Affinage

KIF2A

Kinesin-like protein KIF2A · UniProt O00139

Length
706 aa
Mass
80.0 kDa
Annotated
2026-06-10
86 papers in source corpus 42 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF2A is an M-type kinesin-13 that functions principally as a catalytic, ATP-driven microtubule depolymerase, governing microtubule dynamics across mitosis, ciliogenesis, and neuronal morphogenesis (PMID:7535303, PMID:12887924, PMID:28903043). Structural and biophysical work shows that the KIF2A motor core adopts an activated conformation that captures two tubulin dimers in a transitional 1:2 complex during the pre-hydrolysis ATP state, explaining its processive removal of tubulin from protofilament ends (PMID:28903043). KIF2A acts as a selective minus-end depolymerase: γ-TuRC caps and protects minus ends, and efficient uncapping requires KIF2A together with the severing enzyme katanin, while CEP170B partners with KIF2A to track and depolymerize minus ends and antagonize CAMSAP-mediated stabilization (PMID:37615667, PMID:37014312). Its activity is set by an extensive regulatory network of kinases and adaptors: PLK1 phosphorylation activates depolymerization whereas Aurora A and TTBK2 (S135) inhibit it, with additional ROCK2 (activating) and PAK1/CDK5 (inhibiting) inputs, and recruitment to spindle poles is controlled by DDA3, the MLL/WDR5 complex via a WIN-motif interaction, NuSAP, importin α, and Wnt/Dishevelled signaling (PMID:19351716, PMID:26323690, PMID:26344760, PMID:18411309, PMID:28633016, PMID:40302551, PMID:38117947, PMID:23425906, PMID:34417301). During mitosis KIF2A operates at centrosomes and spindle poles to drive poleward microtubule flux and maintain spindle bipolarity, balanced against MCAK at kinetochores, and scales spindle size to cell size (PMID:15302853, PMID:17538014, PMID:23425906). At the mother centriole, PLK1-phosphorylated KIF2A (T554) and the WDR62–CEP170–KIF2A axis drive primary cilium disassembly (PMID:25660017, PMID:31197141). In postmitotic neurons KIF2A depolymerizes growth-cone microtubules to suppress collateral axon branching, maintain neurite compartment identity, direct migration via a Celsr3 axis, and support neuronal connectivity and survival (PMID:12887924, PMID:29313800, PMID:34582949, PMID:36343267). KIF2A mutations that impair ATP hydrolysis and depolymerase activity cause malformations of cortical development (PMID:23603762, PMID:31919497), and KIF2A loss links to Tau hyperphosphorylation through ERK1/2 upregulation in Alzheimer's disease (PMID:41071932).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 High

    Established KIF2A's foundational identity as a dimeric M-type microtubule motor, the first step toward defining what this kinesin physically is and does.

    Evidence Recombinant protein motility assays and immunoisolation of associated non-synaptic vesicles

    PMID:7535303

    Open questions at the time
    • Motility assay characterized plus-end movement but did not reveal depolymerase activity
    • Cargo/vesicle identity only partially defined
  2. 1997 Medium

    Linked KIF2A to neuronal cargo transport and neurite outgrowth, the earliest functional readout in a postmitotic context.

    Evidence Antisense knockdown with fractionation and immunoisolation in PC12 cells

    PMID:9245793

    Open questions at the time
    • Did not reconcile transport role with later-defined depolymerase function
    • Single cell-line model
  3. 2003 High

    Reframed KIF2A as a microtubule depolymerase that suppresses axon branching, redefining its core molecular activity in neurons.

    Evidence kif2a knockout mouse with live imaging of growth-cone microtubule dynamics

    PMID:12887924

    Open questions at the time
    • Did not establish the structural basis of depolymerization
    • Did not define regulators of activity at the growth cone
  4. 2004 High

    Defined KIF2A's mitotic role at spindle poles and the balance with MCAK at kinetochores required for bipolarity, distinguishing paralog functions.

    Evidence RNAi knockdown with monopolar-spindle phenotype and epistasis with Nuf2/MCAK; extended by systematic kinesin-13 comparison

    PMID:15302853 PMID:17538014

    Open questions at the time
    • Mechanism of differential spindle-location targeting unresolved at this stage
    • How pole-localized activity is regulated not addressed
  5. 2009 High

    Resolved kinase control of KIF2A, showing PLK1 activates and Aurora A/B inhibit depolymerase activity, with ICIS reactivating after Aurora B suppression.

    Evidence In vitro kinase and depolymerization assays, Co-IP, antibody microinjection rescue

    PMID:19327998 PMID:19351716

    Open questions at the time
    • Phosphosites for some kinases not mapped here
    • Spatial coordination of antagonistic kinases on the spindle incompletely defined
  6. 2009 High

    Identified DDA3 as a microtubule-dependent adaptor recruiting KIF2A to spindle poles, defining a recruitment pathway upstream of depolymerase activity.

    Evidence Reciprocal Co-IP, domain dissection, in vitro microtubule binding, RNAi phenocopy and FRAP flux assays

    PMID:18411309 PMID:19738423

    Open questions at the time
    • How DDA3 recruitment integrates with kinase regulation not resolved
    • Later shown to be modulated by Mdp3, not anticipated here
  7. 2012 High

    Extended KIF2A regulation to lipid-kinase signaling, with PIPKα directly binding and enhancing depolymerization to suppress axon branching.

    Evidence Yeast two-hybrid, biochemical pulldown, in vitro depolymerization, neuronal imaging

    PMID:22307638

    Open questions at the time
    • Mechanism by which PIPKα enhances activity not structurally defined
    • In vivo significance in intact brain not tested
  8. 2013 High

    Connected KIF2A depolymerase function to human disease and to developmental spindle-size scaling, establishing physiological consequences of activity tuning.

