{"gene":"KIF5B","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":1998,"finding":"KIF5B (kinesin heavy chain) is essential for mitochondrial and lysosomal dispersion in extraembryonic cells; kif5B-/- knockout mice show perinuclear clustering of mitochondria and impaired lysosomal dispersion, and this phenotype is reversed by exogenous KIF5B expression. Subcellular fractionation confirmed KIF5B associates with mitochondria.","method":"Homologous recombination knockout mouse, subcellular fractionation, rescue by exogenous expression","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined phenotype, rescue experiment, subcellular fractionation; independently foundational study with multiple orthogonal methods","pmids":["9657148"],"is_preprint":false},{"year":2001,"finding":"RanBP2 contains a novel kinesin-binding domain (KBD) located between RBD2 and RBD3 that directly associates with KIF5B and KIF5C (but not KIF5A) both in vitro and in vivo; kinesin light chain and RanGTPase are also part of this macroassembly complex.","method":"Yeast two-hybrid, in vitro binding, co-immunoprecipitation, functional domain mapping","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct in vitro binding plus in vivo co-IP, multiple orthogonal methods in single study","pmids":["11553612"],"is_preprint":false},{"year":2003,"finding":"KIF5B mediates insulin-stimulated long-range movement of GLUT4-containing vesicles on microtubules in adipocytes through a PI3-kinase-independent mechanism; dominant-negative kinesin light chain mutants blocked outward GLUT4 vesicle movement and GLUT4 translocation to the plasma membrane.","method":"Live-cell imaging (GLUT4-YFP/tubulin-CFP), dominant-negative expression, wortmannin inhibition","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — live imaging with defined molecular perturbation (dominant negative), multiple orthogonal methods, clear functional readout","pmids":["12743033"],"is_preprint":false},{"year":2004,"finding":"The ribosome receptor p180 binds KIF5B; the binding site is residues 1294–1413 of p180 and the C-terminal cargo-binding domain of KIF5B (residues 867–907), and the interaction is likely coiled-coil in nature; the p180 binding site on KIF5B is homologous to the kinectin-binding site.","method":"Yeast two-hybrid screen, domain mapping","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single yeast two-hybrid screen, no in vivo validation reported in abstract","pmids":["15184079"],"is_preprint":false},{"year":2007,"finding":"The kinesin-binding domain (KBD) of RanBP2 selectively interacts with KIF5B and KIF5C via a ~100-residue segment spanning a coiled-coil and globular tail cargo-binding domain; a single residue conserved in KIF5B/KIF5C but absent in KIF5A confers isoform specificity. Selective inhibition of KBD–KIF5B/KIF5C interaction causes perinuclear mitochondrial clustering, reduced mitochondrial membrane potential, and cell shrinkage.","method":"Domain mutagenesis, cell-based KBD inhibition, mitochondrial localization assay, membrane potential measurement","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 2 / Strong — mutagenesis defining single residue specificity, functional cellular phenotype upon inhibition, multiple orthogonal readouts","pmids":["17887960"],"is_preprint":false},{"year":2007,"finding":"KIF5B mediates post-Golgi transport of the apical marker p75-GFP in polarized MDCK epithelial cells but not in subconfluent cells; immunoprecipitation demonstrates a polarity-dependent interaction between KIF5B and p75-GFP that is absent before polarization. Dominant-negative KIF5B or function-blocking antibodies selectively block apical (but not basolateral) transport.","method":"Time-lapse microscopy, dominant-negative expression, microinjection of function-blocking antibodies, co-immunoprecipitation","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — live imaging, co-IP showing polarity-dependent interaction, antibody inhibition; multiple orthogonal methods in one study","pmids":["17925227"],"is_preprint":false},{"year":2007,"finding":"KIF5B interacts with Kv1 potassium channels via the T1 domain and mediates their axonal targeting; dominant-negative