{"doi":"10.1101/2025.10.10.681672","title":"A Structure-Guided Kinase–Transcription Factor Interactome Atlas Reveals Docking Landscapes of the Kinome","abstract":"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 Drosophila 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 in vivo . This resource provides a blueprint for dissecting signaling networks and for the rational design of docking-site-specific kinase modulators.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556823,"datarank":0.17068359433497599,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.005891751034759535,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.005891751034759535,"corpus_percentile":32.969753229674325,"corpus_rank":8666,"citation_count":2,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":332403,"name":"Kerui Huang","orcid":"0000-0003-1866-8407","position":1,"is_corresponding":false},{"id":226401,"name":"Jared L. Johnson","orcid":"0000-0003-1802-6527","position":2,"is_corresponding":false},{"id":51771,"name":"Tomer M. Yaron","orcid":"0000-0001-6574-7314","position":3,"is_corresponding":false},{"id":1456923,"name":"Keven Wang","orcid":null,"position":4,"is_corresponding":false},{"id":51785,"name":"Lewis C. Cantley","orcid":"0000-0002-1298-7653","position":5,"is_corresponding":false},{"id":259031,"name":"Yanhui Hu","orcid":"0000-0003-1494-1402","position":6,"is_corresponding":false},{"id":14957,"name":"Norbert Perrimon","orcid":"0000-0001-7542-472X","position":7,"is_corresponding":false},{"id":648169,"name":"Ah‐Ram Kim","orcid":"0000-0001-9597-6759","position":0,"is_corresponding":true}],"reference_count":118,"raw_metadata":null,"created_at":"2026-07-19T02:55:13.130091Z","pmid":"41279736","pmcid":"PMC12632555","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}