Affinage

KATNB1

Katanin p80 WD40 repeat-containing subunit B1 · UniProt Q9BVA0

Length
655 aa
Mass
72.3 kDa
Annotated
2026-06-10
27 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KATNB1 encodes the noncatalytic regulatory (p80) subunit of the microtubule-severing enzyme katanin, where it binds the catalytic A-subunits KATNA1, KATNAL1, and KATNAL2 and acts as a master regulator that maintains their protein abundance and directs their activity to specific microtubule structures (PMID:25521378, PMID:26929214, PMID:34822718). Through this regulatory partnership it is required for proper mitotic spindle formation, and patient-derived fibroblasts carrying KATNB1 mutations show defective spindles, linking KATNB1 loss to microcephaly (PMID:25521378). KATNB1 controls centriole and cilia number and is required for Sonic hedgehog pathway activity during neocortical development, with its loss causing supernumerary centrioles and cilia (PMID:25521379). It coordinates microtubule remodeling with NuMA and cytoplasmic dynein, shuttling between the nucleus and spindle pole in a cell-cycle-dependent manner and driving aster formation (PMID:28079116). Beyond mitosis, KATNB1 is essential across spermatogenesis—governing meiosis, manchette remodeling and sperm head shaping (with KATNAL2 and TUBD1), and blood-testis barrier integrity through coordinated actin and microtubule organization in Sertoli cells (PMID:34822718, PMID:39275889, PMID:40586731)—and is required in motile ciliated lineages for left-right axis determination and CSF flow (PMID:28791777, PMID:36105588). KATNB1 is also recruited to microtubule cut sites with KATNAL1 to mediate bacterially-induced host microtubule disassembly during Klebsiella pneumoniae infection (PMID:30415487).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2013 Medium

    Before its regulation was known, the transcriptional control of KATNB1 was undefined; identifying its promoter and an activating transcription factor established how KATNB1 expression is set.

    Evidence Promoter deletion/reporter assays and EMSA showing Elk1 binding and activation in SH-SY5Y cells

    PMID:23894477

    Open questions at the time
    • Physiological contexts in which Elk1 drives KATNB1 are not defined
    • Link between SUMOylation and promoter repression is correlative
  2. 2014 High

    It was unknown whether KATNB1 regulatory function is required for spindle assembly in humans; patient mutations disrupting the KATNB1–KATNA1 interaction caused defective spindles and microcephaly, establishing KATNB1 as a spindle regulator and disease gene.

    Evidence Exome sequencing of microcephaly patients, patient-fibroblast spindle assays, and zebrafish/Drosophila loss-of-function

    PMID:25521378

    Open questions at the time
    • Structural basis of the KATNB1–KATNA1 interaction not resolved
    • Mechanism linking spindle defects to neuronal depletion not detailed
  3. 2014 High

    Whether katanin regulates centriole and cilia number was unknown; KATNB1 loss produced excess centrioles and cilia yet deficient Hedgehog signaling, revealing a centriole/cilia control function upstream of Shh.

    Evidence Katnb1 knockout mouse embryos, null fibroblast centriole/cilia counting and Hedgehog assays, and zebrafish loss-of-function

    PMID:25521379

    Open questions at the time
    • Molecular mechanism by which katanin limits centriole number unknown
    • Direct connection between cilia defects and Shh output not mechanistically dissected
  4. 2014 Medium

    Whether KATNB1 acts beyond the mitotic spindle in male germ cells was unclear; its localization to the spermatid manchette implicated it in sperm head shaping.

    Evidence Immunostaining and in situ hybridization across stages in human testicular biopsies

    PMID:25280067

    Open questions at the time
    • Functional requirement at the manchette not tested in this descriptive study
    • Catalytic partner at the manchette not identified here
  5. 2016 Medium

    The full set of katanin A-subunit partners and how subunit choice is governed were unresolved; interactome proteomics defined the Katan-ome and showed KATNB1 competes with KATNBL1 for binding A-subunits.

    Evidence Mass spectrometry interactome, in vitro severing assay, and cell-cycle localization

    PMID:26929214

    Open questions at the time
    • Functional consequence of KATNB1 vs KATNBL1 competition in vivo not established
    • Single-lab interactome without orthogonal validation of all partners
  6. 2016 Medium

    The cellular stages of KATNB1 expression during human spermatogenesis were uncharacterized; expression mapping placed it in meiotic and post-meiotic germ cells at centriole and Golgi/dictyosome structures.

