{"gene":"HAUS6","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":2008,"finding":"HAUS6 (Dgt6) is a subunit of the augmin complex, a stable multi-protein complex of Dgt proteins required for centrosome-independent microtubule generation within the spindle; RNAi knockdown of each Dgt protein substantially reduces spindle microtubule generation, leading to reduced kinetochore fiber formation, chromosome misalignment, and spindle bipolarity defects, particularly in the absence of functional centrosomes.","method":"RNAi knockdown in Drosophila S2 cells, co-immunoprecipitation to show stable complex formation, live-cell and fixed imaging of spindle phenotypes","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP establishing complex, RNAi loss-of-function with defined cellular phenotypes, replicated across multiple subunits and independently in the same study","pmids":["18443220"],"is_preprint":false},{"year":2008,"finding":"FAM29A (HAUS6 human homologue) promotes microtubule-dependent microtubule amplification by directly interacting with and recruiting the NEDD1–gamma-tubulin ring complex to spindle microtubules; depletion reduces spindle MT density, impairs kinetochore fiber formation, activates the spindle assembly checkpoint, and delays mitotic progression without affecting centrosome- or chromatin-based MT nucleation.","method":"siRNA knockdown, co-immunoprecipitation (FAM29A–NEDD1–gamma-tubulin), MT regrowth assay after nocodazole washout, immunofluorescence","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP with multiple partners, loss-of-function with specific phenotypic readouts, orthogonal MT regrowth assay distinguishing nucleation pathways","pmids":["19029337"],"is_preprint":false},{"year":2009,"finding":"Drosophila Dgt6 (HAUS6 orthologue) is primarily required for kinetochore fiber (k-fiber) formation; co-precipitates with Msps/XMAP215, D-TACC, gamma-tubulin, Ndc80, and Nuf2; kinetochore-driven k-fiber regrowth after cold exposure is severely impaired in Dgt6-depleted cells, placing Dgt6 at the intersection of MT nucleation/stabilization and Ndc80 complex-mediated kinetochore attachment.","method":"RNAi knockdown, co-immunoprecipitation, MT regrowth assay after cold-induced depolymerization, immunofluorescence of k-fiber markers","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple Co-IP partners, loss-of-function with specific k-fiber regrowth assay, epistasis with gamma-tubulin/Msps/Ndc80 RNAi","pmids":["19836241"],"is_preprint":false},{"year":2009,"finding":"FAM29A (HAUS6) is regulated by Plk1: Plk1 recruits FAM29A to spindle microtubules, which in turn targets NEDD1 to the spindle; Plk1, FAM29A, and NEDD1 form three separate complexes in vivo rather than one single complex; altering FAM29A levels redistributes NEDD1 between the centrosomes and the spindle, demonstrating that FAM29A controls the partitioning of NEDD1 between these two mitotic structures.","method":"Co-immunoprecipitation, overexpression and knockdown with quantitative immunofluorescence of NEDD1 partitioning, epistasis with Plk1","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, two orthogonal functional approaches (OE and KD), quantitative redistribution assay; single lab","pmids":["19596795"],"is_preprint":false},{"year":2011,"finding":"Aurora-A kinase directly binds and phosphorylates the Augmin subunit Hice1 at an N-terminal Ser/Thr-17-21 cluster; phospho-mimetic mutation at this cluster reduces Hice1 microtubule binding activity in vitro, diminishes Hice1 spindle localization, and decreases FAM29A (HAUS6) association with spindles, while phospho-deficient mutation permits intraspindle nucleation but delays spindle pole separation.","method":"In vitro kinase assay, phospho-specific antibody immunostaining, MT cosedimentation/binding assay, phospho-mimetic and phospho-deficient mutagenesis, live-cell imaging","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro kinase assay with site-directed mutagenesis plus in vivo functional validation; single lab but multiple orthogonal methods","pmids":["21705324"],"is_preprint":false},{"year":2017,"finding":"Cross-linking mass spectrometry of in vivo Drosophila Augmin identified that Dgt6 (HAUS6 orthologue) directly binds the gamma-TuRC protein Dgp71WD (NEDD1 orthologue); this interaction is required for gamma-TuRC accumulation on the mitotic spindle but not for Augmin localization itself.","method":"Immuno-affinity purification of Augmin from Drosophila embryos, cross-linking/mass spectrometry, biochemical binding assays, in vivo rescue experiments in Drosophila embryo","journal":"Biology open","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cross-linking MS providing structural distance restraints, biochemical binding validation, in vivo functional confirmation; single lab but orthogonal methods","pmids":["28351835"],"is_preprint":false},{"year":2018,"finding":"The inner nuclear membrane protein Samp1 co-precipitates with gamma-tubulin and the HAUS6 subunit of the Augmin complex in live cells, and Samp1 depletion reduces HAUS6 levels at the mitotic spindle, demonstrating that Samp1 is involved in recruiting HAUS6 and gamma-tubulin to the spindle.","method":"Co-immunoprecipitation from live cells, siRNA knockdown with quantitative immunofluorescence of HAUS6 at spindle, rescue by Samp1 overexpression","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus KD/rescue with defined localization phenotype; single lab, two orthogonal methods","pmids":["29514856"],"is_preprint":false},{"year":2021,"finding":"Conditional knockout of Haus6 in mouse apical neural progenitors causes spindle defects and mitotic delay, triggering massive p53-dependent apoptosis and aborting brain