    Evidence Patient mutation functional ATPase assays; Xenopus extract spindle reconstitution with importin α manipulation; anaphase central-spindle minus-end depolymerization analysis

    PMID:23425906 PMID:23603762 PMID:23960144

    Open questions at the time
    • Importin α ratiometric mechanism characterized in extract, not in intact embryos exhaustively
    • Disease mutation effects assayed in vitro only
  9. 2015 High

    Resolved multiple phospho-regulatory cascades and a ciliary disassembly role, showing distinct phosphosites (S135 by TTBK2, T554 by PLK1, ROCK2/PAK1/CDK5 cascades) tune activity in migration, cilia, and neurite outgrowth.

    Evidence In vitro kinase assays, phosphosite mutagenesis, CRISPR/TALEN KO, phospho-specific antibodies, migration and ciliogenesis assays

    PMID:25660017 PMID:26323690 PMID:26344760

    Open questions at the time
    • Integration of competing phospho-inputs in vivo not fully resolved
    • Crosstalk between distinct phosphosites unaddressed
  10. 2016 High

    Expanded the adaptor and effector network, defining DDA3-Mdp3 control of pole recruitment and a reciprocal KIF2A-AGAP1 enzymatic partnership in migration.

    Evidence Co-IP, domain mapping, in vitro GAP/ATPase assays, RNAi epistasis and migration assays

    PMID:27284004 PMID:27531749

    Open questions at the time
    • Physiological context where AGAP1 stimulates KIF2A ATPase not fully mapped
    • Mdp3 inhibitory mechanism on DDA3 not structurally defined
  11. 2017 High

    Provided the structural mechanism of depolymerization and a second pole-recruitment route via the MLL/WDR5 WIN-motif interaction.

    Evidence X-ray crystallography with SAXS/AUC/AFM/MS; Co-IP, WIN-motif mapping, RNAi spindle phenotypes; cortical-ER localization in ascidian embryos

    PMID:28633016 PMID:28903043 PMID:29030551

    Open questions at the time
    • Structural snapshot of the transitional complex did not capture full hydrolysis cycle dynamics
    • How WDR5 and DDA3 recruitment routes coordinate unknown
  12. 2018 High

    Established KIF2A's roles in cortical development and neurite compartment identity, linking disease variants to migration, proliferation, and dendro-axonal conversion phenotypes.

    Evidence In utero electroporation of patient variants, inducible conditional knockout mouse, electrophysiology

    PMID:29077851 PMID:29313800

    Open questions at the time
    • Molecular basis of compartment identity maintenance not fully defined
    • Coupling of ciliogenesis to cell cycle inferred, not mechanistically dissected
  13. 2020 High

    Causally connected a specific KIF2A missense variant to neuronal apoptosis and defective multipolar-to-bipolar transition through loss of depolymerase function.

    Evidence Conditional knock-in mouse with multiple Cre drivers, in utero electroporation, behavioral analysis

    PMID:31919497

    Open questions at the time
    • Mechanistic link from depolymerase loss to apoptosis not resolved
    • Variant-specific structural consequences not determined
  14. 2021 High

    Broadened upstream control to Wnt/Dishevelled signaling and neuronal migration via Celsr3, and revealed isoform- and interactome-level diversity of KIF2A function.

    Evidence Phosphoproteomics, Co-IP and domain mapping, conditional knockouts, isoform-specific electroporation, BioID interactome

    PMID:33531432 PMID:34417301 PMID:34582949

    Open questions at the time
    • Functional meaning of novel interactome partners (translation factors, mitochondrial proteins) not validated
    • How Wnt and PLK1 inputs converge mechanistically incompletely defined
  15. 2023 High

    Defined KIF2A as a selective minus-end depolymerase regulated by γ-TuRC capping, CEP170B and NuSAP, with WDR62-CEP170 driving cilium disassembly and RGS12-MYCBP2 degrading KIF2A to control cilia.

    Evidence In vitro reconstitution with purified KIF2A/γTuRC/katanin/CEP170B, TIRF/single-molecule imaging, kinase assays, ubiquitination assays, knockouts

    PMID:31197141 PMID:36700049 PMID:36797232 PMID:37014312 PMID:37615667 PMID:38117947

    Open questions at the time
    • Precise coordination of nucleation and depolymerization at native spindle poles not directly observed
    • Cell-type specificity of RGS12-MYCBP2-mediated degradation unclear
  16. 2024 High

    Added APC as a plus-end catastrophe-promoting partner antagonizing CLASP2, refining the cortical microtubule-dynamics circuit.

    Evidence Co-IP, in vitro reconstitution of MT dynamics, mutagenesis, migration assays

    PMID:39640087

    Open questions at the time
    • Relationship between plus-end (APC) and minus-end (CEP170B/γTuRC) activities not unified
    • In vivo context of APC-KIF2A catastrophe not established
  17. 2025 High

    Revealed a context-dependent functional switch from depolymerase to microtubule stabilizer at the cytokinetic bridge, plus atomic detail of the WDR5-KIF2A interface and TTBK2 control of ciliary KIF2A.

    Evidence Genome-engineered ESCs with in vitro ATPase assays and live imaging; WDR5-KIF2A peptide crystal structure with ITC; TTBK2 truncation proteomics and microscopy

    PMID:39930500 PMID:40302551 PMID:40353778

    Open questions at the time
    • Molecular trigger inhibiting ATPase to drive the stabilizer switch not fully defined
    • Generality of the cytokinesis switch beyond ESCs unknown
  18. 2026 Medium

    Connected KIF2A loss to Alzheimer's-disease Tau hyperphosphorylation via ERK1/2, and uncovered a DNA-repair role through tyrosination-triggered nuclear envelope invagination.

