Last updated on April 16, 2014 at 17:34 EDT

Kinexus Identifies Over 966,000 Phosphorylation Sites in the Human Proteome

March 6, 2013

Prediction of over 45 million protein kinase-substrate interactions now
available at PhosphoNET website

VANCOUVER, March 6, 2013 /PRNewswire/ – Kinexus Bioinformatics Corporation, a
world-leader in molecular intelligence research, announced a major
upgrade in its PhosphoNET KnowledgeBase (www.phosphonet.ca) for the study of cell communication systems. This open-access website
now features data on over 177,000 experimentally-confirmed human
phosphorylation sites (P-sites) and 789,000 additional P-sites
predicted with a powerful algorithm trained with over 22,000
kinase-substrate pairs. PhosphoNET provides prediction of which kinases
individually target each human P-site, and whether these P-sites are
retained in proteins from over 20 other diverse organisms. Functionally
critical P-sites that control proteins are more likely to also be found
in other species. This information can guide biomedical researchers in
the discovery of promising diagnostic biomarkers and therapeutic drug

The human genome encodes at least 538 protein kinases that regulate each
other and another 21,500 diverse proteins to coordinate all cellular
operations. Kinases are unique networking enzymes that function by
tagging target proteins at specific P-sites with phosphates, which act
as molecular on/off switches. They are well recognized by the
pharmaceutical and biotech industry as highly productive targets for
drug development with applications for many diseases, including cancer,
diabetes and Alzheimer’s disease. Genetic mutations in the genes that
encode protein kinases and environmental exposures to toxins that
target these kinases have been linked to over 400 human diseases.

Over the last three years, Kinexus and their collaborators in the
Mathematics of Information Technology and Complex Systems (MITACS)
groups at the University of British Columbia and Simon Fraser
University cracked the target specificity codes for about 500 human
protein kinases and then applied this information to predict the
locations of P-sites in all of the proteins encoded by the human
genome. Most recently, these algorithms were further trained with data
generated in-house at Kinexus with the individual testing of purified
preparations of over 200 human protein kinases with the company’s
peptide microarrays. These custom microarrays featured diverse
synthetic peptides that could act as artificial substrates for these
kinases. In combination with Kinexus’ gene expression database (www.TranscriptoNET.ca) with information on the levels of over 22,000 proteins in 600 types of
human cells and tissues, the company is now poised with PhosphoNET for
drafting its first atlas of high resolution maps of the molecular
intelligence system of human cells. The company is using this
information to produce novel antibody probes for tracking key P-sites
with its protein microarray technology for applications in disease
biomarker profiling for its clients.

“After completion of the initial sequencing of the human genome 12 years
ago, the next major challenge was to identify how the various proteins
encoded by these genes interact and are regulated,” commented Dr.
Steven Pelech, President and Chief Scientific Officer of Kinexus and a
professor in the Department of Medicine at the University of British
Columbia. “Progress on this front has been hampered, in part because
only 6 years ago less than 10,000 P-sites were actually known. Today,
with over 966,000 P-sites now identified,  PhosphoNET is a valuable
tool to guide biomedical researchers in more fruitful directions to
define the best biomarkers for disease diagnosis and kinase targets for
development of new drugs.”

Dr. Pelech added, “We believe that the approaches taken at Kinexus to
identify P-sites in protein targets of kinases can be extended broadly
to rapidly elucidate the complex architectures of kinase-based
communications systems for any animal, plant or microbe for which the
complete genome sequence is known.  Our next goal is to use our
algorithms to predict the sensitivities of 500 protein kinases to more
than 500 drugs that have been reported to inhibit these enzymes. By
carefully identifying the specific regions of these kinases that are
important for substrate and drug recognition, we should be able to help
predict those genetic mutations in human genes that have the greatest
impact on human health. Over the next decade, it is expected that
hundreds of thousands of individual genomes will be sequenced, and our
efforts should contribute to further understanding which gene changes
are significant for disease development and what drugs are best suited
for personalized medical treatment.”

Kinexus is a private, biotechnology company engaged in the research and
development of innovative methods to map, track and manipulate cellular
communication networks. The application of this knowledge positions
Kinexus and its clients in drug development, rational drug design,
disease diagnosis and personalized therapies to improve human health.
Kinexus currently has agreements with over 1700 research laboratories
in companies, universities, government institutions and hospitals in
over 35 different countries.

SOURCE Kinexus Bioinformatics Corporation

Source: PR Newswire