Affinage

KIF4A

Chromosome-associated kinesin KIF4A · UniProt O95239

Length
1232 aa
Mass
139.9 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF4A is a plus-end-directed kinesin-4 motor with microtubule-activated ATPase activity built from an N-terminal motor domain, a central coiled-coil stalk, and a C-terminal cargo/tail domain, and it operates across mitotic chromosome architecture, central spindle dynamics, and neuronal transport (PMID:7929562). During mitosis KIF4A partitions into two functionally distinct, kinase-gated pools: a condensin I-bound pool on chromosome arms and a PRC1-bound pool at the anaphase central spindle (PMID:31881080). Chromosome-arm targeting requires Cdk1 phosphorylation at T1161 and S1186, coordination of an Fe-S cluster through its conserved cysteine-rich domain, and motor activity, and these are needed for KIF4A to form a stable, interdependent complex with condensin I that drives lateral compaction of chromatid arms (PMID:29771379, PMID:30576375, PMID:29848660, PMID:27633014, PMID:23166350); mechanistically, a C-terminal short linear motif in KIF4A binds the condensin I HAWK subunit NCAPG, displacing auto-inhibitory SLiMs to directly stimulate condensin I ATPase and DNA loop-extrusion activity (PMID:39690239). At the central spindle KIF4A is recruited by PRC1 and translocates it to antiparallel microtubule plus ends, where the PRC1-KIF4A module slides microtubules, forms self-limiting end-tags that set overlap geometry, and—together with EG5/kinesin-5—generates the force for spindle elongation and chromosome segregation (PMID:15297875, PMID:15625105, PMID:30353849, PMID:33910056). This central-spindle pool is reciprocally phosphoregulated: Aurora B activates KIF4A at T799 while a PP2A-B56γ/ε negative-feedback loop opposes it, with AMPK competing at the overlapping S801 motif to tune central spindle length (PMID:25512391, PMID:28992084), and Aurora A independently activates the condensin I pool for chromosome congression (PMID:31881080). KIF4A is also SUMOylated at K460, which enhances stathmin-1 binding and is required for timely abscission (PMID:32591481). Beyond mitosis, the C-terminal domain suppresses PARP-1 enzymatic activity and is released upon CaMKII-mediated dissociation to support neuron survival, and a patient epilepsy mutation (R728Q) strengthening the KIF4A-PARP1 interaction perturbs the PARP1-TrkB-KCC2 pathway and seizure susceptibility (PMID:16630823, PMID:36482480). As a transport motor its tail domain binds and anterogradely delivers cargoes including L1, ribosomal protein P0, and β1 integrin into axons, and its ATPase activity drives surface delivery of the NTCP receptor required for HBV/HDV entry (PMID:10747093, PMID:19158085, PMID:25260485, PMID:35312737). KIF4A additionally associates with BRCA2 and is recruited to DNA damage sites to support Rad51-dependent homologous recombination (PMID:18604178).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1994 High

    Established the foundational identity of KIF4 as a motor protein, defining its enzymatic and structural basis for force generation along microtubules.

    Evidence cDNA cloning, ATPase and motility assays, and electron microscopy of Sf9-expressed mouse protein

    PMID:7929562

    Open questions at the time
    • Cargo and physiological substrates not yet defined
    • Mitotic role not addressed
  2. 2000 Medium

    Defined KIF4 as an anterograde axonal transport motor, linking its motility to delivery of a specific neuronal cargo required for axon growth.

    Evidence Subcellular fractionation, immunoisolation, and antisense knockdown with L1 cargo phenotype in neurons

    PMID:10747093

    Open questions at the time
    • Direct tail-cargo binding interface not mapped here
    • Did not address mitotic functions
  3. 2004 High

    Revealed a central mitotic role by establishing the PRC1-KIF4A interaction as the determinant of central spindle and midzone organization.

    Evidence RNAi, Co-IP, live imaging, domain mapping, and motor-dead rescue in human cells

    PMID:15297875 PMID:15625105

    Open questions at the time
    • Mechanism of microtubule sliding not yet reconstituted
    • Phosphoregulation of the PRC1 pool not yet defined
  4. 2004 High

    Identified the condensin I/II interaction and chromosome-arm localization, placing KIF4A in chromosome condensation and segregation.

    Evidence RNAi with chromosome morphology readouts and Co-IP with condensin complexes

    PMID:15326200

    Open questions at the time
    • Did not resolve condensin I vs II specificity
    • Phospho-dependence of localization unknown at this stage
  5. 2006 High

    Uncovered a non-motor enzymatic-regulatory function, showing KIF4's C-terminus suppresses PARP-1 to control neuronal survival via calcium signaling.