development; co-deletion of Trp53 rescues cell death but surviving progenitors display exacerbated mitotic errors, chromosomal defects, and increased DNA damage, showing that augmin/HAUS6 is essential for apical progenitor mitosis independent of p53 status.","method":"Conditional knockout mouse model, p53 co-deletion epistasis, live imaging, immunofluorescence of spindle markers and DNA damage","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo conditional KO with epistasis analysis (Trp53 co-deletion), multiple orthogonal phenotypic readouts, mouse model","pmids":["34427181"],"is_preprint":false},{"year":2022,"finding":"RNAi-mediated depletion of Dgt6 (HAUS6 Drosophila orthologue) causes a significant delay in kinetochore-driven microtubule regrowth (KDMTR) after colcemid-induced depolymerization in S2 cells, placing HAUS6/augmin as a positive regulator of kinetochore-driven spindle reassembly.","method":"RNAi reverse genetics, colcemid-induced MT depolymerization and regrowth assay, immunofluorescence quantification of KDMTR kinetics","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean RNAi loss-of-function with specific MT regrowth assay; single lab, single method","pmids":["35883570"],"is_preprint":false},{"year":2022,"finding":"HAUS6 knockdown in colorectal cancer cell lines suppresses cell proliferation and arrests cell cycle at G0/G1 by reducing p53 and p21 degradation (activating the p53/p21 pathway), while HAUS6 overexpression increases cell viability; these effects are observed both in vitro and in vivo xenograft models.","method":"siRNA knockdown, overexpression, cell viability/proliferation assays, flow cytometry cell cycle analysis, in vivo xenograft, western blot of p53/p21 protein levels","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD and OE with defined phenotypic readout plus pathway analysis; single lab, multiple orthogonal assays","pmids":["35096810"],"is_preprint":false},{"year":2024,"finding":"HAUS6 is essential for spindle bipolarization in human oocytes; loss-of-function studies identified HAUS6 as required for the transition from multipolar intermediates (formed at minor poles from kinetochore clusters) to a bipolar spindle; mutations in HAUS6 were identified in infertile patients with oocyte or embryo defects.","method":"High-resolution live imaging in >1800 human oocytes, loss-of-function experiments, patient mutation identification","journal":"Science (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct loss-of-function in human oocytes with defined spindle bipolarization phenotype plus patient mutation data; single study","pmids":["39172836"],"is_preprint":false},{"year":2025,"finding":"Cryo-EM structure of an augmin subcomplex on the microtubule reveals that the conserved calponin-homology (CH) domain of Haus6 (HAUS6) directly contacts the MT lattice and is a bona fide MT binding site; the Haus6 CH domain increases augmin's affinity for MTs and, together with a second binding site in the disordered N-terminus of Haus8, establishes the shallow branch angle of newly nucleated microtubules.","method":"Cryo-electron microscopy structure determination, in vitro MT binding assays, mutagenesis of the CH domain","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cryo-EM structure with in vitro binding validation and mutagenesis; single study but multiple orthogonal methods including structural determination","pmids":["41173848"],"is_preprint":false}],"current_model":"HAUS6 (FAM29A/Dgt6) is a core subunit of the hetero-octameric augmin complex whose conserved CH domain directly binds the microtubule lattice—establishing branch angle and MT affinity—and whose interaction with the NEDD1–gamma-TuRC recruits the nucleation machinery to pre-existing spindle microtubules, thereby amplifying intraspindle microtubule number, promoting kinetochore fiber formation, and enabling bipolar spindle assembly; this activity is regulated upstream by Plk1 (which recruits HAUS6/FAM29A to the spindle) and by Aurora-A (which phosphorylates the Augmin subunit Hice1 to modulate MT binding and HAUS6 spindle association), and is essential in vivo for apical neural progenitor mitosis and human oocyte spindle bipolarization."},"narrative":{"mechanistic_narrative":"HAUS6 (FAM29A/Dgt6) is a core subunit of the augmin complex that drives centrosome-independent, microtubule-dependent microtubule amplification within the mitotic spindle, thereby promoting kinetochore fiber formation and bipolar spindle assembly [PMID:18443220, PMID:19029337]. Mechanistically, its conserved calponin-homology (CH) domain directly contacts the microtubule lattice, increasing augmin's affinity for microtubules and, in concert with a second site in the HAUS8 N-terminus, setting the shallow branch angle of newly nucleated microtubules [PMID:41173848]; in parallel, HAUS6 directly binds NEDD1 (Dgp71WD) and recruits the NEDD1–gamma-tubulin ring complex onto pre-existing spindle microtubules to seed new nucleation, an interaction required for gamma-TuRC spindle accumulation but not for augmin's own localization [PMID:19029337, PMID:28351835]. This amplification is especially required for kinetochore-driven microtubule regrowth and k-fiber formation, where Dgt6 acts together with gamma-tubulin, Msps/XMAP215 and the Ndc80 complex [PMID:19836241, PMID:35883570]. HAUS6 spindle recruitment is controlled upstream by Plk1, which targets HAUS6 to the spindle and thereby partitions NEDD1 between centrosomes and spindle, and by Aurora-A, which phosphorylates the augmin subunit Hice1 to modulate microtubule binding and HAUS6 spindle association [PMID:19596795, PMID:21705324]. Loss of HAUS6 is consequential in vivo: conditional knockout in mouse apical neural progenitors