Affinage

KIF16B

Kinesin-like protein KIF16B · UniProt Q96L93

Length
1317 aa
Mass
152.0 kDa
Annotated
2026-06-10
12 papers in source corpus 9 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF16B is a plus-end-directed kinesin-3 motor that transports endosomal membranes along microtubules to control the balance between cargo recycling to the cell surface and lysosomal degradation (PMID:15882625). It targets to membranes through a PX domain that binds PI(3)P, coupling the Rab5/hVPS34 phosphoinositide axis to early-endosome motility; overexpression drives endosomes to the cell periphery and blocks degradation, while loss causes perinuclear endosome clustering and delayed receptor recycling (PMID:15882625). Cargo selectivity is conferred by direct association with Rab14-GTP, which loads KIF16B onto vesicles carrying FGFR, MT1-MMP, and HIV-1 Env for anterograde delivery; this Rab14-dependent surface delivery sustains FGF signaling during peri-implantation development, MT1-MMP-driven matrix degradation and invasion in macrophages, and Env incorporation into infectious virions, and its failure reroutes cargo to lysosomes (PMID:21238925, PMID:37696580, PMID:37358446). KIF16B also mediates transferrin-receptor transcytosis to apical recycling endosomes in polarized epithelia (PMID:23749212) and somatodendritic positioning of early endosomes in neurons, where an autoinhibitory 'stalk inhibition' mechanism — an ATP-dependent intramolecular interaction of the second and third coiled-coils with the motor domain — restrains microtubule binding and governs cargo localization (PMID:25810535). Beyond endosomal trafficking, KIF16B contributes to mouse oocyte meiotic progression and spindle assembly through CDK1/cyclin B1 activation and the Ran–TPX2–Aurora A–PLK1 axis (PMID:40704502) and to mitochondrial, ER, and Golgi organelle dynamics (PMID:41653015). Kif16b knockout mouse embryos die at peri-implantation, phenocopying FGFR2 loss (PMID:21238925).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2005 High

    Established KIF16B as the microtubule motor that moves early endosomes to the cell periphery and sets the recycling-versus-degradation balance, and defined the PI(3)P/PX-domain link to the Rab5–hVPS34 signaling axis.

    Evidence RNAi, dominant-negative and overexpression with live-cell imaging and endosome localization assays, plus PX-domain PI(3)P-binding assays in cultured cells

    PMID:15882625

    Open questions at the time
    • Did not identify the cargo adaptors that select specific receptors
    • Regulation of motor on/off state not addressed
  2. 2011 High

    Showed that Rab14-GTP is the membrane switch that recruits KIF16B to FGFR vesicles, and that this transport is physiologically required for early embryonic lineage specification.

    Evidence Kif16b knockout mouse with embryo phenotyping, co-immunoprecipitation, and dominant-negative Rab14-GDP FGFR trafficking assays

    PMID:21238925

    Open questions at the time
    • Structural basis of the KIF16B–Rab14 interaction not resolved
    • Whether Rab14 directly relieves autoinhibition unknown
  3. 2013 High

    Extended KIF16B function to polarized epithelia, identifying it as the first motor mediating basal-to-apical transcytosis of transferrin receptor along non-centrosomal microtubules.

    Evidence siRNA knockdown with TfR trafficking and immunofluorescence in AP-1B-deficient polarized epithelial cells

    PMID:23749212

    Open questions at the time
    • Adaptor coupling KIF16B to TfR-containing endosomes not defined
    • Relationship to Rab14 in this context not tested
  4. 2015 High

    Defined an intrinsic autoregulatory mechanism, showing the second and third coiled-coils inhibit motor–microtubule binding and that this controls neuronal early-endosome positioning.

    Evidence KIF16B knockout/knockdown in hippocampal neurons, deletion-mutant phenotyping, and in vitro microtubule-binding assays with isolated domains

    PMID:25810535

    Open questions at the time
    • Physiological trigger that relieves stalk inhibition not identified
    • Link between autoinhibition and Rab14 loading untested
  5. 2023 High

    Generalized the Rab14-dependent recycling role to disease-relevant cargoes, demonstrating KIF16B drives surface delivery of MT1-MMP (macrophage invasion) and HIV-1 Env (virion infectivity) and protects them from lysosomal degradation.

    Evidence siRNA/knockout, dominant-negative C-terminus and motor-deficient mutants, FACS, matrix-degradation, invasion, Env half-life and infectivity assays in macrophages and virus-producing cells

    PMID:37358446 PMID:37696580

    Open questions at the time
    • Whether distinct cargoes share a common adaptor remains unknown
    • In vivo relevance to infection or tumor invasion not established
  6. 2025 Medium

    Implicated KIF16B in meiotic cell-cycle control and spindle assembly, beyond its established trafficking role.