    Evidence In vitro PARP-1 activity assay, Co-IP, live imaging, and CaMKII manipulation

    PMID:16630823

    Open questions at the time
    • Structural basis of PARP-1 suppression not defined
    • Connection to downstream survival effectors limited
  6. 2008 High

    Connected KIF4A to genome maintenance through a BRCA2 association required for Rad51 recruitment and homologous recombination.

    Evidence Co-IP with domain mapping, laser micro-irradiation, I-SceI HR assay, and clonogenic survival

    PMID:18604178

    Open questions at the time
    • Whether motor activity is required at damage sites unresolved
    • Mechanism of Rad51 IRIF support unclear
  7. 2009 Medium

    Extended the axonal cargo repertoire and mapped the tail domain interaction with the ribosomal protein P0, defining transport of translational machinery.

    Evidence Co-IP, domain deletion/mutation, RNAi, and immunofluorescence in DRG neurons

    PMID:19158085

    Open questions at the time
    • Cargo selectivity mechanism not fully defined
    • Single-lab functional data
  8. 2012 High

    Defined KIF4 and condensin as a mutually dependent, parallel pathway for lateral chromatid compaction acting in opposition to topoisomerase IIa.

    Evidence Single and double RNAi epistasis, in vitro chromosome structure assay, and morphology analysis

    PMID:23166350

    Open questions at the time
    • Direct biochemical activation of condensin not yet shown
    • Phospho- and metal-cofactor requirements not addressed here
  9. 2014 High

    Established phosphoregulatory control of the central spindle pool by defining a PP2A-B56-Aurora B negative feedback loop tuning KIF4A ATPase and spindle growth.

    Evidence In vitro phosphatase assays, RNAi epistasis, and phospho-specific antibodies with spindle length measurement

    PMID:25512391

    Open questions at the time
    • Spatial restriction mechanism of the feedback loop partially defined
    • Did not address arm pool regulation
  10. 2016 High

    Resolved condensin I (not II) as the specific mitotic partner and showed motor-activity-dependent loading of condensin I onto chromosome axes.

    Evidence Co-IP, motor mutant analysis, and RNAi with chromosome readouts

    PMID:27108885 PMID:27633014

    Open questions at the time
    • Molecular interface with condensin not yet mapped
    • Did not distinguish phospho-sites driving the interaction
  11. 2018 High

    Mapped the specific molecular determinants of chromosome-arm targeting: Cdk1 phosphorylation at T1161/S1186 and Fe-S cluster coordination via the cysteine-rich domain.

    Evidence Phospho-mimetic/non-phosphorylatable mutants, forced-localization rescue, Co-IP, and in vitro Fe-S binding with CIA machinery epistasis

    PMID:29771379 PMID:29848660 PMID:30576375

    Open questions at the time
    • Role of the Fe-S cluster in catalysis vs structure not resolved
    • Integration of phosphorylation and metal cofactor signals unclear
  12. 2018 High

    Reconstituted the PRC1-KIF4A microtubule-sliding mechanism, revealing geometry-dependent end-tagging that self-limits antiparallel overlap size.

    Evidence In vitro microtubule sliding reconstitution with TIRF and quantitative end-tag analysis; Xenopus extract recruitment assays

    PMID:29187577 PMID:30353849

    Open questions at the time
    • In vivo relevance of overlap scaling not quantified
    • Regulation of end-tagging by kinases not tested in vitro
  13. 2018 High

    Added a competing AMPK input at the S801 motif, integrating metabolic signaling into central spindle length control.

    Evidence In vitro kinase assay, phosphoproteomics, and AMPK perturbation with spindle measurement

    PMID:28992084

    Open questions at the time
    • Physiological metabolic conditions activating this control not defined
    • Interplay with Aurora B/PP2A loop in vivo incomplete
  14. 2019 High

    Separated the two mitotic pools functionally, showing Aurora A activates the condensin I pool for congression while Aurora B governs the PRC1 central-spindle pool.

    Evidence Partner-binding-deficient and Aurora-regulation-deficient point mutants with phenotypic readouts

    PMID:31881080

    Open questions at the time
    • Spatial segregation of Aurora A vs B inputs not fully resolved
    • Crosstalk between pools unclear
  15. 2020 High

    Identified SUMOylation at K460 as a post-translational switch coupling KIF4A to stathmin-1 to time abscission.

