KinaseNET is an open-access, online resource developed by Kinexus Bioinformatics Corporation to foster the investigation of protein kinases to advance biomedical research in academia and industry. It is a module of the larger SigNET KnowledgeBank created by Kinexus. The KinaseNET KnowledgeBase features comprehensive information on over 530 human protein kinases, including their structures, regulation, substrates, tissue distribution, evolutionary conservation, sensitivities to compounds, and linkages to human diseases. KinaseNET also serves as a portal to many other useful websites with additional data about protein kinases. The information provided here has been retrieved from many other reputable websites, including in particular ChEMBL, COSMIC, NCBI GEO, OMIM, Phosphosite Plus, PubChem, STRING and UniProt, as well as hundreds of original scientific publications. In many cases, we have further analyzed the data available on these other websites. Our TranscriptoNET, PhosphoNET and DrugKiNET KnowledgeBases also provide even more comprehensive known and predictive data on the human protein kinases with respective to their tissue distribution, phosphorylation and drug sensitivies.
Phosphorylation and Protein Kinases
Protein kinases are encoded by one of the largest classes of genes in the human genome, and they are the central mediators of communications inside of cells. In humans, over 530 protein kinases catalyze the reversible phosphorylation of proteins on serine, threonine and tyrosine residues. In this chemical reaction, the gamma phosphate group is transferred from the molecule adenosine triphosphate (ATP) to a recipient substrate protein. This phosphorylation event commonly regulates the catalytic activity or other functions of target proteins or their destruction by proteases.
The human genome specifies more than 21,000 proteins, and over 200,000 phosphosites in greater than two thirds of these proteins have already been experimentally shown to exist. As documented in our PhosphoNET KnowledgeBase, Kinexus has been able to predict an additional 760,000 human phosphosites with our proprietary algorithms. We have also been able to identify those protein kinases that are mostly likely to target all of these known and putative phosphosites.
Over 500 human diseases have been connected to protein kinases as documented on this website. Of 250 of the human protein kinases have been linked to the induction of cancer, over 80 are encoded by proto-oncogenes, over 35 are encoded by tumour-suppressor genes, and at least another 30 appear to correspond to tumour requiring proteins. Furthermore, most other known oncogenes specify proteins that either activate kinases or are phosphorylated by kinases. Although the findings are less direct, aberrant cell signalling through protein kinases has also been associated with cardiovascular disease, diabetes, inflammation, arthritis and other immune disorders, and neurological disorders such as Alzheimer's disease.
Protein kinases are the largest family of enzymes with measurable catalytic activities that are suitable to screen for inhibitory drugs. Protein kinases are amongst the most meticulously investigated enzymes by researchers, in part because of their therapeutic potential as drug targets. There is a wealth of data about these enzymes that already serves as a solid foundation from which to build. The three-dimensional structures of over 80 different protein kinases have been elucidated. Extensive artificial mutagenesis of several protein kinases has been performed to establish detailed structure-function relationships. After the proteases, protein kinases represent the most attractive candidates for molecular modelling studies to design new drugs.
It is estimated that over 30% of the drug discovery efforts in pharmaceutical and biotech companies are currently focused on finding and validating protein kinase inhibitors. We believe that this will increase to over 50% over the next decade. Kinase drugs have demonstrated applications for treatment of a wide range of diseases including cancer, inflammation, diabetes, congestive heart failure, and neurological damage. Over 35 kinase-focused therapeutics have already been approved for use by the US FDA and other regulatory agencies. Many of these small molecule drugs and antibodies individually generate annual revenues exceeding US $1 billion. Over 150 more protein kinase inhibitors are currently in advanced clinical trials, and at least another 500 are in pre-clinical studies.
The pharmaceutical industry has clearly come to fully recognize the protein kinase family as a rich source of therapeutic targets. Yet remarkably, most of the kinase drugs in the clinic appear to target less than 20% of the known protein kinases. Consequently, the therapeutic potential of the broad majority of protein kinases remains to be investigated. The growing arsenal of protein kinases inhibitors will clearly have a profound impact on the treatment of human diseases. An exciting area of pharmaceutical research will involve identification of new applications for these kinase drugs for treatment of other disease indications. This website and our DrugKiNET KnowledgeBase were created to facilitate this endeavor. Finally, Kinexus is further dedicated to this prospect by the offering supporting proteomics services and products at our main website at www.kinexus.ca.
KinaseNET is designed to be fast and simple to navigate. You can search for target protein kinase if you know its UniProt ID or one of its common alias names. A list of possible options for protein kinases are generated by typing at least three letters of their name or identification number, and waiting for a few moments for a complete list to appear. A unique protein kinase webpage is created when the search function is activated. The optimum web browsers for using KinaseNET are Internet Explorer, Firefox and Safari.
Funding and Advertising Opportunities
To develop and sustain this free resource, we are seeking sponsorship from foundations and corporations. We gratefully acknowledge financial grant support for KinaseNET from the National Research Council of Canada Industrial Assistance Program and the Natural Sciences and Engineering Research Council of Canada. It is possible for commercial vendors of signal transduction reagents and services to advertise their relevant products and services on this site. Interested parties should contact our Sales and Marketing Department at firstname.lastname@example.org or call toll free in North America 1-866-KINEXUS.