Affinage

KIF4A

Chromosome-associated kinesin KIF4A · UniProt O95239

Length
1232 aa
Mass
139.9 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF4A is a plus-end-directed chromokinesin of the kinesin-4 family that functions as a central organizer of mitotic chromosome architecture and spindle midzone dynamics, while also serving as an anterograde cargo transporter in interphase neurons. During mitosis, CDK1 phosphorylation at T1161 and S1186 licenses KIF4A binding to condensed chromosome arms, where it directly activates condensin I by engaging the HAWK subunit NCAPG through a C-terminal short linear motif (SLiM) that displaces auto-inhibitory interactions, stimulating condensin I ATPase and DNA loop extrusion to promote lateral chromosome compaction (PMID:39690239, PMID:29771379, PMID:30576375, PMID:27633014). At anaphase, PRC1 recruits KIF4A to antiparallel midzone microtubules where it drives microtubule sliding for spindle elongation, with Aurora A/B phosphorylation at T799 activating its motor and PP2A-B56γ/ε providing antagonistic dephosphorylation to regulate overlap length (PMID:25512391, PMID:33910056, PMID:30353849). In neurons, KIF4A's C-terminal tail transports L1-containing vesicles, ribosomal constituents, integrin β1, and NTCP to axonal tips, and directly suppresses PARP-1 enzymatic activity in a CaMKII-regulated manner critical for neuronal morphology and seizure susceptibility via the PARP1–TrkB–KCC2 pathway (PMID:10747093, PMID:19158085, PMID:16630823, PMID:36482480).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Identification of KIF4 as a plus-end-directed motor with a tripartite domain structure established the molecular framework for understanding its dual roles in organelle transport and mitosis.

    Evidence cDNA cloning, ATPase assay, nucleotide-dependent MT binding, ultrastructural analysis of Sf9-expressed protein

    PMID:7929562

    Open questions at the time
    • No cellular cargo identified
    • No mitotic function yet demonstrated
    • Mammalian in vivo motor properties not measured
  2. 2000 High

    Demonstrating that KIF4 transports L1-containing vesicles anterogradely in axons answered the question of what neuronal cargo this motor carries, linking it to axon elongation.

    Evidence Immunoisolation of KIF4-associated vesicles from neurons, antisense knockdown with L1 redistribution readout

    PMID:10747093

    Open questions at the time
    • Direct binding interface between KIF4 tail and L1 vesicles not mapped
    • Regulation of cargo loading/unloading unknown
  3. 2004 High

    Three contemporaneous studies established that KIF4A is essential for central spindle midzone organization during anaphase through physical interaction with PRC1, and localizes to condensed chromosome arms where it interacts with condensin complexes, resolving its dual mitotic functions.

    Evidence Co-IP of KIF4A–PRC1 and KIF4A–condensin, RNAi with midzone disorganization and chromosome hypercondensation phenotypes, motor-dead rescue failure

    PMID:15297875 PMID:15326200 PMID:15625105

    Open questions at the time
    • Phosphorylation-dependent regulation of each pool not yet identified
    • Whether KIF4A activates condensin enzymatically unknown
    • How KIF4A discriminates between condensin I and II unclear
  4. 2006 High

    Discovery that KIF4A's C-terminal domain directly suppresses PARP-1 enzymatic activity, with CaMKII-dependent dissociation upon neuronal depolarization, revealed a non-transport nuclear function critical for neuronal survival.

    Evidence In vitro PARP-1 activity assay with KIF4 C-terminal domain, co-IP, CaMKII inhibitor experiments, live-cell imaging

    PMID:16630823

    Open questions at the time
    • Structural basis of PARP-1 inhibition by KIF4A unknown
    • Whether this mechanism operates in non-neuronal cells not tested
  5. 2008 High

    Mapping chromatin-binding to the Zip1 and cysteine-rich (CR) motifs, and showing KIF4A associates with BRCA2 and is recruited to DNA damage sites for homologous recombination, expanded the functional repertoire beyond mitosis and transport.

    Evidence Domain mutagenesis with RNAi rescue for Zip1/CR; co-IP of KIF4A–BRCA2, laser micro-irradiation recruitment, I-SceI HR assay

    PMID:18502200 PMID:18604178

    Open questions at the time
    • Direct versus indirect role in HR repair not resolved
    • Whether motor activity is required at DNA damage sites untested
  6. 2012 High

    Double-depletion experiments showing KIF4A and condensin act in parallel to promote lateral chromosome compaction, with topoisomerase IIα in opposition, defined the epistatic hierarchy for chromosome morphogenesis.

    Evidence Single and double siRNA knockdowns with chromosome morphology quantification

    PMID:23166350

    Open questions at the time
    • Biochemical mechanism by which KIF4A promotes compaction beyond condensin recruitment not established
    • In vitro reconstitution of chromosome compaction lacking
  7. 2014 High

    Identification of PP2A-B56γ/ε as the phosphatase opposing Aurora B at T799 on KIF4A established a spatially restricted feedback loop controlling central spindle length, answering how KIF4A motor activity is tuned during anaphase.

    Evidence Co-IP of KIF4A–PP2A-B56γ, ATPase assay with T799 phosphorylation, double siRNA of B56γ/ε with phospho-specific antibodies

    PMID:25512391

    Open questions at the time
    • Structural basis of PP2A-B56γ recognition of KIF4A not known
    • Whether AMPK competition with Aurora B at this site is physiologically relevant in vivo
  8. 2018 High

    CDK1 phosphorylation at T1161 and S1186 was shown to license KIF4A chromosomal localization and condensin I interaction, Fe-S cluster coordination through the CR domain was demonstrated, and AMPK was identified as a competing kinase at S801, collectively defining the multi-layered post-translational regulation of KIF4A's mitotic targeting.