    Evidence CRISPR SUMO-site editing, SUMO mapping, binding affinity, and cytokinesis timing assays

    PMID:32591481

    Open questions at the time
    • SUMO E3 ligase for K460 not identified
    • Mechanistic link between STMN1 and abscission machinery incomplete
  16. 2021 High

    Established KIF4A together with EG5 as the force-generating system for anaphase spindle elongation via midzone microtubule sliding.

    Evidence CRISPR, dual depletion, tubulin photoactivation, STED and expansion microscopy

    PMID:33910056

    Open questions at the time
    • Quantitative force contributions of each motor not separated
    • Mechanism of EG5-KIF4A coordination unknown
  17. 2022 High

    Defined an interphase membrane-transport role, showing KIF4A ATPase activity drives surface delivery of the NTCP receptor exploited for HBV/HDV entry.

    Evidence siRNA, ATPase-null mutant rescue, fractionation, Co-IP, and HBV infection assay

    PMID:35312737

    Open questions at the time
    • Direct NTCP-tail binding interface not mapped
    • Regulation of this transport not defined
  18. 2024 High

    Resolved the direct molecular mechanism of condensin activation, showing a KIF4A C-terminal SLiM binds NCAPG to displace auto-inhibition and stimulate condensin I ATPase and loop extrusion.

    Evidence Reconstituted direct binding, competitive binding, in vitro ATPase, and DNA loop extrusion assays

    PMID:39690239

    Open questions at the time
    • How motor translocation couples to SLiM-driven activation in vivo unresolved
    • Structural model of the displaced auto-inhibitory state not provided
  19. 2022 High

    Linked KIF4A to a Mendelian-relevant neurological phenotype, with an epilepsy patient R728Q mutation strengthening KIF4-PARP1 binding and disrupting the PARP1-TrkB-KCC2 axis.

    Evidence Patient mutation, R728Q knock-in mouse, Co-IP affinity, neuromorphology, and NAD rescue

    PMID:36482480

    Open questions at the time
    • Generalizability beyond this mutation unknown
    • Causal chain from PARP1 to seizure circuitry incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KIF4A's motor translocation is mechanically coupled to its diverse regulatory outputs—condensin SLiM-driven activation, PARP-1 suppression, and selective cargo loading—remains unresolved.
  • No unifying structural model links motor cycling to non-motor C-terminal activities
  • Switch logic integrating phosphorylation, SUMOylation, and Fe-S coordination not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005694 chromosome 3 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-9609507 Protein localization 4 R-HSA-112316 Neuronal System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-73894 DNA Repair 1
Partners
BRCA2EB1EG5NCAPGPARP1PRC1STMN1TPX2
Complex memberships
PRC1-KIF4A central spindle modulecondensin I (KIF4A-condensin I complex)

