BMC Genomics 2009, 10:622 http://www.biomedcentral.com/1471-2164/10/622 Quality of the human genomic data is being continuously improved since its first release in 2001 [1]. In the early draft dataset the order of the base pairs in each chromo- somal area has been determined 4 or 5 times (4× or 5×) or even more [1]. However in April 2003 human genome data of better quality was compiled in which additional sequencing improved the accuracy significantly http:// www.ornl.gov/TechResources/Human_Genome/project/ 50yr.html. With the improvements in genome sequencing projects, order of the base pairs in each chromosomal area has been determined 8 or 9 times (8× or 9×) and the qual- ity of the human genomic data improved significantly over the time. The present version of the human genomic data and the annotation are of superior quality compared to the first release about 8 years ago. This accurately anno- tated genomic sequence data set has impact in the quality of other kinds of genome-wide data sets such as, transcript sequences, expression data, disease influenced gene regu- lation and functional information. Alternative splicing is an important mechanism to increase proteomic diversity [6] which produces diverse transcripts and hence potentially diverse protein products from the same gene locus which eventually add significant complexity to the genome. In typical alternative splicing process different combinations of exons within a gene are spliced from RNA precursor and reassembled in the mature mRNA. The nature of splice variant could be fur- ther related to the tissue type, developmental stage and disease versus normal conditions of the cell. Thus splicing could result in multitude of proteins originating from sin- gle gene and these protein products often have interesting diversity in functional properties. For example Drosophila Dscam gene, an axon guidance receptor gene, is a striking example which produces more than a thousand gene products [7]. Alternative splicing mechanism has been studied for various mammalian systems as well as for plants [[8-11]; http://www.itb.cnr.it/kinweb]. Analysis of some of the human kinase splice variants has been per- formed in the past [[11]; http://www.itb.cnr.it/kinweb] which also gives information about their domain combi- nation. Though human and mouse are very close mam- malian species, it has been observed that the conservation of alternative splicing pattern is low [12-14] which might be the reason for the generation of species-specific gene products. Though the human kinome analysis performed in 2001 [2-4] identified over 500 kinases, it was earlier anticipated that the number of human protein kinases might be around 1000 [15]. We suggest that higher esti- mate still holds good as the splicing mechanism in human is very common. Bioinformatics analysis indicates that approximately 40-60% of the human genes are known to alternatively spliced [16-19] with majority of splicing events occurring in 5' untranslated regions. Splicing event allows production of more than one protein isoform from a single gene which may have altered substrate affinities, sub-cellular localizations, and may exhibit different and sometimes antagonistic functional and structural proper- ties [20-22]. In fact, various protein kinase splice variants have been experimentally characterized and they are shown to elicit different expression patterns, differential localization and hence different functional properties [23- 26]. It is known from a previous study that alternative transcripts of protein kinases encode different domain structures and these variants are likely to play important roles in phosphorylation-dependent signaling pathways [8]. Splice variants of human centrosome kinase Nek2 are known to exhibit different pattern of expression in mitosis [24]. Two splice forms of human protein kinase B are shown to have distinct regulatory capacity depending upon presence or absence of phosphorylation site in the carboxy terminal hydrophobic domain [27]. Two splice forms of Mitogen-activated protein (MAP) kinase-inter- acting kinase (Mnk) derived from same gene differ only at their C termini. It has been seen that while Mnk2a con- tains a MAP kinase-binding site in this region, Mnk2b lacks such a sequence and is much less readily activated by MAP kinases in vitro. Mnk2a is cytoplasmic whereas sub- stantial amount of Mnk2b is found in the nucleus [25]. Splice variants of Serum and Glucocorticoid-Inducible Kinase 1 (SGK1) which belongs to AGC group of protein kinase known to be regulated differentially following dif- ferentiation and shown to be markedly upregulated in tumor tissues [28]. TrkC, a receptor tyrosine kinase has a number of naturally occurring splice variants including one with a 14 residues insertion between subdomain VII and VIII in the C-terminal lobe of the kinase domain. This insert in the catalytic domain of TrkC results in defective MAPK activation which may result predominantly from an inhibition of high-affinity Shc binding [29]. Splicing mechanism is very carefully regulated as aberrant regula- tion of alternative splicing in human has been implicated in various diseases [30,31]. Most of the analyses on identification and analysis of comprehensive collection of human gene splice products have been performed before or around the time when the first draft of the human genome sequence data was released. Thus, these analyses were performed using incomplete set of human gene products. Moreover, despite availability of complete human genomic data in the subsequent years, the improvement in the quality of the genomic data has been gradual which has prompted us to identify and analyse repertoire of protein kinase gene products with the present information on splice var- iants of human kinases. Our objective in this analysis is to extend our understanding of repertoire of functions of human protein kinases and extent to which the functional diversity could occur among splice variants of human kinases. Page 2 of 7 (page number not for citation purposes)