Abstract Protein kinases play an important role in the incidence of neurodegenerative diseases. However their incidence in non-human primates is found to be very low. Small differences among the genomes might influence the disease susceptibilities. The present study deals with finding the genetic differences of protein kinases in humans and their three closest evolutionary partners chimpanzee, gorilla and orangutan for three neurodegenerative diseases namely, Alzheimer's, Parkinson's and Huntington's diseases. In total 47 human protein kinases associated with three neurodegenerative diseases and their orthologs from other three non-human primates were identified and analyzed for any possible susceptibility factors in humans. Multiple sequence alignment and pairwise sequence alignment revealed that, 18 human protein kinases including DYRK1A, RPS6KB1, and {GRK6} contained significant indels and substitutions. Further phosphorylation site analysis revealed that eight kinases including {MARK2} and {LTK} contained sites of phosphorylation exclusive to human genomes which could be particular candidates in determining disease susceptibility between human and non-human primates. Final pathway analysis of these eight kinases and their targets revealed that these kinases could have long range consequences in important signaling pathways which are associated with neurodegenerative diseases.
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