Affinage

KIF3C

Kinesin-like protein KIF3C · UniProt O14782

Length
793 aa
Mass
89.5 kDa
Annotated
2026-06-10
17 papers in source corpus 11 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF3C is a neuronally enriched kinesin-2 family motor that drives anterograde, microtubule-based transport and shapes microtubule dynamics in neurons (PMID:9487132, PMID:9450952). It assembles combinatorially within the KIF3 family, forming a heterodimer with KIF3A but not with KIF3B, and associates with a distinct population of membrane vesicles and the Golgi complex while binding microtubules in a nucleotide-dependent manner (PMID:9487132, PMID:9450952). As a transport motor it moves FMRP-containing RNA granules into dendrites using FMRP as a molecular adaptor (PMID:17881655), and the KIF3AC heterodimer together with the Rab11 adaptor RCP recycles endocytosed β1-integrin and EGFR cargo back to the plasma membrane to support cell migration [PMID:bio_10.1101_2024.12.09.627580, PMID:39443476]. Independently of cargo transport, KIF3C regulates microtubule plus-end dynamics at axonal growth cones: it preferentially binds tyrosinated microtubules, localizes to plus-ends via EB3, and promotes microtubule catastrophe, with KIF3C loss producing stable, overgrown, looped microtubules and impaired axon outgrowth and regeneration (PMID:23843507). KIF3C microtubule binding is enhanced by VASH2-mediated tubulin detyrosination, which potentiates EGFR recycling and prolonged PI3K/Akt/mTOR signaling (PMID:39443476). KIF3C expression is controlled post-transcriptionally by METTL3/IGF2BP1-dependent m6A mRNA stabilization (antagonized by miR-320d) (PMID:34537760) and transcriptionally by ZNF513 (PMID:37752101). Germline Kif3c knockout mice are viable, fertile, and develop normally (PMID:11463814), though they show defective cerebellar development with reduced granule cell precursor proliferation [PMID:bio_10.1101_2024.12.02.626415].

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 High

    Established that KIF3C is a kinesin motor that assembles combinatorially with KIF3A (but not KIF3B) and functions as a vesicle-associated anterograde transporter, defining its core identity as a motor.

    Evidence Reciprocal immunoprecipitation, sucrose density sedimentation, subcellular fractionation, microtubule-binding assays, and nerve-ligation accumulation in rat and mouse brain

    PMID:9450952 PMID:9487132

    Open questions at the time
    • Cargo specificity of the vesicle population not defined
    • Motility/directionality not directly measured at single-motor level
  2. 1998 Medium

    Localized KIF3C to the Golgi complex and demonstrated proximal accumulation upon nerve ligation, fixing its directional role as an anterograde axonal motor.

    Evidence Double immunolabeling with anti-giantin and nerve-ligation accumulation assay in spinal cord neurons

    PMID:9450952

    Open questions at the time
    • Single-lab localization
    • Cargo carried during anterograde transport unidentified
  3. 2001 High

    Tested whether KIF3C is essential in vivo; knockout mice being viable and normal indicated functional redundancy rather than an indispensable role in neural development.

    Evidence Two independent homologous-recombination knockout strains with phenotypic analysis

    PMID:11463814

    Open questions at the time
    • Redundant partners not identified at this stage
    • Subtle or context-specific phenotypes not assessed
  4. 2007 High

    Identified a specific cargo by showing FMRP acts as a molecular adaptor linking RNA granules to KIF3C, establishing KIF3C as a dendritic RNA-granule transporter.

    Evidence Reciprocal co-immunoprecipitation of KIF3C with FMRP and time-lapse imaging of granule transport with dominant-negative KIF3C

    PMID:17881655

    Open questions at the time
    • Direct motor-adaptor binding interface not mapped
    • Single lab
  5. 2013 High

    Revealed a transport-independent function: KIF3C regulates microtubule catastrophe at growth cones via tyrosinated-microtubule and EB3 binding, controlling axon outgrowth and regeneration.