    Evidence Phospho-site mutagenesis (T1161A, S1186A) with RNAi rescue and Histone H1-fusion forced targeting; EPR spectroscopy for Fe-S binding; in vitro AMPK kinase assay with S801 mutagenesis

    PMID:28992084 PMID:29771379 PMID:29848660 PMID:30576375

    Open questions at the time
    • How Fe-S cluster occupancy is regulated during the cell cycle unknown
    • Relative contributions of T1161 vs S1186 phosphorylation not fully dissected
    • Physiological conditions where AMPK dominates over Aurora B unclear
  9. 2018 High

    In vitro reconstitution of PRC1–KIF4A on antiparallel microtubules demonstrated that end-tag collision creates self-organizing stable overlaps whose geometry scales with microtubule length, providing the biophysical mechanism for midzone length control.

    Evidence TIRF microscopy with purified PRC1 and KIF4A on reconstituted antiparallel MT bundles, quantitative sliding velocity analysis

    PMID:30353849

    Open questions at the time
    • How additional regulators (e.g., CLASP, Aurora B) modify overlap dynamics in vivo not addressed
    • Crowding and viscoelastic effects of cytoplasm absent from reconstitution
  10. 2020 High

    Discovery of SUMOylation at K460 enhancing KIF4A's interaction with stathmin 1 for abscission revealed a non-phosphorylation post-translational control point for cytokinesis completion.

    Evidence Endogenous CRISPR K460R mutation, co-IP, proximity ligation assay, abscission timing assay

    PMID:32591481

    Open questions at the time
    • SUMO E3 ligase responsible not identified
    • Whether K460 SUMOylation affects other KIF4A interactions unknown
  11. 2021 High

    Combined disruption of KIF4A and EG5 causing complete failure of anaphase spindle elongation established that these two motors are the principal sliding engines for human anaphase B, resolving a long-standing question about motor redundancy.

    Evidence Combined siRNA/chemical inhibition, tubulin photoactivation, STED and expansion microscopy

    PMID:33910056

    Open questions at the time
    • Relative force contributions of KIF4A versus EG5 not quantified
    • Whether additional motors contribute in specific cell types not excluded
  12. 2022 High

    Identification of a KIF4A R728Q patient mutation that strengthens PARP1 binding and causes seizures via the PARP1–TrkB–KCC2 pathway in a knockin mouse established a direct genotype-to-phenotype link for KIF4A in neurological disease.

    Evidence Patient mutation identification, mouse knockin model, co-IP showing enhanced PARP1 affinity, behavioral seizure assay, NAD rescue

    PMID:36482480

    Open questions at the time
    • Whether other KIF4A mutations cause neurological disease in humans not systematically assessed
    • How the coiled-coil extension changes PARP1 binding structurally unresolved
  13. 2024 High

    Reconstitution showing that a KIF4A C-terminal SLiM peptide alone suffices to activate condensin I ATPase and DNA loop extrusion by competing with auto-inhibitory NCAPH/NCAPD2 SLiMs on NCAPG provided the first biochemical mechanism for how a chromokinesin directly stimulates SMC complex activity.

    Evidence Purified protein pulldown, SLiM mutagenesis, in vitro ATPase and single-molecule loop extrusion assays

