In Silico Analysis of Human NEK10 Reveals Novel Domain Architecture and Protein-Protein Interactions

Cancer is the second leading cause of death worldwide, with an estimated 27.5 million new cases projected by 2040. Disruptions in cell cycle control cause DNA replication errors to accumulate during cell growth, leading to genomic instability and tumor development. Proteins that regulate cell cycle progression and checkpoint mechanisms are crucial targets for cancer therapy. NIMA-related kinases (NEKs) are a family of serine/threonine kinases involved in regulating various aspects of the cell cycle and mitotic checkpoints in humans. Among these, NEK10 is the most divergent member and has been associated with both cancer and ciliopathies, a group of disorders caused by defects in cilia structure or function. Despite its biological significance and distinctive domain architecture, the structural details of NEK10 remain largely unknown. To address this gap, we employed computational modeling techniques to predict the complete structure of the NEK10 protein. Our analysis revealed a catalytic domain flanked by two coiled-coil domains, armadillo repeats (ARM repeats), an ATP binding site, two putative ubiquitin-associated (UBA) domains, and a PEST sequence known to regulate protein degradation. Furthermore, we mapped a comprehensive interactome of NEK10, uncovering previously unreported interactions with the cancer-related proteins MAP3K1 and HSPB1. MAP3K1, a serine/threonine kinase and E3 ubiquitin ligase frequently mutated in cancers, interacts with the catalytic region of NEK10. The interaction with HSPB1, a molecular chaperone associated with poor cancer prognosis, is mediated by NEK10's ARM repeats. Our findings highlight a potential connection between NEK10, ciliogenesis, and cancer, suggesting an important role in cancer development and progression.