Affinage

KATNA1

Katanin p60 ATPase-containing subunit A1 · UniProt O75449

Length
491 aa
Mass
56.0 kDa
Annotated
2026-06-10
24 papers in source corpus 13 papers cited in narrative 13 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

KATNA1 encodes katanin p60, the catalytic AAA+ ATPase subunit that drives microtubule severing and thereby governs cytoskeletal remodeling in mitotic and meiotic spindle assembly, cytokinesis, and neuronal morphogenesis (PMID:26929214, PMID:31685876, PMID:37882691). Its severing activity is tuned by accessory subunits: KATNBL1 and the regulatory subunit KATNB1 compete for binding to KATNA1 and modulate its activity in vitro, and disruption of the KATNB1–KATNA1 interaction underlies defective mitotic spindle formation in patient fibroblasts (PMID:26929214, PMID:25521378). Severing output is further potentiated by direct partners that engage distinct domains — CRMP3 and EEF1B2 bind the MIT domain (residues 1–77) and the AAA+ ATPase domain respectively to enhance severing and synergistically promote neurite outgrowth and branching (PMID:39938451, PMID:42002067) — and by SUMO2 conjugation at K330, which augments severing and hippocampal neurite outgrowth (PMID:35868557). Through a MIT-domain interaction with the ESCRT-III subunit CHMP3, KATNA1 is recruited to cytokinetic midbody bridges to execute abscission (PMID:36107470). Transcriptionally, p53 binds the KATNA1 promoter and activates its expression, while Elk1 and miR-124-3p impose post-transcriptional repression of katanin-p60 protein (PMID:31715301, PMID:30789974). Genetically, KATNA1 is essential in mice, with haploinsufficiency impairing neuronal progenitor proliferation, and it acts both cooperatively with its paralogue KATNAL1 in male meiosis and spermatid remodeling and in a KATNAL1-independent manner in oocyte spindle function and early embryo development (PMID:31685876, PMID:37882691, PMID:40668235).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2014 Medium

    Established that the physical KATNA1–KATNB1 interaction is functionally required for mitotic spindle assembly, linking katanin subunit assembly to human disease.

    Evidence Exome sequencing of a patient cohort plus KATNB1-mutant/KATNA1 interaction studies and spindle analysis in patient-derived fibroblasts

    PMID:25521378

    Open questions at the time
    • No reconstitution defining how the interaction modulates KATNA1 catalytic activity
    • Mechanism linking spindle defect to specific developmental phenotype unresolved
  2. 2016 High

    Defined the regulatory architecture of katanin by showing KATNBL1 modulates KATNA1 severing activity and competes with KATNB1 for binding the catalytic subunit.

    Evidence Mass spectrometry interactome (Katan-ome), in vitro microtubule-severing assay, and competition binding assay

    PMID:26929214

    Open questions at the time
    • Quantitative balance between KATNB1 and KATNBL1 occupancy in vivo not established
    • Structural basis of competition unknown
  3. 2018 Medium

    Distinguished KATNA1 from its paralogue KATNAL1, attributing KATNA1's lower severing activity and faster turnover to its N-terminal half.

    Evidence Tissue expression profiling, in-cell severing assays, cycloheximide-chase stability assay, domain-swap chimeras, and siRNA knockdown in Neuro2a cells

    PMID:30448058

    Open questions at the time
    • Degradation pathway controlling protein stability not identified
    • No effect on Neuro2a process elongation leaves cell-type specificity open
  4. 2019 Medium

    Identified opposing transcriptional/post-transcriptional control of KATNA1 by p53 (activation) and Elk1 (mRNA up, protein down), placing katanin under regulatory checkpoints.

    Evidence Promoter binding/ChIP and expression assays in isogenic p53 WT vs KO HCT116 cells, and Elk1 5'UTR binding with mRNA/protein readouts plus methylation analysis in SH-SY5Y cells

    PMID:30789974 PMID:31715301

    Open questions at the time
    • Mechanism of Elk1-driven post-transcriptional repression undefined
    • Integration of p53 and Elk1 inputs in a single cell context untested
  5. 2019 Medium

    Established KATNA1 as essential and dose-sensitive for neuronal progenitor proliferation in vivo.

    Evidence Constitutive Katna1 knockout and haploinsufficient mice with BrdU/EdU proliferation analysis of SVZ and DG and behavioral testing

    PMID:31685876

    Open questions at the time
    • Molecular link between severing activity and progenitor proliferation not dissected
    • Cell-autonomous vs non-autonomous contribution unresolved
  6. 2022 High

    Revealed how KATNA1 is spatially targeted to the abscission machinery via a direct MIT–CHMP3 (ESCRT-III) interaction required for cytokinetic abscission.