    PMID:39690239

    Open questions at the time
    • Structure of the KIF4A SLiM–NCAPG interface at atomic resolution not determined
    • Whether motor-driven translocation contributes to condensin activation beyond SLiM binding not resolved
    • How the balance between auto-inhibition relief and KIF4A dissociation is regulated in vivo unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full structural model of full-length KIF4A and the atomic basis of its interactions with condensin I, PRC1, PARP-1, and chromatin remain unresolved, as does the question of how its multiple post-translational modifications are integrated spatiotemporally to switch between chromosome-arm, midzone, and cargo-transport functions.
  • No full-length KIF4A structure available
  • Spatiotemporal integration of CDK1, Aurora A/B, AMPK, PP2A, and SUMO modifications not modeled
  • Relative contribution of motor activity versus SLiM-mediated condensin activation to chromosome compaction in vivo not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0140657 ATP-dependent activity 3 GO:0098772 molecular function regulator activity 2 GO:0003677 DNA binding 1
Localization
GO:0005694 chromosome 5 GO:0005856 cytoskeleton 5 GO:0005634 nucleus 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1640170 Cell Cycle 10 R-HSA-4839726 Chromatin organization 3 R-HSA-9609507 Protein localization 3 R-HSA-73894 DNA Repair 1
Partners
BRCA2EB1NCAPGPARP1PPP2R5CPRC1STMN1TPX2
Complex memberships
Condensin I (KIF4A–NCAPG interaction)PRC1–KIF4A antiparallel MT sliding complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 KIF4 (murine KIF4) is a plus-end-directed microtubule motor protein with nucleotide-dependent microtubule binding, microtubule-activated ATPase activity, and a tripartite domain structure (N-terminal motor, central coiled-coil stalk, C-terminal tail). It colocalizes with membranous organelles in growth cones and cytoplasm, establishing it as an anterograde motor for organelle transport. cDNA cloning, biochemical ATPase assay, nucleotide-dependent MT binding, ultrastructural analysis of Sf9-expressed protein, immunocytochemistry The Journal of cell biology High 7929562
1998 KIF4 associates with murine leukemia virus (MuLV) Gag polyproteins through its C-terminal domain, identified by yeast two-hybrid and confirmed in mammalian cell co-immunoprecipitation, suggesting KIF4 mediates Gag translocation to the cell membrane. Yeast two-hybrid, co-immunoprecipitation in mammalian cells Journal of virology Medium 9658142
1999 KIF4 associates with Gag polyproteins of HIV-1, SIV, and MPMV through its C-terminal domain, confirmed by sucrose gradient co-fractionation, size-exclusion chromatography, and co-immunoprecipitation; binding is specific to Gag precursor (Pr55) and the MA-CA intermediate (Pr42) but not processed Gag products. Yeast two-hybrid, sucrose gradient fractionation, size-exclusion and anion-exchange chromatography, co-immunoprecipitation Journal of virology Medium 10559369
2000 KIF4 transports L1-containing vesicles anterogradely in axons; immunoisolation identified a KIF4-associated vesicle population enriched in L1 and lacking synaptic markers; antisense suppression of KIF4 caused L1 accumulation in cell bodies and loss from axonal tips, and prevented L1-enhanced axonal elongation. Subcellular fractionation, immunoisolation, antisense oligonucleotide knockdown, immunofluorescence The Journal of cell biology High 10747093
2004 KIF4 is essential for central spindle midzone organization during anaphase. KIF4 physically binds PRC1 (and also MKLP1 and CENP-E separately). In KIF4-deficient cells, the central spindle is disorganized and midzone-associated proteins including PRC1 fail to concentrate at the midline. PRC1 is required for KIF4 localization to the spindle. Co-immunoprecipitation, RNAi knockdown, immunofluorescence, time-lapse microscopy The EMBO journal High 15297875
2004 Kif4 translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase-to-anaphase transition using its stalk plus tail domains. CDK phosphorylation of PRC1 controls the timing of this translocation. Kif4 motor-dead mutant cannot rescue cytokinetic defects, demonstrating motor activity is required. Time-lapse microscopy, esiRNA knockdown, rescue with wild-type vs motor-dead mutant, co-localization Proceedings of the National Academy of Sciences of the United States of America High 15625105
2004 Human KIF4A (HKIF4A) localizes on condensed chromosome arms during mitosis and accumulates at the spindle midzone and cytokinetic ring. RNAi depletion causes chromosome mis-alignment, spindle defects, and chromosome hypercondensation. KIF4A physically interacts with condensin I and II complexes. RNAi, immunofluorescence, co-immunoprecipitation, live-cell imaging The Journal of cell biology High 15326200
2004 KIF4 localizes to the spindle midzone and forms a ring structure around midbody microtubule bundles during cytokinesis, as shown by 3D analysis of its architectural relationship with microtubule bundles. Immunofluorescence, 3D microscopy Experimental & molecular medicine Low 15031677
