{"gene":"CENPQ","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2006,"finding":"CENP-Q is identified as a component of the CENP-A nucleosome distal (CAD) complex, assembling downstream of the CENP-A NAC (which includes CENP-M, CENP-N, CENP-T, CENP-U, CENP-C, CENP-H). Disruption of the CENP-A NAC causes errors in chromosome alignment and segregation.","method":"Co-immunoprecipitation, stable isotope labeling, mass spectrometry, RNAi knockdown with mitotic phenotype readout","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP and MS identification replicated across multiple subunits, with functional KD phenotype; foundational study replicated in subsequent work","pmids":["16622419"],"is_preprint":false},{"year":2010,"finding":"CENP-Q binds microtubules in vitro, suggesting a direct role in linking centromeric DNA to microtubule plus ends as part of the CENP-A NAC/CAD complex.","method":"In vitro microtubule binding assay","journal":"Nature cell biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro biochemical assay, but single lab, single method reported briefly in abstract","pmids":["20228811"],"is_preprint":false},{"year":2011,"finding":"PBIP1 (CENP-U) directly interacts with CENP-Q, and this interaction is mutually required for their stability and centromere localization. Plk1 forms a ternary complex with PBIP1 and CENP-Q via the self-generated p-T78 motif on PBIP1, enabling Plk1-dependent phosphorylation of PBIP1-bound CENP-Q and subsequent delocalization of the PBIP1-CENP-Q complex from mitotic centromeres.","method":"Co-immunoprecipitation, phosphorylation assay, immunofluorescence, RNAi knockdown","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, phosphorylation assay, and localization experiments with functional consequence, single lab with multiple orthogonal methods","pmids":["21454580"],"is_preprint":false},{"year":2012,"finding":"CENP-P/O/R/Q/U subunits exist in a tightly packed sub-complex with multifold protein-protein interactions. The complex is not pre-assembled in the cytoplasm but assembled on kinetochores via step-wise recruitment during S-phase. CENP-P/O/R/Q/U binding to CCAN is mediated through CENP-L and CENP-K. CENP-Q and CENP-U (but not CENP-R) undergo oligomerization during late S-phase after kinetochore binding, representing a pre-mitotic maturation step.","method":"Fluorescent three-hybrid (F3H) assay, FRET in living mammalian cells, SNAP-tag experiments, immunostaining, FRAP","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal live-cell imaging methods (F3H, FRET, SNAP-tag, FRAP) in a single study establishing both interaction topology and dynamic behavior","pmids":["23028590"],"is_preprint":false},{"year":2014,"finding":"In budding yeast, Okp1 (CENP-Q ortholog) forms a DNA-binding complex with Ame1 (CENP-U ortholog). This complex associates with the KMN network via a short Mtw1 recruitment motif in the N-terminus of Ame1. Point mutations disrupting the Ame1 motif prevent KMN assembly on chromatin, abolishing kinetochore function. Ame1-Okp1 also directly associates with the CENP-C homologue Mif2 to form a cooperative binding platform for outer kinetochore assembly.","method":"Biochemical reconstitution, genetic epistasis/point mutation analysis, structural analysis, DNA-binding assay","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstitution experiments plus mutagenesis plus structural analysis, multiple orthogonal methods in a single rigorous study","pmids":["25135934"],"is_preprint":false},{"year":2014,"finding":"CENP-Q is required for chromosome congression via two mechanisms: (1) recruitment of CENP-E to kinetochores, and (2) a CENP-E-independent role in depolymerization-coupled pulling. Both functions are abolished by the S50A point mutation of CENP-Q (a residue phosphorylated in vivo), without affecting Plk1 loading or CENP-O complex integrity, demonstrating that phosphoregulation of CENP-Q coordinates distinct congression pathways.","method":"RNAi knockdown, point mutation (S50A), live-cell imaging, kinetochore protein localization assay, chromosome congression assay","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean KD with specific rescue by separation-of-function mutation, multiple phenotypic readouts, single lab with orthogonal methods","pmids":["25395579"],"is_preprint":false},{"year":2014,"finding":"In fission yeast, Fta7 (CENP-Q ortholog) associates with Eic1, a Mis18-interacting protein that bridges CENP-A loading machinery (Mis18) with the CCAN/Mis6/Ctf19 complex, connecting CENP-A maintenance to the constitutive kinetochore network.","method":"Co-immunoprecipitation, genetic analysis, immunofluorescence","journal":"Open biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — Co-IP and genetic data in fission yeast ortholog, single lab","pmids":["24789708"],"is_preprint":false},{"year":2015,"finding":"Plk1 phosphorylates CENP-Q at multiple sites (at least nine Plk1-dependent sites). Mutation of all nine sites to Ala (9A) enhanced CENP-Q chromatin association and prolonged kinetochore localization; mutation to phospho-mimicking Asp/Glu (9D/E) dissociated CENP-Q from chromatin and prevented localization to interphase prekinetochores. Both 9A and 9D/E mutants caused chromosome segregation defects, demonstrating that timely Plk1-dependent phosphorylation and delocalization of the PBIP1·CENP-Q complex are critical for normal M-phase progression.","method":"In vitro kinase assay, site-directed mutagenesis (9A and 9D/E mutants), chromatin fractionation, immunofluorescence, chromosome segregation assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro kinase assay combined with mutagenesis and functional cellular phenotype, multiple orthogonal