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 KIF4 (mouse ortholog) is a microtubule plus-end-directed motor protein with nucleotide-dependent microtubule binding, microtubule-activated ATPase activity, and anterograde motility. The protein has three domains: an NH2-terminal globular motor domain, a central alpha-helical stalk domain, and a COOH-terminal tail domain. It colocalizes with membranous organelles in growth cones and cytoplasm. cDNA cloning, biochemical characterization, ATPase assay, electron microscopy of Sf9-expressed protein, immunocytochemistry The Journal of cell biology High 7929562
1998 KIF4 (mouse ortholog) binds murine leukemia virus Gag polyproteins; the interaction maps to the C-terminal region of KIF4. KIF4-MuLV Gag associations were detected in vitro and in mammalian cells, suggesting KIF4 may mediate Gag transport. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation in mammalian cells Journal of virology Medium 9658142
1999 Human KIF4 associates with HIV-1 Gag precursor (Pr55) and a matrix-capsid processing intermediate (Pr42) but not with other processed Gag products. KIF4 and HIV-1 Gag cofractionate by sucrose gradient, size-exclusion, and anion-exchange chromatography. Gag binding is mediated by a domain of KIF4 proximal to its C-terminus. Sucrose gradient fractionation, size-exclusion chromatography, anion-exchange chromatography, immunoprecipitation, yeast two-hybrid Journal of virology Medium 10559369
2000 KIF4 mediates anterograde transport of L1-containing vesicles in neurons. KIF4-associated vesicles are highly concentrated in growth cones, contain L1 (a cell adhesion molecule for axonal elongation), and lack synaptic vesicle markers. Antisense suppression of KIF4 causes accumulation of L1 in cell bodies, its disappearance from axonal tips, and prevents L1-enhanced axonal elongation. Subcellular fractionation, immunoisolation, antisense oligonucleotide knockdown, immunofluorescence The Journal of cell biology Medium 10747093
2004 KIF4 binds PRC1 (a microtubule-bundling protein) and is essential for central spindle organization and midzone formation during anaphase. In KIF4-deficient cells, the central spindle is disorganized and all midzone-associated proteins including PRC1 fail to concentrate at the midline. PRC1 is required for KIF4 localization to the spindle. RNAi knockdown, immunofluorescence, protein interaction assay (co-immunoprecipitation) The EMBO journal High 15297875
2004 Kif4 translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase-to-anaphase transition. Kif4 binds PRC1 through its 'stalk plus tail' domains. This translocation is required for midzone formation and cytokinesis; a motor-dead Kif4 mutant cannot rescue PRC1 translocation or cytokinesis defects. CDK phosphorylation of PRC1 controls the timing of PRC1 translocation by Kif4. Time-lapse microscopy, esiRNA knockdown, domain mapping, motor-dead mutant rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 15625105
2004 Human KIF4A (HKIF4A) localizes to condensed chromosome arms during mitosis and accumulates in the midzone during late anaphase and the cytokinetic ring during cytokinesis. RNAi depletion causes defective prometaphase organization, chromosome mis-alignment, spindle defects, and chromosome mis-segregation. KIF4A interacts with condensin I and II complexes, and its depletion results in chromosome hypercondensation. RNAi knockdown, immunofluorescence, co-immunoprecipitation with condensin complexes The Journal of cell biology High 15326200
2004 KIF4 localizes to the midzone and midbody during ana/telophase and cytokinesis in dividing HeLa cells, forming a ring structure around microtubule bundles at the cytokinetic bridge. Immunofluorescence, 3D microscopy analysis Experimental & molecular medicine Low 15031677
2006 The C-terminal domain of KIF4 suppresses PARP-1 enzymatic activity. Upon neuronal stimulation by membrane depolarization, CaMKII-mediated calcium signaling induces dissociation of KIF4 from PARP-1, resulting in upregulation of PARP-1 activity that supports neuron survival. After dissociation, KIF4 moves from the nucleus to the cytoplasm and toward distal neurites in a microtubule-dependent manner. In vitro PARP-1 activity assay, co-immunoprecipitation, live cell imaging, calcium signaling manipulation, CaMKII inhibitor experiments Cell High 16630823
2008 Kif4A associates with BRCA2; the interaction is mediated by the Kif4A C-terminal cargo-binding domain and BRCA2 C-terminal conserved region. Upon nuclear laser micro-irradiation, Kif4A is rapidly recruited to sites of DNA damage. Kif4A depletion impairs Rad51 IRIF formation (but not γ-H2AX or NBS1 IRIF) and decreases homologous recombination efficiency, rendering cells hypersensitive to ionizing radiation. Co-immunoprecipitation, domain mapping, laser micro-irradiation, shRNA knockdown, I-SceI endonuclease HR assay, clonogenic survival assay Cell cycle (Georgetown, Tex.) High 18604178
2008 Disrupting KIF4 function slows HIV-1 Gag trafficking through intermediates, inhibits virus-like particle production, and leads to increased Gag degradation. When KIF4 function is blocked, Gag accumulates in perinuclear clusters that colocalize with KIF4, Ubc9 (E2 SUMO-1 conjugating enzyme), and SUMO. Reintroduction of KIF4 rescues intracellular Gag levels. KIF4 knockdown, KIF4 reintroduction rescue, immunofluorescence colocalization, VLP production assay, western blot Journal of virology Medium 18684836
