Affinage

KIF3A

Kinesin-like protein KIF3A · UniProt Q9Y496

Length
699 aa
Mass
80.0 kDa
Annotated
2026-06-10
88 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF3A is the motor subunit of the heterotrimeric kinesin-2 complex that drives microtubule plus end-directed (anterograde) transport of membrane organelles and ciliary cargo (PMID:7515068, PMID:7559760). It functions as a plus end-directed motor both as a recombinant heavy chain and as a heterodimer with KIF3B that forms a ~50 nm rod with two motor heads and a single tail, which associates with membranous organelles (PMID:7515068, PMID:7559760); addition of the non-motor adaptor KAP3 to the KIF3A/B tail produces the heterotrimeric KIF3 complex and couples the motor to membrane cargo without altering intrinsic motor activity (PMID:8710890, PMID:10330409), and KIF3A can substitute KIF3C for KIF3B to form distinct neuronal motors (PMID:9487132). The motor is held inactive by an autoinhibitory beta-hairpin motif in the kinesin-2 tail that mimics microtubule binding; KAP3 binding provides a multipartite cargo-adaptor platform — engaged through a tail 'Hitchdock domain' — that occludes the beta-hairpin and is relieved by adaptors such as APC to license motility. Mechanistically the heterodimer is processive through rear-head gating, with load-dependent properties intermediate between the homodimers and set by the motor domains (PMID:25657001, PMID:25866395). Functionally, KIF3A is the ancestral intraflagellar transport motor required for flagellar/ciliary assembly from Chlamydomonas to mammals: it localizes between axonemal doublets and the ciliary membrane, drives IFT particle movement, and is needed for inner dynein arm delivery to the distal axoneme (PMID:8522608, PMID:8027176, PMID:8609169, PMID:10220415, PMID:10330409); loss of KIF3A ablates nodal cilia and randomizes left-right asymmetry, and kidney-specific loss removes primary cilia and produces polycystic kidney disease with elevated beta-catenin and c-Myc (PMID:10220415, PMID:10330409, PMID:12672950). As a transport motor it delivers specific cargoes including opsin in photoreceptors (PMID:17065525), N-cadherin to dendritic spines under activity-dependent control (PMID:26335646), MT1-MMP vesicles for matrix degradation and invasion (PMID:20505159, PMID:35122963), GLUT4 with the Axin/TNKS2 complex during insulin signaling (PMID:22473005), and ApoER2 via direct binding to Dab1 (PMID:38919020). Beyond cilia, KIF3A restrains canonical Wnt/beta-catenin signaling through a non-ciliary mechanism involving constitutive CKI-dependent Dishevelled phosphorylation and sequestration of beta-arrestin from a DVL2/Axin complex (PMID:18084282, PMID:27596264). The KIF3A C-terminal tail is a phosphoregulatory hub: PKA and CaMKIIalpha phosphorylation regulates cargo loading (PMID:26335646) and HSV-1 kinase US3 phosphorylates Ser687 to downregulate CD1d (PMID:25878107), although systematic phosphomimetic analysis shows tail phosphorylation is dispensable for ciliogenesis itself (PMID:38405607). KIF3A additionally contributes to epithelial migration and lumen morphogenesis (PMID:23658710) and to spindle and organelle organization in oocyte meiosis (PMID:38587639).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1994 High

    Established the founding function of KIF3A as the motor required for intraflagellar transport and flagellar assembly, defining its ancestral role before any vertebrate work.

    Evidence Temperature-sensitive FLA10/KHP1 mutant analysis with IFT particle imaging and immunolocalization in Chlamydomonas

    PMID:8027176 PMID:8522608

    Open questions at the time
    • Did not define the molecular cargo carried by IFT
    • Motor directionality not directly demonstrated in this organism
  2. 1994 High

    Defined KIF3A as a plus end-directed (anterograde) microtubule motor associated with membrane organelles, settling its directionality and transport role.

    Evidence In vitro microtubule gliding with baculovirus-expressed KIF3A, nerve ligation accumulation, and fractionation in neurons

    PMID:7515068

    Open questions at the time
    • Functional cargo identity unresolved
    • Subunit composition of the native motor not yet established
  3. 1995 High

    Showed KIF3A operates as a heterodimer with KIF3B, establishing the obligate two-headed motor architecture.

    Evidence Baculovirus reconstitution, IP, in vitro sliding assay and EM of the recombinant KIF3A/B rod

    PMID:7559760

    Open questions at the time
    • Did not identify the cargo-coupling adaptor
    • Regulation of motor activity not addressed
  4. 1996 High

    Identified KAP3 as the third subunit binding the KIF3A/B tail, completing the heterotrimer and implicating it in membrane organelle coupling.

    Evidence Sf9 reconstitution, fractional IP, and EM domain mapping

    PMID:8710890

    Open questions at the time
    • How KAP3 selects specific cargo not defined
    • Mechanism of activity regulation by KAP3 not resolved
  5. 1996 High

    Refined the IFT role by showing FLA10/KHP1 is specifically required to deliver inner (not outer) dynein arms to the distal axoneme, and localized the motor through the cell cycle.

    Evidence Dikaryon rescue epistasis with dynein arm markers; immunolocalization and motor-domain mutation sequencing in Chlamydomonas

    PMID:8609169 PMID:8907700

    Open questions at the time
    • Cargo selectivity mechanism for dynein arms unknown
    • Mitotic spindle association function not functionally tested
  6. 1998 Medium

    Expanded the motor repertoire by showing KIF3A can pair with KIF3C to form a distinct neuronal motor on a separate vesicle population.