    Evidence Conditional knockout in adult brain, 5xFAD model, human post-mortem brain, ERK1/2 inhibition; KIF2A knockdown with 53BP1/lamin B1 imaging and DNA damage assays

    PMID:41071932 PMID:41591845

    Open questions at the time
    • Direct biochemical link between KIF2A and ERK1/2 not established
    • NE-invagination/NHEJ role rests on single-lab loss-of-function without reconstitution

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the full repertoire of competing kinase inputs, adaptors, and lattice-state sensing is integrated to switch KIF2A between minus-end depolymerase, plus-end catastrophe factor, and microtubule stabilizer in real time remains unresolved.
  • No unified model linking phospho-state to depolymerase-versus-stabilizer mode switching
  • Spatial logic coordinating distinct adaptors at the same structure unknown
  • Therapeutic targeting in disease contexts not explored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0140096 catalytic activity, acting on a protein 4 GO:0140657 ATP-dependent activity 4 GO:0016787 hydrolase activity 3 GO:0003774 cytoskeletal motor activity 1
Localization
GO:0005815 microtubule organizing center 4 GO:0005856 cytoskeleton 4 GO:0005929 cilium 3 GO:0005634 nucleus 1 GO:0005635 nuclear envelope 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-162582 Signal Transduction 2 R-HSA-73894 DNA Repair 1
Partners
AGAP1APCCEP170BDDA3NUSAPPLK1TTBK2WDR5
Complex memberships
DDA3-Mdp3 complexKIF2A-CEP170B complexMLL/WDR5 complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 KIF2A (KIF2) is a plus-end-directed anterograde microtubule motor whose motor domain is located in the center of the molecule (M-type kinesin); recombinant KIF2 exists as a dimer and moves microtubules at ~0.47 µm/s in vitro. Immunoisolation with anti-KIF2 antibody identified a distinct population of non-synaptic vesicles associated with KIF2, different from those carried by conventional kinesin or KIF3A. Recombinant protein motility assay, immunoprecipitation/immunoisolation, immunocytology, nerve ligation accumulation assay The Journal of cell biology High 7535303
1997 KIF2A (KIF2) transports a specific class of non-synaptic vesicles containing the IGF-1 receptor variant betagc to neuronal growth cones; antisense knockdown of KIF2 causes betagc to accumulate in the cell body and disappear from growth cones, and dramatically inhibits neurite outgrowth in PC12 cells. Antisense oligonucleotide knockdown, subcellular fractionation, sucrose density centrifugation, immunoisolation, immunofluorescence The Journal of cell biology Medium 9245793
2003 KIF2A depolymerizes microtubules at growth cone edges to suppress collateral axon branch extension; kif2a knockout mice show reduced microtubule-depolymerizing activity at growth cones and aberrant overextension of collateral branches. kif2a knockout mouse analysis, live imaging of microtubule dynamics at growth cones, microtubule depolymerization assay Cell High 12887924
2004 KIF2A localizes to centrosomes and spindle poles during mitosis and is required for bipolar spindle assembly; its loss causes monopolar spindles that can be rescued by nocodazole treatment, loss of Nuf2 (kinetochore attachment), or loss of MCAK, establishing that KIF2A activity at poles must be balanced by MCAK activity at kinetochores for spindle bipolarity. RNAi knockdown in cultured cells, immunofluorescence, epistasis analysis with Nuf2 and MCAK co-knockdown The Journal of cell biology High 15302853
2007 Kif2a, Kif2b, and MCAK (Kif2c) fulfill distinct functions during mitosis in human cells; Kif2a-deficient cells form monopolar spindles, and bipolar spindle assembly can be restored by simultaneous deficiency of MCAK or Nuf2, or by low-dose nocodazole, but not by perturbing NuMA/HSET (which rescues Kif2b loss), demonstrating that the three kinesin-13 paralogs act at different spindle locations. RNAi knockdown of individual kinesin-13 members, GFP-tagging for localization, epistasis double-knockdown, live imaging Molecular biology of the cell High 17538014
2008 DDA3 (PSRC1) directly interacts with KIF2A in a microtubule-dependent manner and recruits KIF2A to the mitotic spindle poles; DDA3 depletion phenocopies partial KIF2A knockdown (increased spindle microtubule density, unaligned chromosomes, reduced poleward flux), placing DDA3 upstream of KIF2A in spindle dynamics regulation. Co-immunoprecipitation, RNAi knockdown, immunofluorescence, spindle microtubule turnover assay (FRAP), functional genomics screen The Journal of cell biology High 18411309
2009 PLK1 interacts with KIF2A in a mitosis-specific and kinase-activity-dependent manner, phosphorylates KIF2A, and enhances its microtubule-depolymerizing activity in vitro; Aurora A also phosphorylates KIF2A but suppresses its depolymerase activity. Antagonistic regulation by PLK1 (activating) and Aurora A (inhibiting) controls KIF2A localization on microtubules and spindle microtubule intensity in vivo. Proteomic analysis, Co-immunoprecipitation, in vitro kinase assay, in vitro microtubule depolymerization assay, immunofluorescence after kinase inhibition/depletion Journal of cell science High 19351716
2009 ICIS (inner centromere KinI stimulator) reactivates KIF2A after Aurora B-mediated inhibition; ICIS N-terminus binds Aurora B/INCENP/TD60 while its central region binds KIF2A and microtubules. Antibody injection blocking ICIS-KIF2A interaction generates monopolar spindles rescued by anti-Nuf2 co-injection, establishing ICIS as a scaffold that co-regulates KIF2A depolymerase with the chromosomal passenger complex. Structure-function analysis, Co-immunoprecipitation, antibody microinjection, epistasis rescue experiments Current biology : CB Medium 19327998