Kif5B blocks axonal localization of endogenous Kv1.1, Kv1.2, and Kv1.4 in cortical neurons, and Kv1.2 co-immunoprecipitates with Kif5B from brain lysate.","method":"Dominant-negative expression, co-immunoprecipitation from brain lysate, co-localization in cortical neurons","journal":"The European journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP from native tissue plus dominant-negative functional experiment, single lab","pmids":["17241275"],"is_preprint":false},{"year":2007,"finding":"Kif5B and the minus-end kinesin Kifc1 interact, co-localize on early endocytic vesicles (>90% of Kifc1-positive vesicles also contain Kif5B), mediate plus- and minus-end motility respectively, and both activities are required for vesicle fission; inhibition of either motor reduces fission frequency.","method":"In vitro microtubule-binding/motility assay, antibody inhibition, co-immunoprecipitation after FLAG-Kifc1 expression in 293T cells","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro motility assay with antibody inhibition and co-IP, single lab, multiple methods","pmids":["17360972"],"is_preprint":false},{"year":2008,"finding":"KIF5B (kinesin-1) is required for bidirectional positioning of COPII-coated ER exit sites (ERES) and for ER-to-Golgi transport; knockdown of KIF5B inhibits ER-to-Golgi transport and alters the morphology of transport carriers.","method":"siRNA knockdown, high-resolution 2D Gaussian localization of ERES, ER-to-Golgi trafficking assay","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA KD with quantitative localization and trafficking assay, single lab","pmids":["18817524"],"is_preprint":false},{"year":2009,"finding":"RANBP2, through its kinesin-binding domain flanked by RBD2 and RBD3, activates the ATPase activity of KIF5B ~30-fold in the presence of microtubules and ATP in a minimal purified system; activation is biphasic and cooperative, and deletion of one RBD reduces activation threefold and abolishes cooperativity. RBD2-KBD-RBD3 also induces KIF5B unfolding in the absence of microtubules.","method":"In vitro ATPase assay with purified components, domain deletion mutagenesis","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstituted in vitro ATPase assay with purified components and systematic domain mutagenesis; first demonstration of a native allosteric activator of KIF5B","pmids":["19305391"],"is_preprint":false},{"year":2009,"finding":"Syntabulin acts as a KIF5B motor adaptor mediating anterograde axonal transport of presynaptic cargoes and mitochondria in sympathetic neurons; interference with syntabulin–KIF5B interaction delays synaptic activity, impairs transmission, reduces mitochondrial distribution, and these defects are rescued by ATP application.","method":"RNAi knockdown, dominant-negative interference with syntabulin–KIF5B interaction, electrophysiology, mitochondrial distribution assay, ATP rescue","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with specific molecular interference, electrophysiological readout, rescue experiment; multiple orthogonal methods","pmids":["19828815"],"is_preprint":false},{"year":2009,"finding":"Kif5b is essential for anterograde (forward) trafficking of the cardiac potassium channel Kv1.5 from the Golgi to the cell surface; overexpression of Kif5b increases Kv1.5 current density in a Golgi-dependent manner (blocked by Brefeldin A), and Kif5b dominant-negative blocks surface expression of newly induced Kv1.5.","method":"Patch-clamp electrophysiology, dominant-negative expression, Brefeldin A treatment, tetracycline-inducible Kv1.5 system","journal":"The Journal of physiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — electrophysiological quantification combined with pharmacological and dominant-negative interventions, multiple orthogonal methods","pmids":["19675065"],"is_preprint":false},{"year":2009,"finding":"Daxx functions as a scaffold assembling a complex of GLUT4, JNK1, and KIF5B; Daxx interacts with KIF5B through the 6xTPR domain of kinesin light chain. Depletion of Daxx causes partial translocation of GLUT4 from storage compartment to endosomes.","method":"Co-immunoprecipitation, two-hybrid protein-protein