causes spindle defects, mitotic delay and p53-dependent apoptosis that aborts brain development [PMID:34427181], and HAUS6 is required for spindle bipolarization in human oocytes, with patient mutations linked to oocyte/embryo defects [PMID:39172836].","teleology":[{"year":2008,"claim":"Established that HAUS6/Dgt6 is a stable subunit of the augmin complex required for centrosome-independent microtubule generation inside the spindle, defining the complex responsible for intraspindle MT amplification.","evidence":"RNAi knockdown of Dgt proteins plus co-immunoprecipitation and spindle imaging in Drosophila S2 cells","pmids":["18443220"],"confidence":"High","gaps":["Did not define the molecular activity of HAUS6 within the complex","Mechanism of how augmin generates new MTs not resolved"]},{"year":2008,"claim":"Identified the molecular mechanism of amplification: the human homologue FAM29A directly binds and recruits the NEDD1–gamma-tubulin ring complex to spindle MTs, linking augmin to the nucleation machinery without affecting centrosome- or chromatin-based nucleation.","evidence":"siRNA knockdown, FAM29A–NEDD1–gamma-tubulin co-IP, and nocodazole-washout MT regrowth assay","pmids":["19029337"],"confidence":"High","gaps":["Direct vs bridged nature of the FAM29A–NEDD1 contact not structurally defined","How NEDD1 is activated for nucleation on the spindle unresolved"]},{"year":2009,"claim":"Placed Dgt6 at the interface of nucleation and kinetochore attachment by showing it is primarily required for k-fiber formation and physically associates with k-fiber and kinetochore components.","evidence":"RNAi, co-IP with Msps/D-TACC/gamma-tubulin/Ndc80/Nuf2, and cold-induced MT regrowth assay in Drosophila","pmids":["19836241"],"confidence":"High","gaps":["Whether interactions with Ndc80/Nuf2 are direct or indirect not established","Order of recruitment between k-fiber nucleation and Ndc80 attachment unclear"]},{"year":2009,"claim":"Defined upstream regulation: Plk1 recruits FAM29A to the spindle, and FAM29A levels in turn govern partitioning of NEDD1 between centrosomes and spindle, showing these factors form separate in vivo complexes rather than one.","evidence":"Co-IP, overexpression/knockdown with quantitative NEDD1 partitioning immunofluorescence, Plk1 epistasis","pmids":["19596795"],"confidence":"High","gaps":["Direct Plk1 phosphorylation site(s) on FAM29A not mapped","Single-lab finding"]},{"year":2011,"claim":"Added a second kinase regulatory layer: Aurora-A phosphorylates the augmin subunit Hice1, reducing its MT binding and HAUS6 spindle association, coupling spindle pole dynamics to augmin activity.","evidence":"In vitro kinase assay, phospho-mimetic/deficient mutagenesis, MT cosedimentation, and live imaging","pmids":["21705324"],"confidence":"High","gaps":["Effect operates via Hice1, not HAUS6 directly","In vivo phosphorylation timing during mitosis not fully resolved"]},{"year":2017,"claim":"Provided structural-proximity evidence that Dgt6 directly binds the gamma-TuRC adaptor Dgp71WD/NEDD1 and that this contact is required for gamma-TuRC spindle accumulation but dispensable for augmin localization.","evidence":"Cross-linking mass spectrometry of in vivo Drosophila augmin, biochemical binding, and in vivo rescue","pmids":["28351835"],"confidence":"High","gaps":["Atomic-resolution interface not defined","Stoichiometry of the augmin–NEDD1 contact unknown"]},{"year":2018,"claim":"Implicated the inner nuclear membrane protein Samp1 in delivering HAUS6 and gamma-tubulin to the spindle, expanding the recruitment pathway beyond Plk1.","evidence":"Co-IP from live cells, siRNA knockdown with quantitative spindle immunofluorescence, and rescue","pmids":["29514856"],"confidence":"Medium","gaps":["Whether the Samp1–HAUS6 interaction is direct not shown","Single lab, two methods"]},{"year":2021,"claim":"Demonstrated in vivo essentiality: HAUS6 is required for apical neural progenitor mitosis, with loss causing spindle defects and p53-dependent apoptosis that aborts brain development independent of p53 status.","evidence":"Conditional Haus6 knockout mouse with Trp53 co-deletion epistasis, live imaging, and DNA damage immunofluorescence","pmids":["34427181"],"confidence":"High","gaps":["Tissue-specificity of HAUS6 requirement beyond neural progenitors not addressed","Molecular trigger of the mitotic checkpoint response not dissected"]},{"year":2022,"claim":"Confirmed HAUS6 as a positive regulator of kinetochore-driven microtubule regrowth, reinforcing its role in spindle reassembly after depolymerization.","evidence":"RNAi plus colcemid-induced depolymerization/regrowth kinetics in Drosophila S2 cells","pmids":["35883570"],"confidence":"Medium","gaps":["Single method, single lab","Quantitative contribution relative to other regrowth pathways not parsed"]},{"year":2022,"claim":"Linked HAUS6 to proliferative control in cancer, showing knockdown arrests colorectal cancer cells at G0/G1 by stabilizing p53/p21, connecting its mitotic function to tumor cell growth.","evidence":"siRNA/overexpression, cell cycle flow cytometry, xenografts, and p53/p21 western blot","pmids":["35096810"],"confidence":"Medium","gaps":["Mechanism linking spindle function to p53/p21 protein turnover not defined","Whether effect is augmin-dependent or moonlighting unclear"]},{"year":2024,"claim":"Established HAUS6 as required for spindle bipolarization in human oocytes and linked HAUS6 mutations to human infertility, extending its essentiality to human reproduction.","evidence":"High-resolution live imaging of >1800 human oocytes, loss-of-function, and patient mutation identification","pmids":["39172836"],"confidence":"Medium","gaps":["Functional impact of specific patient mutations