{"gene":"KATNB1","run_date":"2026-04-28T18:06:54","timeline":{"discoveries":[{"year":2014,"finding":"KATNB1 (katanin p80) is the regulatory subunit of the microtubule-severing enzyme Katanin; loss-of-function mutations disrupt its interaction with KATNA1 (the catalytic subunit) and other microtubule-associated proteins, leading to defective mitotic spindle formation in patient-derived fibroblasts.","method":"Exome sequencing of patient cohort, functional analysis in patient-derived fibroblasts, interaction studies with KATNA1, zebrafish and Drosophila loss-of-function models","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — reciprocal interaction studies, multiple orthogonal model systems (human cells, zebrafish, fly), replicated across two independent 2014 papers","pmids":["25521378","25521379"],"is_preprint":false},{"year":2014,"finding":"Loss of KATNB1 in mice causes excess centrioles, supernumerary cilia, and deficient Hedgehog (Sonic hedgehog) signaling, revealing an unexpected role for KATNB1 in regulating centriole number, mother centriole number, and cilia number.","method":"Katnb1 knockout mouse model, immunofluorescence, centriole counting, Hedgehog signaling assays in null fibroblasts","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — clean KO mouse model with multiple defined cellular phenotypes (excess centrioles, supernumerary cilia, deficient Hh signaling)","pmids":["25521379"],"is_preprint":false},{"year":2014,"finding":"In Drosophila, loss of kat80 (KATNB1 ortholog) in asymmetrically dividing neuroblasts causes supernumerary centrosomes and spindle abnormalities during mitosis, leading to cell cycle progression delays and reduced cell numbers; kat80 loss also produces dendritic arborization defects in sensory and motor neurons.","method":"Drosophila kat80 loss-of-function, live imaging, immunostaining of mitotic spindles and centrosomes","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — genetic loss-of-function in model organism with defined cellular phenotypes and functional consequences in neuroblasts and neurons","pmids":["25521378"],"is_preprint":false},{"year":2017,"finding":"KATNB1 (p80) shuttles between the nucleus and spindle pole in synchrony with the cell cycle; it cooperates with NuMA and cytoplasmic dynein to regulate microtubule remodeling and is essential for aster formation and maintenance in vitro.","method":"siRNA knockdown, live-cell imaging, in vitro aster formation assay, patient-derived iPSCs and brain organoids, embryonic brain electroporation","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 — in vitro functional assay combined with live imaging, patient iPSCs, and in vivo mouse brain experiments; multiple orthogonal methods","pmids":["28079116"],"is_preprint":false},{"year":2017,"finding":"NuMA depletion and p80 (KATNB1) depletion produce overlapping mitotic and neurogenesis phenotypes, placing KATNB1 in a common pathway with NuMA for microtubule organization at the centrosome/spindle pole during neurogenesis and neuronal migration.","method":"siRNA co-depletion epistasis in cultured mouse embryonic fibroblasts, in utero electroporation in mouse embryonic brain","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis by co-depletion, single lab","pmids":["28079116"],"is_preprint":false},{"year":2016,"finding":"KATNB1 assembles a mammalian Katanin interaction network; mass spectrometry proteomics defined its protein interactors, and KATNB1 was shown to compete with KATNBL1 for binding to KATNA1 and KATNAL1, demonstrating that KATNB1 regulates which regulatory subunit associates with the catalytic subunits.","method":"Mass spectrometry-based proteomics (pulldown/AP-MS), competitive binding assays, in vitro microtubule-severing assays","journal":"Molecular & cellular proteomics","confidence":"High","confidence_rationale":"Tier 1-2 — AP-MS interactome plus in vitro competition and severing assays in a single study","pmids":["26929214"],"is_preprint":false},{"year":2013,"finding":"The KATNB1 promoter is TATA-less and contains a critical CpG island and GC boxes; the transcription factor Elk1 directly binds the KATNB1 promoter (shown by EMSA) and activates KATNB1 transcription, increasing both mRNA and protein levels of katanin p80 in SH-SY5Y cells. SUMOylation (induced by KCl) decreases KATNB1 promoter activity.","method":"Promoter deletion analysis (luciferase reporter), EMSA, qRT-PCR, western blotting, KCl/SUMOylation treatment","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 — EMSA plus functional reporter assays; single lab","pmids":["23894477"],"is_preprint":false},{"year":2021,"finding":"KATNB1 is a master regulator of all katanin catalytic A-subunits during mammalian spermatogenesis; it is required to maintain the abundance of katanin A-subunits (KATNA1, KATNAL1, KATNAL2), and complete loss of KATNB1 from germ cells abolishes sperm production with defects in meiosis, acrosome formation, sperm tail assembly, and seminiferous epithelium integrity.","method":"Allelic loss-of-function series (conditional KO mice), western blotting for A-subunit abundance, histology, immunofluorescence","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 — multiple alleles in mice, quantitative protein-level evidence for regulatory role over all A-subunits, multiple orthogonal phenotypic readouts","pmids":["34822718"],"is_preprint":false},{"year":2017,"finding":"KATNAL2 can partner with KATNB1 or act independently depending on cellular context during spermatogenesis; KATNB1 is required as a regulatory partner for multiple katanin A-subunits in the seminiferous epithelium.","method":"KATNAL2 knockout mouse model, co-immunoprecipitation, immunofluorescence","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2-3 — co-IP evidence for interaction, single lab","pmids":["29136647"],"is_preprint":false},{"year":2017,"finding":"Katnb1 