    Evidence Reciprocal co-IP and sucrose gradient fractionation in neurons

    PMID:9487132

    Open questions at the time
    • Distinct cargo of the KIF3A/C motor not identified
    • Functional difference from KIF3A/B not established
  7. 1998 Low

    Proposed a nuclear, condensin-linked role for the complex via KAP3-HCAP interaction.

    Evidence Yeast two-hybrid and nuclear-fraction co-IP

    PMID:9506951

    Open questions at the time
    • Functional significance not directly tested
    • Single co-IP from nuclear fraction without reciprocal in vivo validation
  8. 1999 High

    Demonstrated that the Chlamydomonas IFT function is conserved in mammals and essential for embryonic ciliogenesis and left-right asymmetry.

    Evidence Kif3a knockout mice with node SEM and in situ hybridization of L-R markers; brain IP confirming the heterotrimer

    PMID:10220415 PMID:10330409

    Open questions at the time
    • Cargo transported into nodal cilia not identified
    • Mechanism linking cilia to asymmetric gene expression not resolved here
  9. 1999 Medium

    Revealed dual subcellular roles of KIF3A within a single cell type by localizing it to both the photoreceptor connecting cilium and the presynaptic ribbon.

    Evidence ImmunoEM and fractionation in vertebrate photoreceptors

    PMID:9920666

    Open questions at the time
    • Synaptic ribbon function of KIF3A not functionally tested
    • Cargo at the ribbon unidentified
  10. 2002 Medium

    Explained heterodimerization specificity at the biophysical level, showing electrostatic complementarity of unstructured neck-hinge regions drives selective pairing.

    Evidence CD spectroscopy, redox exchange, and urea denaturation of KIF3A coiled-coil peptide analogs

    PMID:12064947

    Open questions at the time
    • Behavior of full-length proteins not tested
    • Relevance to motor regulation not addressed
  11. 2003 High

    Linked KIF3A-dependent ciliogenesis to disease and downstream signaling by showing renal cilium loss causes polycystic kidney disease with altered beta-catenin signaling.

    Evidence Kidney-specific conditional knockout with histology and molecular phenotyping

    PMID:12672950

    Open questions at the time
    • Whether signaling changes are cilium-dependent or independent not separated here
    • Direct cargo underlying cyst phenotype unknown
  12. 2006 High

    Identified opsin as a primary KIF3A-dependent transport cargo, distinguishing a transport defect from structural cilium failure.

    Evidence Synchronous RHO-Cre conditional knockout with Western time course and immunofluorescence

    PMID:17065525

    Open questions at the time
    • Adaptor coupling opsin to KIF3A not defined
    • Other photoreceptor cargoes not enumerated
  13. 2007 High

    Distinguished ciliary from non-ciliary regulation of Wnt signaling, showing KIF3A restrains the pathway in part through CKI-dependent Dishevelled phosphorylation independent of cilia.

    Evidence Conditional KO embryos/fibroblasts, phosphorylation assays, CKI inhibitor rescue, comparison of three ciliogenic mutations

    PMID:18084282

    Open questions at the time
    • Molecular intermediary linking KIF3A to CKI activity unknown
    • Whether motor activity is required for the non-ciliary effect untested
  14. 2010 Medium

    Extended cargo range to MT1-MMP vesicles, connecting KIF3A to surface protease delivery and ECM degradation in macrophages.

    Evidence siRNA knockdown, live vesicle imaging, flow cytometry, ECM degradation assay

    PMID:20505159

    Open questions at the time
    • Direct cargo adaptor not identified
    • Single cell type tested
  15. 2011 Medium

    Showed KIF3A controls planar polarity through both cilia and a non-ciliary route involving cortical PAK activity and basal body positioning.

    Evidence Inner-ear conditional knockout with PAK activity/localization and basal body analysis

    PMID:21752934

    Open questions at the time
    • How KIF3A regulates cortical PAK not defined
    • Direct vs. indirect effect on basal body unresolved
  16. 2011 Low

    Added RNF33/TRIM60 as a tail-binding partner engaging KIF3A independently of KAP3.

    Evidence Yeast two-hybrid, co-IP, deletion mapping

    PMID:21909995

    Open questions at the time
    • No functional follow-up on cargo transport
    • Single lab without reciprocal in vivo validation
  17. 2012 Medium

    Placed KIF3A in insulin-regulated GLUT4 trafficking via an Axin/TNKS2 ternary complex.

    Evidence Reciprocal co-IP, siRNA knockdown, co-localization, glucose uptake, and TNKS2 knockout mice

    PMID:22473005

    Open questions at the time
    • Direct GLUT4-KIF3A contact not demonstrated
    • Single lab
  18. 2013 Medium

    Established extra-ciliary roles in spermatid morphogenesis and in epithelial migration, microtubule dynamics, and lumen formation.

    Evidence Conditional KO with interactor co-IP in sperm; inducible knockdown with live MT imaging, migration and 3D collagen assays in MDCK

    PMID:23658710 PMID:23831641

    Open questions at the time
    • Mechanism linking KIF3A to leading-edge MT dynamics unknown
    • MNS1 interaction function not dissected
  19. 2015 High

    Resolved the motility mechanism, showing KIF3A processivity is governed by rear-head gating and that heterodimer load behavior derives from the motor domains.

