Exploring the Phosphoregulatory Network of Human Sucrose Non-Fermenting 1-Related Kinase

Sucrose non-fermenting 1-related kinase (SNRK) is an understudied serine/threonine kinase of the CAMKL family, known for its role in metabolic regulation and cell signaling. Despite its emerging relevance in various biological processes and diseases, the phosphoregulatory landscape of human SNRK (valid substrates or role of its phosphosites) remains unexplored and demands robust, large-scale, data-oriented approaches to predict the potential substrates. A comprehensive analysis of global human phosphoproteomics datasets was performed to systematically identify class I phosphosites on SNRK, along with their predicted upstream kinases, potential downstream substrates, and coregulated phosphoproteins. Our analysis resulted in the identification of 33 dark SNRK phosphosites, of which 19 were differentially regulated across an array of experimental conditions. Among them, S518 and S569, outside their kinase domain, were the most frequently regulated and co-occurred phosphosites under diverse conditions. Notably, S569 is predicted as a candidate autophosphorylation site of SNRK. In these contexts, coregulation analysis of proteins and their phosphorylation sites suggested associations of phospho-SNRK in cell cycle progression, chromatin organization, and DNA replication. Uncovering candidate upstream kinases and potential substrates for prioritized validation, this study provides the first comprehensive phosphoproteomic map of SNRK, serving as a foundation for future investigations into its signaling network associations and therapeutic approaches.