methods, single lab","pmids":["25670858"],"is_preprint":false},{"year":2017,"finding":"In Kluyveromyces lactis, the Okp1 (CENP-Q ortholog) subunit is a multi-segmented nexus with distinct binding sites for Ame1 (CENP-U), Nkp1-Nkp2, and Ctf19-Mcm21. Crystal structure of Ctf19-Mcm21 RWD domains bound to Okp1 reveals the molecular contacts of this inner kinetochore joint. Loss of the Ctf19-Mcm21 binding motif in Okp1 results in mitotic checkpoint dependence for viability.","method":"Nanoflow electrospray ionization mass spectrometry, hydrogen-deuterium exchange MS, X-ray crystallography, genetic viability assay","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus orthogonal MS topology mapping plus genetic epistasis, multiple rigorous methods in one study","pmids":["29046335"],"is_preprint":false},{"year":2018,"finding":"Reconstitution of a stoichiometric 11-subunit human CCAN core shows that the CENP-OPQUR complex binds to a joint interface on CENP-HIKM and CENP-LN complexes. The disordered, basic N-terminal tail of CENP-Q binds microtubules and promotes accurate chromosome alignment, cooperating with KMN in microtubule binding. The N-terminal basic tail of NDC80 can functionally replace the CENP-Q tail.","method":"Biochemical reconstitution of 26-subunit kinetochore particle, in vitro microtubule binding assay, mutagenesis (CENP-Q tail deletion/swap), chromosome alignment assay in cells","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstitution, in vitro microtubule binding, mutagenesis, and cellular functional validation combined in one rigorous study","pmids":["30174292"],"is_preprint":false},{"year":2021,"finding":"CENP-U is recruited to kinetochores by the CENP-P and CENP-Q subunits of the CENP-O complex, and CENP-U and Bub1 redundantly recruit Plk1 to kinetochores to stabilize kinetochore-microtubule attachments. Unlike budding yeast COMA complex, the human CENP-O complex does not regulate centromeric localization of Aurora B.","method":"siRNA depletion, kinase inhibitor treatment, immunofluorescence, chromosome segregation assay, epistasis analysis","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD epistasis with kinase inhibitors and multiple cellular phenotype readouts, single lab","pmids":["34551298"],"is_preprint":false},{"year":2021,"finding":"The C-terminal half of CENP-Q and residues 241-360 of CENP-U are essential to form a hetero-complex and interact with the CENP-O/P sub-complex in vitro. CENP-R does not directly interact with CENP-O/P in vitro but interacts with CENP-U and CENP-Q via both its N- and C-termini.","method":"In vitro binding assay, co-immunoprecipitation, domain mapping/truncation analysis","journal":"Journal of molecular recognition : JMR","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — in vitro binding and Co-IP with domain mapping, single lab, single study","pmids":["33660361"],"is_preprint":false},{"year":2014,"finding":"When CENP-U is disrupted in mouse ES cells, all CENP-O complex proteins (including CENP-Q) disappear from kinetochores, while other kinetochore proteins are still recruited, establishing that CENP-U is required for kinetochore localization of the entire CENP-O complex.","method":"Conditional knockout in mouse ES cells, immunofluorescence localization of CENP-O complex components","journal":"Chromosome research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined localization phenotype for the complex, replicated in two cell types (DT40 and ES cells), single lab","pmids":["24481920"],"is_preprint":false}],"current_model":"CENP-Q is a constitutive kinetochore component of the CENP-O complex (CENP-O/P/Q/R/U) within the CCAN, where it forms a stable heterodimer with CENP-U required for mutual stability and centromere localization; its disordered basic N-terminal tail directly binds microtubules to cooperate with the KMN network in chromosome alignment, its phosphorylation by Plk1 at multiple sites (mediated through a ternary complex with PBIP1/CENP-U) drives timely delocalization from mitotic kinetochores, and its phosphorylation at S50 (independent of Plk1 recruitment) coordinates CENP-E loading and depolymerization-coupled chromosome congression."},"narrative":{"mechanistic_narrative":"CENP-Q is a constitutive component of the CCAN that assembles as part of the CENP-O/P/Q/R/U sub-complex on kinetochores and is required for accurate chromosome alignment and segregation [PMID:16622419, PMID:23028590]. It forms a stable heterodimer with CENP-U through its C-terminal half, and this interaction is mutually required for the stability and centromere localization of both proteins; loss of CENP-U abolishes kinetochore loading of the entire CENP-O complex [PMID:21454580, PMID:33660361, PMID:24481920]. The CENP-OPQUR complex docks onto the CCAN at a joint interface formed by the CENP-HIKM and CENP-LN complexes, and is assembled step-wise on kinetochores during S-phase rather than pre-formed in the cytoplasm, with CENP-Q and CENP-U undergoing a maturation oligomerization step in late S-phase [PMID:23028590, PMID:30174292]. Functionally, the disordered basic N-terminal tail of CENP-Q binds microtubules directly and cooperates with the KMN network to promote chromosome alignment [PMID:20228811, PMID:30174292]. CENP-Q activity is phospho-regulated: Plk1 forms a ternary complex with PBIP1/CENP-U and phosphorylates CENP-Q at multiple sites, and timely Plk1-dependent phosphorylation drives delocalization of the PBIP1·CENP-Q complex from mitotic kinetochores as a prerequisite for normal M-phase progression [PMID:21454580, PMID:25670858]. A separate phosphorylation event at S50 coordinates two distinct congression pathways—recruitment of CENP-E to kinetochores