sProt formats. This sequence is subjected to basic quality assurance checks before the hmmpfam search job is queued for execution on a multi-node Linux cluster. The user is then provided with a job ID, and the interface is asynchronous, returning a status page to the user which is updated automatically. The user can bookmark the results page and return at a later time. In addition, an optional field allows the user to associate arbitrary comments with their job, a useful feature to allow otherwise similar jobs to be distinguished. There are no additional parameters that are userselectable. This allows for a clean and straightforward interface form. The results are displayed as a formatted HTML page with the group classification clearly indicated. This shows to which protein kinase group Kinomer v. 1.0 has assigned the sequence. In addition, alternative assignments are given and a summary of all potential significant matches shown. Kinomer v. 1.0 will typically show matches to many kinase group HMMs spanning several kinase groups. All the top-scoring HMMs for one particular group will be the most significant matches, followed by closely related groups. The detailed alignment for each HMM match is linked further down the screen. As some users may wish for more details, the Kinomer v. 1.0 results page also provides a link to the raw HMMer output. TMS biological activity DISCUSSION The 43 species considered here span a number of phylogenetic lineages, genome sizes and display a range of adaptations to their environment. The genome-wide kinase group assignments are consistent with our previously published results in that seven protein kinase groups are present in all species surveyed and some kinases in these groups are likely to be essential. Kinases of the groups RGC, TK, TKL, Alpha and PDHK are late innovations in specific phyla or have been lost secondarily in specific lines of descent. The presence of a discrete number of putative PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19816862 TKs in photosynthetic organisms and the pathogen Entamoeba histolytica suggests that TKs are also likely to have had an ancient origin. This observation D248 Nucleic Acids Research, 2009, Vol. 37, Database issue has recently been strengthened by the finding of animallike signalling molecules in the green alga Chlamydomonas reinhardtii. These include scavenger receptor cysteine rich and C-type lectin domain proteins, both of which play key roles in the innate immune system of metazoa. The identification of SH2 domain proteins in photosynthetic organisms suggests that phosphotyrosine-SH2 domain signalling also has an ancient origin and that important cell signalling and adhesion domains evolved before the divergence of the animal lineage. The observation that many species outside the Opisthokont group lack important kinase groups, as is the case of TKs in Apicomplexa, and which have many lineage-specific groups of kinases, suggests that the group level is the most specific level for the automatic classification of kinomes based on models constructed from sequences outside the taxonomic clade under investigation. With the availability of a number of Deuterostome, Protostome and pre-bilaterian genome sequences, having all kinases belonging to a particular kinase group enables novel analyses to be performed. For example, it is now possible to trace the evolution of receptor tyrosine kinase families and that of their ligands. Since receptor tyrosine kinases are multi-domain proteins, diverging rates of evolution of the various domains, and