interaction, Daxx depletion","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP and two-hybrid interactions plus depletion phenotype, single lab","pmids":["18932217"],"is_preprint":false},{"year":2010,"finding":"KIF5B and KIF3A/KIF3B kinesins regulate bidirectional transport of MT1-MMP-positive vesicles along microtubules in human macrophages; siRNA knockdown of KIF5B reduces delivery of MT1-MMP to the cell surface and impairs surface-associated MT1-MMP functions including CD44 shedding and extracellular matrix degradation at podosomes.","method":"siRNA knockdown, live-cell vesicle tracking, MT1-MMP surface exposure assay, ECM degradation assay","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — siRNA KD in primary human macrophages with multiple functional readouts (surface exposure, shedding, ECM degradation), live imaging","pmids":["20505159"],"is_preprint":false},{"year":2013,"finding":"KIF5B promotes anterograde transport of Nav1.8 to the plasma membrane and axons in DRG neurons; the N terminus of Nav1.8 directly interacts with the 511–620 aa stalk domain of KIF5B (co-immunoprecipitation); KIF5B mutants defective in ATP hydrolysis or cargo binding fail to increase Nav1.8 surface expression; disrupting the KIF5B–Nav1.8 interaction abolishes KIF5B-enhanced Nav1.8 current and axonal accumulation.","method":"Co-immunoprecipitation, domain mutagenesis, patch-clamp, overexpression/knockdown in DRG neurons, Brefeldin A treatment","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct interaction mapped by co-IP with domain mutants, functional electrophysiological validation, multiple orthogonal approaches","pmids":["24198377"],"is_preprint":false},{"year":2013,"finding":"Kif5b mediates anterograde transport of α-sarcomeric actin, non-muscle myosin IIB, desmin, and nestin to the growing tips of elongating myotubes; conditional Kif5b knockout in myogenic cells causes aggregation of these proteins and defective myofibril assembly and linkage to myotendinous junctions. A 64-amino acid α-helix domain in the tail region of Kif5b directly interacts with desmin.","method":"Conditional knockout (Cre-loxP), immunofluorescence, rescue by Kif5b re-expression, functional domain mapping (direct interaction with desmin)","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with clear phenotype, rescue, and direct domain–cargo interaction mapping","pmids":["23293293"],"is_preprint":false},{"year":2013,"finding":"KIF5B is required for axonal localization of Kv1 channels and is required for female meiosis progression; RNAi silencing of Kif5b in mouse oocytes delays germinal vesicle breakdown and causes failure of first polar body extrusion; in mitotic cells, knockdown causes centrosome amplification and chromosomal segregation defects.","method":"RNAi silencing in mouse oocytes and mitotic cells, live imaging of meiotic progression","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi with clear meiotic and mitotic phenotypes, single lab","pmids":["23560038"],"is_preprint":false},{"year":2013,"finding":"For nuclear positioning during myogenesis, both the kinesin light chain (KLC) binding domain and the autoinhibitory peptide in the globular tail of Kif5b are indispensable; the coiled-coil stalk/tail domain (containing KLC-binding sites) targets to the perinuclear region, while the globular tail domain alone cannot, and rescue of nuclear positioning in Kif5b-deficient myoblasts requires both regions.","method":"Domain truncation rescue experiments in Kif5b-deficient myoblasts, immunofluorescence localization","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain deletion rescue in null cells, single lab, clear functional readout","pmids":["23402760"],"is_preprint":false},{"year":2014,"finding":"KIF5B directly interacts with BNIP-2 via its BCH domain at both the motor and tail domains of KIF5B; KIF5B mediates microtubule-dependent anterograde transport of BNIP-2 to endosomes in C2C12 cells. KIF5B modulates p38MAPK activity through BNIP-2 transport, promoting myogenic differentiation; disruption of anterograde transport by dominant-negative KIF5B abolishes BNIP-2's promyogenic effects.","method":"Co-immunoprecipitation, far-Western