{"uniprot":"Q6PI98","gene":"INO80C","name":"INO80 complex subunit C","organism":"Homo sapiens (Human)","status":"dark","length":192,"sequence":"MAAQIPIVATTSTPGIVRNSKKRPASPSHNGSSGGGYGASKKKKASASSFAQGISMEAMSENKMVPSEFSTGPVEKAAKPLPFKDPNFVHSGHGGAVAGKKNRTWKNLKQILASERALPWQLNDPNYFSIDAPPSFKPAKKYSDVSGLLANYTDPQSKLRFSTIEEFSYIRRLPSDVVTGYLALRKATSIVP","function_summary":"A nuclear chromatin-remodeling scaffold that integrates into an ATP-dependent remodeling assembly to organize and target nucleosome remodeling at active chromatin. By stabilizing and positioning the remodeling machinery in the nucleoplasm, it promotes nucleosome reconfiguration that supports transcriptional activation, coordinates with histone methylation pathways, and modulates DNA replication and chromosome architecture. Through these assemblies it influences cell-cycle progression and broader chromatin-based regulation.","plain_language":"INO80C has barely been studied. The model's best guess: A nuclear chromatin-remodeling scaffold that integrates into an ATP-dependent remodeling assembly to organize and target nucleosome remodeling at active chromatin. By stabilizing and positioning the remodeling machinery in the nucleoplasm, it promotes nucleosome reconfiguration that supports transcriptional activation, coordinates with histone methylation pathways, and modulates DNA replication and chromosome architecture.","uniprot_summary":"Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0051726","label":"regulation of cell cycle"},{"id":"GO:0006338","label":"chromatin remodeling"},{"id":"GO:0006275","label":"regulation of DNA replication"},{"id":"GO:0033044","label":"regulation of chromosome organization"},{"id":"GO:0045893","label":"positive regulation of DNA-templated transcription"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"},{"id":"GO:0097346","label":"INO80-type complex"},{"id":"GO:0071339","label":"MLL1 complex"}]},"interpro":[{"id":"IPR013272","name":"Vps72/YL1, C-terminal","type":"domain","start":141,"end":170},{"id":"IPR029525","name":"INO80 complex, subunit Ies6","type":"family","start":57,"end":191}],"reasoning":"I begin with the InterPro architecture. The polypeptide carries IPR029525 (INO80 complex, subunit Ies6 family) spanning residues 57–191, which defines it as a core architectural subunit of the INO80 ATP-dependent chromatin-remodeling assembly. Nested within this region lies IPR013272 (Vps72/YL1, C-terminal domain) from residues 141–170. The Ies6-family signature dictates stable incorporation into the INO80 complex and positions the protein as a structural hub that organizes other remodeler subunits. The embedded Vps72/YL1 C-terminal module is characteristic of the YL1/Vps72 axis that mediates histone-handling and adaptor functions within chromatin-remodeling and nucleosome assembly pathways. This tandem of Ies6-core and YL1-like C-terminus causes a non-catalytic, multivalent scaffold that binds partner proteins and nucleic-acid-associated assemblies rather than performing enzymatic chemistry itself. Consequently, the primary molecular function is protein binding (GO:0005515), executed through cooperative assembly and targeting roles.\n\nFrom this binding-centric architecture, the biological roles follow. As an INO80 subunit, the protein stabilizes and targets an ATP-dependent remodeler that repositions nucleosomes and modulates chromatin accessibility. This structural role directly drives chromatin remodeling (GO:0006338). By tuning nucleosome occupancy and histone exchange, the complex regulates higher-order chromosome architecture, aligning with regulation of chromosome organization (GO:0033044). Remodeling at replication origins and along replication forks modulates initiation and elongation efficiency, supporting regulation of DNA replication (GO:0006275). Remodeling-mediated transcriptional activation—especially at promoters responsive to signaling pathways—accounts for positive regulation of DNA-templated transcription (GO:0045893). Because chromatin state gates checkpoint and S-phase entry, this assembly exerts broader control over cell-cycle transitions, consistent with regulation of cell cycle (GO:0051726).\n\nCellular localization is dictated by function and partners. Chromatin remodeling and transcriptional control occur in the nuclear interior, so the protein resides in the nucleoplasm (GO:0005654). Its defining Ies6 identity places it within the INO80-type complex (GO:0097346). Cross-talk between remodeling and H3K4 methylation pathways explains association with MLL1-containing assemblies; thus, participation in the MLL1 complex (GO:0071339) is expected as part of a chromatin-modification network that coordinates nucleosome remodeling with histone methylation.\n\nMechanistically, the Ies6/Vps72-like scaffold recruits and stabilizes INO80’s catalytic and accessory modules, positioning them on nucleosomes and at sites of active transcription and replication. By coupling to MLL1-associated machinery, it likely helps channel H3K4 methylation and transcriptional activation at specific loci. I therefore hypothesize that this subunit nucleates transient assemblies with INO80 ATPase and AAA+ partners, histone chaperones, and MLL1 complex components, enabling precise targeting and efficient chromatin remodeling that propagates to replication and cell-cycle control.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6PI98.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6PI98"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6PI98/entry","atlas":"/p/Q6PI98"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}