is ubiquitously expressed during mouse embryonic development with stronger expression in the crown cells of the node (gastrulation organizer); loss-of-function Katnb1 mutations cause impaired left-right signaling and cardiac malformations, establishing a role for KATNB1 in cilia-mediated left-right axis determination.","method":"Knockin-knockout mouse model of Katnb1 dysfunction, in situ hybridization, histology","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2 — defined genetic model with specific phenotypic readouts, single lab","pmids":["28791777"],"is_preprint":false},{"year":2016,"finding":"KATNB1 protein localizes to the manchette microtubules in human spermatids and to the cleaving centriole just before the first meiotic division, as well as to the Golgi complex of pachytene spermatocytes, supporting roles in spindle formation and spermiogenesis structures.","method":"Immunohistochemistry/immunofluorescence on human testicular biopsy samples, in situ hybridization, RT-PCR","journal":"Fertility and sterility","confidence":"Medium","confidence_rationale":"Tier 3 — localization by immunostaining without direct functional manipulation in human tissue","pmids":["27717557"],"is_preprint":false},{"year":2014,"finding":"KATNB1 protein localizes to manchette microtubules in human spermatids, a structure required for sperm head shaping.","method":"Immunostaining of human testis tissue sections","journal":"Andrology","confidence":"Low","confidence_rationale":"Tier 3 — single localization method, no functional manipulation","pmids":["25280067"],"is_preprint":false},{"year":2018,"finding":"During Klebsiella pneumoniae infection of lung epithelia, both KATNAL1 and KATNB1 localize specifically to microtubule cut sites and are required for bacteria-induced microtubule severing; knockdown of either subunit maintained intact microtubules in infected cells.","method":"KATNAL1/KATNB1 knockout in lung epithelial cells, immunofluorescence localization to cut sites, in vitro and in vivo infection models","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 — KO phenotype (maintained microtubules) combined with localization to cut sites, single lab","pmids":["30415487"],"is_preprint":false},{"year":2022,"finding":"In zebrafish, Katnb1 is essential for motile cilia function in brain ependymal cells; katnb1 mutants show abnormal CSF flow and cell stress responses, uncoupling ependymal cilia/Reissner fiber defects from spinal curvature and identifying CSF flow disruption as a shared pathogenic signature for scoliosis.","method":"Zebrafish katnb1 mutant characterization, cilia motility imaging, CSF flow analysis","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 — genetic loss-of-function in zebrafish with mechanistic uncoupling experiments, single lab","pmids":["36105588"],"is_preprint":false},{"year":2024,"finding":"KATNB1 knockdown in Sertoli cells disrupts tight junction (blood-testis barrier) permeability and causes aberrant microtubule and actin cytoskeleton organization, leading to mislocalization of TJ and basal ES proteins; overexpression of KATNB1 in vivo blocks cadmium-induced blood-testis barrier disruption.","method":"RNAi knockdown in primary Sertoli cells, tight junction permeability assay, immunofluorescence, in vivo KATNB1 overexpression in rat testis","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 — both loss- and gain-of-function with defined cellular phenotypes, single lab","pmids":["39275889"],"is_preprint":false},{"year":2025,"finding":"TUBD1 (delta tubulin) works in partnership with KATNAL2 and KATNB1 to regulate manchette remodeling and sperm head shaping in haploid spermatogenic cells.","method":"Conditional knockout mouse model of TUBD1, co-localization and genetic interaction analysis with KATNAL2 and KATNB1","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — conditional KO mouse with defined partnership phenotype, single lab","pmids":["40586731"],"is_preprint":false},{"year":2023,"finding":"KATNA1 and KATNAL1 interact with KATNB1 as part of a mammalian testis interactome that includes cytoskeletal and vesicle trafficking proteins, defined by proteomics; KATNB1 acts as the shared regulatory hub for both A-subunits during meiosis and spermiogenesis.","method":"AP-MS proteomics of KATNA1, KATNAL1, and KATNB1 from mouse testis, double/single KO mice","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 — mass spectrometry interactome plus multiple genetic KO models, single lab","pmids":["37882691"],"is_preprint":false}],"current_model":"KATNB1 encodes the noncatalytic regulatory p80 subunit of the microtubule-severing enzyme katanin, where it physically interacts with and controls the localization and activity of the catalytic KATNA1 subunit (and paralogs KATNAL1/KATNAL2); it shuttles between nucleus and spindle pole in a cell-cycle-dependent manner, cooperates with NuMA and dynein for aster/spindle formation, regulates centriole and cilia number (thereby gating Hedgehog signaling), and acts as a master regulatory hub for all katanin A-subunits during spermatogenesis, with loss-of-function causing defective mitotic/meiotic spindles, microcephaly/lissencephaly, ciliopathy phenotypes, left-right asymmetry defects, and male infertility."