blot, live microscopy with organelle markers, dominant-negative KIF5B, knockdown/gain-of-function","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct interaction confirmed by far-Western and co-IP, live transport imaging, pathway placement via gain/loss-of-function with signaling readout","pmids":["25378581"],"is_preprint":false},{"year":2014,"finding":"Palmitate causes dissociation of KIF5B from mitochondria via Ca2+-dependent effects, disrupting mitophagy; Rheb and KIF5B interact with the mitochondrial outer membrane, and their disruption blocks mitochondrial degradation and promotes NLRP3 inflammasome activation and IL-1β-dependent insulin resistance; Rheb/KIF5B overexpression attenuates these effects.","method":"Overexpression/knockdown, Ca2+ signaling inhibitors, mitophagy assays, ROS measurement","journal":"Redox biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — functional rescue by overexpression, Ca2+ dependence shown, but mechanism of KIF5B–mitochondria interaction not directly characterized at molecular level","pmids":["25462067"],"is_preprint":false},{"year":2014,"finding":"PRIP and GABARAP function in a complex to regulate KIF5B-mediated insulin secretory vesicle transport; GABARAP knockdown reduces co-localization of insulin vesicles with KIF5B and decreases insulin secretion; free GABARAP (released by PRIP silencing or interference peptide) enhances co-localization of vesicles with microtubules and promotes mobility.","method":"siRNA knockdown, co-immunofluorescence, density step-gradient fractionation, live-cell vesicle tracking","journal":"Biology open","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA KD with co-localization and functional secretion readout, single lab","pmids":["24812354"],"is_preprint":false},{"year":2016,"finding":"KIF5B induces relocalization of the nuclear pore component Nup358 into the cytoplasm during HIV-1 infection in a capsid-dependent manner; cytoplasmic Nup358 then directly associates with viral cores. KIF5B knockdown prevents nuclear entry and infection by HIV-1 but not by N74D or P90A capsid mutants that do not rely on Nup358.","method":"siRNA knockdown, fluorescence microscopy of Nup358 relocalization, infection assays with capsid mutants","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — KD phenotype confirmed by capsid-mutant epistasis, multiple orthogonal readouts (localization + infectivity), mechanistic pathway placement","pmids":["27327622"],"is_preprint":false},{"year":2017,"finding":"PLD2-generated phosphatidic acid (PA) directly and specifically binds to the C-terminus of KIF5B in vitro (liposome pull-down); this PA–KIF5B interaction is required for vesicular association of KIF5B, surface localization of MT1-MMP, invadopodia formation, and invasion in breast cancer cells.","method":"Liposome pull-down screen, in vitro binding assay, KIF5B C-terminal domain mapping, MT1-MMP surface localization assay, invasion assay","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct in vitro lipid binding with domain mapping, functional cellular consequence (MT1-MMP trafficking, invasion) linked to the interaction","pmids":["29033361"],"is_preprint":false},{"year":2018,"finding":"Kif5b directly interacts with clathrin heavy chain (CHC) and preferentially localizes to relatively large clathrin-coated vesicles (CCVs); Kif5b promotes uncoating of large CCVs in vitro (uncoating decreased in cortex CCVs from kif5b cKO mice, increased by adding Kif5b fragments containing the CHC-binding site). Kif5b depletion inhibits cellular entry of vesicular stomatitis virus via large CCV, linking anterograde transport to clathrin-mediated endocytosis.","method":"Co-immunoprecipitation, in vitro CCV uncoating assay with kif5b cKO cortex, dominant-negative fragment, virus entry assay","journal":"Cell discovery","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct interaction, in vitro uncoating assay with KO tissue, dominant-negative, virus entry functional readout; multiple orthogonal methods","pmids":["30603101"],"is_preprint":false},{"year":2018,"finding":"The dynamin-related GTPase Mx1 interacts (directly or indirectly) with Kif5B and