2008 Two conserved chromatin-binding motifs in Kif4A are required for its mitotic function: the first leucine Zip motif (Zip1) within the ZBZ region, and a cysteine-rich (CR) motif in the C-terminal region. Kif4A mutants lacking either Zip1 or CR, or the K94A ATPase-dead mutant, cannot rescue RNAi-induced mitotic defects, indicating that both chromatin binding and ATPase activity are required for Kif4A mitotic function. Mutagenesis, RNAi rescue experiments, chromatin-binding assays Biochemical and biophysical research communications Medium 18502200
2009 The C-terminal tail domain of KIF4 directly interacts with P0, a major ribosomal protein. KIF4 is required for anterograde transport of ribosomal constituents to axons; RNAi suppression of KIF4 or expression of tail-domain-deleted or ATP-binding-site-mutated KIF4 causes accumulation of P0 and ribosomal proteins in the cell body and their disappearance from axons. An ERM-like domain in KIF4's second coiled-coil region is required for clustering of ribosomal constituents and for anterograde transport of L1. Co-immunoprecipitation, domain deletion/mutation analysis, RNAi, immunofluorescence in DRG neurons The Journal of biological chemistry Medium 19158085
2012 KIF4 cooperates with condensin complexes in a parallel pathway to promote lateral compaction of chromatid arms. KIF4 and condensin are mutually dependent for their dynamic localization on chromatid axes. Depletion of either causes sister chromatids to expand. Simultaneous depletion of KIF4 and condensin causes complete loss of chromosome morphology. Topoisomerase IIα promotes axial shortening of chromatids, acting in opposition to KIF4 and condensins. RNAi (single and double depletion), morphological analysis, in vitro chromosome structure assay, immunofluorescence The Journal of cell biology High 23166350
2014 Kif4 interacts directly with the N-terminal domain of EB1 via its tail domain. Kif4 localizes to ends of stable microtubules and acts downstream of Rho-mDia-EB1 to induce selective microtubule stabilization in fibroblasts. Kif4 depletion blocks mDia- and EB1-induced stable MT formation and inhibits cell migration into wounded monolayers. Co-immunoprecipitation, direct binding studies (domain mapping), immunofluorescence, shRNA knockdown, wound healing assay PloS one Medium 24658398
2014 KIF4A and PP2A-B56γ/ε form a spatially restricted negative 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- and microtubule-stimulated KIF4A ATPase activity. Combined silencing of PP2A-B56γ and -ε increases KIF4A T799 phosphorylation and decreases central spindle growth in anaphase B. Biochemical phosphatase assays, immunoprecipitation, RNAi (single and double depletion), phospho-specific antibodies, spindle length measurement The Journal of cell biology High 25512391
2014 Knockdown of Kif4a in rat primary hippocampal neurons alters the balance between excitatory and inhibitory synaptic transmission, suggesting KIF4A regulates synaptic function. shRNA knockdown in primary rat hippocampal neurons, electrophysiological recordings of synaptic transmission Journal of medical genetics Medium 24812067
2014 Kif4A co-localizes with β1 integrin in vesicles in neurons and non-neuronal cells, and the two molecules co-immunoprecipitate. Knockdown of KIF4A reduces β1 integrin levels in axons of developing neurons and reduces neurite elongation on laminin. Co-immunoprecipitation, immunofluorescence colocalization, shRNA knockdown, neurite elongation assay Molecular and cellular neurosciences Medium 25260485
2015 KIF4-dependent PRC1-1 (isoform 1 of PRC1) translocation to astral microtubule tips during prometaphase causes fatal sister chromatid alignment errors when Cdk1 activity is insufficient. Gene ablation of KIF4 or abrogation of KIF4 motor activity rescues Cdk1-inhibition-induced chromosome alignment defects. Large-scale RNAi screen, KIF4 gene ablation, motor-dead mutant, live cell imaging of chromosome alignment Scientific reports Medium 26423135
2016 KIF4A is phosphorylated specifically during mitosis, dependent on Cdk1 and Aurora B activity. This phosphorylation is required for KIF4A to interact with condensin I. Mass spectrometry phosphoproteomics, phospho-specific antibody, kinase inhibitor treatments, co-immunoprecipitation Biomedical research (Tokyo, Japan) Medium 27108885
2016 KIF4A associates specifically with condensin I (not condensin II) during mitosis. Condensin I enrichment on chromosomal axes depends on its association with KIF4A in a manner that requires KIF4A motor activity. This interaction is required for condensin I to confer physiological properties to chromosomes. Co-immunoprecipitation, mutational analysis, immunofluorescence, RNAi Genes & development High 27633014
2017 GTSE1 depletion increases stable mitotic spindle microtubules, which leads to diminished Aurora B kinase recruitment to chromosome arms and consequently decreased Kif4A binding to chromosome arms. RNAi knockdown, immunofluorescence, microtubule stability assays The Journal of cell biology Medium 28821562