    Evidence RT-PCR, in situ hybridization, and immunohistochemistry across 80 human testicular biopsies

    PMID:27717557

    Open questions at the time
    • Localization is descriptive without functional perturbation
    • Role at the Golgi/dictyosome not defined
  7. 2017 High

    How KATNB1 is spatially deployed during mitosis was unclear; it was shown to shuttle between nucleus and spindle pole with NuMA and dynein and to be required for aster formation, linking it functionally to neurogenesis.

    Evidence siRNA depletion in MEFs, in vitro aster assay, live imaging, mouse brain electroporation, and patient iPSC organoids

    PMID:28079116

    Open questions at the time
    • Whether KATNB1 shuttling depends on its severing partners is unknown
    • Direct biochemical interaction with NuMA/dynein not mapped
  8. 2017 Medium

    Whether katanin contributes to embryonic left-right patterning was unknown; Katnb1 mutations impaired left-right signaling and caused cardiac malformations, with strong node expression.

    Evidence Knockin-knockout mouse model, embryonic expression analysis, and phenotyping of null/hypomorphic embryos

    PMID:28791777

    Open questions at the time
    • Direct demonstration of nodal cilia motility defects not provided
    • Cell-type-specific requirement at the node not isolated
  9. 2017 Medium

    Whether KATNB1 is obligatory for all A-subunit activities was open; KATNAL2 was shown to act with or without KATNB1 depending on context, indicating context-dependent dependence.

    Evidence KATNAL2 knockout mouse with co-immunoprecipitation and immunolocalization with KATNB1

    PMID:29136647

    Open questions at the time
    • Determinants of KATNB1-dependent vs autonomous KATNAL2 activity unknown
    • Co-IP not reciprocally validated
  10. 2018 Medium

    Whether katanin participates in host responses to infection was unknown; KATNB1 and KATNAL1 were found at microtubule cut sites and required for bacterially-induced microtubule disassembly.

    Evidence siRNA knockdown and immunofluorescence localization in K. pneumoniae-infected lung epithelial cells

    PMID:30415487

    Open questions at the time
    • Bacterial signal triggering recruitment unidentified
    • Consequence for infection outcome not established
  11. 2021 High

    The hierarchy among katanin subunits in germ cells was unresolved; an allelic series placed KATNB1 upstream of all A-subunits, controlling their abundance and being indispensable for spermatogenesis.

    Evidence Multiple germ-cell Katnb1 knockout alleles with histology, A-subunit immunostaining, and stage-specific phenotyping

    PMID:34822718

    Open questions at the time
    • Mechanism by which KATNB1 stabilizes A-subunit protein unknown
    • Whether stabilization is direct or via localization not distinguished
  12. 2023 Medium

    The native tissue partners of KATNB1 were incompletely defined; testis AP-MS mapped a cytoskeletal and vesicle-trafficking interactome including KATNA1 and KATNAL1.

    Evidence Affinity purification mass spectrometry from mouse testis

    PMID:37882691

    Open questions at the time
    • Functional significance of vesicle-trafficking associations untested
    • Single-lab dataset without orthogonal confirmation
  13. 2024 Medium

    Whether KATNB1 contributes to the blood-testis barrier was unknown; reciprocal loss/gain of function showed it maintains tight junction barrier function via actin and microtubule organization in Sertoli cells.

    Evidence RNAi knockdown in primary Sertoli cells with TJ permeability assays and KATNB1 overexpression in a rat cadmium injury model

    PMID:39275889

    Open questions at the time
    • How KATNB1 coordinates actin in addition to microtubules is unclear
    • Catalytic A-subunit mediating this effect not identified
  14. 2025 Medium

    How manchette remodeling is controlled in haploid germ cells was incompletely understood; KATNB1 was shown to work with KATNAL2 and TUBD1 to regulate manchette remodeling and sperm head shaping.