    Evidence RNAi, KIF3C knockout mice, EB3 interaction assays, live microtubule-dynamics imaging, in vivo regeneration assays, and local-translation assays

    PMID:23843507

    Open questions at the time
    • Molecular mechanism by which KIF3C promotes catastrophe not resolved
    • Relationship between motor activity and catastrophe-promoting activity unclear
  6. 2015 Medium

    Extended KIF3C function to cancer cell biology, linking its activity to TGF-β-driven EMT, metastasis, and cell-cycle progression.

    Evidence shRNA knockdown, flow cytometry, xenograft model, and TGF-β pathway Western blots in breast cancer cells

    PMID:26272184

    Open questions at the time
    • No mechanistic reconstitution linking KIF3C to TGF-β signaling
    • Single lab
  7. 2021 Medium

    Defined post-transcriptional control of KIF3C, showing m6A modification by METTL3/IGF2BP1 stabilizes its mRNA and is antagonized by miR-320d.

    Evidence m6A assays, RIP, luciferase reporters, and miR-320d rescue experiments in prostate cancer cells

    PMID:34537760

    Open questions at the time
    • Downstream effector pathways of KIF3C in prostate cancer not detailed
    • Single lab
  8. 2023 Medium

    Identified transcriptional regulation of KIF3C by ZNF513 and a disease-associated variant, with genetic epistasis showing combined ZNF513/KIF3C mutation causes gingival hyperplasia.

    Evidence ChIP/binding assay, knock-in mouse genetic epistasis, and PI3K/AKT/mTOR and Ras/ERK pathway Western blots

    PMID:37752101

    Open questions at the time
    • Mechanism by which p.R410H activates PI3K and KCNQ1 not resolved
    • Single lab
  9. 2024 Medium

    Linked tubulin detyrosination to KIF3C function, showing VASH2-mediated detyrosination enhances KIF3C microtubule binding and EGFR endosomal recycling to sustain PI3K/Akt/mTOR signaling.

    Evidence VASH2 knockdown/overexpression, detyrosination assays, co-IP, EGFR recycling assays, and xenograft with detyrosination inhibitor in lung squamous carcinoma

    PMID:39443476

    Open questions at the time
    • Whether KIF3C directly motors EGFR-laden endosomes not shown
    • Single lab
  10. 2024 Medium

    Defined a KIF3AC/RCP cargo-recycling axis, showing the heterodimer recycles β1-integrin after focal adhesion disassembly to drive polarized cell migration.

    Evidence Biochemical pulldown, RNAi of KIF3C/KIF3A, and live imaging of FA disassembly and integrin recycling in fibroblasts (preprint)

    PMID:bio_10.1101_2024.12.09.627580

    Open questions at the time
    • Not yet peer reviewed
    • Direct vs RCP-mediated integrin association not fully separated
  11. 2024 Medium

    Uncovered a developmental requirement for KIF3C in cerebellar growth via a Hedgehog-independent, putative Notch/Hes1 mechanism, contrasting with the originally normal-appearing knockout.

    Evidence Kif3c knockout cerebellar phenotyping, CGNP proliferation quantification, Hedgehog reporter (no change), and Hes1/Bergmann glia analysis (preprint)

    PMID:bio_10.1101_2024.12.02.626415

    Open questions at the time
    • Notch dependence inferred, not directly demonstrated
    • Not yet peer reviewed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KIF3C's transport-motor activity and its microtubule-catastrophe-promoting activity are mechanistically coordinated, and which functions depend on the KIF3AC heterodimer versus KIF3C alone, remain unresolved.
  • No structural model of the KIF3AC motor or its plus-end catastrophe mechanism
  • Unclear which in vivo cargoes require heterodimerization with KIF3A

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 2 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005768 endosome 2 GO:0005794 Golgi apparatus 1 GO:0005856 cytoskeleton 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 2
Partners
EB3EGFRFMRPITGB1KIF3ARCP
Complex memberships
KIF3AC heterodimer