and a CENP-E-independent depolymerization-coupled pulling activity—without affecting Plk1 loading or CENP-O complex integrity [PMID:25395579]. Conserved yeast orthologs (Okp1, Fta7) reinforce this role, acting as DNA-binding, multi-segmented nexus subunits that bridge the inner kinetochore to the outer KMN network [PMID:25135934, PMID:29046335].","teleology":[{"year":2006,"claim":"Established CENP-Q as a bona fide constitutive kinetochore protein by placing it within the CENP-A nucleosome distal (CAD) complex downstream of the CENP-A NAC, linking it to chromosome alignment and segregation.","evidence":"Co-IP, SILAC mass spectrometry, and RNAi knockdown with mitotic phenotype readout in human cells","pmids":["16622419"],"confidence":"High","gaps":["Did not define CENP-Q's specific molecular activity within the complex","Assembly hierarchy and direct binding partners unresolved"]},{"year":2010,"claim":"Provided the first biochemical evidence that CENP-Q can directly bind microtubules, hinting at a role in coupling centromeric chromatin to microtubule ends.","evidence":"In vitro microtubule binding assay","pmids":["20228811"],"confidence":"Medium","gaps":["Microtubule-binding region not mapped","Single method reported briefly","Cellular relevance not yet demonstrated"]},{"year":2011,"claim":"Defined the CENP-Q/CENP-U(PBIP1) heterodimer as mutually stabilizing and showed Plk1 forms a ternary complex with PBIP1 to phosphorylate CENP-Q and drive its delocalization, introducing phosphoregulation of CENP-Q at mitosis.","evidence":"Co-IP, phosphorylation assay, immunofluorescence, and RNAi in human cells","pmids":["21454580"],"confidence":"High","gaps":["Did not enumerate all Plk1 phosphosites","Functional consequence of delocalization for segregation not fully resolved"]},{"year":2012,"claim":"Resolved the topology and assembly dynamics of the CENP-O/P/Q/R/U sub-complex, showing it is built step-wise on kinetochores via CENP-L/CENP-K rather than pre-assembled, with a late-S-phase CENP-Q/CENP-U oligomerization maturation step.","evidence":"F3H, FRET, SNAP-tag, immunostaining, and FRAP in living mammalian cells","pmids":["23028590"],"confidence":"High","gaps":["Molecular trigger for oligomerization unknown","Functional purpose of the maturation step not defined"]},{"year":2014,"claim":"Demonstrated through yeast orthologs that the Okp1(CENP-Q)/Ame1(CENP-U) complex is DNA-binding and recruits the KMN network via an Ame1 motif, establishing the complex as a bridge between inner chromatin and outer kinetochore assembly.","evidence":"Biochemical reconstitution, point mutagenesis/genetic epistasis, structural and DNA-binding assays in budding yeast","pmids":["25135934"],"confidence":"High","gaps":["Conservation of the Ame1 KMN-recruitment motif in human CENP-U not directly tested here","Specific contribution of Okp1/CENP-Q to DNA binding not isolated"]},{"year":2014,"claim":"Showed CENP-U is required for kinetochore localization of the entire CENP-O complex including CENP-Q, fixing the dependency hierarchy for complex recruitment.","evidence":"Conditional knockout in mouse ES cells with immunofluorescence localization of CENP-O components","pmids":["24481920"],"confidence":"Medium","gaps":["Did not address whether CENP-Q reciprocally affects CENP-U recruitment in all contexts","Mechanism of the localization dependency not structurally defined"]},{"year":2014,"claim":"Identified S50 phosphorylation of CENP-Q as a regulatory switch coordinating two distinct chromosome congression pathways—CENP-E recruitment and CENP-E-independent depolymerization-coupled pulling—through a clean separation-of-function mutation.","evidence":"RNAi knockdown, S50A point mutation, live-cell imaging, and congression assays in human cells","pmids":["25395579"],"confidence":"High","gaps":["Kinase responsible for S50 phosphorylation not identified","Mechanistic basis of depolymerization-coupled pulling unresolved"]},{"year":2014,"claim":"Connected the CENP-Q ortholog Fta7 to CENP-A maintenance via Eic1/Mis18, linking the constitutive kinetochore network to new CENP-A loading in fission yeast.","evidence":"Co-IP, genetic analysis, and immunofluorescence in fission yeast","pmids":["24789708"],"confidence":"Medium","gaps":["Whether this CENP-A maintenance link is conserved in human CENP-Q untested","Direct vs indirect nature of the association unclear"]},{"year":2015,"claim":"Mapped at least nine Plk1-dependent phosphosites on CENP-Q and showed that both non-phosphorylatable and phosphomimetic mutants cause segregation defects, establishing that timely, balanced phosphorylation governs CENP-Q chromatin association and kinetochore residence.","evidence":"In vitro kinase assay, 9A/9D-E mutagenesis, chromatin fractionation, and segregation assays in human cells","pmids":["25670858"],"confidence":"High","gaps":["Individual contributions of the nine sites not dissected","Phosphatase that reverses these sites unknown"]},{"year":2017,"claim":"Crystallographic and topology mapping of the yeast ortholog revealed Okp1(CENP-Q) as a multi-segmented nexus with discrete binding sites for Ame1, Nkp1-Nkp2, and Ctf19-Mcm21, defining CENP-Q's architectural role as an inner kinetochore joint.","evidence":"Native MS, HDX-MS, X-ray crystallography, and genetic viability assays in K. lactis","pmids":["29046335"],"confidence":"High","gaps":["Structure of the human CENP-Q complex not solved here","How these interfaces are remodeled during the cell cycle unaddressed"]},{"year":2018,"claim":"Reconstitution of the human CCAN core localized the CENP-OPQUR complex to a CENP-HIKM/CENP-LN interface and demonstrated that the disordered basic N-terminal tail of CENP-Q binds microtubules and