},"narrative":{"teleology":[{"year":2013,"claim":"Before transcriptional control of KATNB1 was characterized, its upstream regulation was unknown; identification of Elk1 as a direct transcriptional activator of the TATA-less, CpG-island-containing KATNB1 promoter established that KATNB1 expression is regulated by MAP kinase signaling-responsive transcription factors and modulated by SUMOylation.","evidence":"Promoter deletion/luciferase reporter, EMSA for Elk1 binding, KCl-induced SUMOylation in SH-SY5Y cells","pmids":["23894477"],"confidence":"Medium","gaps":["In vivo relevance of Elk1-mediated KATNB1 regulation not tested","Whether SUMOylation-dependent repression operates during cell-cycle transitions is unknown"]},{"year":2014,"claim":"The core molecular function and disease relevance of KATNB1 were simultaneously established: it is the regulatory subunit of katanin that physically interacts with KATNA1, and its loss-of-function mutations cause microcephaly/lissencephaly by disrupting mitotic spindle formation in neural progenitors, while also causing excess centrioles, supernumerary cilia, and deficient Hedgehog signaling through deregulated centriole number control.","evidence":"Exome sequencing of patient families; functional studies in patient fibroblasts, Katnb1 KO mice, Drosophila kat80 mutants, and zebrafish morphants with centrosome counts, Hedgehog signaling assays, and spindle analyses","pmids":["25521378","25521379"],"confidence":"High","gaps":["Structural basis of p80-KATNA1 interaction not resolved","How KATNB1 limits centriole duplication mechanistically remains unclear","Whether ciliary and spindle phenotypes are separable contributions to microcephaly is unresolved"]},{"year":2016,"claim":"KATNB1 was shown to function as a competitive regulatory hub that assembles and selects among katanin complexes: mass spectrometry defined its interaction network, and KATNB1 competes with KATNBL1 for binding to KATNA1 and KATNAL1, establishing that the identity of the regulatory subunit gates catalytic complex composition.","evidence":"AP-MS proteomics, competitive binding assays, in vitro microtubule-severing reconstitution","pmids":["26929214"],"confidence":"High","gaps":["Stoichiometry and dynamics of KATNB1 vs KATNBL1 competition in vivo not determined","Whether complex switching occurs in a cell-cycle or tissue-specific manner is unknown"]},{"year":2017,"claim":"The mechanism by which KATNB1 organizes the mitotic spindle was clarified: p80 shuttles between nucleus and spindle pole in synchrony with the cell cycle and cooperates with NuMA and dynein for aster formation, placing it in a shared pathway for microtubule organization at the centrosome during neurogenesis.","evidence":"siRNA knockdown, live-cell imaging, in vitro aster assays, patient iPSC-derived brain organoids, in utero electroporation in mouse brain","pmids":["28079116"],"confidence":"High","gaps":["Direct physical interaction between KATNB1 and NuMA not demonstrated biochemically","Whether p80 nuclear-cytoplasmic shuttling is phosphorylation-regulated is unknown"]},{"year":2017,"claim":"Beyond mitosis, KATNB1 was found to be essential for cilia-mediated left-right axis determination: Katnb1 loss-of-function in mice causes impaired laterality signaling and cardiac malformations, extending KATNB1's role to nodal ciliary function.","evidence":"Knockin-knockout Katnb1 mouse model, in situ hybridization, histology of embryonic laterality defects","pmids":["28791777"],"confidence":"Medium","gaps":["Whether the laterality defect reflects altered ciliary motility, number, or both is not resolved","Not confirmed in a second independent model"]},{"year":2017,"claim":"The partnership between KATNB1 and individual A-subunits was shown to be context-dependent: KATNAL2 partners with KATNB1 during certain spermatogenic stages but can also function independently, indicating the modularity of katanin complex assembly.","evidence":"KATNAL2 KO mouse model, co-immunoprecipitation, immunofluorescence in seminiferous epithelium","pmids":["29136647"],"confidence":"Medium","gaps":["Structural determinants of KATNB1-KATNAL2 versus KATNB1-independent KATNAL2 modes unresolved","Co-IP evidence from a single lab without reciprocal pulldown"]},{"year":2018,"claim":"KATNB1 was shown to be co-opted during bacterial infection: both KATNAL1 and KATNB1 localize to microtubule cut sites during Klebsiella pneumoniae infection of lung epithelia, and their knockdown prevents pathogen-induced microtubule severing.","evidence":"KATNAL1/KATNB1 knockout in lung epithelial cells, immunofluorescence, in vitro/in vivo infection models","pmids":["30415487"],"confidence":"Medium","gaps":["Mechanism by which bacteria recruit or activate katanin at cut sites is unknown","Relevance to other bacterial pathogens not tested"]},{"year":2021,"claim":"KATNB1 was established as a master regulator of all katanin A-subunits in mammalian spermatogenesis: conditional loss from germ cells abolishes KATNA1, KATNAL1, and KATNAL2 protein abundance and eliminates sperm production, with defects spanning meiosis, acrosome biogenesis, and sperm tail assembly.","evidence":"Allelic loss-of-function series in conditional KO mice, western blotting for A-subunit levels, histology, immunofluorescence","pmids":["34822718"],"confidence":"High","gaps":["Whether KATNB1 stabilizes A-subunits through direct chaperoning or indirectly through complex formation is unknown","Contribution of individual A-subunits to each spermatogenic step not fully disentangled"]},{"year":2022,"claim":"KATNB1's role in motile cilia was extended to brain ependymal cells: zebrafish katnb1 mutants show defective ependymal cilia, abnormal CSF flow, and cell stress, revealing disrupted CSF circulation as a shared pathogenic mechanism linking katanin deficiency to scoliosis.","evidence":"Zebrafish katnb1 mutant, cilia motility imaging, CSF flow analysis","pmids":["36105588"],"confidence":"Medium","gaps":["Whether KATNB1 loss affects ciliary ultrastructure or only ciliary beating dynamics is unclear","Relevance of the CSF flow mechanism to mammalian scoliosis not validated"]},{"year":2023,"claim":"AP-MS proteomics from mouse testis defined the KATNB1-centered interactome that includes cytoskeletal and vesicle trafficking proteins, confirming KATNB1 as the shared regulatory hub for KATNA1 and KATNAL1 during meiosis and