2009 The N-terminal domain of DDA3 does not bind microtubules but acts dominantly to prevent endogenous DDA3 from associating with the spindle, reduces spindle-associated KIF2A, and increases spindle microtubule density; the C-terminal domain of DDA3 directly binds microtubules in vitro and recruits KIF2A to the spindle. Domain deletion analysis, in vitro microtubule binding assay, ectopic overexpression, immunofluorescence Cell cycle (Georgetown, Tex.) Medium 19738423
2010 KIF2A interacts with TRAX (translin-associated protein X), and functional interaction between KIF2A and TRAX is required for A2A adenosine receptor-mediated rescue of neuritogenesis; redistribution of KIF2A from the nucleus to the cytoplasm upon NGF treatment is a prerequisite for neurite outgrowth, and nuclear-retained KIF2A (NLS-KIF2A) fails to rescue neurite outgrowth. Co-immunoprecipitation, KIF2A fragment expression (dominant negative), nuclear localization signal fusion, immunofluorescence colocalization, neurite outgrowth assay Developmental neurobiology Medium 20506231
2012 Phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) directly binds KIF2A (yeast two-hybrid and biochemical assays), co-localizes with KIF2A at growth cones, and enhances KIF2A's microtubule-depolymerizing activity both in vitro and in vivo; PIPKα suppresses axon branch elongation in a KIF2A-dependent manner. Immunoprecipitation, yeast two-hybrid, in vitro microtubule depolymerization assay, confocal/PALM microscopy, in vivo overexpression in neurons Proceedings of the National Academy of Sciences of the United States of America High 22307638
2013 KIF2A disease-causing mutations (identified in patients with MCD) affect ATP hydrolysis, disrupting the microtubule-depolymerizing activity of the protein, as demonstrated by functional studies of mutant proteins. Mutant protein functional assay (ATP hydrolysis), patient mutation identification by sequencing Nature genetics Medium 23603762
2013 Kif2a controls the length and alignment of central spindle microtubules during anaphase by depolymerizing their minus ends; Aurora B phosphorylation excludes Kif2a from the spindle midzone, restricting its activity to the distal ends of the central spindle, and the Aurora B activity gradient determines steady-state central spindle length. RNAi knockdown, overactivation constructs, immunofluorescence, photoactivation, computational modeling The Journal of cell biology High 23960144
2013 Kif2a scales the mitotic spindle size during Xenopus development; its microtubule-destabilizing activity is inhibited in large (stage 3) spindles by importin α, and activated in small (stage 8) spindles when importin α partitions to a membrane pool, providing a ratiometric mechanism coupling spindle size to cell size. Xenopus embryo cytoplasmic extract system, spindle reconstitution in vitro, importin α manipulation, immunodepletion eLife High 23425906
2015 KIF2A, phosphorylated at T554 by PLK1, exhibits microtubule-depolymerizing activity at the mother centriole to disassemble the primary cilium in response to growth signals; KIF2A-deficient cells show impaired cilia disassembly after growth stimulation, and the PLK1-KIF2A pathway is constitutively active in cells from PCS syndrome patients causing defective ciliogenesis. CRISPR/TALEN KIF2A knockout in hTERT-RPE1 cells, phospho-specific antibody, PLK1 kinase assay, immunofluorescence, patient cell analysis Cell reports High 25660017
2015 TTBK2 kinase, anchored to microtubule plus ends by EB1/3, phosphorylates KIF2A at S135 in intact cells in an EB1/3-dependent fashion; this phosphorylation inactivates KIF2A's microtubule-depolymerizing activity in vitro. TTBK2 depletion reduces MT lifetime and impairs cell migration, phenotypes partially rescued by KIF2A co-depletion; nonphosphorylatable KIF2A (S135A) reduces MT lifetime and slows migration. In vitro kinase assay, phospho-site mutagenesis (S135A), siRNA co-depletion, live imaging of microtubule dynamics, cell migration assay The Journal of cell biology High 26323690
2015 KIF2A undergoes two distinct phosphorylation cascades: A-type phosphorylation (by ROCK2, induced by LPA) accelerates MT depolymerization and suppresses neurite outgrowth; B-type phosphorylation (by PAK1 and CDK5, stimulated by BDNF) decreases MT depolymerizing activity and enhances neural process outgrowth. Quantitative phosphoproteomics, in vitro kinase assays, phosphomimetic/non-phosphorylatable mutants, neurite outgrowth assays Cell reports High 26344760
2016 DDA3 and Mdp3 (MAP7D3) form a complex that controls KIF2A recruitment to the spindle minus ends; Mdp3 inhibits DDA3-mediated KIF2A recruitment, and aberrant KIF2A activity at spindle minus ends upon Mdp3 depletion causes spindle instability, chromosome misalignment and bridges. Co-immunoprecipitation, RNAi, immunofluorescence, chromosome segregation analysis Journal of cell science Medium 27284004
2017 KIF2A catalytically depolymerizes microtubules by forming a transitional 1:2 KIF2core:tubulin complex during the pre-hydrolysis state of ATP hydrolysis; the KIF2core domain adopts an activated conformation revealed by X-ray crystallography that sustains binding to two tubulin dimers, explaining processive depolymerization from protofilament ends. Atomic force microscopy, size-exclusion chromatography, multi-angle light scattering, SAXS, analytical ultracentrifugation, mass spectrometry, X-ray crystallography Cell reports High 28903043
2017 The MLL/WDR5 complex associates with KIF2A through a conserved WDR5-interaction (Win) motif in KIF2A (residues engaging the WIN site of WDR5); this interaction is required for KIF2A's spindle localization during mitosis. Loss of MLL complex causes defects in chromosome congression and spindle assembly phenocopying KIF2A mislocalization. Co-immunoprecipitation, RNAi, immunofluorescence, direct binding assay (Win motif mapping) Developmental cell High 28633016