    Evidence Quantitative pairwise MIT–ESCRT-III tail binding assays, midbody localization, and functional abscission assays

    PMID:36107470

    Open questions at the time
    • Whether severing at the midbody is required for abscission, versus a scaffolding role, not separated
    • Temporal coordination with ESCRT polymerization unknown
  7. 2022 High

    Demonstrated a site-specific PTM (SUMO2 at K330) that directly enhances severing and neurite outgrowth, adding a covalent activity switch.

    Evidence MS interactome (UBC9), GST pull-down/Co-IP, K77R/K157R/K330R mutagenesis, severing assay in COS7, and hippocampal neurite outgrowth assay

    PMID:35868557

    Open questions at the time
    • Structural mechanism by which SUMOylation enhances ATPase/severing unknown
    • Physiological signals triggering K330 SUMOylation unidentified
  8. 2023 Medium

    Mapped paralogue-specific and shared roles of KATNA1 and KATNAL1 in male meiosis, cytokinesis, and spermatid remodeling, and defined the testis interactome.

    Evidence Single and double knockout mice with spermatogenic phenotyping and MS-based testis interactome

    PMID:37882691

    Open questions at the time
    • Direct substrates among spermatid structures not pinpointed
    • Functional validation of interactome hits beyond catalog lacking
  9. 2023 Low

    Proposed miR-124-3p as a post-transcriptional repressor of KATNA1 in neuroblastoma cells.

    Evidence Bioinformatic prediction plus pre-miR-124-3p mimic transfection with qRT-PCR and western blot in SH-SY5Y cells

    PMID:37439368

    Open questions at the time
    • No 3'-UTR reporter or RISC pull-down to confirm direct targeting
    • Single method, single cell line
    • Physiological relevance untested
  10. 2025 High

    Identified CRMP3 as a MIT-domain partner that enhances severing and synergizes with KATNA1 to promote neurite length and branching.

    Evidence GST pull-down, reciprocal Co-IP, domain mapping (MIT 1–77 / CRMP3 D region 64–413), in-cell severing assay, and single/double KO neurite outgrowth assays

    PMID:39938451

    Open questions at the time
    • Mechanism by which CRMP3 binding stimulates the AAA+ ATPase cycle unknown
    • Whether CRMP3 competes with CHMP3 for the shared MIT domain untested
  11. 2025 Medium

    Established KATNA1-specific (KATNAL1-independent) requirements in oocyte spindle morphology and early embryo development.

    Evidence ZP3-CreLox conditional knockout of KATNA1 and KATNAL1 with spindle analysis, fertilization-rate measurement, and blastocyst/parthenogenetic development assays

    PMID:40668235

    Open questions at the time
    • Molecular basis of the MII spindle defect not resolved
    • Source of preimplantation developmental failure (maternal vs embryonic) unclear
  12. 2026 Medium

    Identified EEF1B2 as an AAA+-domain partner that potentiates severing and enhances KATNA1-dependent neurite outgrowth, extending the catalog of activity-enhancing partners that bind distinct KATNA1 domains.

    Evidence Proteomic screen, GST pull-down, Co-IP, domain mapping to the AAA+ ATPase domain, severing assay in COS7, EEF1B2 knockdown, and neurite outgrowth in primary cortical neurons

    PMID:42002067

    Open questions at the time
    • Whether EEF1B2 acts on nucleotide cycling versus oligomerization unknown
    • Relationship to canonical EEF1B2 translation-factor role unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple activity-enhancing inputs (KATNB1/KATNBL1 occupancy, K330 SUMOylation, CRMP3, EEF1B2) are integrated to set katanin severing output in a given cell type, and what microtubule substrates are targeted in each developmental context, remain open.
  • No integrated structural/biochemical model of combinatorial regulation
  • Physiological substrate specificity across spindle, midbody, and neurite contexts undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0008092 cytoskeletal protein binding 2 GO:0140657 ATP-dependent activity 2 GO:0016787 hydrolase activity 1
Localization
GO:0005856 cytoskeleton 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-1474165 Reproduction 2 R-HSA-1640170 Cell Cycle 2
Partners
CHMP3CRMP3EEF1B2KATNB1KATNBL1SUMO2UBC9
Complex memberships
katanin (p60/p80 microtubule-severing complex)

