{"uniprot":"A6NLX3","gene":"SPDYE4","name":"Speedy protein E4","organism":"Homo sapiens (Human)","status":"dark","length":237,"sequence":"MASGQARPPFEEESPQPSTTVRSPEVVVDDEVPGPSAPWIDPSPQPQSLGLKRKSEWSDESEEELEEELELERAPEPEDTWVVETLCGLKMKLKRKRASSVLPEHHEAFNRLLGDPVVQKFLAWDKDLRVSDKYLLAMVIAYFSRAGLFSWQYQRIHFFLALYLASDMEEDNQAPKQDIFSFLYGKNYSQRPLFHKLRYQLLCSMRWRTWVSPEEMEEIQAYDPEHWVWARDRTLIS","function_summary":"A nucleoplasmic adaptor that promotes S-phase entry and progression by assembling and potentiating cyclin-dependent kinase complexes. Its conserved Speedy/E-subfamily scaffold architecture favors multivalent protein binding and dimerization, enabling it to stabilize and enhance kinase-driven transitions of the cell cycle. By coordinating assembly of nuclear regulatory modules, it advances replication and checkpoint programs within the nucleoplasm.","plain_language":"SPDYE4 has barely been studied. The model's best guess: A nucleoplasmic adaptor that promotes S-phase entry and progression by assembling and potentiating cyclin-dependent kinase complexes. Its conserved Speedy/E-subfamily scaffold architecture favors multivalent protein binding and dimerization, enabling it to stabilize and enhance kinase-driven transitions of the cell cycle.","uniprot_summary":"Involved in cell cycle regulation. Promotes cell cycle progression during S-phase.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0045787","label":"positive regulation of cell cycle"},{"id":"GO:0045737","label":"positive regulation of cyclin-dependent protein serine/threonine kinase activity"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR057742","name":"Speedy E","type":"family","start":36,"end":236},{"id":"IPR020984","name":"Speedy","type":"family","start":104,"end":233}],"reasoning":"I begin with the InterPro architecture. The polypeptide carries IPR057742 (Speedy E family) spanning residues 36–236 and an internal overlap with IPR020984 (Speedy family) from residues 104–233. This tandem of Speedy/E-subfamily signatures defines a conserved, non-enzymatic module that forms obligate dimers and binds partner proteins rather than catalyzing reactions. The absence of catalytic motifs and the dominance of family-level binding/adaptor signatures causally point to a scaffold that regulates other proteins through multivalent contacts. This architecture directly supports GO:0005515 protein binding as the primary molecular function.\n\nA Speedy/E-subfamily scaffold typically tunes cell-cycle transitions by docking to cyclin–CDK assemblies and their regulators. By stabilizing and activating cyclin-dependent kinase complexes, such scaffolds increase the effective activity of serine/threonine kinases that drive S-phase entry and progression. This causal role—assembly and potentiation of CDK complexes—maps to GO:0045737 positive regulation of cyclin-dependent protein serine/threonine kinase activity. Because enhanced CDK output advances checkpoint passage and replication programs, the same mechanism advances GO:0045787 positive regulation of cell cycle.\n\nCellular placement follows from function and sequence logic. Speedy/E-subfamily regulators often operate where DNA replication and checkpoint signaling converge—the nucleoplasm. The soluble, adaptor-like architecture and lack of transmembrane features argue for a nuclear, non-membranous environment, aligning with GO:0005654 nucleoplasm and the broader nuclear localization inferred from function.\n\nMechanistically, the Speedy/E scaffold likely dimerizes to create a composite surface that captures cyclin–CDK assemblies and their modulators, thereby stabilizing active kinase states and coordinating replication licensing. From this nucleoplasmic hub, I hypothesize interactions with cyclin–CDK complexes (e.g., E2F–DP–CDK and S-phase CDKs), replication licensing factors, and checkpoint adaptors. Such partnerships would allow the scaffold to couple kinase activation with DNA replication onset and checkpoint tuning, ensuring orderly S-phase entry and progression.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-A6NLX3.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/A6NLX3"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/A6NLX3/entry","atlas":"/p/A6NLX3"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}