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暗激酶知识库:一个在线的知识和实验结果汇编,涵盖了研究较少的激酶。

The Dark Kinase Knowledgebase: an online compendium of knowledge and experimental results of understudied kinases.

机构信息

Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Nucleic Acids Res. 2021 Jan 8;49(D1):D529-D535. doi: 10.1093/nar/gkaa853.

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.

摘要

激酶构成了许多细胞信号通路的骨干,其功能障碍同样与多种病理学有关。由于它们具有可成药性,激酶成为癌症、传染病和自身免疫性疾病等疾病治疗开发努力的主要焦点。尽管它们的重要性显而易见,但近三分之一激酶的作用或生物学功能在很大程度上仍是未知的。在这里,我们描述了一个名为 Dark Kinase Knowledgebase(DKK;https://darkkinome.org)的数据资源,该资源专门为更广泛的研究社区提供这些研究不足的激酶的数据和试剂。DKK 通过 NIH 的 Illuminating the Druggable Genome(IDG)计划得到支持,专注于为 162 种研究不足或“黑暗”激酶生成数据和知识。DKK 提供的类型的数据包括用于定量蛋白质组学的平行反应监测 (PRM) 肽、蛋白质相互作用、NanoBRET 试剂和激酶特异性化合物。更高层次的数据也在生成和整合中,例如组织基因表达谱,并且从长远来看,通过扰动研究得出功能关系。该网站还提供了相关的网络工具,帮助研究人员查询内部和外部数据。作为一个不断发展的资源,DKK 旨在不断支持和增强这些潜在高影响力的可成药靶标的知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f783/7778917/362c4b866c89/gkaa853fig1.jpg

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