{"uniprot":"Q9H079","gene":"KATNBL1","name":"KATNB1-like protein 1","organism":"Homo sapiens (Human)","status":"dark","length":304,"sequence":"MASETHNVKKRNFCNKIEDHFIDLPRKKISNFTNKNMKEVKKSPKQLAAYINRTVGQTVKSPDKLRKVIYRRKKVHHPFPNPCYRKKQSPGSGGCDMANKENELACAGHLPEKLHHDSRTYLVNSSDSGSSQTESPSSKYSGFFSEVSQDHETMAQVLFSRNMRLNVALTFWRKRSISELVAYLLRIEDLGVVVDCLPVLTNCLQEEKQYISLGCCVDLLPLVKSLLKSKFEEYVIVGLNWLQAVIKRWWSELSSKTEIINDGNIQILKQQLSGLWEQENHLTLVPGYTGNIAKDVDAYLLQLH","function_summary":"A soluble adaptor that assembles and targets a microtubule-severing module to remodel the cytoskeleton. By using a katanin p80-like C-terminal assembly/targeting domain, it concentrates severing activity at centrosomes, spindle poles, and the midbody, thereby promoting orderly interphase and mitotic array dynamics and enhancing cytoskeletal reorganization. It operates through multivalent protein binding to build a microtubule-associated complex that redistributes microtubules during spindle assembly and cytokinesis, with transient nucleoplasmic and nucleolar pools that prime the complex for subsequent cell-cycle transitions.","plain_language":"KATNBL1 has barely been studied. The model's best guess: A soluble adaptor that assembles and targets a microtubule-severing module to remodel the cytoskeleton. By using a katanin p80-like C-terminal assembly/targeting domain, it concentrates severing activity at centrosomes, spindle poles, and the midbody, thereby promoting orderly interphase and mitotic array dynamics and enhancing cytoskeletal reorganization.","uniprot_summary":"Involved in microtubule severing.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0031122","label":"cytoplasmic microtubule organization"},{"id":"GO:0051495","label":"positive regulation of cytoskeleton organization"}],"cellular_component":[{"id":"GO:0005875","label":"microtubule associated complex"},{"id":"GO:0030496","label":"midbody"},{"id":"GO:0005654","label":"nucleoplasm"},{"id":"GO:0032154","label":"cleavage furrow"},{"id":"GO:0097431","label":"mitotic spindle pole"},{"id":"GO:0005730","label":"nucleolus"}]},"interpro":[{"id":"IPR028021","name":"Katanin p80 subunit, C-terminal","type":"domain","start":149,"end":299},{"id":"IPR042404","name":"KATNB1-like protein 1","type":"family","start":1,"end":304}],"reasoning":"I begin with the InterPro architecture. The sequence is covered end-to-end by IPR042404 (KATNB1-like protein 1 family, residues 1–304), marking it as a bona fide katanin p80-like regulator rather than a catalytic core enzyme. Within this scaffold, the C-terminal half contains IPR028021 (Katanin p80 subunit, C-terminal domain, residues 149–299). In canonical katanin assemblies, the p80-like C-terminal module mediates oligomerization and high-affinity docking to the catalytic p60 AAA+ ATPase, and it also targets the complex to centrosomes and spindle structures. The ordered layout—an N-terminal katanin-like platform followed by a defined p80 C-terminal targeting/assembly domain—creates a soluble adaptor that nucleates and positions a microtubule-severing machine without providing catalytic activity itself. This architecture dictates a primary molecular function of multivalent protein binding (GO:0005515), because the p80-like fold is specialized for assembling and localizing partner proteins rather than catalysis.\n\nFrom this binding-centric core, I infer the biological role. By recruiting and positioning the severing apparatus at precise cytoskeletal sites, a p80-like adaptor actively sculpts the microtubule array. Such positioning causes remodeling of interphase arrays and mitotic structures, which directly supports cytoplasmic microtubule organization (GO:0031122). Moreover, by concentrating severing activity at centrosomes, spindle poles, and the midbody, the adaptor amplifies cytoskeletal reconfiguration—this is a textbook case of positive regulation of cytoskeleton organization (GO:0051495). The causal chain is: p80-like assembly domain targets and stabilizes the severing complex; targeted severing redistributes microtubule mass; redistribution enables orderly assembly/disassembly cycles that refine network architecture.\n\nCellular placement follows from the targeting logic embedded in the C-terminal domain and the soluble nature of the scaffold. The adaptor assembles a microtubule-associated complex (GO:0005875) and concentrates it at mitotic landmarks. Its enrichment at spindle poles and the cytokinetic bridge explains localization to the mitotic spindle pole (GO:0097431) and midbody (GO:0030496). During furrow ingression, coupling of microtubule remodeling to cortex-driven constriction rationalizes presence at the cleavage furrow (GO:0032154). Between divisions, nucleocytoplasmic shuttling and assembly/disassembly cycles account for nucleoplasm (GO:0005654) and nucleolus (GO:0005730) residency, consistent with adaptor pools that prepare for subsequent mitotic assembly. Overall, the soluble, targeting-optimized architecture explains a dynamic itinerary across these compartments.\n\nMechanistically, I hypothesize that the protein forms a soluble adaptor hub that binds the catalytic severing subunit and additional cytoskeletal regulators. The p80-like C-terminal domain concentrates the complex at centrosomes and spindle poles, where severing releases microtubules from anchorage to enable spindle assembly and turnover. At the midbody and cleavage furrow, the same targeting logic promotes final abscission by clearing residual microtubules. Likely partners include the catalytic severing ATPase, centrosomal scaffolds, and spindle/midbody organizers; together they create a regulated severing module that both organizes and remodels the microtubule cytoskeleton in space and time.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9H079.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9H079"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9H079/entry","atlas":"/p/Q9H079"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}