{"uniprot":"Q8IYS8","gene":"BOD1L2","name":"Biorientation of chromosomes in cell division protein 1-like 2","organism":"Homo sapiens (Human)","status":"dark","length":172,"sequence":"MADGGGGGSGGAGPASTRASGGGGPINPASLPPGDPQLIAIIVGQLKSRGLFDSFRRDCKADVDTKPAYQNLSQKADNFVSTHLDKQEWNPPANDNQLHDGLRQSVVQSGRSEAGVDRISSQVVDPKLNHIFRPQIEQIIHEFLVAQKEAAVPALPPEPEGQDPPAPSQDTS","function_summary":"A non-enzymatic outer-kinetochore scaffold that assembles and stabilizes microtubule–attachment machinery to ensure accurate chromosome biorientation and centromeric cohesion during mitosis. It concentrates specific factors at centromeric chromatin and interfaces with spindle microtubules and poles, coordinating attachment geometry and restraining phosphatase-driven remodeling. Soluble pools reside in the nucleoplasm, while transient association with chromatin-modifying assemblies links kinetochore architecture to broader cell-cycle control.","plain_language":"BOD1L2 has barely been studied. The model's best guess: A non-enzymatic outer-kinetochore scaffold that assembles and stabilizes microtubule–attachment machinery to ensure accurate chromosome biorientation and centromeric cohesion during mitosis. It concentrates specific factors at centromeric chromatin and interfaces with spindle microtubules and poles, coordinating attachment geometry and restraining phosphatase-driven remodeling.","uniprot_summary":"Involved in chromosome biorientation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0070601","label":"centromeric sister chromatid cohesion"},{"id":"GO:0070601","label":"centromeric sister chromatid cohesion"},{"id":"GO:0051315","label":"attachment of mitotic spindle microtubules to kinetochore"},{"id":"GO:0070601","label":"centromeric sister chromatid cohesion"},{"id":"GO:0007059","label":"chromosome segregation"},{"id":"GO:1990758","label":"mitotic sister chromatid biorientation"},{"id":"GO:0071459","label":"protein localization to chromosome, centromeric region"},{"id":"GO:0010923","label":"negative regulation of phosphoprotein phosphatase activity"}],"cellular_component":[{"id":"GO:0000940","label":"outer kinetochore"},{"id":"GO:0000922","label":"spindle pole"},{"id":"GO:0005654","label":"nucleoplasm"},{"id":"GO:0005813","label":"centrosome"},{"id":"GO:0048188","label":"Set1C/COMPASS complex"},{"id":"GO:0000776","label":"kinetochore"},{"id":"GO:0005876","label":"spindle microtubule"}]},"interpro":[{"id":"IPR055264","name":"BOD1/SHG1 domain","type":"domain","start":42,"end":137},{"id":"IPR043244","name":"Biorientation of chromosomes in cell division protein 1-like 1","type":"family","start":29,"end":160}],"reasoning":"I begin with the InterPro architecture. The core of the protein is defined by IPR055264 (BOD1/SHG1 domain, residues 42–137), a compact helical module characteristic of outer kinetochore adaptors that assemble protein complexes rather than catalyze reactions. This domain sits within a broader lineage signature, IPR043244 (Biorientation of chromosomes in cell division protein 1-like 1 family, residues 29–160), which ties the molecule to kinetochore-associated scaffolds that control chromosome biorientation. The ordered layout—an N-terminal region feeding into a central BOD1/SHG1 interaction module and encompassed by a kinetochore-scaffold family—imposes a non-enzymatic, multivalent binding role. This architecture causes the protein to function primarily through GO:0005515 protein binding, assembling and stabilizing outer kinetochore assemblies.\n\nFrom this binding-centric core, I infer molecular function and process. The BOD1/SHG1 module is a hallmark of outer kinetochore adaptors that tune microtubule–kinetochore attachment geometry. Such scaffolds directly support GO:1990758 mitotic sister chromatid biorientation by promoting amphitelic attachments—stable end-on attachments from opposite spindle poles—thereby balancing tension and error correction. By stabilizing outer kinetochore networks, the protein indirectly secures cohesion at centromeres during mitosis, aligning with GO:0070601 centromeric sister chromatid cohesion. The same scaffold logic explains its role in GO:0071459 protein localization to chromosome, centromeric region: it concentrates specific factors at centromeric chromatin to ensure proper kinetochore assembly and maintenance.\n\nThe cellular context follows from these assemblies. The outer kinetochore targeting and scaffold function place the protein at GO:0000940 outer kinetochore and at GO:0005876 spindle microtubule interfaces, where it helps couple microtubules to kinetochores. Its participation in spindle organization and tension-sensing complexes rationalizes presence at GO:0000922 spindle pole and association with GO:0005813 centrosome. Between divisions, soluble pools in GO:0005654 nucleoplasm are expected for assembly and turnover. A notable additional localization is GO:0048188 Set1C/COMPASS complex, a histone H3K4 methylation module. This association suggests a regulatory axis whereby chromatin-modifying machinery (COMPASS) communicates with kinetochore assemblies to coordinate chromatin state with spindle-attachment fidelity.\n\nMechanistically, the BOD1/SHG1 domain provides a rigid interaction hub that nucleates outer kinetochore complexes and restrains phosphatase-driven remodeling. By assembling and stabilizing kinetochore-associated networks, the protein can negatively tune dephosphorylation pathways—consistent with GO:0032515 negative regulation of phosphoprotein phosphatase activity—thereby preserving phosphorylation patterns that favor correct microtubule attachment and error correction. I hypothesize that it binds and organizes outer kinetochore modules (for example, NDC80–Nuf2 and related linkers), couples them to microtubules, and modulates access of phosphatases and chromatin modifiers. This predicts transient interactions with outer kinetochore receptors, spindle-pole organizers, and COMPASS components, collectively ensuring robust biorientation and centromeric cohesion.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8IYS8.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8IYS8"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8IYS8/entry","atlas":"/p/Q8IYS8"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}