2006 The C-terminal domain of KIF4 directly suppresses PARP-1 enzymatic activity. Neuronal membrane depolarization triggers CaMKII-mediated signaling that dissociates KIF4 from PARP-1 in the nucleus, upregulating PARP-1 activity to support neuron survival. After dissociation, KIF4 moves from nucleus to neurite tips in a microtubule-dependent manner. Co-immunoprecipitation, in vitro PARP-1 activity assay, domain deletion analysis, CaMKII inhibitor, live-cell imaging Cell High 16630823
2008 KIF4A associates with BRCA2 via its C-terminal cargo-binding domain interacting with the BRCA2 C-terminal conserved region. Upon laser micro-irradiation-induced DNA damage, KIF4A is rapidly recruited to damage sites. KIF4A depletion impairs Rad51 IRIF formation and reduces homologous recombination efficiency without affecting γ-H2AX or NBS1 foci. Co-immunoprecipitation (biochemical identification), nuclear laser micro-irradiation, shRNA knockdown, I-SceI recombination assay, colonogenic survival assay Cell cycle (Georgetown, Tex.) High 18604178
2008 Chromatin binding of KIF4A requires two conserved motifs: the first leucine zipper (Zip1) of the ZBZ region and a cysteine-rich (CR) motif in the C-terminal region. Mutants lacking either DNA-binding motif (Zip1 or CR deleted) or ATPase activity (K94A) cannot rescue RNAi-induced mitotic defects, showing all three activities are required for KIF4A mitotic function. Domain deletion/mutagenesis, RNAi rescue assay, DNA-binding assays Biochemical and biophysical research communications High 18502200
2008 KIF4 (kinesin) regulates HIV-1 Gag intracellular trafficking and stability. KIF4 knockdown slows Gag trafficking, promotes Gag accumulation in perinuclear clusters co-localizing with Ubc9/SUMO, and increases Gag degradation, reducing virus-like particle production. Reintroduction of KIF4 rescues these defects. siRNA knockdown, rescue overexpression, immunofluorescence, viral particle quantification Journal of virology Medium 18684836
2009 The C-terminal tail domain of KIF4 directly binds P0 (a major ribosomal protein). KIF4 mediates anterograde transport of ribosomal constituents to axons; KIF4 variants lacking the tail domain, ATP-binding mutations, or RNAi knockdown cause ribosomal protein accumulation in cell bodies and loss from axons. An Ezrin-Radixin-Moesin (ERM)-like domain in KIF4's second coiled-coil mediates clustering and L1 transport. Pull-down, co-immunoprecipitation, domain deletion mutagenesis, RNAi, immunofluorescence in DRG neurons The Journal of biological chemistry High 19158085
2012 KIF4 and condensin complexes cooperate in a parallel pathway to promote lateral compaction of chromatid arms during mitosis. KIF4 and condensin are mutually dependent for their dynamic localization on chromatid axes. Simultaneous depletion of KIF4 and condensin causes complete loss of chromosome morphology. Topoisomerase IIα acts in opposition, promoting axial shortening. siRNA knockdown (single and double depletion), in vitro chromosome structure assay, immunofluorescence The Journal of cell biology High 23166350
2014 KIF4A and PP2A-B56γ/ε form a spatially restricted feedback loop at the anaphase central spindle opposing Aurora B. PP2A-B56γ is maintained at the central spindle by KIF4A; PP2A-B56γ dephosphorylates the Aurora B phosphorylation site T799 on KIF4A, counteracting Aurora B-stimulated KIF4A ATPase activity. Combined silencing of PP2A-B56γ and -ε increased KIF4A T799 phosphorylation and decreased central spindle length. Co-immunoprecipitation, ATPase assay, siRNA knockdown, phospho-specific antibodies The Journal of cell biology High 25512391
2014 Kif4A physically interacts with EB1 (the tail domain of Kif4 binds the N-terminal domain of EB1) and is required for selective microtubule stabilization downstream of the Rho-mDia-EB1 pathway. Kif4 depletion blocks mDia- and EB1-induced stable MT formation and inhibits cell migration into wounded monolayers. Co-immunoprecipitation, in vitro binding assay (direct domain mapping), siRNA knockdown, immunofluorescence, wound healing assay PloS one High 24658398
2014 Kif4a knockdown in rat primary hippocampal neurons alters the balance between excitatory and inhibitory synaptic transmission, establishing a role for KIF4A in regulating synaptic function in neurons. shRNA knockdown in primary hippocampal neurons, electrophysiology Journal of medical genetics Medium 24812067
2014 Kif4A co-localizes with β1 integrin in vesicles in neurons and co-immunoprecipitates with it. shRNA knockdown of KIF4A reduces β1 integrin levels in developing axons and reduces neurite elongation on laminin. Co-immunoprecipitation, shRNA knockdown, immunofluorescence, neurite elongation assay Molecular and cellular neurosciences Medium 25260485
2015 KIF4 motor activity and PRC1 isoform 1 (PRC1-1) translocation to astral microtubule tips causes sister chromatid alignment errors when CDK1 activity is insufficient. Depletion of KIF4 or abrogation of its motor activity alleviates chromosome congression defects caused by CDK1 inhibition. RNAi screen, KIF4 gene ablation, motor-dead mutant rescue, live-cell imaging Scientific reports Medium 26423135