cooperates with KMN, functionally interchangeable with the NDC80 tail.","evidence":"Biochemical reconstitution of a 26-subunit kinetochore particle, in vitro microtubule binding, tail deletion/swap mutagenesis, and cellular alignment assays","pmids":["30174292"],"confidence":"High","gaps":["In vivo regulation of the CENP-Q tail-microtubule interaction not fully defined","Relationship between tail microtubule binding and Plk1/S50 phosphoregulation unexplored"]},{"year":2021,"claim":"Refined the recruitment logic of the complex, showing CENP-P and CENP-Q recruit CENP-U, which together with Bub1 redundantly recruits Plk1 to stabilize kinetochore-microtubule attachments, and that the human complex does not regulate Aurora B localization.","evidence":"siRNA depletion, kinase inhibitors, immunofluorescence, and epistasis in human cells","pmids":["34551298"],"confidence":"Medium","gaps":["Direct CENP-Q contacts with Plk1 vs CENP-U-mediated not separated","Divergence from yeast COMA function mechanistically unexplained"]},{"year":2021,"claim":"Mapped the domain architecture of the human complex, showing the C-terminal half of CENP-Q and residues 241-360 of CENP-U mediate the heterocomplex and its binding to CENP-O/P, with CENP-R engaging via CENP-U/CENP-Q.","evidence":"In vitro binding, Co-IP, and truncation/domain-mapping analysis","pmids":["33660361"],"confidence":"Medium","gaps":["Residue-level interface not resolved","Single in vitro study without structural validation"]},{"year":null,"claim":"How CENP-Q's microtubule-binding tail, its multi-site Plk1 phosphoregulation, and S50-dependent congression control are integrated within a single kinetochore during error correction remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Phosphatases reversing CENP-Q phosphorylation unidentified","Kinase for S50 unknown","No human structural model of the CENP-Q tail engaging microtubules in situ"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,9]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[3,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[5,10]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,3,12]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[2,7]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,5,7]}],"complexes":["CENP-O complex (CENP-OPQUR)","CCAN","kinetochore"],"partners":["CENPU","CENPP","CENPO","CENPR","PLK1","CENPE","CENPL","CENPK"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q7L2Z9","full_name":"Centromere protein Q","aliases":[],"length_aa":268,"mass_kda":30.6,"function":"Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex (PubMed:16622420). Plays an important role in chromosome congression and in the recruitment of CENP-O complex (which comprises CENPO, CENPP, CENPQ and CENPU), CENPE and PLK1 to the kinetochores (PubMed:25395579)","subcellular_location":"Nucleus; Chromosome, centromere","url":"https://www.uniprot.org/uniprotkb/Q7L2Z9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CENPQ","classification":"Not Classified","n_dependent_lines":33,"n_total_lines":1208,"dependency_fraction":0.027317880794701987},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"RPS16","stoichiometry":0.2},{"gene":"SRP9","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CENPQ","total_profiled":1310},"omim":[{"mim_id":"611511","title":"MLF1-INTERACTING PROTEIN; MLF1IP","url":"https://www.omim.org/entry/611511"},{"mim_id":"611506","title":"CENTROMERIC PROTEIN Q; CENPQ","url":"https://www.omim.org/entry/611506"},{"mim_id":"611505","title":"CENTROMERIC PROTEIN P; CENPP","url":"https://www.omim.org/entry/611505"},{"mim_id":"611504","title":"CENTROMERIC PROTEIN O; CENPO","url":"https://www.omim.org/entry/611504"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CENPQ"},"hgnc":{"alias_symbol":["FLJ10545","CENP-Q"],"prev_symbol":["C6orf139"]},"alphafold":{"accession":"Q7L2Z9","domains":[{"cath_id":"-","chopping":"72-130","consensus_level":"medium","plddt":85.4636,"start":72,"end":130}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7L2Z9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7L2Z9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7L2Z9-F1-predicted_aligned_error_v6.png","plddt_mean":73.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CENPQ","jax_strain_url":"https://www.jax.org/strain/search?query=CENPQ"},"sequence":{"accession":"Q7L2Z9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7L2Z9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7L2Z9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7L2Z9"}},"corpus_meta":[{"pmid":"16622419","id":"PMC_16622419","title":"The human CENP-A 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26-Subunit Human Kinetochore Reveals Cooperative Microtubule Binding by CENP-OPQUR and NDC80.","date":"2018","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/30174292","citation_count":62,"is_preprint":false},{"pmid":"21454580","id":"PMC_21454580","title":"Mammalian polo-like kinase 1-dependent regulation of the PBIP1-CENP-Q complex at kinetochores.