spermiogenesis.","evidence":"AP-MS of KATNA1, KATNAL1, KATNB1 from mouse testis, combined with double/single KO mice","pmids":["37882691"],"confidence":"Medium","gaps":["Functional validation of the broader interactome (vesicle trafficking partners) is lacking","Whether the interactome composition changes across spermatogenic stages is not resolved"]},{"year":2024,"claim":"KATNB1's function was extended to blood–testis barrier integrity: knockdown in Sertoli cells disrupts tight junction permeability and causes aberrant microtubule and actin cytoskeleton organization, while in vivo overexpression protects the barrier from cadmium-induced damage.","evidence":"RNAi in primary Sertoli cells, TJ permeability assay, in vivo KATNB1 overexpression in rat testis","pmids":["39275889"],"confidence":"Medium","gaps":["Whether this barrier role depends on catalytic severing activity or a scaffolding function of KATNB1 is unknown","Single-lab finding not yet independently replicated"]},{"year":2025,"claim":"TUBD1 (delta tubulin) was identified as a functional partner of KATNAL2-KATNB1 in regulating manchette remodeling and sperm head shaping, linking tubulin diversity to katanin-mediated spermatid morphogenesis.","evidence":"Conditional TUBD1 KO mouse, co-localization and genetic interaction with KATNAL2 and KATNB1","pmids":["40586731"],"confidence":"Medium","gaps":["Whether TUBD1 is incorporated into manchette microtubules as a substrate or acts as a cofactor is unresolved","Physical interaction between TUBD1 and KATNB1 not biochemically validated"]},{"year":null,"claim":"Critical open questions remain: how KATNB1 mechanistically limits centriole duplication, the structural basis of its competitive assembly of distinct katanin complexes, and whether its nuclear-cytoplasmic shuttling is regulated by post-translational modifications.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of full-length KATNB1 or its complex with any A-subunit","Post-translational modifications regulating KATNB1 localization and activity are uncharacterized","Mechanism by which KATNB1 controls centriole number is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,3,5]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[5,7,8]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[10,11,15]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,9,13]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,2,3]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,9,13]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[9]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[7,14,16]}],"complexes":["Katanin (p60/p80 heterodimer)"],"partners":["KATNA1","KATNAL1","KATNAL2","KATNBL1","NUMA1","TUBD1"],"other_free_text":[]},"mechanistic_narrative":"KATNB1 encodes the regulatory (p80) subunit of the microtubule-severing enzyme katanin, functioning as a central scaffold that physically interacts with and controls the localization, stability, and activity of all katanin catalytic A-subunits (KATNA1, KATNAL1, KATNAL2), competing with the alternative regulatory subunit KATNBL1 for A-subunit binding [PMID:26929214, PMID:34822718]. KATNB1 shuttles between the nucleus and spindle pole in a cell-cycle-dependent manner and cooperates with NuMA and cytoplasmic dynein to organize mitotic asters and spindles; its loss causes supernumerary centrioles, excess cilia, deficient Hedgehog signaling, and impaired left-right axis determination through disrupted nodal cilia function [PMID:28079116, PMID:25521379, PMID:28791777]. Loss-of-function mutations in KATNB1 cause autosomal recessive microcephaly with lissencephaly, linked to defective mitotic spindle formation in neural progenitors [PMID:25521378, PMID:25521379]. In the male germline, KATNB1 is a master regulator required for meiotic spindle integrity, manchette-mediated sperm head shaping, acrosome biogenesis, and blood–testis barrier maintenance, with complete germ-cell loss of KATNB1 abolishing spermatogenesis [PMID:34822718, PMID:39275889]."},"prefetch_data":{"uniprot":{"accession":"Q9BVA0","full_name":"Katanin p80 WD40 repeat-containing subunit B1","aliases":["p80 katanin"],"length_aa":655,"mass_kda":72.3,"function":"Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth","subcellular_location":"Cytoplasm; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle pole; Cytoplasm, cytoskeleton; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/Q9BVA0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KATNB1","classification":"Not Classified","n_dependent_lines":547,"n_total_lines":1208,"dependency_fraction":0.45281456953642385},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KATNB1","total_profiled":1310},"omim":[{"mim_id":"616235","title":"KATANIN, p80 SUBUNIT, B-LIKE 1; KATNBL1","url":"https://www.omim.org/entry/616235"},{"mim_id":"616212","title":"LISSENCEPHALY 6 WITH MICROCEPHALY; LIS6","url":"https://www.omim.org/entry/616212"},{"mim_id":"610454","title":"LEUCINE ZIPPER, PUTATIVE TUMOR SUPPRESSOR 2; LZTS2","url":"https://www.omim.org/entry/610454"},{"mim_id":"607432","title":"LISSENCEPHALY 1; LIS1","url":"https://www.omim.org/entry/607432"},{"mim_id":"606696","title":"KATANIN, p60 SUBUNIT, A1; KATNA1","url":"https://www.omim.org/entry/606696"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"Plasma membrane","reliability":"Additional"},{"location":"Microtubules","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/KATNB1"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9BVA0","domains":[{"cath_id":"2.130.10.10","chopping":"11-308_372-378","consensus_level":"high","plddt":94.275,"start":11,"end":378},{"cath_id":"-","chopping":"503-652","consensus_level":"high","plddt":89.5606,"start":503,"end":652}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BVA0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BVA0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BVA0-F1-predicted_aligned_error_v6.png","plddt_mean":79.