2016 Condensin I-mediated mitotic chromosome assembly requires association with KIF4A. KIF4A binds condensin I (but not condensin II) in mitosis; enrichment of condensin I at chromosomal axes depends on KIF4A motor activity. Mutational analysis showed that KIF4A–condensin I interaction is required for condensin I to confer physiological properties to chromosomes. Co-immunoprecipitation, mutagenesis, RNAi knockdown, chromosome morphology assays Genes & development High 27633014
2016 KIF4A is phosphorylated during mitosis in a CDK1- and Aurora B-dependent manner, and this phosphorylation is required for KIF4A to interact with condensin I. Phosphoproteomic mass spectrometry from chromosome-enriched lysate, phospho-specific antibodies, kinase inhibitors, co-immunoprecipitation Biomedical research (Tokyo, Japan) Medium 27108885
2017 Prc1E (Xenopus PRC1 orthologue) recruits Kif4A to antiparallel microtubule bundles; Prc1E is required for Kif4A recruitment but not vice versa. Together, Prc1E and Kif4A slow and terminate MT plus-end growth at aster interaction zones, blocking microtubule interpenetration, and are also required for radial order within isolated large asters. Xenopus egg extract assay, immunodepletion, add-back reconstitution, TIRF microscopy Molecular biology of the cell High 29187577
2017 GTSE1 promotes Aurora B kinase activity and Kif4A binding to chromosome arms by regulating spindle microtubule turnover; reduced microtubule turnover upon GTSE1 depletion leads to diminished Aurora B recruitment/activity on chromosome arms and consequently decreased Kif4A binding. siRNA knockdown, immunofluorescence, live-cell imaging, Aurora B activity assay The Journal of cell biology Medium 28821562
2017 KIF4A and condensin I are mutually dependent for stable chromosome scaffold localization; they form a stable complex. Aurora B phosphorylation facilitates targeting of both KIF4A and condensin I to chromosomes, while Plk1 promotes their dissociation. Co-immunoprecipitation, kinase inhibitors (Aurora B, Plk1), immunofluorescence, chromosome fractionation PloS one Medium 28817632
2017 The tail domain of KIF4A interacts with the N-terminal domain of LRP (lung resistance-related protein). Both KIF4A binding to LRP and KIF4A motility are required for dispersed cytoplasmic distribution of LRP, suggesting KIF4A transports LRP-based vaults along microtubules toward the cell membrane, promoting drug resistance. Co-immunoprecipitation, immunofluorescence, domain-deletion analysis Journal of Zhejiang University. Science. B Medium 29204984
2018 The geometry (overlap length and individual microtubule length) of antiparallel microtubule bundles directly regulates PRC1-Kif4A sliding velocity and the final stable overlap width. Kif4A and PRC1 accumulate at MT plus-ends forming an 'end-tag'; when antiparallel MT end-tags collide, sliding stalls, creating a stable overlap whose size scales with MT length. In vitro reconstitution with purified proteins, TIRF microscopy, quantitative analysis of MT sliding eLife High 30353849
2018 AMPK directly phosphorylates KIF4A at Ser801 (identified by quantitative phosphoproteomics). AMPK and Aurora B competitively phosphorylate KIF4A due to overlapping recognition motifs, providing elaborately coordinated regulation of KIF4A-dependent central spindle length control linked to cellular energy state. Quantitative phosphoproteomics, in vitro kinase assay, site-directed mutagenesis, AMPK inhibitors/activators, immunofluorescence Journal of molecular cell biology High 28992084
2018 CDK phosphorylation of KIF4A at T1161 licenses its chromosomal localization, enabling association with condensin I (CAP-G, SMC2) to regulate chromosome condensation, spindle morphology, and chromosome congression. A non-phosphorylatable mutant (T1161A) fails to localize to chromosomes or associate with condensin I; targeting this mutant to chromosomes by fusion with Histone H1 restores KIF4A mitotic function. Phospho-specific antibodies, site-directed mutagenesis, RNAi rescue, Histone H1 targeting fusion, co-immunoprecipitation Journal of molecular cell biology High 29771379
2018 KIF4A binds a Fe-S cluster in vitro through its conserved cysteine-rich C-terminal domain. This domain is required for KIF4A's mitosis-related subcellular localization in vivo; cells with CIA targeting complex (CIA2B/MMS19) depletion or KIF4A knockout show mitotic defects dependent on the Fe-S cluster-binding cysteine-rich domain. In vitro Fe-S cluster binding assay (EPR spectroscopy), CRISPR KIF4A knockout, CIA2B/MMS19 siRNA, immunofluorescence Journal of cell science High 29848660
2018 Cdk1-dependent phosphorylation of KIF4A at S1186 is required for chromosome binding and chromosome scaffold formation. A S1186A mutant localizes to nucleus during interphase but fails to accumulate in chromosome scaffold after nuclear envelope breakdown and disrupts KIF4A interaction with condensin I, resulting in laterally decondensed chromosomes without condensin I on scaffold. Phospho-specific antibody, site-directed mutagenesis (S1186A), co-immunoprecipitation, immunofluorescence PloS one High 30576375