2016 Direct interaction between Kif2A and AGAP1 (Arf GAP): GLD and PH domains of AGAP1 bind the motor domain of Kif2A; Kif2A increases GAP activity of AGAP1, and a GLD-PH fragment of AGAP1 increases ATPase activity of Kif2A. Double-knockdown shows that functional Kif2A-AGAP1 complex controls cytoskeletal remodeling during cell spreading and migration. Co-immunoprecipitation, in vitro GAP activity assay, in vitro ATPase assay, siRNA knockdown, domain mapping, cell spreading/migration assay The Journal of biological chemistry High 27531749
2019 WDR62 interacts with CEP170 and promotes CEP170's localization to the basal body of primary cilia; CEP170 in turn recruits microtubule-depolymerizing KIF2A to the basal body to drive cilium disassembly. WDR62 depletion reduces KIF2A's basal body localization, and overexpression of KIF2A partially rescues cilium length defects and NPC proliferation impairment caused by WDR62 loss. Co-immunoprecipitation, immunofluorescence, KIF2A overexpression rescue, mouse knockout and cerebral organoids, siRNA knockdown Nature communications High 31197141
2017 Kif2 localizes to a cortical subdomain of endoplasmic reticulum in ascidian embryos; this localization is responsible for local depolymerization of astral microtubules, driving asymmetric spindle positioning and unequal cell division. Inhibition of Kif2 prevents aster asymmetry and spindle pole movement toward the ER subdomain. Live fluorescence imaging, Kif2 inhibition (dominant-negative/morpholino), local microtubule depolymerization manipulation Nature communications Medium 29030551
2018 KIF2A disease-causing variants disrupt projection neuron positioning, interneuron migration, and progenitor proliferation; further, ciliogenesis regulation is altered during the progenitor cell cycle, suggesting that deregulation of the coupling between ciliogenesis and cell cycle contributes to KIF2A-related brain malformations. In utero electroporation, cellular assays, patient variant expression Human molecular genetics Medium 29077851
2018 KIF2A is required for dentate granule cell neurite length regulation in the postnatal hippocampus; conditional knockout of Kif2a causes mossy fiber sprouting and dendro-axonal conversion (aberrant overextended dendrites that develop axonal properties), demonstrating a role for KIF2A in maintaining distinct neurite compartment identity. Tamoxifen-inducible conditional knockout (Kif2a-cKO) mouse, immunofluorescence, electrophysiology eLife High 29313800
2019 Kif2a scales meiotic spindle size in Hymenochirus boettgeri through an activating phosphorylation site present in H. boettgeri but absent from X. laevis kif2a; this phosphorylation modulates kif2a's microtubule-destabilizing activity for spindle size regulation. Egg extract spindle reconstitution, phosphorylation site comparison, species-comparative analysis Current biology : CB Medium 31630945
2021 Planar cell polarity protein Celsr3 physically interacts with Kif2a; conditional inactivation of Kif2a in the forebrain recapitulates the Celsr3 knockout phenotype (loss of neuroblast directionality from SVZ to olfactory bulb, aberrant LP branching, decreased MT growth rate), defining a Celsr3-Kif2a axis that specifies the direction of tangential neuronal migration in the postnatal brain. Co-immunoprecipitation, conditional knockout mice (Celsr3-cKO and Kif2a forebrain-cKO), live imaging, immunofluorescence Progress in neurobiology High 34582949
2021 Wnt signaling recruits KIF2A to the mitotic spindle via Dishevelled (DVL), which binds KIF2A through its N-terminal and motor domains; LRP6 signalosome formation during cell division promotes DVL-KIF2A interaction. Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A spindle localization. Inhibition of basal Wnt signaling leads to chromosome misalignment in somatic cells and pluripotent stem cells. Phosphoproteomics, Co-immunoprecipitation, Wnt pathway inhibition, immunofluorescence, domain mapping Proceedings of the National Academy of Sciences of the United States of America High 34417301
2021 Different KIF2A alternative isoforms have distinct functions in cortical development: two isoforms sustain radial migration, but a third isoform lacking a key N-terminal region does not. Proximity-based interactome mapping revealed novel KIF2A interaction partners including translation factors, ribonucleoproteins, and mitochondrial proteins; a disease-causing mutation shows extensive depletion of mitochondrial proteins from the KIF2A interactome. In utero electroporation of individual isoforms, proximity-based interactome mapping (BioID), migration assays Development (Cambridge, England) Medium 33531432
2022 KIF2A is required postnatally for neuronal maturation, connectivity, and survival; conditional inactivation in mature cortical neurons disrupts microtubule dynamics and multiple microtubule-dependent processes including neuronal polarity, neuritogenesis, synaptogenesis, and axonal transport, leading to aberrant electrophysiology, loss of connectivity, and neuronal death. Conditional KIF2A knockout (NestinCre, NexCre, CaMKII-Cre) in mice, electrophysiology, immunofluorescence, axonal transport assays, synaptogenesis analysis Proceedings of the National Academy of Sciences of the United States of America High 36343267
2023 KIF2A is a selective microtubule minus-end depolymerase (in contrast to its paralog MCAK which acts at plus ends); γ-TuRC acts as a protective cap shielding minus ends from KIF2A binding. Efficient γTuRC uncapping requires combined action of KIF2A and a microtubule-severing enzyme (katanin), leading to KIF2A-driven treadmilling of uncapped microtubules, providing a molecular mechanism for coordinating nucleation and depolymerization at spindle poles for poleward flux. In vitro reconstitution with purified proteins (KIF2A, γTuRC, katanin), TIRF microscopy, single-molecule assays The Journal of cell biology High 37615667