    Evidence Stopped-flow kinetics, single-molecule and optical-trap assays, neck-linker mutants on reconstituted motors

    PMID:25657001 PMID:25866395

    Open questions at the time
    • Did not address tail autoinhibition in this regulation
    • In vivo relevance of gating differences not tested
  20. 2015 High

    Defined the KIF3A C-terminal tail as a phosphoregulatory hub controlling cargo loading and exploited by a viral kinase.

    Evidence Phosphoproteomics, phosphosite mutagenesis, kinase inhibitors and live transport imaging for N-cadherin; MS, in vitro kinase and S687A mutagenesis for US3/CD1d

    PMID:25878107 PMID:26335646

    Open questions at the time
    • How phosphorylation structurally alters cargo loading not resolved
    • Generality of phospho-control across cargoes unknown
  21. 2016 Medium

    Defined the molecular basis of non-ciliary Wnt restraint, showing KIF3A sequesters beta-arrestin from a DVL2/Axin complex to limit beta-catenin stabilization.

    Evidence siRNA knockdown, KIF3A-beta-arrestin co-IP, beta-catenin reporter, pharmacological ciliogenesis inhibition in NSCLC cells

    PMID:27596264

    Open questions at the time
    • Direct beta-arrestin binding interface not mapped
    • Relationship to the CKI/Dvl mechanism not integrated
  22. 2022 Medium

    Refined MT1-MMP trafficking into sequential steps, with KIF3A and KIF13A handling Golgi-to-endosome transport relevant to cancer invasion.

    Evidence siRNA knockdown, live vesicle imaging, collagen degradation and invasion assays

    PMID:35122963

    Open questions at the time
    • Switching mechanism between the two motors unknown
    • Adaptor coupling KIF3A to these vesicles undefined
  23. 2024 Medium

    Identified Dab1 as a direct, KIF3A-specific cargo adaptor linking the motor to ApoER2 surface delivery.

    Evidence Yeast two-hybrid, GST pulldown, co-IP, co-localization and dominant-negative ApoER2 surface assay

    PMID:38919020

    Open questions at the time
    • In vivo requirement not tested
    • Single lab
  24. 2024 Medium

    Challenged the requirement of tail phosphorylation for ciliogenesis, showing phosphomimetic tail mutants rescue cilia in double-knockout cells.

    Evidence Phosphomimetic mutant library rescue in Kif3a-/-;Kif3b-/- MEFs

    PMID:38405607

    Open questions at the time
    • Does not exclude phospho-control of non-ciliary cargo loading
    • Single lab negative finding
  25. 2024 Medium

    Added a meiotic role, implicating KIF3A in spindle pole protein localization, microtubule stability via HDAC6, and organelle distribution in oocytes.

    Evidence Depletion with mRNA rescue, LC-MS interactome, SAC markers, HDAC6 activity assay

    PMID:38587639

    Open questions at the time
    • Direct vs. indirect effect on NuMA/gamma-tubulin unresolved
    • Single lab
  26. 2025 High

    Provided the structural mechanism of autoinhibition and cargo-mediated activation, defining a tail beta-hairpin that mimics microtubule binding and a KAP3/APC cargo platform that relieves it.

    Evidence Cryo-EM of the KIF3A/B/KAP3 complex with APC, single-molecule motility, mutagenesis and MD simulations (preprint)

    Open questions at the time
    • Peer review pending (preprint)
    • Whether all cargoes activate via the same Hitchdock platform unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct cargo adaptors achieve selectivity and how phosphorylation, autoinhibition, and KAP3-mediated activation are coordinated across the many KIF3A cargoes and tissues remains unresolved.
  • Unified model linking tail phospho-state to autoinhibition release not established
  • Cargo-specific adaptor codes incompletely mapped

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:0140096 catalytic activity, acting on a protein 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005929 cilium 4 GO:0031410 cytoplasmic vesicle 4 GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2
Partners
APCBETA-ARRESTINDAB1KAP3KIF13AKIF3BKIF3CMNS1
Complex memberships
Axin/TNKS2/KIF3A complexKIF3A/KIF3C heterodimerkinesin-2 (KIF3A/KIF3B/KAP3)