not biochemically validated","Single study"]},{"year":2025,"claim":"Resolved the structural basis of microtubule engagement: the HAUS6 CH domain directly contacts the MT lattice, raises augmin's MT affinity, and together with the HAUS8 N-terminus sets the shallow branch angle of nucleated microtubules.","evidence":"Cryo-EM of an augmin subcomplex on microtubules with in vitro MT binding assays and CH-domain mutagenesis","pmids":["41173848"],"confidence":"High","gaps":["Full-length octamer–gamma-TuRC structure on the lattice not resolved","How regulatory phosphorylation alters the CH-domain contact unknown"]},{"year":null,"claim":"How upstream kinase regulation (Plk1, Aurora-A) and recruitment factors (Samp1) mechanistically couple to the CH-domain MT-binding and NEDD1-recruitment activities to control branch nucleation in time and space remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No integrated structural model of the regulated augmin–gamma-TuRC nucleation event","Direct phosphorylation sites on HAUS6 itself remain unmapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[11,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,5,3]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[11,0]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,1,7]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,1,5]}],"complexes":["augmin (HAUS) complex"],"partners":["NEDD1","HAUS8","HICE1","PLK1","GAMMA-TUBULIN","NDC80","SAMP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q7Z4H7","full_name":"HAUS augmin-like complex subunit 6","aliases":[],"length_aa":955,"mass_kda":108.6,"function":"Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin","subcellular_location":"Cytoplasm, cytoskeleton; Cytoplasm, cytoskeleton, spindle; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/Q7Z4H7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/HAUS6","classification":"Common Essential","n_dependent_lines":1196,"n_total_lines":1208,"dependency_fraction":0.9900662251655629},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ARFIP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/HAUS6","total_profiled":1310},"omim":[{"mim_id":"613434","title":"HAUS AUGMIN-LIKE COMPLEX, SUBUNIT 8; HAUS8","url":"https://www.omim.org/entry/613434"},{"mim_id":"613433","title":"HAUS AUGMIN-LIKE COMPLEX, SUBUNIT 6; HAUS6","url":"https://www.omim.org/entry/613433"},{"mim_id":"613432","title":"HAUS AUGMIN-LIKE COMPLEX, SUBUNIT 5; HAUS5","url":"https://www.omim.org/entry/613432"},{"mim_id":"613431","title":"HAUS AUGMIN-LIKE COMPLEX, SUBUNIT 4; HAUS4","url":"https://www.omim.org/entry/613431"},{"mim_id":"613430","title":"HAUS AUGMIN-LIKE COMPLEX, SUBUNIT 3; HAUS3","url":"https://www.omim.org/entry/613430"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Centriolar satellite","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Acrosome","reliability":"Approved"},{"location":"Nuclear speckles","reliability":"Additional"},{"location":"Connecting piece","reliability":"Additional"},{"location":"Mid piece","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/HAUS6"},"hgnc":{"alias_symbol":["FLJ20060","KIAA1574","dgt6"],"prev_symbol":["FAM29A"]},"alphafold":{"accession":"Q7Z4H7","domains":[{"cath_id":"-","chopping":"2-146","consensus_level":"medium","plddt":83.8593,"start":2,"end":146},{"cath_id":"-","chopping":"271-331","consensus_level":"medium","plddt":73.6761,"start":271,"end":331},{"cath_id":"-","chopping":"351-402","consensus_level":"high","plddt":75.641,"start":351,"end":402},{"cath_id":"1.20.5","chopping":"161-218","consensus_level":"medium","plddt":87.5114,"start":161,"end":218},{"cath_id":"1.20.5","chopping":"231-262","consensus_level":"medium","plddt":80.3934,"start":231,"end":262}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z4H7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z4H7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z4H7-F1-predicted_aligned_error_v6.png","plddt_mean":55.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=HAUS6","jax_strain_url":"https://www.jax.org/strain/search?query=HAUS6"},"sequence":{"accession":"Q7Z4H7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z4H7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z4H7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z4H7"}},"corpus_meta":[{"pmid":"18443220","id":"PMC_18443220","title":"Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle.","date":"2008","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/18443220","citation_count":321,"is_preprint":false},{"pmid":"19029337","id":"PMC_19029337","title":"FAM29A promotes microtubule amplification via recruitment of the NEDD1-gamma-tubulin complex to the mitotic spindle.","date":"2008","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19029337","citation_count":95,"is_preprint":false},{"pmid":"31043753","id":"PMC_31043753","title":"A transcriptome-wide association study of high-grade serous epithelial ovarian cancer identifies new susceptibility genes and splice variants.","date":"2019","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31043753","citation_count":89,"is_preprint":false},{"pmid":"19836241","id":"PMC_19836241","title":"Drosophila Dgt6 interacts with Ndc80, Msps/XMAP215, and gamma-tubulin to promote kinetochore-driven MT formation.","date":"2009","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/19836241","citation_count":46,"is_preprint":false},{"pmid":"27121553","id":"PMC_27121553","title":"Identification of ZCCHC8 as fusion partner of ROS1 in a case of congenital glioblastoma multiforme with a t(6;12)(q21;q24.3).","date":"2016","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/27121553","citation_count":33,"is_preprint":false},{"pmid":"21705324","id":"PMC_21705324","title":"Aurora-A phosphorylates Augmin complex component Hice1 protein at an N-terminal serine/threonine cluster to modulate its microtubule binding activity during spindle assembly.