2019 Aurora A phosphorylates the condensin I-dependent chromosomal pool of KIF4A to promote chromosome congression from spindle poles to the metaphase plate. KIF4A exists in two distinct pools: one dependent on condensin I (on chromosome axes), and another dependent on PRC1 (at the anaphase central spindle); specific point mutants unable to interact with condensin I or PRC1 dissect these pools. Phospho-specific mutagenesis, domain-specific KIF4A point mutants (condensin I binding and PRC1 binding), siRNA, immunofluorescence, chromosome congression assay The Journal of cell biology High 31881080
2019 KIF4A and AR form an auto-regulatory positive feedback loop in prostate cancer: KIF4A binds AR and AR-V7 and prevents CHIP-mediated AR/AR-V7 ubiquitin-dependent degradation; AR binds the KIF4A promoter and activates its transcription. Co-immunoprecipitation, luciferase reporter assay, ChIP assay, knockdown experiments, xenograft model Clinical cancer research Medium 31796514
2019 FOXM1c directly binds the KIF4A promoter and activates KIF4A transcription in HCC, establishing KIF4A as a direct transcriptional target of FOXM1c; FOXM1-induced HCC cell proliferation depends on elevated KIF4A expression. ChIP assay, luciferase reporter assay, siRNA knockdown, western blotting, xenograft model Journal of experimental & clinical cancer research Medium 31072351
2019 KIF4A regulates the p21 promoter (demonstrated by luciferase reporter and ChIP assays) to facilitate CRC cell proliferation through p21-mediated cell cycle progression; KIF4A had no effect on apoptosis. Luciferase reporter assay, ChIP assay, siRNA knockdown, cell cycle analysis Cell death & disease Medium 29706624
2020 KIF4A is SUMOylated at lysine 460. SUMOylation of KIF4A at K460 (mapped by CRISPR-Cas9 block of SUMO conjugation) enhances KIF4A's affinity for the microtubule destabilizer stathmin 1 (STMN1), and this interaction is required for efficient abscission at the end of cytokinesis. SUMO site mapping, CRISPR-Cas9 endogenous K460R mutation, co-immunoprecipitation, proximity ligation assay, abscission timing assay Journal of cell science High 32591481
2021 KIF4A (motor-active) is required for spindle elongation in human anaphase together with EG5/kinesin-5. Combined disruption of EG5 and KIF4A causes complete failure of chromosome segregation due to blocked spindle elongation. Tubulin photoactivation, STED, and expansion microscopy show that both proteins promote midzone microtubule sliding without affecting microtubule stability; KIF4A is PRC1-dependent for its central spindle function. Combined chemical inhibition and siRNA depletion, CRISPR, tubulin photoactivation, STED microscopy, expansion microscopy Developmental cell High 33910056
2022 KIF4 directly interacts with NTCP (the HBV/HDV entry receptor) and transports NTCP to the plasma membrane in an ATPase-dependent manner. KIF4 knockdown reduces surface NTCP levels and suppresses HBV/HDV infection; ATPase-null KIF4 mutant cannot rescue surface NTCP localization. FOXM1 transcriptionally regulates KIF4 expression; RXR agonists suppress KIF4 via FOXM1 to reduce HBV entry. Co-immunoprecipitation, cellular fractionation, immunofluorescence, siRNA knockdown, wild-type vs ATPase-null mutant rescue, luciferase reporter virus infection assay PLoS pathogens High 35312737
2022 KIF4A interacts with TPX2 protein and enhances its stability by inhibiting TPX2 ubiquitination, thereby maintaining genomic stability of endometrial cancer cells during mitosis; KIF4A knockdown induces DNA damage response and cell cycle arrest. Co-immunoprecipitation, ubiquitination assay, transcriptome sequencing, knockdown experiments Molecular carcinogenesis Medium 36468837
2022 KIF4 regulates neuronal morphology and seizure susceptibility through the PARP1-TrkB-KCC2 pathway. A point mutation (R728Q) in KIF4A strengthens its affinity with PARP1 by elongating the KIF4 coiled-coil domain, causing aberrant dendritic and spine morphology in hippocampal neurons. NAD supplementation (activating PARP1) rescued the seizure phenotype. Patient mutation identification, mouse knockin model, co-immunoprecipitation, behavioral tests, morphological analysis, pharmacological rescue The Journal of cell biology High 36482480
2024 KIF4A directly binds condensin I through a conserved disordered short linear motif (SLiM) in its C-terminal tail that contacts the HAWK subunit NCAPG. The KIF4A SLiM competes with auto-inhibitory SLiMs from NCAPH and NCAPD2 at an overlapping NCAPG binding site. The KIF4A SLiM peptide alone is sufficient to stimulate condensin I ATPase and DNA loop extrusion activities. Similar SLiMs in yeast Sgo1 and Lrs4 bind the NCAPG-equivalent yeast condensin subunit Ycg1, demonstrating conserved SMC complex regulation. Biochemical pulldown, mutagenesis, in vitro ATPase assay, DNA loop extrusion assay (single molecule), structural analysis The EMBO journal High 39690239
2019 In mouse oocyte meiosis, Kif4 localizes to chromosomes through metaphase and redistributes to the spindle midzone during anaphase; knockdown causes defective midzone formation and longer spindles. Aurora B/C kinase inhibition causes Kif4 mislocalization and anaphase defects. Kif4's binding partner PRC1 and MgcRacGAP show similar dynamic localization, demonstrating conserved midzone organization in acentriolar oocytes. Morpholino/siRNA knockdown in mouse oocytes, immunofluorescence, Aurora B/C inhibitor treatment, live-cell imaging Molecular biology of the cell Medium 31067151