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 KATNA1 contains a MIT domain that directly interacts with the ESCRT-III subunit CHMP3; this interaction recruits KATNA1 to cytokinetic midbody membrane bridges and is required for cytokinetic abscission. Comprehensive pairwise MIT–ESCRT-III tail binding assays (228 pairwise interactions quantified), localization to midbody bridges, and functional abscission assays eLife High 36107470
2022 KATNA1 is SUMOylated at K330 by SUMO2; this modification enhances KATNA1-driven microtubule severing and promotes hippocampal neurite outgrowth. Mutation K330R abolishes both SUMOylation and the enhanced severing activity. Mass spectrometry identification of UBC9 in KATNA1 interactome; GST pull-down and co-immunoprecipitation for KATNA1–SUMO2 interaction; site-directed mutagenesis (K77R, K157R, K330R); microtubule-severing assay in COS7 cells; neurite outgrowth assay in hippocampal neurons The Journal of biological chemistry High 35868557
2025 KATNA1 interacts with CRMP3 via its MIT domain (residues 1–77) and the CRMP3 D region (residues 64–413); CRMP3 enhances KATNA1 microtubule-severing efficiency, and co-expression of both proteins in hippocampal neurons synergistically promotes neurite length and branching. GST pull-down, co-immunoprecipitation, domain-mapping experiments, microtubule-severing assay, neurite outgrowth assay in hippocampal neurons, KATNA1 and CRMP3 single and double knockout Biochemical and biophysical research communications High 39938451
2016 KATNA1 (p60/A-subunit) is the catalytic microtubule-severing subunit of katanin; KATNBL1 associates with KATNA1 and regulates its microtubule-severing activity in vitro; KATNB1 can compete with KATNBL1 for binding to KATNA1. Mass spectrometry-based proteomic interactome mapping (Katan-ome); in vitro microtubule-severing assay; competition binding assay Molecular & cellular proteomics : MCP High 26929214
2014 Disrupted interaction between mutant KATNB1 (regulatory subunit) and KATNA1 (catalytic subunit) underlies defective mitotic spindle formation in patient-derived fibroblasts carrying KATNB1 mutations. Exome sequencing of patient cohort; interaction studies between KATNB1 mutants and KATNA1 in patient-derived fibroblasts; mitotic spindle analysis Neuron Medium 25521378
2019 Constitutive homozygous Katna1 knockout is lethal in mice; haploinsufficiency causes accumulation of neuronal progenitors in the subventricular zone during corticogenesis and impairs progenitor proliferation in the adult hippocampal dentate gyrus subgranular zone, establishing KATNA1's role in neuronal progenitor proliferation. Katna1 knockout mouse generation; histological and BrdU/EdU proliferation analysis of SVZ and DG; behavioral testing Scientific reports Medium 31685876
2023 KATNA1 and its paralogue KATNAL1 cooperatively regulate the male meiotic spindle, cytokinesis, and midbody abscission, as well as spermatid remodeling events including Golgi organization, acrosome and manchette formation; proteomic mapping defines the KATNA1 testis interactome including cytoskeletal and vesicle trafficking proteins. Single and double gene knockout mice; histological and spermatogenic phenotype analysis; mass spectrometry-based testis interactome Development (Cambridge, England) Medium 37882691
2025 Oocyte-specific deletion of KATNA1 causes a ~50% decrease in fertility, a modest defect in MII spindle morphology, decreased fertilization rate, and impaired preimplantation embryo development; KATNAL1 deletion does not affect fertility, indicating KATNA1-specific roles in oocyte and early embryo function. ZP3-CreLox conditional knockout of KATNA1 and KATNAL1; spindle morphology analysis; fertilization rate measurement; parthenogenetic activation and blastocyst development assay Molecular human reproduction Medium 40668235
2018 KATNA1 (katanin A1/p60) shows ubiquitous tissue expression in mice and lower microtubule-severing activity compared to KATNAL1; the amino-terminal half of the protein determines its lower activity and faster intracellular degradation. KATNA1 knockdown in Neuro2a cells showed no effect on process elongation, in contrast to KATNAL1 knockdown. Tissue expression profiling; in-cell microtubule-severing assay comparing KATNA1 vs KATNAL1; cycloheximide chase protein stability assay; chimeric molecule domain-swap experiments; siRNA knockdown in Neuro2a cells Biochemical and biophysical research communications Medium 30448058
2019 Elk1 transcription factor binds the KATNA1 5' UTR regulatory region; Elk1 overexpression increases KATNA1 mRNA but decreases katanin-p60 protein levels, indicating a post-transcriptional repressive mechanism. KATNA1 promoter methylation reduces Elk1 binding. KATNA1 5' UTR characterization; Elk1 overexpression with qRT-PCR (mRNA) and western blot (protein) in SH-SY5Y cells; methylation analysis of binding sites PloS one Medium 30789974
2019 p53 binds the KATNA1 promoter and transcriptionally activates KATNA1 gene expression; p53 overexpression increases both KATNA1 mRNA and katanin-p60 protein levels and alters the microtubule network in HCT 116 cells. KATNA1 promoter activity assays in HCT116 WT and p53(-/-) cells; p53–KATNA1 promoter ChIP/binding demonstration; p53 overexpression and knockdown with qRT-PCR and western blot; microtubule network imaging Gene Medium 31715301
2026 EEF1B2 physically interacts with KATNA1 at its AAA+ ATPase domain and potentiates KATNA1-dependent microtubule severing in COS7 cells; EEF1B2 knockdown attenuates KATNA1-driven microtubule loss. In primary cortical neurons, EEF1B2 enhances KATNA1-induced neurite outgrowth and branching in a KATNA1-dependent manner. Proteomic screening; GST pull-down; co-immunoprecipitation; domain mapping to AAA+ ATPase domain; microtubule-severing assay in COS7; EEF1B2 knockdown; neurite outgrowth assay in primary cortical neurons Neuroscience Medium 42002067
2023 miR-124-3p reduces KATNA1 mRNA and katanin-p60 protein levels in SH-SY5Y neuroblastoma cells, suggesting post-transcriptional regulation of KATNA1 expression. Bioinformatic prediction of miR-124-3p binding to KATNA1 mRNA; transfection of pre-miR-124-3p mimics; qRT-PCR and western blot for KATNA1 expression Cytoskeleton (Hoboken, N.J.) Low 37439368