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21705324","citation_count":30,"is_preprint":false},{"pmid":"39172836","id":"PMC_39172836","title":"Mechanisms of minor pole-mediated spindle bipolarization in human oocytes.","date":"2024","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/39172836","citation_count":26,"is_preprint":false},{"pmid":"28351835","id":"PMC_28351835","title":"Cross-linking mass spectrometry identifies new interfaces of Augmin required to localise the γ-tubulin ring complex to the mitotic spindle.","date":"2017","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/28351835","citation_count":22,"is_preprint":false},{"pmid":"19596795","id":"PMC_19596795","title":"FAM29A, a target of Plk1 regulation, controls the partitioning of NEDD1 between the mitotic spindle and the centrosomes.","date":"2009","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/19596795","citation_count":21,"is_preprint":false},{"pmid":"32526247","id":"PMC_32526247","title":"mRNA and microRNA selection for breast cancer molecular subtype stratification using meta-heuristic based algorithms.","date":"2020","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/32526247","citation_count":20,"is_preprint":false},{"pmid":"29514856","id":"PMC_29514856","title":"Mitotic spindle assembly and γ-tubulin localisation depend on the integral nuclear membrane protein Samp1.","date":"2018","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/29514856","citation_count":19,"is_preprint":false},{"pmid":"34427181","id":"PMC_34427181","title":"Augmin deficiency in neural stem cells causes p53-dependent apoptosis and aborts brain development.","date":"2021","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/34427181","citation_count":17,"is_preprint":false},{"pmid":"35096810","id":"PMC_35096810","title":"Down-Regulating HAUS6 Suppresses Cell Proliferation by Activating the p53/p21 Pathway in Colorectal Cancer.","date":"2022","source":"Frontiers in cell and developmental 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patients with colorectal cancer recurrence.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36324506","citation_count":4,"is_preprint":false},{"pmid":"19641730","id":"PMC_19641730","title":"Microtubule amplification in the assembly of mitotic spindle and the maturation of kinetochore fibers.","date":"2009","source":"Communicative & integrative biology","url":"https://pubmed.ncbi.nlm.nih.gov/19641730","citation_count":3,"is_preprint":false},{"pmid":"41173848","id":"PMC_41173848","title":"How augmin establishes the angle of the microtubule branch site.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41173848","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11242,"output_tokens":3373,"usd":0.04216,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10840,"output_tokens":4021,"usd":0.077363,"stage2_stop_reason":"end_turn"},"total_usd":0.119523,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2008,\n      \"finding\": \"HAUS6 (Dgt6) is a subunit of the augmin complex, a stable multi-protein complex of Dgt proteins required for centrosome-independent microtubule generation within the spindle; RNAi knockdown of each Dgt protein substantially reduces spindle microtubule generation, leading to reduced kinetochore fiber formation, chromosome misalignment, and spindle bipolarity defects, particularly in the absence of functional centrosomes.\",\n      \"method\": \"RNAi knockdown in Drosophila S2 cells, co-immunoprecipitation to show stable complex formation, live-cell and fixed imaging of spindle phenotypes\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP establishing complex, RNAi loss-of-function with defined cellular phenotypes, replicated across multiple subunits and independently in the same study\",\n      \"pmids\": [\"18443220\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"FAM29A (HAUS6 human homologue) promotes microtubule-dependent microtubule amplification by directly interacting with and recruiting the NEDD1–gamma-tubulin ring complex to spindle microtubules; depletion reduces spindle MT density, impairs kinetochore fiber formation, activates the spindle assembly checkpoint, and delays mitotic progression without affecting centrosome- or chromatin-based MT nucleation.\",\n      \"method\": \"siRNA knockdown, co-immunoprecipitation (FAM29A–NEDD1–gamma-tubulin), MT regrowth assay after nocodazole washout, immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP with multiple partners, loss-of-function with specific phenotypic readouts, orthogonal MT regrowth assay distinguishing nucleation pathways\",\n      \"pmids\": [\"19029337\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Drosophila Dgt6 (HAUS6 orthologue) is primarily required for kinetochore fiber (k-fiber) formation; co-precipitates with Msps/XMAP215, D-TACC, gamma-tubulin, Ndc80, and Nuf2; kinetochore-driven k-fiber regrowth after cold exposure is severely impaired in Dgt6-depleted cells, placing Dgt6 at the intersection of MT nucleation/stabilization and Ndc80 complex-mediated kinetochore attachment.\",\n      \"method\": \"RNAi knockdown, co-immunoprecipitation, MT regrowth assay after cold-induced depolymerization, immunofluorescence of k-fiber markers\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple Co-IP partners, loss-of-function with specific k-fiber regrowth assay, epistasis with gamma-tubulin/Msps/Ndc80 RNAi\",\n      \"pmids\": [\"19836241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"FAM29A (HAUS6) is regulated by Plk1: Plk1 recruits FAM29A to spindle microtubules, which in turn targets NEDD1 to the spindle; Plk1, FAM29A, and NEDD1 form three separate complexes in vivo rather than one single complex; altering FAM29A levels redistributes NEDD1 between the centrosomes and the spindle, demonstrating that FAM29A controls the partitioning of NEDD1 between these two mitotic structures.