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21454580","citation_count":44,"is_preprint":false},{"pmid":"25395579","id":"PMC_25395579","title":"Chromosome congression is promoted by CENP-Q- and CENP-E-dependent pathways.","date":"2014","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/25395579","citation_count":43,"is_preprint":false},{"pmid":"15331170","id":"PMC_15331170","title":"Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray.","date":"2004","source":"Cancer 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Series A, Biological sciences and medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35180297","citation_count":8,"is_preprint":false},{"pmid":"24803682","id":"PMC_24803682","title":"Label-free, real-time detection of the dynamic processes of protein degradation using oblique-incidence reflectivity difference method.","date":"2014","source":"Applied physics letters","url":"https://pubmed.ncbi.nlm.nih.gov/24803682","citation_count":7,"is_preprint":false},{"pmid":"36046633","id":"PMC_36046633","title":"LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis.","date":"2022","source":"Open medicine (Warsaw, Poland)","url":"https://pubmed.ncbi.nlm.nih.gov/36046633","citation_count":6,"is_preprint":false},{"pmid":"33660361","id":"PMC_33660361","title":"The novel interaction mode among centromere sub-complex CENP-O/P/U/Q/R.","date":"2021","source":"Journal of molecular recognition : JMR","url":"https://pubmed.ncbi.nlm.nih.gov/33660361","citation_count":4,"is_preprint":false},{"pmid":"41502527","id":"PMC_41502527","title":"CSRNP1 Promotes Apoptosis and Mitochondrial Dysfunction via ROS-Mediated JNK/p38 MAPK Pathway Activation in Hepatocellular Carcinoma.","date":"2025","source":"Oncology research","url":"https://pubmed.ncbi.nlm.nih.gov/41502527","citation_count":1,"is_preprint":false},{"pmid":"42003665","id":"PMC_42003665","title":"Integration of Genome-Wide Association Studies With Single-Cell and Bulk Expression Quantitative Trait Locus to Identify Stroke Susceptibility Genes.","date":"2026","source":"Journal of the American Heart Association","url":"https://pubmed.ncbi.nlm.nih.gov/42003665","citation_count":0,"is_preprint":false},{"pmid":"39968732","id":"PMC_39968732","title":"Novel Candidate Genes Detection Using Bayesian Network-Based Genome-Wide Association Study of Latent Traits in F2 Chicken Population.","date":"2025","source":"Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie","url":"https://pubmed.ncbi.nlm.nih.gov/39968732","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15497,"output_tokens":3517,"usd":0.049623,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10953,"output_tokens":4432,"usd":0.082782,"stage2_stop_reason":"end_turn"},"total_usd":0.132405,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"CENP-Q is identified as a component of the CENP-A nucleosome distal (CAD) complex, assembling downstream of the CENP-A NAC (which includes CENP-M, CENP-N, CENP-T, CENP-U, CENP-C, CENP-H). Disruption of the CENP-A NAC causes errors in chromosome alignment and segregation.\",\n      \"method\": \"Co-immunoprecipitation, stable isotope labeling, mass spectrometry, RNAi knockdown with mitotic phenotype readout\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP and MS identification replicated across multiple subunits, with functional KD phenotype; foundational study replicated in subsequent work\",\n      \"pmids\": [\"16622419\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"CENP-Q binds microtubules in vitro, suggesting a direct role in linking centromeric DNA to microtubule plus ends as part of the CENP-A NAC/CAD complex.\",\n      \"method\": \"In vitro microtubule binding assay\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro biochemical assay, but single lab, single method reported briefly in abstract\",\n      \"pmids\": [\"20228811\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PBIP1 (CENP-U) directly interacts with CENP-Q, and this interaction is mutually required for their stability and centromere localization. Plk1 forms a ternary complex with PBIP1 and CENP-Q via the self-generated p-T78 motif on PBIP1, enabling Plk1-dependent phosphorylation of PBIP1-bound CENP-Q and subsequent delocalization of the PBIP1-CENP-Q complex from mitotic centromeres.\",\n      \"method\": \"Co-immunoprecipitation, phosphorylation assay, immunofluorescence, RNAi knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, phosphorylation assay, and localization experiments with functional consequence, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"21454580\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CENP-P/O/R/Q/U subunits exist in a tightly packed sub-complex with multifold protein-protein interactions. The complex is not pre-assembled in the cytoplasm but assembled on kinetochores via step-wise recruitment during S-phase. CENP-P/O/R/Q/U binding to CCAN is mediated through CENP-L and CENP-K. CENP-Q and CENP-U (but not CENP-R) undergo oligomerization during late S-phase after kinetochore binding, representing a pre-mitotic maturation step.\",\n      \"method\": \"Fluorescent three-hybrid (F3H) assay, FRET in living mammalian cells, SNAP-tag experiments, immunostaining, FRAP\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal live-cell imaging methods (F3H, FRET, SNAP-tag, FRAP) in a single study establishing both interaction topology and dynamic behavior\",\n      \"pmids\": [\"23028590\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In budding yeast, Okp1 (CENP-Q ortholog) forms a DNA-binding complex with Ame1 (CENP-U ortholog). This complex associates with the KMN network via a short Mtw1 recruitment motif in the N-terminus of Ame1. Point mutations disrupting the Ame1 motif prevent KMN assembly on chromatin, abolishing kinetochore function. Ame1-Okp1 also directly associates with the CENP-C homologue Mif2 to form a cooperative binding platform for outer kinetochore assembly.\",\n      \"method\": \"Biochemical reconstitution, genetic epistasis/point mutation analysis, structural analysis, DNA-binding assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstitution experiments plus mutagenesis plus structural analysis, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"25135934\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CENP-Q is required for chromosome congression via two mechanisms: (1) recruitment of CENP-E to kinetochores, and (2) a CENP-E-independent role in depolymerization-coupled pulling. Both functions are abolished by the S50A point mutation of CENP-Q (a residue phosphorylated in vivo), without affecting Plk1 loading or CENP-O complex integrity, demonstrating that phosphoregulation of CENP-Q coordinates distinct congression pathways.