α-tubulin as assessed by co-immunoprecipitation; Mx1 aids in vesicle fission and stabilizes the interaction between Kif5B, microtubules, and apical transport carriers in MDCK cells.","method":"Co-immunoprecipitation, live-cell microscopy, nocodazole disruption, Mx1 knockout/mutant","journal":"Traffic (Copenhagen, Denmark)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP, indirect interaction not excluded, single lab","pmids":["30246279"],"is_preprint":false},{"year":2019,"finding":"Neuronal deletion of Kif5b reduces dopamine D2 receptor in synaptic plasma membranes (subcellular fractionation) causing D2-dependent movement initiation defects and hypo-locomotion; dopamine metabolism is impaired in neuronal Kif5b-KO. Deletion of Kif5b only in dopaminergic neurons is not sufficient to produce locomotor defects.","method":"Conditional knockout (neuronal and dopaminergic-specific), HPLC dopamine measurement, subcellular fractionation, pharmacological receptor agonist/antagonist testing","journal":"Journal of neurochemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — cell-type-specific conditional KO, subcellular fractionation linking KIF5B to D2R membrane presentation, epistatic pharmacological dissection","pmids":["30664247"],"is_preprint":false},{"year":2019,"finding":"KIF5B is concentrated in the central spindle during cytokinesis in chondrocytes; KIF5B null chondrocytes fail cytokinesis, leading to incomplete cell rotation, disrupted proliferation and differentiation, and disorganized growth plate.","method":"Conditional knockout in chondrocytes, immunofluorescence of central spindle during cytokinesis, growth plate histology","journal":"Cell & bioscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with clear cytokinesis phenotype and subcellular localization; single lab","pmids":["31636894"],"is_preprint":false},{"year":2020,"finding":"KIF5B and KIF13B jointly transport Rab6-positive secretory vesicles from the Golgi to the cell periphery; KIF5B plays the dominant role while KIF13B helps vesicles reach freshly polymerized microtubule plus ends where KIF5B binds poorly (due to slow MAP7 family protein recruitment). Sub-pixel localization showed both motors localize to the vesicle front during plus-end transport; when vesicles reverse direction, KIF5B shifts to the back while KIF13B moves to the middle, suggesting KIF5B undergoes tug-of-war with a minus-end motor.","method":"siRNA depletion, live-cell imaging with sub-pixel localization, TIRF microscopy, co-localization of dual motors on same vesicle","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — quantitative sub-pixel live imaging, dual-motor depletion, mechanistic dissection of motor positioning; single lab but multiple orthogonal methods","pmids":["33174839"],"is_preprint":false},{"year":2020,"finding":"KIF5B conditional knockout in CaMKIIα-positive neurons causes heightened turnover and lower stability of dendritic spines, reduced PSD95 acquisition, and abolishes the preceding FMRP translocation to the proximity of newly forming spines (both basally and after fear extinction learning).","method":"In vivo two-photon imaging, conditional knockout (CaMKIIα-Cre), spine morphogenesis quantification, FMRP localization tracking","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo two-photon imaging in conditional KO mice with learning-dependent functional readout; multiple orthogonal in vivo measurements","pmids":["38451812"],"is_preprint":false},{"year":2020,"finding":"KIF5B conditional knockout in hippocampal neurons causes deficits in dendritic spine morphogenesis, synaptic plasticity, and memory formation; these functional specificities relative to KIF5A are determined by their divergent carboxyl-termini, where arginine methylation of KIF5B regulates its function.","method":"Conditional knockout mouse, dendritic transport assays, electrophysiology (LTP), behavioral memory tests, domain-swap and arginine methylation experiments","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with multiple orthogonal readouts (morphology, electrophysiology, behavior), PTM mapping, domain-swap experiment","pmids":["31961321"],"is_preprint":false},{"year":2020,"finding":"L-dopa