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KATNB1","jax_strain_url":"https://www.jax.org/strain/search?query=KATNB1"},"sequence":{"accession":"Q9BVA0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BVA0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BVA0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BVA0"}},"corpus_meta":[{"pmid":"16687443","id":"PMC_16687443","title":"Genome-wide 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loss-of-function mutations disrupt its interaction with KATNA1 (the catalytic subunit) and other microtubule-associated proteins, leading to defective mitotic spindle formation in patient-derived fibroblasts.\",\n      \"method\": \"Exome sequencing of patient cohort, functional analysis in patient-derived fibroblasts, interaction studies with KATNA1, zebrafish and Drosophila loss-of-function models\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction studies, multiple orthogonal model systems (human cells, zebrafish, fly), replicated across two independent 2014 papers\",\n      \"pmids\": [\"25521378\", \"25521379\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Loss of KATNB1 in mice causes excess centrioles, supernumerary cilia, and deficient Hedgehog (Sonic hedgehog) signaling, revealing an unexpected role for KATNB1 in regulating centriole number, mother centriole number, and cilia number.\",\n      \"method\": \"Katnb1 knockout mouse model, immunofluorescence, centriole counting, Hedgehog signaling assays in null fibroblasts\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO mouse model with multiple defined cellular phenotypes (excess centrioles, supernumerary cilia, deficient Hh signaling)\",\n      \"pmids\": [\"25521379\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In Drosophila, loss of kat80 (KATNB1 ortholog) in asymmetrically dividing neuroblasts causes supernumerary centrosomes and spindle abnormalities during mitosis, leading to cell cycle progression delays and reduced cell numbers; kat80 loss also produces dendritic arborization defects in sensory and motor neurons.\",\n      \"method\": \"Drosophila kat80 loss-of-function, live imaging, immunostaining of mitotic spindles and centrosomes\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function in model organism with defined cellular phenotypes and functional consequences in neuroblasts and neurons\",\n      \"pmids\": [\"25521378\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KATNB1 (p80) shuttles between the nucleus and spindle pole in synchrony with the cell cycle; it cooperates with NuMA and cytoplasmic dynein to regulate microtubule remodeling and is essential for aster formation and maintenance in vitro.\",\n      \"method\": \"siRNA knockdown, live-cell imaging, in vitro aster formation assay, patient-derived iPSCs and brain organoids, embryonic brain electroporation\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vitro functional assay combined with live imaging, patient iPSCs, and in vivo mouse brain experiments; multiple orthogonal methods\",\n      \"pmids\": [\"28079116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"NuMA depletion and p80 (KATNB1) depletion produce overlapping mitotic and neurogenesis phenotypes, placing KATNB1 in a common pathway with NuMA for microtubule organization at the centrosome/spindle pole during neurogenesis and neuronal migration.\",\n      \"method\": \"siRNA co-depletion epistasis in cultured mouse embryonic fibroblasts, in utero electroporation in mouse embryonic brain\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis by co-depletion, single lab\",\n      \"pmids\": [\"28079116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KATNB1 assembles a mammalian Katanin interaction network; mass spectrometry proteomics defined its protein interactors, and KATNB1 was shown to compete with KATNBL1 for binding to KATNA1 and KATNAL1, demonstrating that KATNB1 regulates which regulatory subunit associates with the catalytic subunits.\",\n      \"method\": \"Mass spectrometry-based proteomics (pulldown/AP-MS), competitive binding assays, in vitro microtubule-severing assays\",\n      \"journal\": \"Molecular & cellular proteomics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — AP-MS interactome plus in vitro competition and severing assays in a single study\",\n      \"pmids\": [\"26929214\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The KATNB1 promoter is TATA-less and contains a critical CpG island and GC boxes; the transcription factor Elk1 directly binds the KATNB1 promoter (shown by EMSA) and activates KATNB1 transcription, increasing both mRNA and protein levels of katanin p80 in SH-SY5Y cells. SUMOylation (induced by KCl) decreases KATNB1 promoter activity.\",\n      \"method\": \"Promoter deletion analysis (luciferase reporter), EMSA, qRT-PCR, western blotting, KCl/SUMOylation treatment\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — EMSA plus functional reporter assays; single lab\",\n      \"pmids\": [\"23894477\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KATNB1 is a master regulator of all katanin catalytic A-subunits during mammalian spermatogenesis; it is required to maintain the abundance of katanin A-subunits (KATNA1, KATNAL1, KATNAL2), and complete loss of KATNB1 from germ cells abolishes sperm production with defects in meiosis, acrosome formation, sperm tail assembly, and seminiferous epithelium integrity.\",\n      \"method\": \"Allelic loss-of-function series (conditional KO mice), western blotting for A-subunit abundance, histology, immunofluorescence\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple alleles in mice, quantitative protein-level evidence for regulatory role over all A-subunits, multiple orthogonal phenotypic readouts\",\n      \"pmids\": [\"34822718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KATNAL2 can partner with KATNB1 or act independently depending on cellular context during spermatogenesis; KATNB1 is required as a regulatory partner for multiple katanin A-subunits in the seminiferous epithelium.