\",\n      \"method\": \"RNAi knockdown, point mutation (S50A), live-cell imaging, kinetochore protein localization assay, chromosome congression assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with specific rescue by separation-of-function mutation, multiple phenotypic readouts, single lab with orthogonal methods\",\n      \"pmids\": [\"25395579\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In fission yeast, Fta7 (CENP-Q ortholog) associates with Eic1, a Mis18-interacting protein that bridges CENP-A loading machinery (Mis18) with the CCAN/Mis6/Ctf19 complex, connecting CENP-A maintenance to the constitutive kinetochore network.\",\n      \"method\": \"Co-immunoprecipitation, genetic analysis, immunofluorescence\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — Co-IP and genetic data in fission yeast ortholog, single lab\",\n      \"pmids\": [\"24789708\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Plk1 phosphorylates CENP-Q at multiple sites (at least nine Plk1-dependent sites). Mutation of all nine sites to Ala (9A) enhanced CENP-Q chromatin association and prolonged kinetochore localization; mutation to phospho-mimicking Asp/Glu (9D/E) dissociated CENP-Q from chromatin and prevented localization to interphase prekinetochores. Both 9A and 9D/E mutants caused chromosome segregation defects, demonstrating that timely Plk1-dependent phosphorylation and delocalization of the PBIP1·CENP-Q complex are critical for normal M-phase progression.\",\n      \"method\": \"In vitro kinase assay, site-directed mutagenesis (9A and 9D/E mutants), chromatin fractionation, immunofluorescence, chromosome segregation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro kinase assay combined with mutagenesis and functional cellular phenotype, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"25670858\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In Kluyveromyces lactis, the Okp1 (CENP-Q ortholog) subunit is a multi-segmented nexus with distinct binding sites for Ame1 (CENP-U), Nkp1-Nkp2, and Ctf19-Mcm21. Crystal structure of Ctf19-Mcm21 RWD domains bound to Okp1 reveals the molecular contacts of this inner kinetochore joint. Loss of the Ctf19-Mcm21 binding motif in Okp1 results in mitotic checkpoint dependence for viability.\",\n      \"method\": \"Nanoflow electrospray ionization mass spectrometry, hydrogen-deuterium exchange MS, X-ray crystallography, genetic viability assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus orthogonal MS topology mapping plus genetic epistasis, multiple rigorous methods in one study\",\n      \"pmids\": [\"29046335\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Reconstitution of a stoichiometric 11-subunit human CCAN core shows that the CENP-OPQUR complex binds to a joint interface on CENP-HIKM and CENP-LN complexes. The disordered, basic N-terminal tail of CENP-Q binds microtubules and promotes accurate chromosome alignment, cooperating with KMN in microtubule binding. The N-terminal basic tail of NDC80 can functionally replace the CENP-Q tail.\",\n      \"method\": \"Biochemical reconstitution of 26-subunit kinetochore particle, in vitro microtubule binding assay, mutagenesis (CENP-Q tail deletion/swap), chromosome alignment assay in cells\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstitution, in vitro microtubule binding, mutagenesis, and cellular functional validation combined in one rigorous study\",\n      \"pmids\": [\"30174292\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CENP-U is recruited to kinetochores by the CENP-P and CENP-Q subunits of the CENP-O complex, and CENP-U and Bub1 redundantly recruit Plk1 to kinetochores to stabilize kinetochore-microtubule attachments. Unlike budding yeast COMA complex, the human CENP-O complex does not regulate centromeric localization of Aurora B.\",\n      \"method\": \"siRNA depletion, kinase inhibitor treatment, immunofluorescence, chromosome segregation assay, epistasis analysis\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD epistasis with kinase inhibitors and multiple cellular phenotype readouts, single lab\",\n      \"pmids\": [\"34551298\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The C-terminal half of CENP-Q and residues 241-360 of CENP-U are essential to form a hetero-complex and interact with the CENP-O/P sub-complex in vitro. CENP-R does not directly interact with CENP-O/P in vitro but interacts with CENP-U and CENP-Q via both its N- and C-termini.\",\n      \"method\": \"In vitro binding assay, co-immunoprecipitation, domain mapping/truncation analysis\",\n      \"journal\": \"Journal of molecular recognition : JMR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — in vitro binding and Co-IP with domain mapping, single lab, single study\",\n      \"pmids\": [\"33660361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"When CENP-U is disrupted in mouse ES cells, all CENP-O complex proteins (including CENP-Q) disappear from kinetochores, while other kinetochore proteins are still recruited, establishing that CENP-U is required for kinetochore localization of the entire CENP-O complex.