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 KIF3A (FLA10/KHP1) encodes a kinesin-homologous protein required for intraflagellar transport (IFT) and flagellar assembly/maintenance in Chlamydomonas; temperature-sensitive inactivation of FLA10 abolishes both bidirectional IFT particle movement and bead motility on the flagellar membrane, and KHP1 protein immunolocalizes to the region between outer doublet microtubules and the flagellar membrane. Temperature-sensitive mutant analysis, immunolocalization, light microscopy of IFT particles, electron microscopy of flagellar rafts The Journal of cell biology High 8027176 8522608
1994 KIF3A is a microtubule plus end-directed (anterograde) motor in neurons; recombinant KIF3A heavy chain demonstrates plus end-directed microtubule motility in vitro, native KIF3A associates with membrane organelle fractions, and KIF3A accumulates with anterogradely moving organelles after nerve ligation. In vitro microtubule gliding assay with baculovirus-expressed KIF3A, nerve ligation accumulation assay, subcellular fractionation The Journal of cell biology High 7515068
1995 KIF3A forms a heterodimer with KIF3B; recombinant KIF3A/B complex (~50 nm rod with two globular heads and a single globular tail) demonstrates plus end-directed microtubule sliding activity in vitro; the complex associates with membrane fractions other than synaptic vesicles and with membranous organelles. Baculovirus reconstitution, immunoprecipitation, in vitro microtubule sliding assay, electron microscopy, subcellular fractionation The Journal of cell biology High 7559760
1996 KAP3 (kinesin superfamily-associated protein 3) binds to the tail domain of KIF3A/B in a globular region; reconstitution in Sf9 cells shows KAP3 is a globular protein that binds KIF3A/B tail without affecting KIF3A/B motor activity; KAP3 associates with the membrane-bound form of KIF3A/B and may regulate membrane organelle binding. Baculovirus-Sf9 reconstitution, immunoprecipitation, fractional immunoprecipitation, EM Proceedings of the National Academy of Sciences of the United States of America High 8710890
1996 FLA10/KHP1 activity is required specifically for inner dynein arms (but not outer dynein arms) to reach the distal portion of the flagellar axoneme; rescue experiments in dikaryons at non-permissive temperature for fla10 show inner dynein arm assembly is blocked while outer dynein arm rescue proceeds normally. Dikaryon rescue assay with immunofluorescence using inner and outer dynein arm markers at permissive and non-permissive temperatures The Journal of cell biology High 8609169
1996 FLA10/KHP1 localizes to basal bodies and the proximal portion of flagella in interphase, moves in punctate structures to the tip of developing axonemes during flagellar regeneration, and associates with centrioles and the mitotic spindle during cell division; a C-to-A transversion at amino acid 329 in the motor domain causes the fla10-1 temperature-sensitive phenotype. Immunofluorescence throughout cell cycle, mutant sequencing, flagellar regeneration assay Journal of cell science High 8907700
1998 KIF3A forms a novel neuronal heteromeric kinesin with KIF3C (but not KIF3B); KIF3C associates with KIF3A by immunoprecipitation and co-fractionates with a distinct population of membrane vesicles in neurons. Immunoprecipitation, sucrose density gradient fractionation, subcellular fractionation Molecular biology of the cell Medium 9487132
1998 KAP3 (SMAP) binds to HCAP (human XCAP-E condensin subunit) and both KAP3 and HCAP are present in nuclear fractions; SMAP is extracted as a ternary complex with HCAP and KIF3B from the nuclear fraction in the presence of Mg-ATP, suggesting KAP3 serves as a linker between chromosomal condensin and KIF3A/B in the nucleus. Subcellular fractionation, immunoprecipitation from nuclear fraction, yeast two-hybrid The Journal of biological chemistry Low 9506951
1999 KIF3A localizes to two distinct sites in vertebrate photoreceptors: the basal body of the connecting cilium axoneme and the presynaptic ribbon; immunoelectron microscopy shows KIF3A at the ribbon matrix and on docked vesicles, suggesting dual functions within a single cell type. Immunoelectron microscopy, subcellular fractionation (detergent-extractable and resistant fractions) The Journal of neuroscience Medium 9920666
1999 KIF3A is essential for embryonic cilia formation at the node; KIF3A knockout mice die at ~10 dpc with randomized left-right asymmetry, and the earliest detectable abnormality is loss of nodal cilia at E7.5 prior to asymmetric gene expression, demonstrating kinesin-based transport for ciliary morphogenesis is conserved from Chlamydomonas to mammals. Knockout mouse generation, scanning electron microscopy of embryonic node, whole-mount in situ hybridization of L-R markers Proceedings of the National Academy of Sciences of the United States of America High 10220415 10330409
1999 KIF3A forms a heterotrimeric KIF3 complex with KIF3B (or KIF3C) and KAP3; the complex is ubiquitously expressed but predominantly in neural tissues. Immunoprecipitation from mouse brain, co-purification The Journal of cell biology Medium 10330409