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors. Neuron 89 25521378
2018 Clinical relevance of cytoskeleton associated proteins for ovarian cancer. Journal of cancer research and clinical oncology 42 30094535
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
2022 Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission. eLife 28 36107470
2022 Genome-wide association analysis of nine reproduction and morphological traits in three goat breeds from Southern China. Animal bioscience 16 35760404
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
2022 SUMOylation of microtubule-cleaving enzyme KATNA1 promotes microtubule severing and neurite outgrowth. The Journal of biological chemistry 11 35868557
2020 Cardiomyocyte Proteome Remodeling due to Isoproterenol-Induced Cardiac Hypertrophy during the Compensated Phase. Proteomics. Clinical applications 11 32506788
2019 The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis. Scientific reports 11 31685876
2018 KATNAL1 is a more active and stable isoform of katanin, and is expressed dominantly in neurons. Biochemical and biophysical research communications 11 30448058
2013 Katanin-p80 gene promoter characterization and regulation via Elk1. PloS one 11 23894477
2019 Elk1 affects katanin and spastin proteins via differential transcriptional and post-transcriptional regulations. PloS one 10 30789974
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
2020 Transcriptome Analysis of Juvenile Tilapia (Oreochromis niloticus) Blood, Fed With Different Concentrations of Resveratrol. Frontiers in physiology 8 33362577
2019 p53 regulates katanin-p60 promoter in HCT 116 cells. Gene 6 31715301
2022 Effects of DISC1 on Alzheimer's disease cell models assessed by iTRAQ proteomics analysis. Bioscience reports 5 34981809
2024 SUMOylation of nuclear receptor Nor1/NR4A3 coordinates microtubule cytoskeletal dynamics and stability in neuronal cells. Cell & bioscience 4 38997783
2025 The interaction between KATNA1 and CRMP3 modulates microtubule dynamics and neurite outgrowth. Biochemical and biophysical research communications 3 39938451
2023 Whole-genome sequencing of cryopreserved resources from French Large White pigs at two distinct sampling times reveals strong signatures of convergent and divergent selection between the dam and sire lines. Genetics, selection, evolution : GSE 3 36864379
2023 A potential posttranscriptional regulator for p60-katanin: miR-124-3p. Cytoskeleton (Hoboken, N.J.) 2 37439368
2025 Fertility is compromised after oocyte-specific deletion of microtubule severing protein Katanin A1. Molecular human reproduction 1 40668235
2023 Selection and validation of novel stable reference genes for qPCR analysis in EMT and MET. Experimental cell research 1 37146958
2026 EEF1B2 interacts with KATNA1 to potentiate microtubule severing and neurite outgrowth. Neuroscience 0 42002067
2025 Germline lung cancer SNPs dysregulate known (LATS1) and novel (ADCY2) oncogenes through distal, spatially-constrained eQTLs. Cancer genetics 0 41317429

Missed literature

Know a paper Affinage missed for KATNA1? Flag it for the maintainers and the community.

No submissions yet.