    Evidence KIF16B knockdown in mouse oocytes with immunofluorescence, western blots for CDK1/cyclin B1/Aurora A/PLK1/HDAC6/BubR1/Bub3, and kinetochore-microtubule attachment analysis

    PMID:40704502

    Open questions at the time
    • No rescue or in vitro reconstitution
    • Direct versus indirect connection to the Ran–TPX2 axis not resolved
  7. 2026 Medium

    Linked KIF16B depletion to broad organelle dysregulation (mitochondrial fission, ER, Golgi) and oocyte developmental competence.

    Evidence KIF16B knockdown in mouse oocytes with organelle imaging, Drp1/Fis1 and ER-stress marker western blots, and parthenogenetic activation assays

    PMID:41653015

    Open questions at the time
    • Pathway links rely on correlation with Drp1/Fis1 levels
    • No rescue; direct motor involvement versus secondary stress effects unclear
  8. 2025 Medium

    Proposed a tubule-forming mechanism by which KIF16B delivers the MET receptor to invadopodia to promote TNBC invasion.

    Evidence Live-cell imaging, degradation-defective MET mutant, siRNA, RAB14 dominant-negative and invasion assays in TNBC cells (preprint)

    PMID:bio_10.1101_2025.09.23.677683

    Open questions at the time
    • Preprint, not peer-reviewed
    • Mechanism of vesicular tubule formation not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single motor's autoinhibition, Rab14 loading, and PI(3)P binding are integrated to select among diverse cargoes and switch between trafficking and spindle/organelle roles remains unresolved.
  • No structural model of the autoinhibited or Rab14-bound motor
  • Cargo-specific adaptors not identified
  • Mechanistic basis for meiotic/organelle functions versus trafficking not reconciled

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:0008289 lipid binding 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005768 endosome 4 GO:0005856 cytoskeleton 3 GO:0031410 cytoplasmic vesicle 3 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-9609507 Protein localization 2 R-HSA-1266738 Developmental Biology 1 R-HSA-1640170 Cell Cycle 1
Partners
FGFRMT1-MMPPIK3C3RAB14RAB5TPX2