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 KIF3C forms a heteromeric kinesin complex with KIF3A (but not KIF3B) in rat brain, associates with a distinct population of membrane vesicles, and binds microtubules in a nucleotide-dependent manner, suggesting it functions as a vesicle-associated anterograde motor both independently and in association with KIF3A. Immunoprecipitation, sucrose density gradient sedimentation, subcellular fractionation, microtubule-binding assay, immunocytochemistry Molecular biology of the cell High 9450952 9487132
1998 KIF3C and KIF3B are 'variable' subunits that each associate with KIF3A but not with each other, indicating combinatorial heterodimer assembly within the KIF3 family. Immunoprecipitation from mouse brain; ligation-induced accumulation at proximal side of sciatic nerve indicating anterograde transport direction Molecular biology of the cell High 9450952 9487132
1998 KIF3C localizes to the Golgi complex in spinal cord neurons and accumulates at the proximal side of ligated sciatic nerve, establishing it as an anterograde axonal motor. Double immunolabeling with anti-giantin, nerve ligation accumulation assay, immunocytochemistry Molecular biology of the cell Medium 9450952
2001 Homozygous Kif3C knockout mice are viable, fertile, and develop normally, demonstrating that KIF3C is dispensable for normal neural development and behavior in mice. Homologous recombination knockout (two independent strains), phenotypic analysis Molecular and cellular biology High 11463814
2007 FMRP acts as a molecular adaptor between RNA granules and KIF3C; KIF3C is a novel FMRP-interacting protein, and a KIF3C dominant-negative construct impedes distal transport of FMRP-containing RNA granules in dendrites. Co-immunoprecipitation of KIF3C with FMRP, time-lapse videomicroscopy of RNA granule dynamics with dominant-negative KIF3C expression Human molecular genetics High 17881655
2013 KIF3C preferentially binds to tyrosinated microtubules in the growth cone; its interaction with EB3 is necessary for localization at microtubule plus-ends. KIF3C depletion decreases microtubule catastrophe frequency, causing stable, overgrown, looped microtubules, and impairs axon outgrowth and regeneration after injury. KIF3C protein is locally translated in embryonic axons after injury. RNAi knockdown, KIF3C knockout mice, EB3 co-immunoprecipitation/interaction assay, live imaging of microtubule dynamics, in vitro and in vivo axon regeneration assays, local translation assay The Journal of neuroscience High 23843507
2015 Silencing KIF3C by shRNA in breast cancer cells inhibits epithelial-mesenchymal transition and metastasis by inhibiting TGF-β signaling and induces G2/M phase arrest suppressing proliferation. shRNA knockdown, flow cytometry cell cycle analysis, xenograft mouse model, Western blot for TGF-β pathway markers Cancer letters Medium 26272184
2021 METTL3-mediated m6A modification on KIF3C mRNA stabilizes it via IGF2BP1; miR-320d inhibits KIF3C expression by targeting METTL3, thereby reducing m6A-dependent KIF3C mRNA stabilization in prostate cancer cells. m6A modification assay, RIP, luciferase reporter, miR-320d overexpression, rescue experiments Aging Medium 34537760
2024 VASH2-induced tubulin detyrosination increases KIF3C binding to microtubules and enhances KIF3C-dependent endosomal recycling of EGFR, leading to prolonged activation of PI3K/Akt/mTOR signaling in lung squamous cell carcinoma. VASH2 knockdown/overexpression, tubulin detyrosination assay, co-immunoprecipitation, EGFR recycling assay, xenograft model with TCP inhibitor Cell death & disease Medium 39443476
2023 ZNF513 transcription factor binds KIF3C exon 1 and positively regulates KIF3C expression in gingival fibroblasts; the KIF3C p.R410H variant activates PI3K and KCNQ1 potassium channels. Double heterozygous mutations in ZNF513 and KIF3C together cause gingival hyperplasia in knock-in mice, whereas either mutation alone does not produce the phenotype. Chromatin immunoprecipitation/binding assay (ZNF513 to KIF3C exon 1), knock-in mouse model, in vitro functional assays, Western blot for PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathway markers International journal of oral science Medium 37752101
2024 The KIF3AC heterodimer (KIF3A+KIF3C) and the Rab11 adaptor RCP are required for recycling of endocytosed β1-integrin back to the plasma membrane after focal adhesion disassembly; KIF3C associates with β1-integrin in an RCP-dependent manner only after FA disassembly. KIF3AC knockdown inhibits cell migration, RCP trafficking toward the leading edge, and polarized FA formation. Biochemical pulldown (KIF3C with β1-integrin), RNAi knockdown of KIF3C/KIF3A, live imaging of FA disassembly and integrin recycling, Rab11 endocytic compartment accumulation assay in mouse and human fibroblasts bioRxivpreprint Medium bio_10.1101_2024.12.09.627580
2024 KIF3C is required for proper cerebellar development: Kif3c-/- mice show reduced CGNP proliferation, cerebellar hypoplasia, and altered Bergmann glia density/patterning associated with reduced Hes1 expression, in a Hedgehog-independent but putative Notch-dependent manner. Kif3c germline knockout mouse analysis, quantification of CGNP proliferation, Hedgehog pathway reporter assay (no change detected), Hes1 expression measurement, Bergmann glia immunostaining bioRxivpreprint Medium bio_10.1101_2024.12.02.626415