2017 KIF4A forms a stable complex with condensin I, and KIF4 and condensin I are interdependent for localization to the chromosome scaffold. Phosphorylation of KIF4 and condensin I by Aurora B promotes their chromosome targeting, whereas Plk1 activity promotes their dissociation from chromosomes. Co-immunoprecipitation, kinase inhibitor treatment (Aurora B, Plk1), immunofluorescence PloS one Medium 28817632
2017 PHF14 directly binds to and co-localizes with KIF4A to form a functional complex during cell division. PHF14 silencing causes similar mitotic defects to KIF4A depletion (prolonged M phase, mitotic defects), and the two proteins have a synergistic effect on cell proliferation. Co-immunoprecipitation, immunofluorescence co-localization, RNAi knockdown, cell cycle analysis Oncotarget Medium 28160558
2017 Prc1E (Xenopus egg ortholog of PRC1) and Kif4A are recruited to antiparallel bundles at microtubule interaction zones in Xenopus egg extracts. Prc1E is required for Kif4A recruitment (but not vice versa). Prc1E and Kif4A together slow and terminate microtubule plus-end growth preferentially at interaction zones, blocking interpenetration of asters. They are also required for radial order of large asters growing in isolation. Xenopus egg extract reconstitution, immunodepletion, TIRF/live microscopy Molecular biology of the cell High 29187577
2017 KIF4A tail domain interacts with the N-terminal region of LRP (lung resistance-related protein). Both the ability to bind LRP and KIF4A motility are required for dispersed cytoplasmic distribution of LRP, suggesting KIF4A transports LRP-based vaults toward the cell membrane to confer drug resistance. Co-immunoprecipitation (domain mapping), immunofluorescence Journal of Zhejiang University. Science. B Medium 29204984
2018 In vitro reconstitution shows that PRC1-Kif4A collectively slide antiparallel microtubules, accumulate at microtubule plus-ends ('end-tag'), and stall sliding when end-tags on antiparallel microtubules collide to form a stable overlap. Sliding velocity scales with initial microtubule overlap length, and final overlap width scales with microtubule lengths. In vitro microtubule sliding reconstitution, TIRF microscopy, quantitative analysis of end-tag formation eLife High 30353849
2018 AMPK phosphorylates KIF4A directly at Ser801. AMPK and Aurora B competitively phosphoregulate KIF4A due to overlapping recognition motifs, resulting in regulation of KIF4A-dependent central spindle length control. AMPK α2 subunits are sequentially associated with mitotic apparatus throughout cell division. Quantitative phosphoproteomics, in vitro kinase assay, AMPK inhibitor/activation experiments, spindle length measurement Journal of molecular cell biology High 28992084
2018 Cdk phosphorylation of human Kif4A at T1161 is required for chromosomal localization. Phosphorylated or Cdk phospho-mimetic Kif4A associates with chromosomes and condensin I (CAP-G and SMC2 subunits) to regulate chromosome condensation, spindle morphology, and chromosome congression. Non-phosphorylatable Kif4A (T1161A) cannot localize to chromosomes or associate with condensin I; targeting it to chromosomes via histone H1 fusion restores function. Phospho-mimetic and non-phosphorylatable mutant analysis, RNAi rescue experiments, co-immunoprecipitation, histone H1 fusion targeting Journal of molecular cell biology High 29771379
2018 KIF4A binds a Fe-S cluster in vitro through its conserved cysteine-rich domain. This Fe-S cluster coordination is required for KIF4A's mitosis-related localization. Downregulation of CIA targeting complex components (CIA2B/MMS19) impairs KIF4A Fe-S cluster acquisition, leading to mislocalization and mitotic defects phenocopying KIF4A knockout. In vitro Fe-S cluster binding assay, co-localization studies, CIA2B/MMS19 knockdown, KIF4A knockout Journal of cell science High 29848660
2018 Cdk1-dependent phosphorylation of KIF4A at S1186 is required for chromosome binding, chromosome scaffold formation, and interaction with condensin I complex. Non-phosphorylatable KIF4A (S1186A) localizes to the nucleus in interphase but fails to accumulate in the chromosome scaffold after nuclear envelope breakdown, leading to laterally decondensed chromosomes without condensin I and chromosome bridge formation during segregation. Phospho-mutant analysis, immunofluorescence, co-immunoprecipitation, Cdk1 inhibitor treatment PloS one Medium 30576375
2018 Kif4 localizes to chromosomes in metaphase I and II mouse oocytes and redistributes to the spindle midzone during anaphase. Kif4 depletion results in defective midzone formation and longer spindles. Aurora B/C kinase inhibition causes Kif4 mislocalization and anaphase defects. Kif4 interacts with kinetochore proteins CENP-C and Ndc80 (confirmed by co-localization and proximity ligation assay). Aurora kinase and Cdk activity is required for Kif4 kinetochore localization and interaction with Ndc80 and CENP-C. Morpholino antisense knockdown, immunofluorescence, proximity ligation assay, kinase inhibitor treatment, spindle length measurement PloS one Medium 28125646