    Evidence TUBD1 conditional knockout mouse with genetic interaction analysis and spermatogenesis phenotyping

    PMID:40586731

    Open questions at the time
    • Biochemical interaction between KATNB1, KATNAL2, and TUBD1 not mapped
    • Order of action among the three proteins not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural and biochemical basis by which KATNB1 stabilizes and spatially targets each katanin A-subunit, and how it switches between mitotic, ciliary, and germ-cell functions, remains unresolved.
  • No structure of the KATNB1–A-subunit complex
  • Mechanism of A-subunit protein stabilization unknown
  • Determinants of tissue- and context-specific partner selection undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 3 GO:0005815 microtubule organizing center 2 GO:0005929 cilium 2 GO:0005634 nucleus 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-1474165 Reproduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-162582 Signal Transduction 1
Partners
KATNA1KATNAL1KATNAL2KATNBL1NUMA1TUBD1
Complex memberships
Katanin (p60/p80) microtubule-severing complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 KATNB1 (katanin p80) is the regulatory subunit of the microtubule-severing enzyme Katanin, and its interaction with KATNA1 (the catalytic subunit) and other microtubule-associated proteins is required for proper mitotic spindle formation; patient-derived fibroblasts carrying KATNB1 mutations show defective mitotic spindle formation due to disrupted KATNB1–KATNA1 interactions. Exome sequencing of patient cohort; functional analysis of patient-derived fibroblasts (spindle formation assay); loss-of-function in zebrafish (katnb1) and Drosophila (kat80) with microcephaly phenotype; Drosophila neuroblast analysis showing supernumerary centrosomes and spindle abnormalities Neuron High 25521378
2014 Loss of KATNB1 causes a remarkable excess of centrioles with supernumerary cilia but deficient Hedgehog signaling, revealing an unexpected role for KATNB1 in regulating centriole number, mother centriole number, and cilia number, as well as in Sonic hedgehog pathway activity during neocortical development. Katnb1 knockout mouse embryos (hallmarks of aberrant Shh signaling including holoprosencephaly); KATNB1-deficient human cells (proliferation and spindle structure assays); Katnb1 null fibroblasts (centriole counting, cilia quantification, Hedgehog signaling assays); zebrafish katnb1 loss-of-function Neuron High 25521379
2017 KATNB1 (p80) regulates microtubule remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein; p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle (a feature shared with NuMA), and is essential for aster formation and maintenance in vitro. Depletion of p80 and/or NuMA induces abnormal mitotic phenotypes and aberrant neurogenesis/neuronal migration, confirmed in patient-derived iPSCs and brain organoids. siRNA-mediated depletion of p80 and/or NuMA in mouse embryonic fibroblasts; in vitro aster formation assay; live imaging of cell-cycle-dependent nuclear/spindle pole shuttling; mouse embryonic brain electroporation; patient-derived iPSCs and brain organoids Scientific reports High 28079116
2016 KATNB1 interacts with the katanin A-subunits KATNA1 and KATNAL1 (and KATNAL2 in some contexts) as part of the mammalian Katanin family interaction network; proteomic analysis (mass spectrometry) defined the Katanin family interactome (Katan-ome), and KATNB1 was shown to compete with KATNBL1 for binding to KATNA1 and KATNAL1. Mass spectrometry-based proteomics (pull-down/affinity purification); in vitro microtubule-severing activity assay for KATNBL1; localization studies during cell cycle Molecular & cellular proteomics : MCP Medium 26929214
2021 KATNB1 is a master regulator of all katanin enzymatic A-subunits (KATNA1, KATNAL1, KATNAL2) during mammalian spermatogenesis; it is required to maintain katanin A-subunit protein abundance, and complete loss of KATNB1 from germ cells is incompatible with sperm production. KATNB1 has essential roles in male meiosis, acrosome formation, sperm tail assembly, regulation of the Sertoli and germ cell cytoskeletons during sperm nuclear remodelling, and maintenance of seminiferous epithelium integrity. Allelic loss-of-function series (multiple mouse knockout alleles) of KATNB1 in germ cells; histological analysis of seminiferous epithelium; immunostaining for katanin A-subunit abundance; phenotypic readouts across spermatogenesis stages Development (Cambridge, England) High 34822718
