{"uniprot":"A0A0U1RR11","gene":"CENPVL1","name":"Centromere protein V-like protein 1","organism":"Homo sapiens (Human)","status":"dark","length":272,"sequence":"MGRVRNRATAQRRRRKRPGDPPAACAAIAVTGASRAQCPRVQVGVGSHAAAKRWLGRWRRKRRWRRVRKAGPRDLLPSAPTPDPPGPAPSPKDLDLGAQRERWETFRKLRGLSCEGAAKVLLDTFEYPGLVHHTGGCHCGAVRFAVWAPADLRVVDCSCRLCRKKQHRHFLVPASRFTLLQGAESIVTYRSNTHPALHSFCSRCGVQSFHAAVSDPRVYGVAPHCLDEGTVRSVVIEEVGGGDPGEEAAEEHKAIHKTSSQSAPACPREQEQ","function_summary":"A human mitotic scaffold that assembles and stabilizes higher-order complexes controlling chromosome–microtubule coupling and late mitotic events. It concentrates at kinetochores and subsequently at the spindle midzone and midbody, where it organizes multiprotein assemblies essential for faithful cell division. The protein operates as a soluble adaptor that cycles between cytosolic and nucleoplasmic pools, interfaces with nuclear-envelope–proximal structures, and promotes complex assembly that underpins kinetochore integrity and cytokinesis.","plain_language":"CENPVL1 has barely been studied. The model's best guess: A human mitotic scaffold that assembles and stabilizes higher-order complexes controlling chromosome–microtubule coupling and late mitotic events. It concentrates at kinetochores and subsequently at the spindle midzone and midbody, where it organizes multiprotein assemblies essential for faithful cell division.","uniprot_summary":"May be involved in cell division.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0065003","label":"protein-containing complex assembly"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"},{"id":"GO:0030496","label":"midbody"},{"id":"GO:0051233","label":"spindle midzone"},{"id":"GO:0005654","label":"nucleoplasm"},{"id":"GO:0000776","label":"kinetochore"},{"id":"GO:0031965","label":"nuclear membrane"}]},"interpro":[{"id":"IPR011057","name":"Mss4-like superfamily","type":"homologous_superfamily","start":131,"end":228},{"id":"IPR006913","name":"CENP-V/GFA domain","type":"domain","start":133,"end":246},{"id":"IPR052355","name":"Centromere protein V-like","type":"family","start":94,"end":257}],"reasoning":"I begin with the InterPro architecture. The central-to-C-terminal half of the protein is defined by IPR052355 (Centromere protein V-like family, residues 94–257), which frames the overall identity and function of this polypeptide. Nested within this region is IPR011057 (Mss4-like superfamily, residues 131–228), a structural superfamily that commonly forms small-molecule– or protein-interaction folds used to stabilize multiprotein assemblies rather than to catalyze reactions. Overlapping this core lies IPR006913 (CENP-V/GFA domain, residues 133–246), a hallmark module of CENP-V/Gimzy-like proteins that mediates binding to other kinetochore and spindle apparatus components. The ordered layout—family-defining CENP-V-like region encompassing an Mss4-like fold and a CENP-V/GFA interaction module—creates a composite scaffold optimized for multivalent protein binding and higher-order assembly.\n\nThis architecture dictates the molecular function. The absence of catalytic motifs and the presence of interaction-centric folds (Mss4-like superfamily) together with a dedicated binding domain (CENP-V/GFA) cause the protein to act primarily through GO:0005515 protein binding. The CENP-V-like family signature further implies affinity for kinetochore and spindle-associated partners, reinforcing a role as an adaptor that nucleates and stabilizes macromolecular complexes.\n\nFrom this binding-centric mechanism, the biological process follows. A scaffold that avidly engages multiple partners is primed to drive GO:0065003 protein-containing complex assembly. In mitosis, such assembly is not generic: it is directed toward kinetochore formation and spindle apparatus organization. The CENP-V-like identity and the spindle-associated localization together indicate that the scaffold assembles and maintains the kinetochore and midzone structures that couple chromosomes to microtubules and coordinate late mitotic events.\n\nCellular location is a direct consequence of this assembly logic and temporal control. The soluble nature of the scaffold and its role in complex assembly support residence in the GO:0005829 cytosol and GO:0005654 nucleoplasm, where assembly intermediates and transient pools exist. Its operational site during chromosome-microtubule coupling is the GO:0000776 kinetochore. The assembly’s continuation into anaphase and cytokinesis explains accumulation at the GO:0051233 spindle midzone and GO:0030496 midbody, where midzone crosslinkers and ESCRT-associated factors concentrate. Association with the GO:0031965 nuclear membrane is consistent with kinetochore–nuclear envelope interfaces and mitotic envelope dynamics that transiently recruit kinetochore scaffolds.\n\nMechanistically, I infer that the CENP-V-like core forms a rigid interaction hub that captures and organizes outer kinetochore receptors and microtubule-attachment modules, then transitions to the spindle midzone to coordinate cytokinesis. Likely partners include outer kinetochore assemblies (e.g., NDC80 and KNL1 complexes), microtubule-coupling factors, and midzone organizers. Through these interactions, the scaffold seeds higher-order assemblies that ensure robust kinetochore formation, faithful microtubule attachment, and orderly progression into midzone and midbody structures.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-A0A0U1RR11.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/A0A0U1RR11"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/A0A0U1RR11/entry","atlas":"/p/A0A0U1RR11"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}