2000 GADD34 interacts with the tail domain of KIF3A; this interaction was identified by yeast two-hybrid screening and confirmed by in vivo two-hybrid analysis in NIH3T3 cells. Yeast two-hybrid, in vivo two-hybrid assay in mammalian cells Biochemical and biophysical research communications Low 10631107
2002 The neck-hinge region of KIF3A (residues 356-416) contains a predicted coiled-coil (residues 356-377) that folds autonomously in solution; electrostatic attractions between oppositely charged unstructured regions drive specificity of heterodimerization of the KIF3A coiled-coil, without affecting stability relative to the most stable homodimer. Circular dichroism spectroscopy, redox disulfide exchange experiments, urea denaturation studies of synthetic peptide analogs Journal of structural biology Medium 12064947
2003 Kidney-specific inactivation of KIF3A abolishes primary cilia on renal tubular epithelial cells and produces polycystic kidney disease; cyst epithelial cells show increased proliferation and apoptosis, apical mislocalization of EGF receptor, increased β-catenin and c-Myc expression, and inhibition of p21CIP1. Conditional knockout (Cre-lox) in kidney epithelia, histology, immunofluorescence, Western blot Proceedings of the National Academy of Sciences of the United States of America High 12672950
2006 Loss of KIF3A in rod photoreceptors (via synchronous Cre-mediated excision) causes ectopic accumulation of opsin before photoreceptor degeneration, with normal cilium and disc membrane formation initially; this establishes opsin as a primary KIF3A-dependent cargo in photoreceptor cells. Conditional knockout (RHO-Cre;Kif3a-flox), Western blot time course, immunofluorescence, histology Investigative ophthalmology & visual science High 17065525
2007 Kif3a loss restrains canonical Wnt/β-catenin signaling through two mechanisms: (1) a ciliary mechanism shared with other ciliogenic gene mutations (Ift88, Ofd1) that normally restricts Wnt pathway activity, and (2) a non-ciliary mechanism specific to Kif3a loss, involving constitutive CKI-dependent phosphorylation of Dishevelled (Dvl); pharmacological inhibition of casein kinase I reverses constitutive Dvl phosphorylation and abrogates pathway hyper-responsiveness. Conditional knockout mouse embryos and primary fibroblasts, phosphorylation assays, CKI inhibitor treatment, genetic comparison of three ciliogenic mutations Nature cell biology High 18084282
2010 KIF3A and KIF3B kinesins regulate MT1-MMP-positive vesicle transport bidirectionally along microtubules in primary human macrophages; siRNA knockdown of KIF3A/KIF3B impairs MT1-MMP delivery to the cell surface, shedding of CD44 and syndecan-1, and ECM degradation at podosomes. siRNA knockdown, live-cell imaging of MT1-MMP vesicles, flow cytometry, ECM degradation assay Blood Medium 20505159
2011 Kif3a regulates planar polarization of auditory hair cells through both ciliary mechanisms (kinocilium formation) and non-ciliary mechanisms; the non-ciliary function involves Kif3a-regulated localized cortical activity of PAK kinases, which controls basal body positioning along the apicobasal and planar polarity axes. Conditional knockout in inner ear, immunofluorescence of PAK activity/localization, basal body positioning analysis Development (Cambridge, England) Medium 21752934
2011 RNF33/TRIM60 interacts with KIF3A and KIF3B via its RB and B30.2 domains binding to the respective C-terminal non-motor tail domains; this interaction is independent of the KAP3 adaptor, leaving the motor head section free for cargo binding. Yeast two-hybrid, co-immunoprecipitation, deletion mapping Molecular and cellular biochemistry Low 21909995
2012 The Axin/TNKS2 complex interacts with KIF3A to form a ternary complex required for insulin-stimulated GLUT4 translocation to the plasma membrane; in the absence of insulin, Axin/TNKS2/KIF3A co-localize with GLUT4 on the trans-Golgi network; insulin suppresses TNKS ADP-ribosylase activity, stabilizing the complex via Akt; specific knockdown of each component attenuates GLUT4 translocation. Co-immunoprecipitation, siRNA knockdown, co-localization imaging, glucose uptake assays, TNKS2 knockout mice Cell research Medium 22473005
2013 KIF3A is required for spermatid elongation, sperm tail formation, and manchette function; depletion of KIF3A causes severe impairments in sperm tail formation and affects manchette organization and nuclear shaping; several novel interacting partners were identified including MNS1, which co-localizes with KIF3A in the manchette and principal piece. Conditional knockout, co-immunoprecipitation/interactor identification, immunofluorescence co-localization Molecular and cellular endocrinology Medium 23831641
2013 Kif3a depletion in MDCK cells slows epithelial cell migration, dampens microtubule dynamics at the leading edge (microtubules fail to grow perpendicularly into the leading edge), retards lateral membrane specification, and completely prevents formation of 3D lumen-containing spheres in collagen; these are extra-ciliary functions. Tetracycline-inducible Kif3a knockdown, live-cell microtubule dynamics imaging, wound-healing migration assay, 3D collagen sphere assay PloS one Medium 23658710