\",\n      \"method\": \"Conditional knockout in mouse ES cells, immunofluorescence localization of CENP-O complex components\",\n      \"journal\": \"Chromosome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined localization phenotype for the complex, replicated in two cell types (DT40 and ES cells), single lab\",\n      \"pmids\": [\"24481920\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CENP-Q is a constitutive kinetochore component of the CENP-O complex (CENP-O/P/Q/R/U) within the CCAN, where it forms a stable heterodimer with CENP-U required for mutual stability and centromere localization; its disordered basic N-terminal tail directly binds microtubules to cooperate with the KMN network in chromosome alignment, its phosphorylation by Plk1 at multiple sites (mediated through a ternary complex with PBIP1/CENP-U) drives timely delocalization from mitotic kinetochores, and its phosphorylation at S50 (independent of Plk1 recruitment) coordinates CENP-E loading and depolymerization-coupled chromosome congression.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CENP-Q is a constitutive component of the CCAN that assembles as part of the CENP-O/P/Q/R/U sub-complex on kinetochores and is required for accurate chromosome alignment and segregation [#0, #3]. It forms a stable heterodimer with CENP-U through its C-terminal half, and this interaction is mutually required for the stability and centromere localization of both proteins; loss of CENP-U abolishes kinetochore loading of the entire CENP-O complex [#2, #11, #12]. The CENP-OPQUR complex docks onto the CCAN at a joint interface formed by the CENP-HIKM and CENP-LN complexes, and is assembled step-wise on kinetochores during S-phase rather than pre-formed in the cytoplasm, with CENP-Q and CENP-U undergoing a maturation oligomerization step in late S-phase [#3, #9]. Functionally, the disordered basic N-terminal tail of CENP-Q binds microtubules directly and cooperates with the KMN network to promote chromosome alignment [#1, #9]. CENP-Q activity is phospho-regulated: Plk1 forms a ternary complex with PBIP1/CENP-U and phosphorylates CENP-Q at multiple sites, and timely Plk1-dependent phosphorylation drives delocalization of the PBIP1·CENP-Q complex from mitotic kinetochores as a prerequisite for normal M-phase progression [#2, #7]. A separate phosphorylation event at S50 coordinates two distinct congression pathways—recruitment of CENP-E to kinetochores and a CENP-E-independent depolymerization-coupled pulling activity—without affecting Plk1 loading or CENP-O complex integrity [#5]. Conserved yeast orthologs (Okp1, Fta7) reinforce this role, acting as DNA-binding, multi-segmented nexus subunits that bridge the inner kinetochore to the outer KMN network [#4, #8].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established CENP-Q as a bona fide constitutive kinetochore protein by placing it within the CENP-A nucleosome distal (CAD) complex downstream of the CENP-A NAC, linking it to chromosome alignment and segregation.\",\n      \"evidence\": \"Co-IP, SILAC mass spectrometry, and RNAi knockdown with mitotic phenotype readout in human cells\",\n      \"pmids\": [\"16622419\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define CENP-Q's specific molecular activity within the complex\", \"Assembly hierarchy and direct binding partners unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Provided the first biochemical evidence that CENP-Q can directly bind microtubules, hinting at a role in coupling centromeric chromatin to microtubule ends.\",\n      \"evidence\": \"In vitro microtubule binding assay\",\n      \"pmids\": [\"20228811\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Microtubule-binding region not mapped\", \"Single method reported briefly\", \"Cellular relevance not yet demonstrated\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined the CENP-Q/CENP-U(PBIP1) heterodimer as mutually stabilizing and showed Plk1 forms a ternary complex with PBIP1 to phosphorylate CENP-Q and drive its delocalization, introducing phosphoregulation of CENP-Q at mitosis.\",\n      \"evidence\": \"Co-IP, phosphorylation assay, immunofluorescence, and RNAi in human cells\",\n      \"pmids\": [\"21454580\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not enumerate all Plk1 phosphosites\", \"Functional consequence of delocalization for segregation not fully resolved\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Resolved the topology and assembly dynamics of the CENP-O/P/Q/R/U sub-complex, showing it is built step-wise on kinetochores via CENP-L/CENP-K rather than pre-assembled, with a late-S-phase CENP-Q/CENP-U oligomerization maturation step.\",\n      \"evidence\": \"F3H, FRET, SNAP-tag, immunostaining, and FRAP in living mammalian cells\",\n      \"pmids\": [\"23028590\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular trigger for oligomerization unknown\", \"Functional purpose of the maturation step not defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated through yeast orthologs that the Okp1(CENP-Q)/Ame1(CENP-U) complex is DNA-binding and recruits the KMN network via an Ame1 motif, establishing the complex as a bridge between inner chromatin and outer kinetochore assembly.\",\n      \"evidence\": \"Biochemical reconstitution, point mutagenesis/genetic epistasis, structural and DNA-binding assays in budding yeast\",\n      \"pmids\": [\"25135934\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Conservation of the Ame1 KMN-recruitment motif in human CENP-U not directly tested here\", \"Specific contribution of Okp1/CENP-Q to DNA binding not isolated\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Showed CENP-U is required for kinetochore localization of the entire CENP-O complex including CENP-Q, fixing the dependency hierarchy for complex recruitment.