\",\n      \"method\": \"KATNAL2 knockout mouse model, co-immunoprecipitation, immunofluorescence\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — co-IP evidence for interaction, single lab\",\n      \"pmids\": [\"29136647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Katnb1 is ubiquitously expressed during mouse embryonic development with stronger expression in the crown cells of the node (gastrulation organizer); loss-of-function Katnb1 mutations cause impaired left-right signaling and cardiac malformations, establishing a role for KATNB1 in cilia-mediated left-right axis determination.\",\n      \"method\": \"Knockin-knockout mouse model of Katnb1 dysfunction, in situ hybridization, histology\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — defined genetic model with specific phenotypic readouts, single lab\",\n      \"pmids\": [\"28791777\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KATNB1 protein localizes to the manchette microtubules in human spermatids and to the cleaving centriole just before the first meiotic division, as well as to the Golgi complex of pachytene spermatocytes, supporting roles in spindle formation and spermiogenesis structures.\",\n      \"method\": \"Immunohistochemistry/immunofluorescence on human testicular biopsy samples, in situ hybridization, RT-PCR\",\n      \"journal\": \"Fertility and sterility\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — localization by immunostaining without direct functional manipulation in human tissue\",\n      \"pmids\": [\"27717557\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KATNB1 protein localizes to manchette microtubules in human spermatids, a structure required for sperm head shaping.\",\n      \"method\": \"Immunostaining of human testis tissue sections\",\n      \"journal\": \"Andrology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single localization method, no functional manipulation\",\n      \"pmids\": [\"25280067\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"During Klebsiella pneumoniae infection of lung epithelia, both KATNAL1 and KATNB1 localize specifically to microtubule cut sites and are required for bacteria-induced microtubule severing; knockdown of either subunit maintained intact microtubules in infected cells.\",\n      \"method\": \"KATNAL1/KATNB1 knockout in lung epithelial cells, immunofluorescence localization to cut sites, in vitro and in vivo infection models\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO phenotype (maintained microtubules) combined with localization to cut sites, single lab\",\n      \"pmids\": [\"30415487\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In zebrafish, Katnb1 is essential for motile cilia function in brain ependymal cells; katnb1 mutants show abnormal CSF flow and cell stress responses, uncoupling ependymal cilia/Reissner fiber defects from spinal curvature and identifying CSF flow disruption as a shared pathogenic signature for scoliosis.\",\n      \"method\": \"Zebrafish katnb1 mutant characterization, cilia motility imaging, CSF flow analysis\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function in zebrafish with mechanistic uncoupling experiments, single lab\",\n      \"pmids\": [\"36105588\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KATNB1 knockdown in Sertoli cells disrupts tight junction (blood-testis barrier) permeability and causes aberrant microtubule and actin cytoskeleton organization, leading to mislocalization of TJ and basal ES proteins; overexpression of KATNB1 in vivo blocks cadmium-induced blood-testis barrier disruption.\",\n      \"method\": \"RNAi knockdown in primary Sertoli cells, tight junction permeability assay, immunofluorescence, in vivo KATNB1 overexpression in rat testis\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — both loss- and gain-of-function with defined cellular phenotypes, single lab\",\n      \"pmids\": [\"39275889\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TUBD1 (delta tubulin) works in partnership with KATNAL2 and KATNB1 to regulate manchette remodeling and sperm head shaping in haploid spermatogenic cells.\",\n      \"method\": \"Conditional knockout mouse model of TUBD1, co-localization and genetic interaction analysis with KATNAL2 and KATNB1\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — conditional KO mouse with defined partnership phenotype, single lab\",\n      \"pmids\": [\"40586731\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"KATNA1 and KATNAL1 interact with KATNB1 as part of a mammalian testis interactome that includes cytoskeletal and vesicle trafficking proteins, defined by proteomics; KATNB1 acts as the shared regulatory hub for both A-subunits during meiosis and spermiogenesis.\",\n      \"method\": \"AP-MS proteomics of KATNA1, KATNAL1, and KATNB1 from mouse testis, double/single KO mice\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — mass spectrometry interactome plus multiple genetic KO models, single lab\",\n      \"pmids\": [\"37882691\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KATNB1 encodes the noncatalytic regulatory p80 subunit of the microtubule-severing enzyme katanin, where it physically interacts with and controls the localization and activity of the catalytic KATNA1 subunit (and paralogs KATNAL1/KATNAL2); it shuttles between nucleus and spindle pole in a cell-cycle-dependent manner, cooperates with NuMA and dynein for aster/spindle formation, regulates centriole and cilia number (thereby gating Hedgehog signaling), and acts as a master regulatory hub for all katanin A-subunits during spermatogenesis, with loss-of-function causing defective mitotic/meiotic spindles, microcephaly/lissencephaly, ciliopathy phenotypes, left-right asymmetry defects, and male infertility.