2015 KIF3A processivity is controlled by rear head gating rather than front head gating: rearward strain in the two-head-bound state does not alter nucleotide binding to the front head (no front-head gating), but the motor dissociates slowly from the low-affinity ADP state (rear head gating); the KIF3A/B heterodimer shows load-dependent properties intermediate between the two homodimers, attributable to motor domain properties rather than neck linkers or coiled-coil stalk. Stopped-flow and steady-state kinetics, single-molecule motility assays, optical trap with feedback control, multimotor assays, AMP-PNP trapping, neck-linker length mutants The Journal of biological chemistry / Current biology High 25657001 25866395
2015 PKA and CaMKIIα phosphorylate the C-terminus of KIF3A to regulate activity-dependent loading of N-cadherin cargo; phosphorylation of the KIF3A C-terminal domain increases N-cadherin transport to dendritic spines, and this transport is enhanced during homeostatic synaptic upregulation (TTX treatment); mutagenesis of the phosphosites abrogates activity-dependent N-cadherin transport. Quantitative phosphoproteomics of KIF3A-bound vs. unbound cargo vesicles, site-directed mutagenesis, kinase inhibitors, live-cell N-cadherin transport imaging, TTX-induced homeostatic plasticity Neuron High 26335646
2015 HSV-1 viral kinase US3 phosphorylates KIF3A predominantly at serine 687, both in vitro and in infected cells; this phosphorylation is required for US3-mediated downregulation of CD1d cell surface expression; ablation of the S687 phosphorylation site abolishes US3-mediated CD1d downregulation. Mass spectrometry of purified KIF3A, in vitro kinase assay, phosphosite mutagenesis (S687A), CD1d surface expression assay Journal of virology High 25878107
2016 KIF3A binds β-arrestin; in NSCLC cells KIF3A depletion allows β-arrestin to form a complex with DVL2 and Axin, thereby stabilizing β-catenin and activating Wnt signaling independently of primary cilia; pharmacological inhibition of ciliogenesis did not increase β-catenin activity, confirming a non-ciliary mechanism. siRNA knockdown, co-immunoprecipitation of KIF3A-β-arrestin, β-catenin reporter assays, pharmacological ciliogenesis inhibition Scientific reports Medium 27596264
2022 KIF3A and KIF13A coordinate to transport the same MT1-MMP-containing vesicles from the trans-Golgi to endosomes, while KIF13A alone transports vesicles from endosomes to the plasma membrane; knockdown of KIF3A and KIF13A inhibits MT1-MMP-dependent collagen degradation and cancer cell invasion. siRNA knockdown, live-cell imaging of MT1-MMP vesicles, collagen degradation assay, invasion assay Matrix biology Medium 35122963
2024 KIF3A directly binds Disabled-1 (Dab1) via the cargo-binding domain (CBD) at its C-terminus; the PTB domain-containing region of Dab1 is essential for KIF3A binding; this interaction is specific to KIF3A (not KIF3B, KIF5B, KIF17, or KAP3); KIF3A dominant-negative expression reduces ApoER2 cell surface expression, suggesting KIF3A transports ApoER2 to the cell surface. Yeast two-hybrid screen, GST pulldown, co-immunoprecipitation in HEK-293T cells, immunofluorescence co-localization, dominant-negative expression assay for ApoER2 surface expression BMB reports Medium 38919020
2024 KIF3A tail domain phosphorylation is dispensable for ciliogenesis in mammalian mouse embryonic fibroblasts; a library of phosphomimetic mutants covering all predicted phosphosites in the KIF3A tail domain rescued ciliogenesis normally in Kif3a-/-;Kif3b-/- MEFs, contrasting with the previously proposed requirement for phosphorylation in IFT regulation. Kif3a-/-;Kif3b-/- MEF ciliogenesis rescue assay with library of phosphomimetic KIF3A tail mutants iScience Medium 38405607
2024 KIF3A (within the KIF3A/KIF3B/KAP3 heterotrimer) is autoinhibited via a conserved beta-hairpin motif in the kinesin-2 tail domain that sequesters motor domains away from microtubules through molecular mimicry; KAP3 binds via a multipartite interface with KIF3A and KIF3B and provides a platform for cargo adaptor engagement that occludes the beta-hairpin, thereby activating motility; the APC cargo adaptor engages this platform to relieve autoinhibition. Cryo-EM structural determination, single-molecule motility assays, cell biological assays, mutagenesis of beta-hairpin motif bioRxivpreprint High
2025 High-resolution cryo-EM structures of the KIF3A/KIF3B/KAP3 complex bound to APC cargo reveal a 'Hitchdock domain' in the KIF3 tail that mediates interactions with both KAP3 adaptor and APC cargo; KIF3A helical regions within the Hitchdock domain mediate specific cargo binding, while the beta-hairpin region and KIF3B provide structural support; mutagenesis and molecular dynamics simulations confirm the domain's functional importance. Cryo-EM structure determination, site-directed mutagenesis, molecular dynamics simulations bioRxivpreprint High
2024 KIF3A associates with KIFC1 to regulate expression and polar localization of NuMA and γ-tubulin during mouse oocyte meiosis; KIF3A depletion activates the spindle assembly checkpoint leading to metaphase I arrest; KIF3A also reduces microtubule stability through altered deacetylation by HDAC6; KIF3A is required for proper organelle (mitochondria, Golgi, ER) distribution in oocytes. KIF3A depletion (siRNA/morpholino), LC-MS interactome analysis, immunofluorescence, spindle assembly checkpoint markers, HDAC6 activity assay, mRNA rescue Cellular and molecular life sciences Medium 38587639

