Abstract
Kinases form the backbone of numerous cell signaling pathways, with their dysfunction similarly implicated in multiple pathologies. Further facilitated by their druggability, kinases are a major focus of therapeutic development efforts in diseases such as cancer, infectious disease and autoimmune disorders. While their importance is clear, the role or biological function of nearly one-third of kinases is largely unknown. Here, we describe a data resource, the Dark Kinase Knowledgebase (DKK; https://darkkinome.org), that is specifically focused on providing data and reagents for these understudied kinases to the broader research community. Supported through NIH’s Illuminating the Druggable Genome (IDG) Program, the DKK is focused on data and knowledge generation for 162 poorly studied or ‘dark’ kinases. Types of data provided through the DKK include parallel reaction monitoring (PRM) peptides for quantitative proteomics, protein interactions, NanoBRET reagents, and kinase-specific compounds. Higher-level data is similarly being generated and consolidated such as tissue gene expression profiles and, longer-term, functional relationships derived through perturbation studies. Associated web tools that help investigators interrogate both internal and external data are also provided through the site. As an evolving resource, the DKK seeks to continually support and enhance knowledge on these potentially high-impact druggable targets.
Highlights
Protein kinases take a central position in many aspects of cellular signaling, with established roles in cellular growth, differentiation, migration and apoptosis
The knowledgebase is divided into several sections to simplify finding and displaying the data collected through the Kinase DRGC
The Dark Kinase Knowledgebase provides a collection of resources dedicated to improving our understanding of understudied kinases
Summary
Protein kinases take a central position in many aspects of cellular signaling, with established roles in cellular growth, differentiation, migration and apoptosis. Protein kinases have the beneficial property of being highly druggable by both allosteric and competitive inhibitors This druggability, combined with their direct or indirect role in numerous diseases, establishes kinases as a key target for current and future therapeutic development efforts. Despite their recognized importance, we lack an understanding of the functional role of roughly one-third of kinases [5]. The potential impact of better understanding these druggable and disease-relevant targets has led to the establishment of NIH’s Illuminating the Druggble Genome (IDG) Program [9] This program seeks to establish a better understanding of the function of poorly studied genes in three major, druggable families, including GPCRs, ion channels and kinases. Centered on kinases, the Kinase DRGC (Data and Resource Generating Center) component of the IDG program is focused on generating, systematizing and disseminating knowledge about dark kinases, the biological
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