Functional diversity of human protein kinase splice variants marks significant expansion of human kinome
1 Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India
2 Current address: Department of Functional Genomics, Institute for Genetics and Molecular and Cellular Biology, 1 rue Laurent Fries/BP 10142/67404 Illkirch Cedex Strasbourg, France
BMC Genomics 2009, 10:622 doi:10.1186/1471-2164-10-622Published: 22 December 2009
Protein kinases are involved in diverse spectrum of cellular processes. Availability of draft version of the human genomic data in the year 2001 enabled recognition of repertoire of protein kinases. However, over the years the human genomic data is being refined and the current release of human genomic data has helped us to recognize a larger repertoire of over 900 human protein kinases represented mainly by splice variants.
Many of these identified protein kinases are alternatively spliced products. Interestingly, some of the human kinase splice variants appear to be significantly diverged in terms of their functional properties as represented by incorporation or absence of one or more domains. Many sets of protein kinase splice variants have substantially different domain organization and in a few sets of splice variants kinase domains belong to different subfamilies of kinases suggesting potential participation in different signal transduction pathways.
Addition or deletion of a domain between splice variants of multi-domain kinases appears to be a means of generating differences in the functional features of otherwise similar kinases. It is intriguing that marked sequence diversity within the catalytic regions of some of the splice variant kinases result in kinases belonging to different subfamilies. These human kinase splice variants with different functions might contribute to diversity of eukaryotic cellular signaling.