2019 Aurora A phosphorylates the condensin I-dependent pool of KIF4A at the chromosome axis during prometaphase to promote chromosome congression. KIF4A point mutants unable to interact with condensin I or PRC1, or deficient for Aurora kinase regulation, were used to show that Aurora A (not Aurora B) specifically regulates the condensin I-bound pool of KIF4A for congression, while Aurora B regulates the PRC1-dependent pool at the anaphase central spindle. KIF4A point mutants (condensin I-binding deficient, PRC1-binding deficient, Aurora kinase regulation-deficient), immunofluorescence, kinase assays The Journal of cell biology High 31881080
2019 KIF4A binds androgen receptor (AR) and AR-V7, preventing CHIP-mediated AR and AR-V7 ubiquitin-dependent degradation. AR binds the KIF4A promoter and activates its transcription, forming an auto-regulatory positive feedback loop. KIF4A knockdown reverses enzalutamide resistance in castration-resistant prostate cancer cells. Co-immunoprecipitation, luciferase reporter assay, ChIP assay, western blot, xenograft models Clinical cancer research Medium 31796514
2019 FOXM1c directly regulates KIF4A transcription; FOXM1-induced HCC cell proliferation is dependent on elevated KIF4A expression. KIF4A knockdown abolishes FOXM1-induced proliferation both in vitro and in vivo. ChIP assay, luciferase reporter assay, KIF4A knockdown, western blot, xenograft model Journal of experimental & clinical cancer research Medium 31072351
2020 KIF4A is SUMOylated at lysine 460. CRISPR-Cas9-mediated block of SUMO conjugation at K460 delays cytokinesis. SUMOylation of KIF4A enhances its affinity for the microtubule destabilizer stathmin 1 (STMN1), and this KIF4A-STMN1 interaction regulates abscission. CRISPR-Cas9 genome editing (SUMO site mutation), SUMO site mapping, binding affinity assay (KIF4A-STMN1), cytokinesis timing assay Journal of cell science High 32591481
2021 KIF4A/kinesin-4 together with EG5/kinesin-5 constitutes the force-generating mechanism for spindle elongation in human cells. Dual disruption of EG5 and KIF4A blocks spindle elongation and causes complete failure of chromosome segregation despite poleward chromosome motion. KIF4A's role requires PRC1 (is PRC1-dependent). Tubulin photoactivation, STED, and expansion microscopy show that perturbation of both proteins impairs midzone microtubule sliding without affecting microtubule stability. Combined depletion and inactivation assays, CRISPR, tubulin photoactivation, STED microscopy, expansion microscopy Developmental cell High 33910056
2022 KIF4 mediates surface transport of NTCP (the HBV/HDV entry receptor). KIF4 knockdown reduces surface and raises intracellular NTCP levels. Overexpression of wild-type KIF4 but not an ATPase-null KIF4 mutant restores surface NTCP localization and HBV permissiveness. KIF4 and NTCP colocalize along microtubule filaments and co-immunoprecipitate. siRNA knockdown, ATPase-null mutant overexpression, cellular fractionation, immunofluorescence, co-immunoprecipitation, HBV/NLuc reporter infection assay PLoS pathogens High 35312737
2022 KIF4A interacts with TPX2 via co-immunoprecipitation and enhances TPX2 protein stability by inhibiting its ubiquitination. KIF4A knockdown induces DNA damage response, cell cycle arrest, and apoptosis in endometrial cancer cells. Co-immunoprecipitation, ubiquitination assay, KIF4A knockdown, western blot Molecular carcinogenesis Medium 36468837
2022 KIF4A regulates DNA damage response (DDR) through both its motor domain and tail domain. KIF4A knockdown increases sensitivity of colorectal cancer cells to 5-FU and cisplatin by affecting DDR. Domain-specific mutant analysis (motor and tail domains), KIF4A overexpression/knockdown, DNA damage assays Acta biochimica et biophysica Sinica Low 35882623
2022 KIF4A regulates seizure susceptibility through the PARP1-TrkB-KCC2 pathway. A point mutation (R728Q) in KIF4A, identified in epilepsy patients, strengthens KIF4A affinity for PARP1 by elongating the KIF4 coiled-coil domain, causing aberrant dendritic and spine morphology in hippocampal neurons. NAD supplementation (which activates PARP1) can modulate the TrkB-KCC2 pathway and rescue seizure susceptibility in KIF4-mutant mice. Patient mutation analysis, KIF4A R728Q knock-in mouse model, behavioral tests, co-immunoprecipitation (KIF4-PARP1 affinity), neuromorphological analysis, NAD rescue experiment The Journal of cell biology High 36482480
2024 KIF4A binds directly to the human condensin I HAWK subunit NCAPG via a conserved disordered short linear motif (SLiM) in its C-terminal tail. KIF4A competes for NCAPG binding at an overlapping site with auto-inhibitory SLiMs from NCAPH (N-terminus) and NCAPD2 (C-terminus). The KIF4A SLiM peptide alone is sufficient to stimulate condensin I ATPase and DNA loop extrusion activities. In vitro binding assay (direct interaction), mutagenesis, competitive binding assay, in vitro ATPase assay, DNA loop extrusion assay The EMBO journal High 39690239
2024 KIF4A is expressed in adult vertebrate nervous system (not only during development) and is upregulated in injured peripheral nervous system cells. KIF4A is detected in cell bodies and regrowing axons of injured neurons. Kif4a knockdown significantly reduces Schwann cell proliferation in vitro. Western blot and immunofluorescence of adult/injured tissue, shRNA knockdown, proliferation assay in Schwann cells Neural regeneration research Medium 39665820