Source papers

Stage 0 corpus · 88 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 The Chlamydomonas kinesin-like protein FLA10 is involved in motility associated with the flagellar membrane. The Journal of cell biology 472 8522608
2003 Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proceedings of the National Academy of Sciences of the United States of America 458 12672950
2007 Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nature cell biology 433 18084282
1999 Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. Proceedings of the National Academy of Sciences of the United States of America 431 10220415
1999 Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis. The Journal of cell biology 355 10330409
1995 KIF3A/B: a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport. The Journal of cell biology 256 7559760
1994 KIF3A is a new microtubule-based anterograde motor in the nerve axon. The Journal of cell biology 230 7515068
1994 The Chlamydomonas FLA10 gene encodes a novel kinesin-homologous protein. The Journal of cell biology 196 8027176
1996 Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B. Proceedings of the National Academy of Sciences of the United States of America 174 8710890
2007 Conditional Kif3a ablation causes abnormal hedgehog signaling topography, growth plate dysfunction, and excessive bone and cartilage formation during mouse skeletogenesis. Development (Cambridge, England) 157 17507416
1999 The kinesin motor KIF3A is a component of the presynaptic ribbon in vertebrate photoreceptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 146 9920666
1995 KIF2 is a new microtubule-based anterograde motor that transports membranous organelles distinct from those carried by kinesin heavy chain or KIF3A/B. The Journal of cell biology 146 7535303
2010 KIF5B and KIF3A/KIF3B kinesins drive MT1-MMP surface exposure, CD44 shedding, and extracellular matrix degradation in primary macrophages. Blood 116 20505159
1996 Inner dynein arms but not outer dynein arms require the activity of kinesin homologue protein KHP1(FLA10) to reach the distal part of flagella in Chlamydomonas. The Journal of cell biology 107 8609169
2013 KIF3A is essential for sperm tail formation and manchette function. Molecular and cellular endocrinology 102 23831641
1998 KIF3C and KIF3A form a novel neuronal heteromeric kinesin that associates with membrane vesicles. Molecular biology of the cell 97 9487132
2012 Mechanosensing by the primary cilium: deletion of Kif3A reduces bone formation due to loading. PloS one 85 22428034
2012 Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia. Journal of cell science 83 22357948
2011 Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms. Development (Cambridge, England) 77 21752934
1991 Genetic interactions at the FLA10 locus: suppressors and synthetic phenotypes that affect the cell cycle and flagellar function in Chlamydomonas reinhardtii. Genetics 73 1874415
2012 The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation. Cell research 70 22473005
2015 The Mechanochemical Cycle of Mammalian Kinesin-2 KIF3A/B under Load. Current biology : CB 67 25866395
1996 The kinesin-homologous protein encoded by the Chlamydomonas FLA10 gene is associated with basal bodies and centrioles. Journal of cell science 67 8907700
2006 Analysis of kinesin-2 function in photoreceptor cells using synchronous Cre-loxP knockout of Kif3a with RHO-Cre. Investigative ophthalmology & visual science 63 17065525
1998 Complex formation of SMAP/KAP3, a KIF3A/B ATPase motor-associated protein, with a human chromosome-associated polypeptide. The Journal of biological chemistry 63 9506951
2008 FKBP8 cell-autonomously controls neural tube patterning through a Gli2- and Kif3a-dependent mechanism. Developmental biology 58 18590716
2014 KIF3a promotes proliferation and invasion via Wnt signaling in advanced prostate cancer. Molecular cancer research : MCR 53 24413182
2011 Identification of KIF3A as a novel candidate gene for childhood asthma using RNA expression and population allelic frequencies differences. PloS one 46 21912604
2015 Mechanism of Activity-Dependent Cargo Loading via the Phosphorylation of KIF3A by PKA and CaMKIIa. Neuron 43 26335646
2013 Kif3a is necessary for initiation and maintenance of medulloblastoma. Carcinogenesis 43 23389290
2010 Kif3a deficiency reverses the skeletal abnormalities in Pkd1 deficient mice by restoring the balance between osteogenesis and adipogenesis. PloS one 41 21151991
2004 Overexpression of autocrine motility factor in metastatic tumor cells: possible association with augmented expression of KIF3A and GDI-beta. Laboratory investigation; a journal of technical methods and pathology 39 14968121
2016 Loss of Glis2/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease. Kidney international 38 27181777
1999 Photoreceptor localization of the KIF3A and KIF3B subunits of the heterotrimeric microtubule motor kinesin II in vertebrate retina. Experimental eye research 37 10548469
2016 KIF3A binds to β-arrestin for suppressing Wnt/β-catenin signalling independently of primary cilia in lung cancer. Scientific reports 36 27596264
2020 Disease-associated KIF3A variants alter gene methylation and expression impacting skin barrier and atopic dermatitis risk. Nature communications 33 32796837
2015 Processivity of the kinesin-2 KIF3A results from rear head gating and not front head gating. The Journal of biological chemistry 33 25657001
2015 Herpes Simplex Virus 1 US3 Phosphorylates Cellular KIF3A To Downregulate CD1d Expression. Journal of virology 32 25878107
2019 Gli2 Rescues Delays in Brain Development Induced by Kif3a Dysfunction. Cerebral cortex (New York, N.Y. : 1991) 31 29342244
2014 A ciliopathy with hydrocephalus, isolated craniosynostosis, hypertelorism, and clefting caused by deletion of Kif3a. Reproductive toxicology (Elmsford, N.Y.) 30 24887031
2016 Disruption of KIF3A in patient-derived glioblastoma cells: effects on ciliogenesis, hedgehog sensitivity, and tumorigenesis. Oncotarget 28 26760767
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
2017 Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling. Oncotarget 26 28423710
2013 Kif3a guides microtubular dynamics, migration and lumen formation of MDCK cells. PloS one 26 23658710
2020 Suppression of KIF3A inhibits triple negative breast cancer growth and metastasis by repressing Rb-E2F signaling and epithelial-mesenchymal transition. Cancer science 25 32011034
2020 CircRNA_101951 promotes migration and invasion of colorectal cancer cells by regulating the KIF3A-mediated EMT pathway. Experimental and therapeutic medicine 25 32266033