incorporated post-translationally into the C-terminus of α-tubulin reduces KIF5B binding affinity for microtubules; in L-dopa-treated neuronal cells, mitochondrial anterograde transport velocity is reduced, mitochondria spend more time paused, and fewer reach the distal axon segment.","method":"Biochemical binding assay (KIF5B affinity for dopa-tubulin microtubules), live-cell mitochondrial transport imaging in neuronal cell lines and primary hippocampal neurons","journal":"Neurobiology of disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical binding assay plus live-cell transport imaging, single lab","pmids":["33171229"],"is_preprint":false},{"year":2022,"finding":"De novo heterozygous KIF5B variants at conserved amino acids in the ATPase activity-related motifs of the motor domain cause kyphomelic dysplasia in humans, establishing that KIF5B motor domain function is required for normal skeletal development.","method":"Whole-exome sequencing, de novo variant identification in four individuals, structural mapping to catalytic motifs","journal":"Clinical genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — genetic identification of de novo loss-of-function variants at catalytic residues in multiple unrelated individuals; no in vitro biochemical confirmation in abstract","pmids":["35342932"],"is_preprint":false},{"year":2023,"finding":"Dominant-negative KIF5B variants (p.Asn255del, p.Leu498Pro, p.Leu537Pro) disrupt lysosomal, autophagosome, and mitochondrial organization, and impact cilium biogenesis in vitro; all variants affect multiple developmental processes in zebrafish. One previously reported variant also showed these effects.","method":"In vitro cell microscopy (lysosomal/autophagosome/mitochondrial distribution), cilium biogenesis assay, zebrafish developmental analysis","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro and in vivo (zebrafish) analysis of multiple variants with organelle distribution phenotypes; single lab","pmids":["36018820"],"is_preprint":false},{"year":2023,"finding":"Dominant-negative KIF5B variants (modeled in C. elegans unc-116 Thr90Ile by CRISPR) cause defective mitochondria transport in neurons (time-lapse GFP-mitochondria imaging), abnormal body length and motility suppressed by extra wild-type allele; in human cells, the corresponding p.Thr87Ile variant causes dilated ER, intracellular vacuoles, Golgi maldistribution, and down-regulation of mTOR signaling (RNA-seq, proteomics, bone IHC); leucine supplementation partially rescues mTOR pathway in patient cells.","method":"CRISPR/Cas9 modeling in C. elegans, time-lapse GFP-mitochondria imaging, dominant negative suppression genetics, RNA-seq, proteomics, leucine rescue","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — CRISPR model organism with live transport imaging and genetic epistasis, human cell and patient tissue molecular analysis with multiple omics methods, rescue experiment","pmids":["37934770"],"is_preprint":false},{"year":2025,"finding":"KIF5B actively slides existing microtubules to the β-cell periphery in a glucose-stimulated manner, aligning the sub-membrane microtubule array in pancreatic β cells; this microtubule sliding is part of glucose-triggered microtubule remodeling that regulates insulin secretory granule positioning.","method":"Real-time live imaging, photokinetics (FRAP-like approaches), KIF5B manipulation in MIN6 cells and intact mouse islets","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — live imaging with photokinetics demonstrating active microtubule sliding by KIF5B, validated in both cell line and intact islets","pmids":["41182903"],"is_preprint":false},{"year":2025,"finding":"Cohesin-associated protein Pds5A recruits the deubiquitinase USP14 to the spindle apparatus, which stabilizes KIF5B by deubiquitination, regulating meiotic spindle elongation and chromosome segregation in mouse oocytes.","method":"Morpholino depletion, genetic ablation of Pds5A, spindle organization imaging, USP14 interaction assay, KIF5B ubiquitination/stability analysis","journal":"Science advances","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic depletion