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"KATNB1 encodes the regulatory (p80) subunit of the microtubule-severing enzyme katanin, functioning as a central scaffold that physically interacts with and controls the localization, stability, and activity of all katanin catalytic A-subunits (KATNA1, KATNAL1, KATNAL2), competing with the alternative regulatory subunit KATNBL1 for A-subunit binding [PMID:26929214, PMID:34822718]. KATNB1 shuttles between the nucleus and spindle pole in a cell-cycle-dependent manner and cooperates with NuMA and cytoplasmic dynein to organize mitotic asters and spindles; its loss causes supernumerary centrioles, excess cilia, deficient Hedgehog signaling, and impaired left-right axis determination through disrupted nodal cilia function [PMID:28079116, PMID:25521379, PMID:28791777]. Loss-of-function mutations in KATNB1 cause autosomal recessive microcephaly with lissencephaly, linked to defective mitotic spindle formation in neural progenitors [PMID:25521378, PMID:25521379]. In the male germline, KATNB1 is a master regulator required for meiotic spindle integrity, manchette-mediated sperm head shaping, acrosome biogenesis, and blood–testis barrier maintenance, with complete germ-cell loss of KATNB1 abolishing spermatogenesis [PMID:34822718, PMID:39275889].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Before transcriptional control of KATNB1 was characterized, its upstream regulation was unknown; identification of Elk1 as a direct transcriptional activator of the TATA-less, CpG-island-containing KATNB1 promoter established that KATNB1 expression is regulated by MAP kinase signaling-responsive transcription factors and modulated by SUMOylation.\",\n      \"evidence\": \"Promoter deletion/luciferase reporter, EMSA for Elk1 binding, KCl-induced SUMOylation in SH-SY5Y cells\",\n      \"pmids\": [\"23894477\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"In vivo relevance of Elk1-mediated KATNB1 regulation not tested\",\n        \"Whether SUMOylation-dependent repression operates during cell-cycle transitions is unknown\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The core molecular function and disease relevance of KATNB1 were simultaneously established: it is the regulatory subunit of katanin that physically interacts with KATNA1, and its loss-of-function mutations cause microcephaly/lissencephaly by disrupting mitotic spindle formation in neural progenitors, while also causing excess centrioles, supernumerary cilia, and deficient Hedgehog signaling through deregulated centriole number control.\",\n      \"evidence\": \"Exome sequencing of patient families; functional studies in patient fibroblasts, Katnb1 KO mice, Drosophila kat80 mutants, and zebrafish morphants with centrosome counts, Hedgehog signaling assays, and spindle analyses\",\n      \"pmids\": [\"25521378\", \"25521379\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of p80-KATNA1 interaction not resolved\",\n        \"How KATNB1 limits centriole duplication mechanistically remains unclear\",\n        \"Whether ciliary and spindle phenotypes are separable contributions to microcephaly is unresolved\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"KATNB1 was shown to function as a competitive regulatory hub that assembles and selects among katanin complexes: mass spectrometry defined its interaction network, and KATNB1 competes with KATNBL1 for binding to KATNA1 and KATNAL1, establishing that the identity of the regulatory subunit gates catalytic complex composition.\",\n      \"evidence\": \"AP-MS proteomics, competitive binding assays, in vitro microtubule-severing reconstitution\",\n      \"pmids\": [\"26929214\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Stoichiometry and dynamics of KATNB1 vs KATNBL1 competition in vivo not determined\",\n        \"Whether complex switching occurs in a cell-cycle or tissue-specific manner is unknown\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The mechanism by which KATNB1 organizes the mitotic spindle was clarified: p80 shuttles between nucleus and spindle pole in synchrony with the cell cycle and cooperates with NuMA and dynein for aster formation, placing it in a shared pathway for microtubule organization at the centrosome during neurogenesis.\",\n      \"evidence\": \"siRNA knockdown, live-cell imaging, in vitro aster assays, patient iPSC-derived brain organoids, in utero electroporation in mouse brain\",\n      \"pmids\": [\"28079116\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct physical interaction between KATNB1 and NuMA not demonstrated biochemically\",\n        \"Whether p80 nuclear-cytoplasmic shuttling is phosphorylation-regulated is unknown\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Beyond mitosis, KATNB1 was found to be essential for cilia-mediated left-right axis determination: Katnb1 loss-of-function in mice causes impaired laterality signaling and cardiac malformations, extending KATNB1's role to nodal ciliary function.\",\n      \"evidence\": \"Knockin-knockout Katnb1 mouse model, in situ hybridization, histology of embryonic laterality defects\",\n      \"pmids\": [\"28791777\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the laterality defect reflects altered ciliary motility, number, or both is not resolved\",\n        \"Not confirmed in a second independent model\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The partnership between KATNB1 and individual A-subunits was shown to be context-dependent: KATNAL2 partners with KATNB1 during certain spermatogenic stages but can also function independently, indicating the modularity of katanin complex assembly.