\",\n      \"method\": \"Co-immunoprecipitation, overexpression and knockdown with quantitative immunofluorescence of NEDD1 partitioning, epistasis with Plk1\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, two orthogonal functional approaches (OE and KD), quantitative redistribution assay; single lab\",\n      \"pmids\": [\"19596795\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Aurora-A kinase directly binds and phosphorylates the Augmin subunit Hice1 at an N-terminal Ser/Thr-17-21 cluster; phospho-mimetic mutation at this cluster reduces Hice1 microtubule binding activity in vitro, diminishes Hice1 spindle localization, and decreases FAM29A (HAUS6) association with spindles, while phospho-deficient mutation permits intraspindle nucleation but delays spindle pole separation.\",\n      \"method\": \"In vitro kinase assay, phospho-specific antibody immunostaining, MT cosedimentation/binding assay, phospho-mimetic and phospho-deficient mutagenesis, live-cell imaging\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase assay with site-directed mutagenesis plus in vivo functional validation; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"21705324\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Cross-linking mass spectrometry of in vivo Drosophila Augmin identified that Dgt6 (HAUS6 orthologue) directly binds the gamma-TuRC protein Dgp71WD (NEDD1 orthologue); this interaction is required for gamma-TuRC accumulation on the mitotic spindle but not for Augmin localization itself.\",\n      \"method\": \"Immuno-affinity purification of Augmin from Drosophila embryos, cross-linking/mass spectrometry, biochemical binding assays, in vivo rescue experiments in Drosophila embryo\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cross-linking MS providing structural distance restraints, biochemical binding validation, in vivo functional confirmation; single lab but orthogonal methods\",\n      \"pmids\": [\"28351835\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The inner nuclear membrane protein Samp1 co-precipitates with gamma-tubulin and the HAUS6 subunit of the Augmin complex in live cells, and Samp1 depletion reduces HAUS6 levels at the mitotic spindle, demonstrating that Samp1 is involved in recruiting HAUS6 and gamma-tubulin to the spindle.\",\n      \"method\": \"Co-immunoprecipitation from live cells, siRNA knockdown with quantitative immunofluorescence of HAUS6 at spindle, rescue by Samp1 overexpression\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus KD/rescue with defined localization phenotype; single lab, two orthogonal methods\",\n      \"pmids\": [\"29514856\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Conditional knockout of Haus6 in mouse apical neural progenitors causes spindle defects and mitotic delay, triggering massive p53-dependent apoptosis and aborting brain development; co-deletion of Trp53 rescues cell death but surviving progenitors display exacerbated mitotic errors, chromosomal defects, and increased DNA damage, showing that augmin/HAUS6 is essential for apical progenitor mitosis independent of p53 status.\",\n      \"method\": \"Conditional knockout mouse model, p53 co-deletion epistasis, live imaging, immunofluorescence of spindle markers and DNA damage\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo conditional KO with epistasis analysis (Trp53 co-deletion), multiple orthogonal phenotypic readouts, mouse model\",\n      \"pmids\": [\"34427181\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RNAi-mediated depletion of Dgt6 (HAUS6 Drosophila orthologue) causes a significant delay in kinetochore-driven microtubule regrowth (KDMTR) after colcemid-induced depolymerization in S2 cells, placing HAUS6/augmin as a positive regulator of kinetochore-driven spindle reassembly.\",\n      \"method\": \"RNAi reverse genetics, colcemid-induced MT depolymerization and regrowth assay, immunofluorescence quantification of KDMTR kinetics\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean RNAi loss-of-function with specific MT regrowth assay; single lab, single method\",\n      \"pmids\": [\"35883570\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"HAUS6 knockdown in colorectal cancer cell lines suppresses cell proliferation and arrests cell cycle at G0/G1 by reducing p53 and p21 degradation (activating the p53/p21 pathway), while HAUS6 overexpression increases cell viability; these effects are observed both in vitro and in vivo xenograft models.\",\n      \"method\": \"siRNA knockdown, overexpression, cell viability/proliferation assays, flow cytometry cell cycle analysis, in vivo xenograft, western blot of p53/p21 protein levels\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD and OE with defined phenotypic readout plus pathway analysis; single lab, multiple orthogonal assays\",\n      \"pmids\": [\"35096810\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"HAUS6 is essential for spindle bipolarization in human oocytes; loss-of-function studies identified HAUS6 as required for the transition from multipolar intermediates (formed at minor poles from kinetochore clusters) to a bipolar spindle; mutations in HAUS6 were identified in infertile patients with oocyte or embryo defects.