2023 CEP170B forms a complex with KIF2A that depolymerizes microtubule minus ends; CEP170B autonomously tracks growing MT minus ends and blocks minus-end growth, and together with KIF2A acts as a potent MT minus-end depolymerase capable of antagonizing CAMSAP-mediated stabilization, thereby controlling the spatial distribution of MT minus ends and establishing cell polarity. In vitro reconstitution, Co-immunoprecipitation, TIRF microscopy, RNAi knockdown, immunofluorescence in HeLa and epithelial cells The EMBO journal High 37014312
2023 NuSAP interacts with KIF2A and prevents excessive microtubule depolymerization by reducing KIF2A localization at spindle poles; Aurora A phosphorylates NuSAP at Ser-240 during mitosis, which promotes NuSAP interaction with KIF2A on the spindle body, reduces KIF2A at spindle poles, and maintains proper spindle microtubule flux. NuSAP knockout causes shorter spindles with faster flux and chromosome misalignment. Co-immunoprecipitation, Aurora A kinase assay, NuSAP knockout, immunofluorescence, FRAP for flux measurement The Journal of cell biology High 38117947
2023 RGS12 associates with and activates MYCBP2 (E3 ubiquitin ligase) to promote ubiquitination and degradation of KIF2A in synovial fibroblasts and tumor-associated macrophages; KIF2A degradation increases cilia length and number. KIF2A overexpression blocks cilia elongation downstream of RGS12. Co-immunoprecipitation, LC-MS protein interaction analysis, ubiquitination assay, RGS12 knockout mice, KIF2A overexpression International journal of oral science / Molecular therapy. Nucleic acids Medium 36700049 36797232
2024 APC forms a complex with KIF2A at the cell edge and promotes KIF2A-induced microtubule catastrophe at MT plus ends; biochemical characterization and mutational analysis identified key residues for the APC-KIF2A interaction. In vitro reconstitution demonstrates APC potentiates KIF2A-induced MT catastrophes and antagonizes CLASP2-mediated stabilization. Co-immunoprecipitation, in vitro reconstitution of MT dynamics, mutagenesis, immunofluorescence, cell migration assay Cell insight High 39640087
2025 Crystal structure of WDR5 in complex with a KIF2A-derived peptide (residues 114-122) at 1.85 Å resolution reveals KIF2A engages both the WIN and S7 sites of WDR5 via Arg117 and Ser121; Ser121 forms hydrogen bonds with WDR5 Tyr191 and Lys259, driving Tyr191 rotation and opening the S7 pocket. ITC mutagenesis confirmed critical roles of Arg117 and Ser121. X-ray crystallography, isothermal titration calorimetry (ITC), site-directed mutagenesis Acta biochimica et biophysica Sinica High 40302551
2025 TTBK2 phosphorylates KIF2A to restrain its microtubule-depolymerizing activity during cilia growth and maintenance; disease-related TTBK2 truncations that cannot localize to the mother centriole cause defective cilia elongation linked to aberrant KIF2A turnover. Concentration of TTBK2 at the mother centriole is required for full ciliogenesis. Biochemical approaches, proteomics, CRISPR genetic engineering, advanced microscopy, TTBK2 truncation analysis Cell communication and signaling : CCS Medium 39930500
2025 During cytokinesis in mouse embryonic stem cells, KIF2A switches from a microtubule depolymerase (at spindle poles in metaphase) to a microtubule stabilizer at intercellular bridge microtubules; this conversion is driven by inhibition of KIF2A's ATPase activity (increasing lattice affinity) and a preference for compacted microtubule lattices. KIF2A at the intercellular bridge maintains microtubule length/number and controls microtubule acetylation, prolonging cytokinesis to maintain pluripotency. Genome-engineered mouse ESCs, in vitro ATPase assay, immunofluorescence, live imaging, microtubule acetylation analysis, mRNA homeostasis analysis The Journal of cell biology High 40353778
2026 KIF2A deficiency in the adult mouse cortex and hippocampus leads to reduced dendritic spine density and cognitive decline followed by increased Tau phosphorylation through MAPK ERK1/2 upregulation. KIF2A protein levels are drastically reduced in Alzheimer's disease patients (but not in primary tauopathies), and Aβ accumulation alters KIF2A expression in neurons, linking Aβ → KIF2A downregulation → ERK1/2 upregulation → Tau hyperphosphorylation. Conditional KIF2A knockout in adult mouse cortex/hippocampus, 5xFAD mouse model analysis, post-mortem human brain IHC/western blot, ERK1/2 inhibitor experiments Brain : a journal of neurology High 41071932
2026 Damage-induced α-tubulin tyrosination triggers KIF2A binding to microtubules, and KIF2A mediates nuclear envelope (NE) invagination through the LINC complex and lamin B1; this NE invagination creates a stable environment for NHEJ repair near the NE, facilitating 53BP1 foci formation. Loss of KIF2A disrupts NE invagination after DNA damage and impairs NHEJ. KIF2A knockdown, immunofluorescence (53BP1 foci, lamin B1, α-tubulin), DNA damage assays, live imaging of NE dynamics Nucleic acids research Medium 41591845
2020 KIF2A missense variants causing brain malformations (p.His321Asp) expressed via conditional knock-in increase neuronal apoptosis and cause abnormal multipolar-to-bipolar transition in newborn neurons, and these phenotypes are linked to deficiency in the microtubule-depolymerizing function of KIF2A. Cre-mediated conditional knock-in mouse (NestinCre, NexCre, RosaCre), in utero electroporation, immunofluorescence, behavioral analysis Human molecular genetics High 31919497