2013 The KATNB1 gene is driven by a 518-bp TATA-less promoter containing a critical CpG island and GC boxes; sequential deletion of these elements reduces promoter activity. The transcription factor Elk1 binds the KATNB1 promoter (demonstrated by EMSA) and activates it, increasing both KATNB1 mRNA and protein levels. KCl treatment that increases SUMOylation decreases KATNB1 promoter activity. Promoter deletion/reporter assays; EMSA (Elk1 binding to KATNB1 promoter); qRT-PCR and western blot for mRNA and protein levels after Elk1 manipulation; KCl/SUMOylation treatment in SH-SY5Y cells PloS one Medium 23894477
2014 KATNB1 protein localizes to the microtubules of the manchette in human spermatids, a structure required for sperm head shaping, supporting a role in sperm morphogenesis beyond spindle formation. Immunostaining/immunofluorescence of human testicular biopsy samples; RT-PCR and in situ hybridization for mRNA expression across spermatogenesis stages Andrology Medium 25280067
2016 KATNB1 protein is expressed exclusively in germ cells during human spermatogenesis; it localizes to type B spermatogonia entering meiosis, the Golgi complex of pachytene spermatocytes, colocalizes with the cleaving centriole just before the first meiotic division, and is found in early round spermatids in the dictyosome, supporting roles in spindle formation and microtubule-based structures during spermiogenesis. RT-PCR, RT-qPCR, in situ hybridization, immunohistochemistry/immunofluorescence on 80 human testicular biopsy samples across normal and impaired spermatogenesis Fertility and sterility Medium 27717557
2017 Katnb1 is ubiquitously expressed during mouse embryonic development with stronger expression in the crown cells of the gastrulation organizer (murine node); null and hypomorphic Katnb1 mutations result in impaired left-right signaling and cardiac malformations, demonstrating a role for katanin in heart development. Knockin-knockout mouse model of Katnb1 dysfunction; in situ hybridization/expression analysis during embryogenesis; phenotypic characterization of null and hypomorphic embryos Developmental dynamics Medium 28791777
2022 In zebrafish, Katnb1 has an essential role in motile ciliated lineages; katnb1 mutants display defects in ependymal cell cilia and abnormal CSF flow that are associated with scoliosis, uncoupling ependymal cilia and Reissner fiber formation defects from spinal curvature while identifying abnormal CSF flow as a shared pathogenic signature. Zebrafish katnb1 mutant characterization; cilia motility assays; CSF flow measurement; spine curvature quantification; comparison across multiple scoliosis zebrafish models iScience Medium 36105588
2018 During Klebsiella pneumoniae infection of lung epithelial cells, KATNB1 and KATNAL1 localize specifically to microtubule cut sites and act as gatekeepers for the microtubule-severing event; knockdown of either protein in infected cells maintained intact microtubules, demonstrating that KATNB1 is required for bacterially-induced host microtubule disassembly. siRNA knockdown of KATNB1 and KATNAL1 in lung epithelial cells; immunofluorescence localization to microtubule cut sites during K. pneumoniae infection; assessment of microtubule integrity in KD cells Cellular microbiology Medium 30415487
2024 KATNB1 knockdown in rat primary Sertoli cells disrupts tight junction (TJ) permeability barrier function and causes perturbations in microtubule and actin cytoskeleton organization, leading to improper distribution of TJ and basal ectoplasmic specialization (ES) proteins. Conversely, overexpression of KATNB1 in the testis in vivo blocks cadmium-induced blood-testis barrier (BTB) disruption by maintaining proper cytoskeletal organization. RNAi knockdown of KATNB1 in primary Sertoli cells (TJ permeability assay); immunofluorescence colocalization with α-tubulin; KATNB1 overexpression in rat testis in vivo (cadmium injury model); western blot and immunostaining for cytoskeletal and junction proteins FASEB journal Medium 39275889
2025 KATNB1 works in partnership with KATNAL2 and TUBD1 (delta tubulin) in haploid male germ cells to regulate manchette remodeling and sperm head shaping, as demonstrated in a TUBD1 conditional knockout mouse model. Conditional knockout mouse model for TUBD1; genetic interaction analysis with KATNAL2 and KATNB1; immunostaining and phenotypic analysis of spermatogenesis The Journal of cell biology Medium 40586731
2017 KATNAL2 can partner with KATNB1 or act autonomously depending on cellular context during spermatogenesis; KATNB1 is not universally required for all katanin A-subunit activities. KATNAL2 knockout mouse model with analysis of spermatogenesis; immunolocalization and co-immunoprecipitation of KATNAL2 with KATNB1 PLoS genetics Medium 29136647
2023 The mammalian testis KATNB1 interactome (defined by proteomics) includes a network of cytoskeletal and vesicle trafficking proteins, with KATNB1 physically associating with KATNA1 and KATNAL1 in testis. Affinity purification mass spectrometry (AP-MS) from mouse testis to define KATNB1 interactome Development (Cambridge, England) Medium 37882691

