{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Kim AR"],"funding":["NCI NIH HHS","NIAMS NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["Protein kinases orchestrate cellular processes through phosphorylation, yet the structural basis for their specific binding partner interactions remains largely unmapped. Here, we present a structure-guided atlas of the human and <i>Drosophila</i> kinome, built by applying a new interface-aware scoring framework (iLIS) to AlphaFold-Multimer predictions. The resulting atlas recapitulates hallmark sequence preferences, confirms previously reported and functionally related protein-protein interactions, and uncovers unrecognized docking interactions. Notably, our analysis predicts a potentially widespread docking motif on homeodomain transcription factors that mediates interactions with basophilic kinases. Furthermore, we map putative allosteric interaction hotspots across the kinome and provide proof-of-concept evidence that targeting these surfaces can inhibit kinase activity. Finally, we demonstrate the physiological utility of the atlas by identifying a novel regulatory mechanism between Sgg/GSK3 and Hnf4 that controls lipid metabolism <i>in vivo</i>. This resource provides a blueprint for dissecting signaling networks and for the rational design of docking-site-specific kinase modulators."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.10.10.681672"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12632555"],"repository":["biostudies-literature"],"pubmed_title":["A Structure-Guided Kinase-Transcription Factor Interactome Atlas Reveals Docking Landscapes of the Kinome."],"pmcid":["PMC12632555"],"funding_grant_id":["R01 AR057352","P41 GM132087","R35 CA197588","P01 CA117969","P01 CA120964"],"pubmed_authors":["Johnson JL","Hu Y","Perrimon N","Kim AR","Cantley LC","Huang K","Yaron-Barir TM","Wang K"],"additional_accession":[]},"is_claimable":false,"name":"A Structure-Guided Kinase-Transcription Factor Interactome Atlas Reveals Docking Landscapes of the Kinome.","description":"Protein kinases orchestrate cellular processes through phosphorylation, yet the structural basis for their specific binding partner interactions remains largely unmapped. Here, we present a structure-guided atlas of the human and <i>Drosophila</i> kinome, built by applying a new interface-aware scoring framework (iLIS) to AlphaFold-Multimer predictions. The resulting atlas recapitulates hallmark sequence preferences, confirms previously reported and functionally related protein-protein interactions, and uncovers unrecognized docking interactions. Notably, our analysis predicts a potentially widespread docking motif on homeodomain transcription factors that mediates interactions with basophilic kinases. Furthermore, we map putative allosteric interaction hotspots across the kinome and provide proof-of-concept evidence that targeting these surfaces can inhibit kinase activity. Finally, we demonstrate the physiological utility of the atlas by identifying a novel regulatory mechanism between Sgg/GSK3 and Hnf4 that controls lipid metabolism <i>in vivo</i>. This resource provides a blueprint for dissecting signaling networks and for the rational design of docking-site-specific kinase modulators.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-10T03:13:32.005Z","creation":"2026-06-10T03:07:44.35Z"},"accession":"S-EPMC12632555","cross_references":{"pubmed":["41279736"],"doi":["10.1101/2025.10.10.681672"]}}