A subcellular map of the human kinome

The human kinome comprises 538 kinases playing essential functions by catalyzing protein phosphorylation. Annotation of subcellular distribution of the kinome greatly facilitates investigation of normal and disease mechanisms. Here, we present Kinome Atlas (KA), an image-based map of the kinome annotated to 10 cellular compartments. 456 epitope-tagged kinases, representing 85% of the human kinome, were expressed in HeLa cells and imaged by immunofluorescent microscopy under a similar condition. KA revealed kinase family-enriched subcellular localizations and discovered a collection of new kinase localizations at mitochondria, plasma membrane, extracellular space, and other structures. Furthermore, KA demonstrated the role of liquid-liquid phase separation in formation of kinase condensates. Identification of MOK as a mitochondrial kinase revealed its function in cristae dynamics, respiration, and oxidative stress response. Although limited by possible mislocalization due to overexpression or epitope tagging, this subcellular map of the kinome can be used to refine regulatory mechanisms involving protein phosphorylation.

Automated summary

The human kinome consists of 538 kinases that play essential roles in catalyzing protein phosphorylation. The annotation and visualization of the subcellular distribution of these kinases in the Kinome Atlas (KA) provide insights into their functions and mechanisms, including new kinase localizations and the role of liquid-liquid phase separation in kinase condensate formation. Despite limitations such as potential mislocalization, the subcellular map of the kinome can be utilized to enhance our understanding of regulatory mechanisms involving protein phosphorylation.