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: relevance to neuronal network perturbation. Human molecular genetics 113 16687443
2014 Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors. Neuron 89 25521378
2014 Katanin p80 regulates human cortical development by limiting centriole and cilia number. Neuron 86 25521379
2017 Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse. PLoS genetics 53 29136647
2016 Optimizing a Male Reproductive Aging Mouse Model by D-Galactose Injection. International journal of molecular sciences 48 26771610
2016 Proteomic Analysis of the Mammalian Katanin Family of Microtubule-severing Enzymes Defines Katanin p80 subunit B-like 1 (KATNBL1) as a Regulator of Mammalian Katanin Microtubule-severing. Molecular & cellular proteomics : MCP 42 26929214
2017 Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics. Scientific reports 35 28079116
2019 Subcortical heterotopic gray matter brain malformations: Classification study of 107 individuals. Neurology 31 31484711
2024 Mediterranean diet protects against a neuroinflammatory cortical transcriptome: Associations with brain volumetrics, peripheral inflammation, social isolation, and anxiety in nonhuman primates (Macaca fascicularis). Brain, behavior, and immunity 23 38636565
2021 KATNB1 is a master regulator of multiple katanin enzymes in male meiosis and haploid germ cell development. Development (Cambridge, England) 23 34822718
2016 Expression of katanin p80 in human spermatogenesis. Fertility and sterility 19 27717557
2014 KATNB1 in the human testis and its genetic variants in fertile and oligoasthenoteratozoospermic infertile men. Andrology 18 25280067
2015 A syndrome of microcephaly, short stature, polysyndactyly, and dental anomalies caused by a homozygous KATNB1 mutation. American journal of medical genetics. Part A 13 26640080
2017 Mutations in the Katnb1 gene cause left-right asymmetry and heart defects. Developmental dynamics : an official publication of the American Association of Anatomists 12 28791777
2013 Katanin-p80 gene promoter characterization and regulation via Elk1. PloS one 11 23894477
2023 The katanin A-subunits KATNA1 and KATNAL1 act co-operatively in mammalian meiosis and spermiogenesis to achieve male fertility. Development (Cambridge, England) 8 37882691
2016 A 16q12.2q21 deletion identified in a patient with developmental delay, epilepsy, short stature, and distinctive features. Congenital anomalies 8 27230627
2022 Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model. iScience 6 36105588
2018 Klebsiella pneumoniae disassembles host microtubules in lung epithelial cells. Cellular microbiology 6 30415487
2015 Characterization of Ambra1 in asexual cycle of a non-vertebrate chordate, the colonial tunicate Botryllus schlosseri, and phylogenetic analysis of the protein group in Bilateria. Molecular phylogenetics and evolution 5 26611831
2024 Katanin regulatory subunit B1 (KATNB1) regulates BTB dynamics through changes in cytoskeletal organization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 39275889
2023 Haplotype-GGGT in long non-coding RNA MALAT1 inhibits brain metastatic lung cancer and lymph nodes of lung cancer via the MALAT1/miR-328/KATNB1. Aging 2 36934373
2023 A potential posttranscriptional regulator for p60-katanin: miR-124-3p. Cytoskeleton (Hoboken, N.J.) 2 37439368
2021 Whole Exome Sequencing Is the Minimal Technological Approach in Probands Born to Consanguineous Couples. Genes 2 34202629
2025 Delta tubulin stabilizes male meiotic kinetochores and aids microtubule remodeling and fertility. The Journal of cell biology 1 40586731
2023 Mediterranean Diet Protects Against a Neuroinflammatory Cortical Transcriptome: Associations with Brain Volumetrics, Peripheral Inflammation, Social Isolation and Anxiety. bioRxiv : the preprint server for biology 1 37961556
2023 The Challenge of Somatic Variants in Focal Cortical Dysplasia. Innovations in clinical neuroscience 0 38193103

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