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 KIF16B (kinesin-3) transports early endosomes toward microtubule plus ends; this process is regulated by the small GTPase Rab5 and its effector, the phosphatidylinositol-3-OH kinase hVPS34. KIF16B overexpression relocates early endosomes to the cell periphery and inhibits degradative transport, while dominant-negative mutants or RNAi-mediated ablation causes perinuclear clustering of early endosomes, delays receptor recycling, and accelerates degradation. RNAi knockdown, dominant-negative mutant expression, overexpression, live-cell imaging, endosome fractionation/localization assays Cell High 15882625
2005 KIF16B contains a PX domain that binds phosphatidylinositol-3-phosphate (PI(3)P)-containing membranes, providing the mechanistic link between PI3K signaling (hVPS34/Rab5 axis) and KIF16B-dependent early endosome transport. Domain analysis, PI(3)P binding assays, functional mutant expression Cell High 15882625
2011 KIF16B directly associates with Rab14-GTP on FGFR-containing vesicles and transports them from Golgi to endosomes toward the plasma membrane. Kif16b knockout mouse embryos die at peri-implantation stage with failure of epiblast and primitive endoderm lineages, phenocopying FGFR2 knockout. Dominant-negative Rab14-GDP expression impairs FGFR transport and FGF signaling, placing Rab14 as a GTP-dependent switch for KIF16B-mediated vesicle transport. Kif16b knockout mouse, co-immunoprecipitation, dominant-negative Rab14-GDP overexpression, FGFR trafficking assays, embryo phenotyping Developmental cell High 21238925
2013 In AP-1B-deficient epithelia, KIF16B mediates transfer of transferrin receptor (TfR) from common recycling endosomes to apical recycling endosomes along non-centrosomal microtubules, enabling apical transcytosis. This represents the first identified microtubule motor involved in basal-to-apical transcytosis. siRNA knockdown of KIF16B, immunofluorescence, TfR trafficking assays in polarized epithelial cells, AP-1B-deficient cell model The EMBO journal High 23749212
2015 KIF16B is required for somatodendritic localization of early endosomes in neurons. A deletion mutant lacking the second and third coiled-coils of the stalk domain mislocalizes early endosomes to axons. The second and third coiled-coils (inhibitory domain) inhibit motor domain binding to microtubules in an ATP-dependent manner via intramolecular interaction, constituting an autoregulatory 'stalk inhibition' mechanism that controls KIF16B activity and cargo localization. KIF16B knockout/knockdown in mouse hippocampal neurons, deletion mutant expression, in vitro microtubule-binding assay with isolated domains, live-cell imaging The Journal of neuroscience High 25810535
2023 KIF16B associates with MT1-MMP on Rab14-positive vesicles and drives fast recycling of MT1-MMP to the surface of primary human macrophages. KIF16B depletion reduces MT1-MMP surface levels, matrix degradation, and macrophage invasion. Overexpression of the cargo-binding C-terminus of KIF16B uncouples MT1-MMP vesicles from endogenous motor, reducing surface MT1-MMP. KIF16B siRNA depletion, C-terminal overexpression as dominant-negative, confocal microscopy, flow cytometry, matrix degradation assay, invasion assay Life science alliance High 37696580
2023 KIF16B mediates anterograde transport of HIV-1 envelope glycoprotein (Env) on Rab14-positive endosomes toward the plasma membrane. In the absence of KIF16B, Env is redirected to lysosomal degradation, reducing its surface expression, virion incorporation, and HIV-1 infectivity/replication. KIF16B knockout cells, motor-deficient KIF16B mutant expression, colocalization imaging, Env half-life measurement, lysosomal inhibitor rescue, virus infectivity assay Journal of virology High 37358446
2025 KIF16B participates in meiotic G2/M transition and spindle assembly in mouse oocytes. KIF16B depletion inactivates CDK1, reduces cyclin B1, and prevents germinal vesicle breakdown. KIF16B concentrates on microtubules after GVBD and its loss causes aberrant spindle assembly, disordered chromosome alignment, improper kinetochore-microtubule attachments with persistent BubR1/Bub3 activation, and destabilization of α-tubulin through HDAC6. KIF16B participates in Ran GTPase-dependent activation of TPX2, which regulates Aurora A-PLK1 phosphorylation for proper spindle assembly. KIF16B knockdown in mouse oocytes, immunofluorescence, western blot for CDK1/cyclin B1/Aurora A/PLK1/HDAC6/BubR1/Bub3, spindle assembly assays, kinetochore-microtubule attachment analysis FASEB journal Medium 40704502
2026 KIF16B regulates mitochondrial distribution and fission (via p-Drp1 and Fis1), ER distribution and function, and Golgi apparatus-based vesicular transport in mouse oocytes. KIF16B depletion disrupts organelle dynamics, causes oxidative stress and ER stress (elevated CHOP and ATF4), and impairs oocyte developmental competence. KIF16B knockdown in mouse oocytes, immunofluorescence, confocal imaging of mitochondria/ER/Golgi, western blot for Drp1/Fis1/ER stress markers, parthenogenetic activation assay FASEB journal Medium 41653015
2025 KIF16B promotes formation of vesicular tubules on RAB14-positive endosomes that mediate surface delivery of the MET receptor tyrosine kinase to invadopodia in TNBC cells, facilitating HGF-stimulated MT1-MMP delivery and cancer cell invasion. Live-cell imaging, degradation-defective MET mutant expression, siRNA depletion, RAB14 dominant-negative, invadopodia formation and invasion assays bioRxiv (preprint)preprint Medium bio_10.1101_2025.09.23.677683

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B. Cell 272 15882625
2011 KIF16B/Rab14 molecular motor complex is critical for early embryonic development by transporting FGF receptor. Developmental cell 96 21238925
2013 The kinesin KIF16B mediates apical transcytosis of transferrin receptor in AP-1B-deficient epithelia. The EMBO journal 53 23749212
2015 Characterizing KIF16B in neurons reveals a novel intramolecular "stalk inhibition" mechanism that regulates its capacity to potentiate the selective somatodendritic localization of early endosomes. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 25810535
2023 KIF16B drives MT1-MMP recycling in macrophages and promotes co-invasion of cancer cells. Life science alliance 10 37696580
2019 Novel genetic variants in KIF16B and NEDD4L in the endosome-related genes are associated with nonsmall cell lung cancer survival. International journal of cancer 10 31618441
2018 KIF16B is a candidate gene for a novel autosomal-recessive intellectual disability syndrome. American journal of medical genetics. Part A 9 29736960
2020 PX Domain-Containing Kinesin KIF16B and Microtubule-Dependent Intracellular Movements. The Journal of membrane biology 8 32140737
2023 KIF16B Mediates Anterograde Transport and Modulates Lysosomal Degradation of the HIV-1 Envelope Glycoprotein. Journal of virology 6 37358446
2025 Kinesin KIF16B Participates in G2/M Transition and Microtubule Dynamics via Aurora A-PLK1 in Oocyte Meiosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 40704502
2026 Loss of Kinesin KIF16B Disrupts Organelle Dynamics for Developmental Potential in Oocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41653015
2013 KIF16B delivers for transcytosis. The EMBO journal 1 23812008

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