\",\n      \"method\": \"High-resolution live imaging in >1800 human oocytes, loss-of-function experiments, patient mutation identification\",\n      \"journal\": \"Science (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct loss-of-function in human oocytes with defined spindle bipolarization phenotype plus patient mutation data; single study\",\n      \"pmids\": [\"39172836\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cryo-EM structure of an augmin subcomplex on the microtubule reveals that the conserved calponin-homology (CH) domain of Haus6 (HAUS6) directly contacts the MT lattice and is a bona fide MT binding site; the Haus6 CH domain increases augmin's affinity for MTs and, together with a second binding site in the disordered N-terminus of Haus8, establishes the shallow branch angle of newly nucleated microtubules.\",\n      \"method\": \"Cryo-electron microscopy structure determination, in vitro MT binding assays, mutagenesis of the CH domain\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cryo-EM structure with in vitro binding validation and mutagenesis; single study but multiple orthogonal methods including structural determination\",\n      \"pmids\": [\"41173848\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"HAUS6 (FAM29A/Dgt6) is a core subunit of the hetero-octameric augmin complex whose conserved CH domain directly binds the microtubule lattice—establishing branch angle and MT affinity—and whose interaction with the NEDD1–gamma-TuRC recruits the nucleation machinery to pre-existing spindle microtubules, thereby amplifying intraspindle microtubule number, promoting kinetochore fiber formation, and enabling bipolar spindle assembly; this activity is regulated upstream by Plk1 (which recruits HAUS6/FAM29A to the spindle) and by Aurora-A (which phosphorylates the Augmin subunit Hice1 to modulate MT binding and HAUS6 spindle association), and is essential in vivo for apical neural progenitor mitosis and human oocyte spindle bipolarization.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"HAUS6 (FAM29A/Dgt6) is a core subunit of the augmin complex that drives centrosome-independent, microtubule-dependent microtubule amplification within the mitotic spindle, thereby promoting kinetochore fiber formation and bipolar spindle assembly [#0, #1]. Mechanistically, its conserved calponin-homology (CH) domain directly contacts the microtubule lattice, increasing augmin's affinity for microtubules and, in concert with a second site in the HAUS8 N-terminus, setting the shallow branch angle of newly nucleated microtubules [#11]; in parallel, HAUS6 directly binds NEDD1 (Dgp71WD) and recruits the NEDD1–gamma-tubulin ring complex onto pre-existing spindle microtubules to seed new nucleation, an interaction required for gamma-TuRC spindle accumulation but not for augmin's own localization [#1, #5]. This amplification is especially required for kinetochore-driven microtubule regrowth and k-fiber formation, where Dgt6 acts together with gamma-tubulin, Msps/XMAP215 and the Ndc80 complex [#2, #8]. HAUS6 spindle recruitment is controlled upstream by Plk1, which targets HAUS6 to the spindle and thereby partitions NEDD1 between centrosomes and spindle, and by Aurora-A, which phosphorylates the augmin subunit Hice1 to modulate microtubule binding and HAUS6 spindle association [#3, #4]. Loss of HAUS6 is consequential in vivo: conditional knockout in mouse apical neural progenitors causes spindle defects, mitotic delay and p53-dependent apoptosis that aborts brain development [#7], and HAUS6 is required for spindle bipolarization in human oocytes, with patient mutations linked to oocyte/embryo defects [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Established that HAUS6/Dgt6 is a stable subunit of the augmin complex required for centrosome-independent microtubule generation inside the spindle, defining the complex responsible for intraspindle MT amplification.\",\n      \"evidence\": \"RNAi knockdown of Dgt proteins plus co-immunoprecipitation and spindle imaging in Drosophila S2 cells\",\n      \"pmids\": [\"18443220\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the molecular activity of HAUS6 within the complex\", \"Mechanism of how augmin generates new MTs not resolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Identified the molecular mechanism of amplification: the human homologue FAM29A directly binds and recruits the NEDD1–gamma-tubulin ring complex to spindle MTs, linking augmin to the nucleation machinery without affecting centrosome- or chromatin-based nucleation.\",\n      \"evidence\": \"siRNA knockdown, FAM29A–NEDD1–gamma-tubulin co-IP, and nocodazole-washout MT regrowth assay\",\n      \"pmids\": [\"19029337\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct vs bridged nature of the FAM29A–NEDD1 contact not structurally defined\", \"How NEDD1 is activated for nucleation on the spindle unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Placed Dgt6 at the interface of nucleation and kinetochore attachment by showing it is primarily required for k-fiber formation and physically associates with k-fiber and kinetochore components.\",\n      \"evidence\": \"RNAi, co-IP with Msps/D-TACC/gamma-tubulin/Ndc80/Nuf2, and cold-induced MT regrowth assay in Drosophila\",\n      \"pmids\": [\"19836241\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether interactions with Ndc80/Nuf2 are direct or indirect not established\", \"Order of recruitment between k-fiber nucleation and Ndc80 attachment unclear\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Defined upstream regulation: Plk1 recruits FAM29A to the spindle, and FAM29A levels in turn govern partitioning of NEDD1 between centrosomes and spindle, showing these factors form separate in vivo complexes rather than one.