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The fragile X mental retardation protein is a molecular adaptor between the neurospecific KIF3C kinesin and dendritic RNA granules. Human molecular genetics 103 17881655
1998 KIF3C and KIF3A form a novel neuronal heteromeric kinesin that associates with membrane vesicles. Molecular biology of the cell 97 9487132
1998 Characterization of the KIF3C neural kinesin-like motor from mouse. Molecular biology of the cell 89 9450952
2013 The kinesin-2 family member KIF3C regulates microtubule dynamics and is required for axon growth and regeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 23843507
2001 Functional analysis of mouse kinesin motor Kif3C. Molecular and cellular biology 45 11463814
2021 METTL3-mediated m6A modification of KIF3C-mRNA promotes prostate cancer progression and is negatively regulated by miR-320d. Aging 36 34537760
2015 Suppression of motor protein KIF3C expression inhibits tumor growth and metastasis in breast cancer by inhibiting TGF-β signaling. Cancer letters 30 26272184
1998 KIF3C, a novel member of the kinesin superfamily: sequence, expression, and mapping to human chromosome 2 at 2p23. Genomics 29 9480755
2001 Expression of KIF3C kinesin during neural development and in vitro neuronal differentiation. Journal of neurochemistry 25 11331403
2020 KIF3C Promotes Proliferation, Migration, and Invasion of Glioma Cells by Activating the PI3K/AKT Pathway and Inducing EMT. BioMed research international 23 33150178
2021 Kinesin family member 3C (KIF3C) is a novel non-small cell lung cancer (NSCLC) oncogene whose expression is modulated by microRNA-150-5p (miR-150-5p) and microRNA-186-3p (miR-186-3p). Bioengineered 13 34193018
2021 MicroRNA-2053 involves in the progression of esophageal cancer by targeting KIF3C. Cell cycle (Georgetown, Tex.) 11 34057012
2024 VASH2 enhances KIF3C-mediated EGFR-endosomal recycling to promote aggression and chemoresistance of lung squamous cell carcinoma by increasing tubulin detyrosination. Cell death & disease 8 39443476
2023 Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis. International journal of oral science 8 37752101
1998 cDNA cloning, genomic organization, and chromosomal localization of a novel human gene that encodes a kinesin-related protein highly similar to mouse Kif3C. Biochemical and biophysical research communications 6 9446808
2024 Targeted therapy for KIF3C: A study on the mechanism of combined therapy with KIF3C signaling pathway, afatinib, and MT-DC (ac)phosphoramide in regulating gastric cancer cell proliferation. Cellular signalling 1 39580063
2025 KIF3C inhibits the progression and proliferation of colorectal cancer. BMC gastroenterology 0 40075273

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