2022 Tumor suppressive role of microRNA-139-5p in bone marrow mesenchymal stem cells-derived extracellular vesicles in bladder cancer through regulation of the KIF3A/p21 axis. Cell death & disease 24 35821021
2020 Kif3a deletion prevents primary cilia assembly on oligodendrocyte progenitor cells, reduces oligodendrogenesis and impairs fine motor function. Glia 24 33368703
2016 Combined deletion of Vhl, Trp53 and Kif3a causes cystic and neoplastic renal lesions. The Journal of pathology 21 27126173
2010 KIF3A, a cilia structural gene on chromosome 5q31, and its polymorphisms show an association with aspirin hypersensitivity in asthma. Journal of clinical immunology 21 20922562
2015 Combined Deletion of Vhl and Kif3a Accelerates Renal Cyst Formation. Journal of the American Society of Nephrology : JASN 19 25788526
2000 Interaction between GADD34 and kinesin superfamily, KIF3A. Biochemical and biophysical research communications 19 10631107
2002 The role of unstructured highly charged regions on the stability and specificity of dimerization of two-stranded alpha-helical coiled-coils: analysis of the neck-hinge region of the kinesin-like motor protein Kif3A. Journal of structural biology 18 12064947
2013 Association of KIF3A, but not OVOL1 and ACTL9, with atopic eczema in Italian patients. The British journal of dermatology 17 23278845
2017 KIF3A knockdown sensitizes bronchial epithelia to apoptosis and aggravates airway inflammation in asthma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 29156524
2016 Disruption of kif3a results in defective osteoblastic differentiation in dental mesenchymal stem/precursor cells via the Wnt signaling pathway. Molecular medicine reports 16 27432616
2022 Coordination of two kinesin superfamily motor proteins, KIF3A and KIF13A, is essential for pericellular matrix degradation by membrane-type 1 matrix metalloproteinase (MT1-MMP) in cancer cells. Matrix biology : journal of the International Society for Matrix Biology 15 35122963
2016 Airway Epithelial KIF3A Regulates Th2 Responses to Aeroallergens. Journal of immunology (Baltimore, Md. : 1950) 15 27794000
2010 Identification and dynamic transcription of KIF3A homologue gene in spermiogenesis of Octopus tankahkeei. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 15 20624476
2020 KIF3A regulates the Wnt/β-catenin pathway via transporting β-catenin during spermatogenesis in Eriocheir sinensis. Cell and tissue research 14 32458081
2011 Association of the testis-specific TRIM/RBCC protein RNF33/TRIM60 with the cytoplasmic motor proteins KIF3A and KIF3B. Molecular and cellular biochemistry 14 21909995
2017 KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility. Oncotarget 12 29221136
2014 Functional Analysis of KIF3A and KIF3B during Spermiogenesis of Chinese Mitten Crab Eriocheir sinensis. PloS one 12 24870586
2021 Deletion of kif3a in CK19 positive cells leads to primary cilia loss, biliary cell proliferation and cystic liver lesions in TAA-treated mice. Biochimica et biophysica acta. Molecular basis of disease 11 34973373
2024 CircRAPGEF5 sponges miR-582-3p and targets KIF3A to regulate bladder cancer cell proliferation, migration and invasion. International immunopharmacology 10 38489970
2018 Analysis of the function of KIF3A and KIF3B in the spermatogenesis in Boleophthalmus pectinirostris. Fish physiology and biochemistry 10 29511984
2011 Molecular characterization of a KIF3A-like kinesin gene in the testis of the Chinese fire-bellied newt Cynops orientalis. Molecular biology reports 10 21773941
2016 Abnormal photoreceptor outer segment development and early retinal degeneration in kif3a mutant zebrafish. Cell biochemistry and function 9 27470972
2015 KIF1-binding protein interacts with KIF3A in haploid male germ cells. Reproduction (Cambridge, England) 8 26245936
2024 Kinesin KIF3A regulates meiotic progression and spindle assembly in oocyte meiosis. Cellular and molecular life sciences : CMLS 7 38587639
2022 lncRNA MIR600HG induces the proliferation and invasion of colorectal cancer cells via regulating miR-144-3p/KIF3A. International immunopharmacology 7 35378445
2019 Expression and potential functions of KIF3A/3B to promote nuclear reshaping and tail formation during Larimichthys polyactis spermiogenesis. Development genes and evolution 7 31486889
2017 Dynamic transcription and expression patterns of KIF3A and KIF3B genes during spermiogenesis in the shrimp, Palaemon carincauda. Animal reproduction science 7 28689636
2021 Molecular characterization, dynamic transcription, and potential function of KIF3A/KIF3B during spermiogenesis in Opsariichthys bidens. Gene 6 34175396
2013 Thyroid-specific inactivation of KIF3A alters the TSH signaling pathway and leads to hypothyroidism. Journal of molecular endocrinology 6 23511952
2000 C. elegans KLP-11/OSM-3/KAP-1: orthologs of the sea urchin kinesin-II, and mouse KIF3A/KIFB/KAP3 kinesin complexes. DNA research : an international journal for rapid publication of reports on genes and genomes 6 10819327
1997 Molecular cloning and expression of the KIF3A gene in the frog brain and testis. Zoological science 6 9520632
2022 KIF3A inhibits nasopharyngeal carcinoma proliferation, migration and invasion by interacting with β-catenin to suppress its nuclear accumulation. American journal of cancer research 3 36504907
2024 The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1). BMB reports 2 38919020
2023 C. elegans vab-6 encodes a KIF3A kinesin and functions cell non-autonomously to regulate epidermal morphogenesis. Developmental biology 2 36893881
2025 Alternative spliceosomal protein Eftud2 mediated Kif3a exon skipping promotes SHH-subgroup medulloblastoma progression. Cell death and differentiation 1 40275081
2023 Ac-SDKP promotes KIF3A-mediated β-catenin suppression through a ciliary mechanism to constrain silica-induced epithelial-myofibroblast transition. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 1 37651800
2023 Inhibitory mechanism of KIF3A gene on nasopharyngeal carcinoma stem cells. Cellular and molecular biology (Noisy-le-Grand, France) 1 37715417
2022 Skin depletion of Kif3a resembles the pediatric atopic dermatitis transcriptome profile. Human molecular genetics 1 34964466
2021 Ift88, but not Kif3a, is required for establishment of the periciliary membrane compartment. Biochemical and biophysical research communications 1 34753064
2019 The correlative hypotheses between Pitchfork and Kif3a in palate development. Medical hypotheses 1 31010494
2024 KIF3A tail domain phosphorylation is not required for ciliogenesis in mouse embryonic fibroblasts. iScience 0 38405607
2020 [Expression of kinesin KIF3A in the kidney of mice with unilateral ureteral obstruction]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 32376524

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