, D. discoideum, D. melanogaster, H. sapiens and M. musculus could be improved as suggested by the Kinomer v. 1.0 HMM group scores. However, careful manual annotation of the kinomes of other species in the same taxonomic clades will be performed in the future to make a more informed decision about the re-classification of such kinases. To our knowledge, Kinomer v. 1.0 is unique in being based on a high-accuracy validated kinase-group classification method. Other databases of protein kinases exist, but none of these offer the combination of breadth and accuracy of kinase classification that is present in Kinomer v. 1.0. These include KinMutBase, a database of clinically validated mutations in human kinases that lead to disease, and RTK.db, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19816210 a database of receptor tyrosine kinases. The Protein Kinase Resource collates data from several databases and includes a subset of protein kinase 3D structures to produce high-quality multiple structure-based alignments. Kinbase contains manually curated kinomes classified according to the Hanks and Hunter classification of protein kinases. Although of high quality, Kinbase only contains kinomes for nine species. Finally, KinG includes protein kinases identified in completed genomes that have been classified by a variety of metazoan kinome-based sequence search methods, but do not provide the confidence in kinase classification that is seen in Kinomer v. 1.0. Different eukaryotic lineages possess lineage-specific kinase groups and families that are just beginning to be characterized and which constitute as much as 50% of their kinomes. The applicability of the KinG approach to non-metazoan kinases needs further testing. A similar limitation is encountered by the PANTHER database. Although not specific to protein kinases, PANTHER provides an extensive and detailed HMM library for kinase families and subfamilies. These family and sub-family HMM libraries are trained on metazoan sequences and thus preclude their use to annotate non-metazoan sequences confidently into kinase families and sub-families w