\",\n      \"evidence\": \"Conditional knockout in mouse ES cells with immunofluorescence localization of CENP-O components\",\n      \"pmids\": [\"24481920\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not address whether CENP-Q reciprocally affects CENP-U recruitment in all contexts\", \"Mechanism of the localization dependency not structurally defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified S50 phosphorylation of CENP-Q as a regulatory switch coordinating two distinct chromosome congression pathways—CENP-E recruitment and CENP-E-independent depolymerization-coupled pulling—through a clean separation-of-function mutation.\",\n      \"evidence\": \"RNAi knockdown, S50A point mutation, live-cell imaging, and congression assays in human cells\",\n      \"pmids\": [\"25395579\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for S50 phosphorylation not identified\", \"Mechanistic basis of depolymerization-coupled pulling unresolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected the CENP-Q ortholog Fta7 to CENP-A maintenance via Eic1/Mis18, linking the constitutive kinetochore network to new CENP-A loading in fission yeast.\",\n      \"evidence\": \"Co-IP, genetic analysis, and immunofluorescence in fission yeast\",\n      \"pmids\": [\"24789708\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether this CENP-A maintenance link is conserved in human CENP-Q untested\", \"Direct vs indirect nature of the association unclear\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Mapped at least nine Plk1-dependent phosphosites on CENP-Q and showed that both non-phosphorylatable and phosphomimetic mutants cause segregation defects, establishing that timely, balanced phosphorylation governs CENP-Q chromatin association and kinetochore residence.\",\n      \"evidence\": \"In vitro kinase assay, 9A/9D-E mutagenesis, chromatin fractionation, and segregation assays in human cells\",\n      \"pmids\": [\"25670858\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Individual contributions of the nine sites not dissected\", \"Phosphatase that reverses these sites unknown\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Crystallographic and topology mapping of the yeast ortholog revealed Okp1(CENP-Q) as a multi-segmented nexus with discrete binding sites for Ame1, Nkp1-Nkp2, and Ctf19-Mcm21, defining CENP-Q's architectural role as an inner kinetochore joint.\",\n      \"evidence\": \"Native MS, HDX-MS, X-ray crystallography, and genetic viability assays in K. lactis\",\n      \"pmids\": [\"29046335\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure of the human CENP-Q complex not solved here\", \"How these interfaces are remodeled during the cell cycle unaddressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Reconstitution of the human CCAN core localized the CENP-OPQUR complex to a CENP-HIKM/CENP-LN interface and demonstrated that the disordered basic N-terminal tail of CENP-Q binds microtubules and cooperates with KMN, functionally interchangeable with the NDC80 tail.\",\n      \"evidence\": \"Biochemical reconstitution of a 26-subunit kinetochore particle, in vitro microtubule binding, tail deletion/swap mutagenesis, and cellular alignment assays\",\n      \"pmids\": [\"30174292\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo regulation of the CENP-Q tail-microtubule interaction not fully defined\", \"Relationship between tail microtubule binding and Plk1/S50 phosphoregulation unexplored\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Refined the recruitment logic of the complex, showing CENP-P and CENP-Q recruit CENP-U, which together with Bub1 redundantly recruits Plk1 to stabilize kinetochore-microtubule attachments, and that the human complex does not regulate Aurora B localization.\",\n      \"evidence\": \"siRNA depletion, kinase inhibitors, immunofluorescence, and epistasis in human cells\",\n      \"pmids\": [\"34551298\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct CENP-Q contacts with Plk1 vs CENP-U-mediated not separated\", \"Divergence from yeast COMA function mechanistically unexplained\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Mapped the domain architecture of the human complex, showing the C-terminal half of CENP-Q and residues 241-360 of CENP-U mediate the heterocomplex and its binding to CENP-O/P, with CENP-R engaging via CENP-U/CENP-Q.\",\n      \"evidence\": \"In vitro binding, Co-IP, and truncation/domain-mapping analysis\",\n      \"pmids\": [\"33660361\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Residue-level interface not resolved\", \"Single in vitro study without structural validation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CENP-Q's microtubule-binding tail, its multi-site Plk1 phosphoregulation, and S50-dependent congression control are integrated within a single kinetochore during error correction remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phosphatases reversing CENP-Q phosphorylation unidentified\", \"Kinase for S50 unknown\", \"No human structural model of the CENP-Q tail engaging microtubules in situ\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 9]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [3, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [5, 10]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 3, 12]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [2, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 5, 7]}\n    ],\n    \"complexes\": [\n      \"CENP-O complex (CENP-OPQUR)\",\n      \"CCAN\",\n      \"kinetochore\"\n    ],\n    \"partners\": [\n      \"CENPU\",\n      \"CENPP\",\n      \"CENPO\",\n      \"CENPR\",\n      \"PLK1\",\n      \"CENPE\",\n      \"CENPL\",\n      \"CENPK\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}