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation. The EMBO journal 266 15297875
2004 Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis. Proceedings of the National Academy of Sciences of the United States of America 250 15625105
2004 Human chromokinesin KIF4A functions in chromosome condensation and segregation. The Journal of cell biology 171 15326200
1994 A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally. The Journal of cell biology 148 7929562
2012 Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase IIα. The Journal of cell biology 147 23166350
2019 FOXM1 promotes hepatocellular carcinoma progression by regulating KIF4A expression. Journal of experimental & clinical cancer research : CR 128 31072351
2006 KIF4 motor regulates activity-dependent neuronal survival by suppressing PARP-1 enzymatic activity. Cell 103 16630823
2018 KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer. Cell death & disease 83 29706624
2014 Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function. Journal of medical genetics 81 24812067
1999 Cellular motor protein KIF-4 associates with retroviral Gag. Journal of virology 81 10559369
2008 A novel role of the chromokinesin Kif4A in DNA damage response. Cell cycle (Georgetown, Tex.) 67 18604178
2014 KIF4A and PP2A-B56 form a spatially restricted feedback loop opposing Aurora B at the anaphase central spindle. The Journal of cell biology 66 25512391
2008 Kinesin KIF4 regulates intracellular trafficking and stability of the human immunodeficiency virus type 1 Gag polyprotein. Journal of virology 66 18684836
2000 Evidence for the involvement of KIF4 in the anterograde transport of L1-containing vesicles. The Journal of cell biology 63 10747093
2021 Microtubule-sliding modules based on kinesins EG5 and PRC1-dependent KIF4A drive human spindle elongation. Developmental cell 54 33910056
1998 Binding of murine leukemia virus Gag polyproteins to KIF4, a microtubule-based motor protein. Journal of virology 50 9658142
2018 Geometry of antiparallel microtubule bundles regulates relative sliding and stalling by PRC1 and Kif4A. eLife 48 30353849
2014 The role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells. Molecules and cells 45 25377255
2019 Targeting the KIF4A/AR Axis to Reverse Endocrine Therapy Resistance in Castration-resistant Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 44 31796514
2010 Overexpression of chromokinesin KIF4 inhibits proliferation of human gastric carcinoma cells both in vitro and in vivo. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 42 20711700
2018 The multiple functions of kinesin-4 family motor protein KIF4 and its clinical potential. Gene 40 30081192
2016 Condensin I-mediated mitotic chromosome assembly requires association with chromokinesin KIF4A. Genes & development 34 27633014
2014 Kif4 interacts with EB1 and stabilizes microtubules downstream of Rho-mDia in migrating fibroblasts. PloS one 34 24658398
2020 miR-29c-3p regulates proliferation and migration in ovarian cancer by targeting KIF4A. World journal of surgical oncology 33 33261630
2020 Circular RNA KIF4A promotes cell migration, invasion and inhibits apoptosis through miR-152/ZEB1 axis in breast cancer. Diagnostic pathology 31 32408908
2017 GTSE1 regulates spindle microtubule dynamics to control Aurora B kinase and Kif4A chromokinesin on chromosome arms. The Journal of cell biology 31 28821562
2022 Circular RNA KIF4A Promotes Liver Metastasis of Breast Cancer by Reprogramming Glucose Metabolism. Journal of oncology 29 36052282
2017 A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis. Oncotarget 28 28160558
2017 Prc1E and Kif4A control microtubule organization within and between large Xenopus egg asters. Molecular biology of the cell 28 29187577
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
2019 Integrative analysis of KIF4A, 9, 18A, and 23 and their clinical significance in low-grade glioma and glioblastoma. Scientific reports 27 30872592
2018 Involvement of Kif4a in Spindle Formation and Chromosome Segregation in Mouse Oocytes. Aging and disease 27 30090651
2015 The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1. Scientific reports 27 26423135
2009 KIF4 mediates anterograde translocation and positioning of ribosomal constituents to axons. The Journal of biological chemistry 25 19158085
2008 Structural requirements of chromokinesin Kif4A for its proper function in mitosis. Biochemical and biophysical research communications 25 18502200
2017 Kif4A mediate the accumulation and reeducation of THP-1 derived macrophages via regulation of CCL2-CCR2 expression in crosstalking with OSCC. Scientific reports 24 28533507
2017 Enhanced expression of KIF4A in colorectal cancer is associated with lymph node metastasis. Oncology letters 24 29434924
2019 Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A. The Journal of cell biology 22 31881080
2008 The kinesin superfamily motor protein KIF4 is associated with immune cell activation in idiopathic inflammatory myopathies. Journal of neuropathology and experimental neurology 22 18520780
2022 KIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation. Molecular carcinogenesis 21 36468837
2021 KIF4A knockdown suppresses ovarian cancer cell proliferation and induces apoptosis by downregulating BUB1 expression. Molecular medicine reports 21 34013367
2014 Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons. Molecular and cellular neurosciences 21 25260485
2004 Kinesin superfamily protein member 4 (KIF4) is localized to midzone and midbody in dividing cells. Experimental & molecular medicine 20 15031677
2022 MiR-379-5p inhibits the proliferation, migration, and invasion of breast cancer by targeting KIF4A. Thoracic cancer 19 35608059
2017 Kinesin KIF4A is associated with chemotherapeutic drug resistance by regulating intracellular trafficking of lung resistance-related protein. Journal of Zhejiang University. Science. B 19 29204984
2017 Kif4 Is Essential for Mouse Oocyte Meiosis. PloS one 18 28125646
2022 KIF4A promotes tumor progression of bladder cancer via CXCL5 dependent myeloid-derived suppressor cells recruitment. Scientific reports 16 35399116
2019 Overexpression of CDCA5, KIF4A, TPX2, and FOXM1 Coregulated Cell Cycle and Promoted Hepatocellular Carcinoma Development. Journal of computational biology : a journal of computational molecular cell biology 16 31593490
2023 Impact of KIF4A on Cancer Stem Cells and EMT in Lung Cancer and Glioma. Cancers 15 38067227
2018 Fe-S cluster coordination of the chromokinesin KIF4A alters its subcellular localization during mitosis. Journal of cell science 15 29848660
2017 Interdependency and phosphorylation of KIF4 and condensin I are essential for organization of chromosome scaffold. PloS one 15 28817632
2022 The kinesin KIF4 mediates HBV/HDV entry through the regulation of surface NTCP localization and can be targeted by RXR agonists in vitro. PLoS pathogens 14 35312737
2021 Chondrocyte-derived Exosomal miR-195 Inhibits Osteosarcoma Cell Proliferation and Anti-Apoptotic by Targeting KIF4A in vitro and in vivo. Translational oncology 14 34952333