\",\n      \"evidence\": \"KATNAL2 KO mouse model, co-immunoprecipitation, immunofluorescence in seminiferous epithelium\",\n      \"pmids\": [\"29136647\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural determinants of KATNB1-KATNAL2 versus KATNB1-independent KATNAL2 modes unresolved\",\n        \"Co-IP evidence from a single lab without reciprocal pulldown\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"KATNB1 was shown to be co-opted during bacterial infection: both KATNAL1 and KATNB1 localize to microtubule cut sites during Klebsiella pneumoniae infection of lung epithelia, and their knockdown prevents pathogen-induced microtubule severing.\",\n      \"evidence\": \"KATNAL1/KATNB1 knockout in lung epithelial cells, immunofluorescence, in vitro/in vivo infection models\",\n      \"pmids\": [\"30415487\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which bacteria recruit or activate katanin at cut sites is unknown\",\n        \"Relevance to other bacterial pathogens not tested\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"KATNB1 was established as a master regulator of all katanin A-subunits in mammalian spermatogenesis: conditional loss from germ cells abolishes KATNA1, KATNAL1, and KATNAL2 protein abundance and eliminates sperm production, with defects spanning meiosis, acrosome biogenesis, and sperm tail assembly.\",\n      \"evidence\": \"Allelic loss-of-function series in conditional KO mice, western blotting for A-subunit levels, histology, immunofluorescence\",\n      \"pmids\": [\"34822718\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether KATNB1 stabilizes A-subunits through direct chaperoning or indirectly through complex formation is unknown\",\n        \"Contribution of individual A-subunits to each spermatogenic step not fully disentangled\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"KATNB1's role in motile cilia was extended to brain ependymal cells: zebrafish katnb1 mutants show defective ependymal cilia, abnormal CSF flow, and cell stress, revealing disrupted CSF circulation as a shared pathogenic mechanism linking katanin deficiency to scoliosis.\",\n      \"evidence\": \"Zebrafish katnb1 mutant, cilia motility imaging, CSF flow analysis\",\n      \"pmids\": [\"36105588\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether KATNB1 loss affects ciliary ultrastructure or only ciliary beating dynamics is unclear\",\n        \"Relevance of the CSF flow mechanism to mammalian scoliosis not validated\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"AP-MS proteomics from mouse testis defined the KATNB1-centered interactome that includes cytoskeletal and vesicle trafficking proteins, confirming KATNB1 as the shared regulatory hub for KATNA1 and KATNAL1 during meiosis and spermiogenesis.\",\n      \"evidence\": \"AP-MS of KATNA1, KATNAL1, KATNB1 from mouse testis, combined with double/single KO mice\",\n      \"pmids\": [\"37882691\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional validation of the broader interactome (vesicle trafficking partners) is lacking\",\n        \"Whether the interactome composition changes across spermatogenic stages is not resolved\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"KATNB1's function was extended to blood–testis barrier integrity: knockdown in Sertoli cells disrupts tight junction permeability and causes aberrant microtubule and actin cytoskeleton organization, while in vivo overexpression protects the barrier from cadmium-induced damage.\",\n      \"evidence\": \"RNAi in primary Sertoli cells, TJ permeability assay, in vivo KATNB1 overexpression in rat testis\",\n      \"pmids\": [\"39275889\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether this barrier role depends on catalytic severing activity or a scaffolding function of KATNB1 is unknown\",\n        \"Single-lab finding not yet independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"TUBD1 (delta tubulin) was identified as a functional partner of KATNAL2-KATNB1 in regulating manchette remodeling and sperm head shaping, linking tubulin diversity to katanin-mediated spermatid morphogenesis.\",\n      \"evidence\": \"Conditional TUBD1 KO mouse, co-localization and genetic interaction with KATNAL2 and KATNB1\",\n      \"pmids\": [\"40586731\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether TUBD1 is incorporated into manchette microtubules as a substrate or acts as a cofactor is unresolved\",\n        \"Physical interaction between TUBD1 and KATNB1 not biochemically validated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Critical open questions remain: how KATNB1 mechanistically limits centriole duplication, the structural basis of its competitive assembly of distinct katanin complexes, and whether its nuclear-cytoplasmic shuttling is regulated by post-translational modifications.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of full-length KATNB1 or its complex with any A-subunit\",\n        \"Post-translational modifications regulating KATNB1 localization and activity are uncharacterized\",\n        \"Mechanism by which KATNB1 controls centriole number is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 3, 5]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [5, 7, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [10, 11, 15]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 9, 13]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 9, 13]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [7, 14, 16]}\n    ],\n    \"complexes\": [\n      \"Katanin (p60/p80 heterodimer)\"\n    ],\n    \"partners\": [\n      \"KATNA1\",\n      \"KATNAL1\",\n      \"KATNAL2\",\n      \"KATNBL1\",\n      \"NUMA1\",\n      \"TUBD1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}