with spindle phenotype, deubiquitinase–KIF5B pathway mechanistically defined, single lab","pmids":["40215310"],"is_preprint":false}],"current_model":"KIF5B is the heavy chain of kinesin-1, a plus-end-directed microtubule motor that transports a diverse array of cargoes (mitochondria, lysosomes, GLUT4 vesicles, MT1-MMP vesicles, Rab6 secretory vesicles, insulin granules, Nav1.8, Nav1.7, Kv1 channels, Kv1.5, BNIP-2, and microtubules themselves) through direct or adaptor-mediated interactions at its cargo-binding C-terminal stalk/tail domain; its ATPase motor activity is allosterically activated ~30-fold by the RanBP2 kinesin-binding domain in vitro, and its activity is regulated by lipid binding (phosphatidic acid), post-translational arginine methylation, interaction with adaptor proteins (syntabulin, RanBP2/KBD, GABARAP/PRIP, Daxx), and by the state of its microtubule track (e.g., L-dopa–modified tubulin reduces binding); loss of KIF5B causes perinuclear mitochondrial clustering, lysosomal and autophagosomal disorganization, impaired ER-to-Golgi transport, disrupted apical epithelial trafficking, defective dendritic spine plasticity and synaptic transmission, failed meiotic spindle elongation, cytokinesis failure in chondrocytes, reduced dopamine D2 receptor presentation at synapses, and skeletal dysplasia."},"narrative":{"mechanistic_narrative":"KIF5B is the heavy chain of the kinesin-1 plus-end-directed microtubule motor that powers anterograde, long-range positioning of organelles and membrane cargoes throughout the cell, with loss of function producing perinuclear mitochondrial clustering and impaired lysosomal dispersion [PMID:9657148, PMID:17887960]. Its C-terminal stalk/tail region serves as a versatile cargo-binding hub, engaging cargoes directly or through adaptors and light-chain interactions: it transports GLUT4 vesicles in adipocytes [PMID:12743033], apical post-Golgi carriers in polarized epithelia [PMID:17925227], MT1-MMP vesicles supporting matrix degradation and invasion [PMID:20505159, PMID:29033361], Rab6 secretory vesicles to the cell periphery [PMID:33174839], voltage-gated Nav1.8 and Kv1.5 channels to neuronal and cardiac surfaces [PMID:24198377, PMID:19675065], desmin and sarcomeric components to elongating myotube tips [PMID:23293293], BNIP-2 toward endosomes to modulate p38MAPK-driven myogenesis [PMID:25378581], and dopamine D2 receptor to synaptic membranes [PMID:30664247]. Motor output is allosterically controlled: the RanBP2 kinesin-binding domain activates KIF5B ATPase ~30-fold and induces motor unfolding [PMID:19305391, PMID:11553612, PMID:17887960], phosphatidic acid binds the C-terminus to license vesicular association [PMID:29033361], divergent C-terminal arginine methylation tunes neuronal specificity [PMID:31961321], and L-dopa-modified tubulin lowers track affinity [PMID:33171229]. Adaptors including syntabulin, Daxx/kinesin light chain, and the PRIP/GABARAP complex couple the motor to specific cargoes [PMID:19828815, PMID:18932217, PMID:24812354]. Beyond cargo hauling, KIF5B slides microtubules themselves to remodel the sub-membrane array in glucose-stimulated β cells [PMID:41182903] and concentrates at the central spindle to drive cytokinesis and meiotic/mitotic spindle function [PMID:31636894, PMID:23560038, PMID:40215310]. De novo heterozygous variants in the ATPase motifs of the motor domain cause kyphomelic/skeletal dysplasia in humans, with dominant-negative alleles disrupting lysosomal, autophagosomal, mitochondrial, and ciliary organization and downregulating mTOR signaling [PMID:35342932, PMID:36018820, PMID:37934770].","teleology":[{"year":1998,"claim":"Established that KIF5B is required in vivo for organelle positioning, defining its core cellular function as anterograde dispersion of mitochondria and lysosomes.","evidence":"Homologous-recombination knockout mice, subcellular fractionation, and rescue by exogenous expression","pmids":["9657148"],"confidence":"High","gaps":["Did not identify the adaptors linking KIF5B to mitochondria or lysosomes","Did not address cargo selectivity among KIF5 paralogs"]},{"year":2001,"claim":"Identified RanBP2 as a direct binding partner