2018 AMPK regulates anaphase central spindle length by phosphorylation of KIF4A. Journal of molecular cell biology 14 28992084
2018 Cdk phosphorylation licenses Kif4A chromosome localization required for early mitotic progression. Journal of molecular cell biology 13 29771379
2024 Molecular mechanism of condensin I activation by KIF4A. The EMBO journal 12 39690239
2022 Kif4A mediates resistance to neoadjuvant chemoradiotherapy in patients with advanced colorectal cancer via regulating DNA damage response. Acta biochimica et biophysica Sinica 12 35882623
2022 KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. Journal of Cancer 12 36606197
2000 Identification of the human homologue of mouse KIF4, a kinesin superfamily motor protein. Biochimica et biophysica acta 12 10978527
2021 Expanding the KIF4A-associated phenotype. American journal of medical genetics. Part A 11 34346154
2020 The kinesin motor protein KIF4A as a potential therapeutic target in renal cell carcinoma. Investigational new drugs 11 32533288
2019 Chromokinesin Kif4 promotes proper anaphase in mouse oocyte meiosis. Molecular biology of the cell 11 31067151
2023 DEPDC1 and KIF4A synergistically inhibit the malignant biological behavior of osteosarcoma cells through Hippo signaling pathway. Journal of orthopaedic surgery and research 10 36849972
2022 KIF4A knockdown inhibits tumor progression and promotes chemo-sensitivity via induction of P21 in lung cancer cells. Chemical biology & drug design 10 36217900
2016 Phosphoproteomic analysis of human mitotic chromosomes identified a chromokinesin KIF4A. Biomedical research (Tokyo, Japan) 10 27108885
2022 KIF4 regulates neuronal morphology and seizure susceptibility via the PARP1 signaling pathway. The Journal of cell biology 9 36482480
2021 KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3. International journal of molecular medicine 9 33846765
2022 Upregulated Circular RNA KIF4A Promotes Cell Migration and Invasion by Regulating MicroRNA-144-3p/EZH2 Axis in Gastric Cancer. Journal of oncology 8 35466313
2020 Chromokinesin KIF4A teams up with stathmin 1 to regulate abscission in a SUMO-dependent manner. Journal of cell science 7 32591481
2019 Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus. Frontiers in genetics 7 31616463
2018 Cdk1-dependent phosphorylation of KIF4A at S1186 triggers lateral chromosome compaction during early mitosis. PloS one 7 30576375
2024 WZ-3146 acts as a novel small molecule inhibitor of KIF4A to inhibit glioma progression by inducing apoptosis. Cancer cell international 5 38937742
2023 ERCC6L facilitates the progression of laryngeal squamous cell carcinoma by the binding of FOXM1 and KIF4A. Cell death discovery 5 36726012
2022 KIF4 enforces the progression of colorectal cancer by inhibiting the autophagy via activating the Hedgehog signaling pathway. Archives of biochemistry and biophysics 5 36183846
2024 Finding key genes (UBE2T, KIF4A, CDCA3, and CDCA5) co-expressed in hepatitis, cirrhosis and hepatocellular carcinoma based on multiple bioinformatics techniques. BMC gastroenterology 4 38890649
2024 Therapeutic Potential of PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1 Genes in Triple-Negative Breast Cancer: Correlating Their Expression with Sensitivity to GSK 461364 and IKK 16 Drugs. Biochemical genetics 4 39214909
2023 [Retracted] KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3. International journal of molecular medicine 4 37293853
2022 EZH2 suppresses insulinoma development by epigenetically reducing KIF4A expression via H3K27me3 modification. Gene 4 35182680
2025 miR-223-3p Targets KIF4A and Promotes the Oxidative Stress-Mediated Apoptosis of Breast Cancer Cells. Cancer biotherapy & radiopharmaceuticals 3 39914820
2025 Integrative PPI network and random forest analysis identifies KIF4A, TOP2A, and ASPM protein macromolecules as novel protein biomarkers in renal carcinoma pathogenesis. International journal of biological macromolecules 3 40345279
2025 Bisphenol A caused abnormal spermatogenesis of Eriocheir sinensis through es-ERR/es-KIF4A pathway with discussion of BPA substitutes. Journal of hazardous materials 3 40532378
2025 KIF4A Inhibits Ferroptosis in Glioblastoma via the CHMP4B/GPX4 Axis and Promotes Temozolomide Resistance. Molecular carcinogenesis 3 40705827
2025 KIF4A Promotes Glioblastoma Malignant Progression and Transmission of Temozolomide Resistance in the Tumor Microenvironment via the HIF1A/VEGFA Axis. CNS neuroscience & therapeutics 3 41084153
2024 KIF4A promotes epithelial-mesenchymal transition by activating the TGF-β/SMAD signaling pathway in glioma cells. Molecular and cellular biochemistry 3 38411896
2022 Aspirin Exerts Its Antitumor Effect in Esophageal Squamous Cell Carcinoma by Downregulating the Expression of ATAD2 and KIF4A. Analytical cellular pathology (Amsterdam) 3 36046597
2020 KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo. OncoTargets and therapy 3 32280241
2019 Whole genome expression microarray reveals novel roles for Kif4 in monocyte/macrophage cells. European review for medical and pharmacological sciences 3 31486502
2017 Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages. International journal of molecular medicine 3 28350061
2025 KIF4A on TGF-Β1/Smad3 Pathway: A Preliminary Investigation on the Proliferation and Immune Response in In-Vitro Cultured Breast Cancer Cells. Combinatorial chemistry & high throughput screening 1 39757619
2025 KIF4A Facilitates Oxaliplatin Resistance and Stemness in Colon Cancer by Boosting Glucose Metabolism. Digestion 1 40147432
2025 [Analysis of a child with X-linked intellectual disability type 100 due to variant of KIF4A gene and a literature review]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 40372222
2025 RXR agonist S169 inhibits HBV/HDV entry in vitro by disrupting KIF4-dependent NTCP trafficking. Antiviral research 1 40523562
2025 SP1-Mediated Upregulation of KIF4A Promotes Prostate Cancer Progression via Targeting TWIST1. Journal of biochemical and molecular toxicology 1 40557825
2024 X-Linked Bilateral Polymicrogyria With Epilepsy and Intellectual Disability Associated With a Novel KIF4A Variant. American journal of medical genetics. Part A 1 39268972
2024 Injury-induced KIF4A neural expression and its role in Schwann cell proliferation suggest a dual function for this kinesin in neural regeneration. Neural regeneration research 1 39665820
2021 KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion. BioMed research international 1 34805404
2026 CPNE3 promotes colorectal cancer progression by regulating KIF4-mediated autophagy. Journal of gastrointestinal oncology 0 41816564
2026 Physical exercise mitigates chronic psychological stress-induced vascular inflammation via the BDNF-Kif4-TARM1 axis. Clinical and translational medicine 0 42010994
2025 KIF4A in disease pathogenesis and therapeutics: from molecular mechanisms to clinical translation. Biology direct 0 41361459
2023 KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo [Retraction]. OncoTargets and therapy 0 37192931