\",\n      \"evidence\": \"Co-IP, overexpression/knockdown with quantitative NEDD1 partitioning immunofluorescence, Plk1 epistasis\",\n      \"pmids\": [\"19596795\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct Plk1 phosphorylation site(s) on FAM29A not mapped\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Added a second kinase regulatory layer: Aurora-A phosphorylates the augmin subunit Hice1, reducing its MT binding and HAUS6 spindle association, coupling spindle pole dynamics to augmin activity.\",\n      \"evidence\": \"In vitro kinase assay, phospho-mimetic/deficient mutagenesis, MT cosedimentation, and live imaging\",\n      \"pmids\": [\"21705324\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Effect operates via Hice1, not HAUS6 directly\", \"In vivo phosphorylation timing during mitosis not fully resolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Provided structural-proximity evidence that Dgt6 directly binds the gamma-TuRC adaptor Dgp71WD/NEDD1 and that this contact is required for gamma-TuRC spindle accumulation but dispensable for augmin localization.\",\n      \"evidence\": \"Cross-linking mass spectrometry of in vivo Drosophila augmin, biochemical binding, and in vivo rescue\",\n      \"pmids\": [\"28351835\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic-resolution interface not defined\", \"Stoichiometry of the augmin–NEDD1 contact unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Implicated the inner nuclear membrane protein Samp1 in delivering HAUS6 and gamma-tubulin to the spindle, expanding the recruitment pathway beyond Plk1.\",\n      \"evidence\": \"Co-IP from live cells, siRNA knockdown with quantitative spindle immunofluorescence, and rescue\",\n      \"pmids\": [\"29514856\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the Samp1–HAUS6 interaction is direct not shown\", \"Single lab, two methods\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrated in vivo essentiality: HAUS6 is required for apical neural progenitor mitosis, with loss causing spindle defects and p53-dependent apoptosis that aborts brain development independent of p53 status.\",\n      \"evidence\": \"Conditional Haus6 knockout mouse with Trp53 co-deletion epistasis, live imaging, and DNA damage immunofluorescence\",\n      \"pmids\": [\"34427181\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue-specificity of HAUS6 requirement beyond neural progenitors not addressed\", \"Molecular trigger of the mitotic checkpoint response not dissected\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Confirmed HAUS6 as a positive regulator of kinetochore-driven microtubule regrowth, reinforcing its role in spindle reassembly after depolymerization.\",\n      \"evidence\": \"RNAi plus colcemid-induced depolymerization/regrowth kinetics in Drosophila S2 cells\",\n      \"pmids\": [\"35883570\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method, single lab\", \"Quantitative contribution relative to other regrowth pathways not parsed\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked HAUS6 to proliferative control in cancer, showing knockdown arrests colorectal cancer cells at G0/G1 by stabilizing p53/p21, connecting its mitotic function to tumor cell growth.\",\n      \"evidence\": \"siRNA/overexpression, cell cycle flow cytometry, xenografts, and p53/p21 western blot\",\n      \"pmids\": [\"35096810\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking spindle function to p53/p21 protein turnover not defined\", \"Whether effect is augmin-dependent or moonlighting unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established HAUS6 as required for spindle bipolarization in human oocytes and linked HAUS6 mutations to human infertility, extending its essentiality to human reproduction.\",\n      \"evidence\": \"High-resolution live imaging of >1800 human oocytes, loss-of-function, and patient mutation identification\",\n      \"pmids\": [\"39172836\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional impact of specific patient mutations not biochemically validated\", \"Single study\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolved the structural basis of microtubule engagement: the HAUS6 CH domain directly contacts the MT lattice, raises augmin's MT affinity, and together with the HAUS8 N-terminus sets the shallow branch angle of nucleated microtubules.\",\n      \"evidence\": \"Cryo-EM of an augmin subcomplex on microtubules with in vitro MT binding assays and CH-domain mutagenesis\",\n      \"pmids\": [\"41173848\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full-length octamer–gamma-TuRC structure on the lattice not resolved\", \"How regulatory phosphorylation alters the CH-domain contact unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How upstream kinase regulation (Plk1, Aurora-A) and recruitment factors (Samp1) mechanistically couple to the CH-domain MT-binding and NEDD1-recruitment activities to control branch nucleation in time and space remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No integrated structural model of the regulated augmin–gamma-TuRC nucleation event\", \"Direct phosphorylation sites on HAUS6 itself remain unmapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [11, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 5, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [0, 1, 3, 6]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [11, 0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 1, 7]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 1, 5]}\n    ],\n    \"complexes\": [\"augmin (HAUS) complex\"],\n    \"partners\": [\"NEDD1\", \"HAUS8\", \"Hice1\", \"Plk1\", \"gamma-tubulin\", \"Ndc80\", \"Samp1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}