In silico identification and analysis of dog kinome

초록

Protein kinases, one of the largest superfamilies of the eukaryotic proteins, have been extensively studied and shown to play various distinct roles in multitudes of cellular processes. In this study, we report in silico identification, prediction, and classification of protein kinases in domestic dog (Canis familiaris). We found at least 521 putative protein kinases in dog. We classified these kinases into groups, families, and subfamilies based on orthology with human kinases. We also reported a dataset of the modeled three-dimensional structures of the ePK domains of these kinases along with the information about other conserved domains found in these kinases. We aligned these modeled structures and clustered the proteins in a two-dimensional MDS plot. We next compared the dog kinome with the kinomes of previously reported higher and lower eukaryotes including human, mouse, rat, fruitfly, sea urchin, nematode, and yeast. We found at least six novel protein kinases in dog namely, ARGL, BSK146L, Erk1L, JAK1L, TIF1gL, and PDHK1L which are not present in human, mouse, and rat. In addition, we found at least three retro-transposed genes in dog, namely CDK4-rt, Erk1-rt, and G11-rt, which are the retro-transposed copies of CDK4, Erk1, and G11 respectively. Our evolutionary rate studies of the dog and human protein kinase orthologs between the disease and non-disease associated subsets reveal that a relatively uniform selective pressure was applied to these two subsets of protein kinase genes.