Source papers

Stage 0 corpus · 86 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nature genetics 367 23603762
2003 Kinesin superfamily protein 2A (KIF2A) functions in suppression of collateral branch extension. Cell 233 12887924
2007 The kinesin-13 proteins Kif2a, Kif2b, and Kif2c/MCAK have distinct roles during mitosis in human cells. Molecular biology of the cell 201 17538014
2004 The KinI kinesin Kif2a is required for bipolar spindle assembly through a functional relationship with MCAK. The Journal of cell biology 195 15302853
2019 Modeling microcephaly with cerebral organoids reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly in neural progenitors. Nature communications 161 31197141
1995 KIF2 is a new microtubule-based anterograde motor that transports membranous organelles distinct from those carried by kinesin heavy chain or KIF3A/B. The Journal of cell biology 146 7535303
2015 The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation. Cell reports 119 25660017
2013 Mitotic spindle scaling during Xenopus development by kif2a and importin α. eLife 98 23425906
2009 Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a. Journal of cell science 85 19351716
2008 DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement. The Journal of cell biology 68 18411309
1997 Suppression of KIF2 in PC12 cells alters the distribution of a growth cone nonsynaptic membrane receptor and inhibits neurite extension. The Journal of cell biology 68 9245793
2013 Aurora B and Kif2A control microtubule length for assembly of a functional central spindle during anaphase. The Journal of cell biology 65 23960144
2017 MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis. Developmental cell 61 28633016
2020 Knockdown of circHIPK3 Facilitates Temozolomide Sensitivity in Glioma by Regulating Cellular Behaviors Through miR-524-5p/KIF2A-Mediated PI3K/AKT Pathway. Cancer biotherapy & radiopharmaceuticals 50 32833501
2015 TTBK2 with EB1/3 regulates microtubule dynamics in migrating cells through KIF2A phosphorylation. The Journal of cell biology 47 26323690
2013 Silencing Kif2a induces apoptosis in squamous cell carcinoma of the oral tongue through inhibition of the PI3K/Akt signaling pathway. Molecular medicine reports 42 24248467
2009 Overexpression of Kif2a promotes the progression and metastasis of squamous cell carcinoma of the oral tongue. Oral oncology 42 20005768
2012 Phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) regulates neuronal microtubule depolymerase kinesin, KIF2A and suppresses elongation of axon branches. Proceedings of the National Academy of Sciences of the United States of America 39 22307638
2009 ICIS and Aurora B coregulate the microtubule depolymerase Kif2a. Current biology : CB 39 19327998
2018 Ciliogenesis and cell cycle alterations contribute to KIF2A-related malformations of cortical development. Human molecular genetics 35 29077851
2020 KIF2A promotes the progression via AKT signaling pathway and is upregulated by transcription factor ETV4 in human gastric cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 32106376
2018 KIF2A regulates the development of dentate granule cells and postnatal hippocampal wiring. eLife 34 29313800
2015 Microtubule Destabilizer KIF2A Undergoes Distinct Site-Specific Phosphorylation Cascades that Differentially Affect Neuronal Morphogenesis. Cell reports 33 26344760
2017 Mechanism of Catalytic Microtubule Depolymerization via KIF2-Tubulin Transitional Conformation. Cell reports 32 28903043
2016 Kif2a regulates spindle organization and cell cycle progression in meiotic oocytes. Scientific reports 30 27991495
2015 Role of KIF2A in the progression and metastasis of human glioma. Molecular medicine reports 29 26707290
2019 Regulation of KIF2A by Antitumor miR-451a Inhibits Cancer Cell Aggressiveness Features in Lung Squamous Cell Carcinoma. Cancers 28 30813343
1996 mRNA expression of KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, KIF5, and cytoplasmic dynein during axonal regeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 8613797
2021 Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A. Annals of medicine 27 34024242
2018 Down-regulation of KIF2A inhibits gastric cancer cell invasion via suppressing MT1-MMP. Clinical and experimental pharmacology & physiology 26 29781531
2016 Recurrent KIF2A mutations are responsible for classic lissencephaly. Neurogenetics 24 27747449
2019 Kif2a Scales Meiotic Spindle Size in Hymenochirus boettgeri. Current biology : CB 23 31630945
2010 The A2A adenosine receptor rescues neuritogenesis impaired by p53 blockage via KIF2A, a kinesin family member. Developmental neurobiology 22 20506231
2016 KIF2A Overexpression and Its Association with Clinicopathologic Characteristics and Poor Prognoses in Patients with Gastric Cancer. Disease markers 21 27773961
2022 KIF2A deficiency causes early-onset neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America 20 36343267
2016 A patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous mutation of KIF2A. Molecular genetics & genomic medicine 20 27896282
2016 KIF2A regulates the spindle assembly and the metaphase I-anaphase I transition in mouse oocyte. Scientific reports 20 27991556
2023 RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling. International journal of oral science 19 36797232
2021 Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis. Proceedings of the National Academy of Sciences of the United States of America 19 34417301
2020 Conditional switching of KIF2A mutation provides new insights into cortical malformation pathogeny. Human molecular genetics 17 31919497
2020 Circular RNA circEIF3I promotes papillary thyroid carcinoma progression through competitively binding to miR-149 and upregulating KIF2A expression. American journal of cancer research 17 32368390
2006 A family-based association study of kinesin heavy chain member 2 gene (KIF2) and schizophrenia. Neuroscience letters 17 16959419
2016 DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics. Journal of cell science 16 27284004
2023 The minus-end depolymerase KIF2A drives flux-like treadmilling of γTuRC-uncapped microtubules. The Journal of cell biology 14 37615667
2021 Roles of developmentally regulated KIF2A alternative isoforms in cortical neuron migration and differentiation. Development (Cambridge, England) 14 33531432
2020 Identification of Kinesin Family Member 2A (KIF2A) as a Promising Therapeutic Target for Osteosarcoma. BioMed research international 14 33204709