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 251 15625105
2004 Human chromokinesin KIF4A functions in chromosome condensation and segregation. The Journal of cell biology 171 15326200
2012 Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase IIα. The Journal of cell biology 148 23166350
1994 A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally. The Journal of cell biology 148 7929562
2019 FOXM1 promotes hepatocellular carcinoma progression by regulating KIF4A expression. Journal of experimental & clinical cancer research : CR 133 31072351
2006 KIF4 motor regulates activity-dependent neuronal survival by suppressing PARP-1 enzymatic activity. Cell 103 16630823
2014 Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function. Journal of medical genetics 84 24812067
2018 KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer. Cell death & disease 83 29706624
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 56 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 49 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
2021 KIF4A knockdown suppresses ovarian cancer cell proliferation and induces apoptosis by downregulating BUB1 expression. Molecular medicine reports 22 34013367
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
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
2018 Fe-S cluster coordination of the chromokinesin KIF4A alters its subcellular localization during mitosis. Journal of cell science 17 29848660
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
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 15 35312737
2017 Interdependency and phosphorylation of KIF4 and condensin I are essential for organization of chromosome scaffold. PloS one 15 28817632
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 14 29771379
2022 Kif4A mediates resistance to neoadjuvant chemoradiotherapy in patients with advanced colorectal cancer via regulating DNA damage response. Acta biochimica et biophysica Sinica 13 35882623
2024 Molecular mechanism of condensin I activation by KIF4A. The EMBO journal 12 39690239
2022 KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. Journal of Cancer 12 36606197
2021 Expanding the KIF4A-associated phenotype. American journal of medical genetics. Part A 12 34346154
2000 Identification of the human homologue of mouse KIF4, a kinesin superfamily motor protein. Biochimica et biophysica acta 12 10978527
2023 DEPDC1 and KIF4A synergistically inhibit the malignant biological behavior of osteosarcoma cells through Hippo signaling pathway. Journal of orthopaedic surgery and research 11 36849972
2022 KIF4A knockdown inhibits tumor progression and promotes chemo-sensitivity via induction of P21 in lung cancer cells. Chemical biology & drug design 11 36217900
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
2022 KIF4 regulates neuronal morphology and seizure susceptibility via the PARP1 signaling pathway. The Journal of cell biology 10 36482480
2016 Phosphoproteomic analysis of human mitotic chromosomes identified a chromokinesin KIF4A. Biomedical research (Tokyo, Japan) 10 27108885
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
2019 Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus. Frontiers in genetics 8 31616463
2018 Cdk1-dependent phosphorylation of KIF4A at S1186 triggers lateral chromosome compaction during early mitosis. PloS one 8 30576375
2020 Chromokinesin KIF4A teams up with stathmin 1 to regulate abscission in a SUMO-dependent manner. Journal of cell science 7 32591481
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 5 40345279
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 KIF4A promotes epithelial-mesenchymal transition by activating the TGF-β/SMAD signaling pathway in glioma cells. Molecular and cellular biochemistry 4 38411896
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
2019 Whole genome expression microarray reveals novel roles for Kif4 in monocyte/macrophage cells. European review for medical and pharmacological sciences 4 31486502
2017 Kif4 regulates the expression of VEGFR1 through the PI3K/Akt signaling pathway in RAW264.7 monocytes/macrophages. International journal of molecular medicine 4 28350061
2025 miR-223-3p Targets KIF4A and Promotes the Oxidative Stress-Mediated Apoptosis of Breast Cancer Cells. Cancer biotherapy & radiopharmaceuticals 3 39914820
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 SP1-Mediated Upregulation of KIF4A Promotes Prostate Cancer Progression via Targeting TWIST1. Journal of biochemical and molecular toxicology 3 40557825
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
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
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 KIF4A in disease pathogenesis and therapeutics: from molecular mechanisms to clinical translation. Biology direct 1 41361459
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 Low KIF4A expression is associated with gastric cancer progression and aggressive phenotypes. Scientific reports 0 42251143
2023 KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo [Retraction]. OncoTargets and therapy 0 37192931

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