2023 IGF2BP1 facilitates non-small cell lung cancer progression by regulating the KIF2A-mediated Wnt/β-catenin pathway. Functional & integrative genomics 13 38102458
2020 Long Non-Coding RNA Paternally Expressed Imprinted Gene 10 (PEG10) Elevates Diffuse Large B-Cell Lymphoma Progression by Regulating Kinesin Family Member 2A (KIF2A) via Targeting MiR-101-3p. Medical science monitor : international medical journal of experimental and clinical research 13 32976381
2017 Kif2 localizes to a subdomain of cortical endoplasmic reticulum that drives asymmetric spindle position. Nature communications 13 29030551
2015 Kif2a depletion generates chromosome segregation and pole coalescence defects in animal caps and inhibits gastrulation of the Xenopus embryo. Molecular biology of the cell 13 25568341
2009 The N-terminal domain of DDA3 regulates the spindle-association of the microtubule depolymerase Kif2a and controls the mitotic function of DDA3. Cell cycle (Georgetown, Tex.) 13 19738423
2024 Connecting neurodevelopment to neurodegeneration: a spotlight on the role of kinesin superfamily protein 2A (KIF2A). Neural regeneration research 12 37488893
2023 The CEP170B-KIF2A complex destabilizes microtubule minus ends to generate polarized microtubule network. The EMBO journal 12 37014312
2021 Modeling Neurodevelopmental Disorders and Epilepsy Caused by Loss of Function of kif2a in Zebrafish. eNeuro 12 34404749
2020 Long Non-Coding RNA BLACAT1 Promotes the Tumorigenesis of Gastric Cancer by Sponging microRNA-149-5p and Targeting KIF2A. Cancer management and research 12 32801897
2021 The Celsr3-Kif2a axis directs neuronal migration in the postnatal brain. Progress in neurobiology 11 34582949
2013 The pesticide dichlorvos disrupts mitotic division by delocalizing the kinesin Kif2a from centrosomes. Environmental and molecular mutagenesis 11 23532982
2022 Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer. Cancer cell international 10 35164763
2013 Stable gene-silence of Kif2a synergistic with 5-fluorouracil suppresses oral tongue squamous cell carcinoma growth in vitro and in vivo. Oral surgery, oral medicine, oral pathology and oral radiology 10 23570661
2023 NuSAP regulates microtubule flux and Kif2A localization to ensure accurate chromosome congression. The Journal of cell biology 8 38117947
2019 KIF2A characterization after spinal cord injury. Cellular and molecular life sciences : CMLS 8 31041455
2022 HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells. Open medicine (Warsaw, Poland) 7 36447525
2021 Knockdown of LncRNA LINC00958 Inhibits the Proliferation and Migration of NSCLC Cells by MiR-204-3p/KIF2A Axis. Cell transplantation 7 34269081
2025 Tau-tubulin kinase 2 restrains microtubule-depolymerizer KIF2A to support primary cilia growth. Cell communication and signaling : CCS 6 39930500
2022 The molecular mechanism of kinesin family member 2A (KIF2A) underlying non-small cell lung cancer: the effect of its knockdown on malignant behaviors, stemness, chemosensitivity, and potential regulated signaling pathways. American journal of translational research 6 35173830
2022 KIF2A participates in the progression of hepatocellular carcinoma and angiogenesis by interacting with Notch1. Experimental and therapeutic medicine 6 36277155
2022 Regulator of G protein signaling 12 drives inflammatory arthritis by activating synovial fibroblasts through MYCBP2/KIF2A signaling. Molecular therapy. Nucleic acids 5 36700049
2021 Variants in KIF2A cause broad clinical presentation; the computational structural analysis of a novel variant in a patient with a cortical dysplasia, complex, with other brain malformations 3. American journal of medical genetics. Part A 5 33506645
2016 Direct Functional Interaction of the Kinesin-13 Family Member Kinesin-like Protein 2A (Kif2A) and Arf GAP with GTP-binding Protein-like, Ankyrin Repeats and PH Domains1 (AGAP1). The Journal of biological chemistry 5 27531749
2025 Crystal structures of Kif2A complexed with WDR5 reveal the structural plasticity of WIN-S7 sites. Acta biochimica et biophysica Sinica 4 40302551
2024 Hsa_circ_0088036 promotes tumorigenesis and chemotherapy resistance in hepatocellular carcinoma via the miR-140-3p/KIF2A axis. Histology and histopathology 4 39587911
2020 KIF2A regulates ovarian development via modulating cell cycle progression and vitollogenin levels. Insect molecular biology 4 33251618
2019 KIF2 mediates the neuroprotection in cerebral ischaemia injury by affecting NF-κB pathway. Clinical and experimental pharmacology & physiology 4 31514228
2022 KIF2A decreases IL-33 production and attenuates allergic asthmatic inflammation. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 3 35718777
2022 Circ_SATB2 knockdown inhibits the tumorigenesis of non-small cell lung cancer via miR-760/KIF2A axis. Histology and histopathology 3 36196919
2025 KIF2A stabilizes intercellular bridge microtubules to maintain mouse embryonic stem cell cytokinesis. The Journal of cell biology 2 40353778
2024 KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells. Biology 2 38534420
2021 Mitotic WNT: aligning chromosomes through KIF2A. Molecular & cellular oncology 2 35419471
2024 APC orchestrates microtubule dynamics by acting as a positive regulator of KIF2A and a negative regulator of CLASPs. Cell insight 1 39640087
2023 Mutations obstructing ATP's emplacement in KIF2A nucleotide-binding pocket causes parenchymal malformations, motor developmental delay, with intellectual disability. Molecular genetics & genomic medicine 1 37331001
2022 [Genetic and clinical analysis of KIF2A gene variant in a Chinese patient with complex cortical dysplasia and other brain malformations]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 35315043
2017 [The expression and significance of microtubule - driven protein KIF2A in epithelial ovarian cancer]. Zhonghua yi xue za zhi 1 29141378
2026 KIF2A downregulation links amyloid-β to Tau phosphorylation in Alzheimer's disease. Brain : a journal of neurology 0 41071932
2026 KIF2A-mediated microtubule-dependent nuclear envelope invagination drives nonhomologous end joining. Nucleic acids research 0 41591845
2026 Dysregulated KIF2A correlates with p53 expression pattern in breast cancer. Molecular and cellular biochemistry 0 42257979
2022 Long Non-Coding RNA BLACAT1 Promotes the Tumorigenesis of Gastric Cancer by Sponging microRNA-149-5p and Targeting KIF2A [Retraction]. Cancer management and research 0 35958948

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