with isoform selectivity for KIF5B/KIF5C, introducing a defined regulatory interaction at the motor.","evidence":"Yeast two-hybrid, in vitro binding, co-IP, and domain mapping","pmids":["11553612"],"confidence":"High","gaps":["Functional consequence of the RanBP2 interaction not yet established","Did not determine effect on motor activity"]},{"year":2003,"claim":"Demonstrated KIF5B drives a hormone-stimulated trafficking event, transporting GLUT4 vesicles for insulin-responsive glucose uptake.","evidence":"Live-cell imaging with dominant-negative kinesin light chain and wortmannin in adipocytes","pmids":["12743033"],"confidence":"High","gaps":["Direct cargo receptor for GLUT4 vesicles not defined here","Regulation linking insulin signaling to motor engagement unresolved"]},{"year":2007,"claim":"Mapped the molecular basis of KIF5B isoform-selective regulation and showed disrupting the RanBP2-KIF5B interaction phenocopies organelle mislocalization, linking the partner to function.","evidence":"Domain mutagenesis defining a single specificity residue plus cell-based KBD inhibition with mitochondrial readouts","pmids":["17887960"],"confidence":"High","gaps":["Did not quantify effect on intrinsic motor ATPase","In vivo relevance of selectivity residue untested"]},{"year":2007,"claim":"Extended KIF5B cargo range to ion channels and endocytic vesicle dynamics, establishing roles in neuronal channel targeting and bidirectional vesicle fission alongside an opposing motor.","evidence":"Co-IP from brain lysate, dominant-negative expression, and in vitro motility/antibody-inhibition assays","pmids":["17241275","17360972"],"confidence":"Medium","gaps":["Direct Kv1-KIF5B binding interface not mapped","Coordination mechanism between KIF5B and KIFC1 on shared vesicles unresolved"]},{"year":2008,"claim":"Placed KIF5B in early secretory trafficking, showing it positions ER exit sites and supports ER-to-Golgi transport.","evidence":"siRNA knockdown with quantitative ERES localization and trafficking assays","pmids":["18817524"],"confidence":"Medium","gaps":["Cargo adaptor for ERES positioning not identified","Single-lab knockdown without rescue"]},{"year":2009,"claim":"Provided the first reconstituted demonstration of a native allosteric activator, showing RanBP2 activates KIF5B ATPase ~30-fold and unfolds the motor.","evidence":"In vitro ATPase assay with purified components and systematic domain deletion","pmids":["19305391"],"confidence":"High","gaps":["Physiological contexts where RanBP2 activates KIF5B in cells not fully defined","Structural basis of cooperative activation unresolved"]},{"year":2009,"claim":"Identified syntabulin and Daxx as cargo adaptors and extended channel transport to Kv1.5, establishing adaptor-mediated coupling of KIF5B to presynaptic, mitochondrial, GLUT4, and channel cargoes.","evidence":"RNAi, dominant-negative interference, co-IP, electrophysiology, and ATP rescue across neuronal and cardiac systems","pmids":["19828815","18932217","19675065"],"confidence":"High","gaps":["Selectivity rules governing which adaptor engages which cargo unclear","Daxx scaffold interaction rests on co-IP/two-hybrid in a single lab"]},{"year":2010,"claim":"Linked KIF5B-driven trafficking to extracellular matrix remodeling by delivering MT1-MMP to the macrophage surface for ECM degradation.","evidence":"siRNA knockdown with surface-exposure, CD44 shedding, and ECM degradation assays plus live tracking in primary macrophages","pmids":["20505159"],"confidence":"High","gaps":["Adaptor coupling KIF5B to MT1-MMP vesicles not yet identified","Coordination with KIF3A/KIF3B mechanism unresolved"]},{"year":2013,"claim":"Mapped direct cargo-binding interfaces (Nav1.8, desmin, BNIP-2) and defined dual roles in cell division, advancing KIF5B from a generic motor to one with cargo-specific tail contacts and spindle functions.","evidence":"Co-IP with domain mutants, far-Western, conditional knockout with rescue, patch-clamp, and RNAi in oocytes/mitotic cells","pmids":["24198377","23293293","23402760","25378581","23560038"],"confidence":"High","gaps":["How motor versus tail binding to BNIP-2 is coordinated unclear","Mechanism of central-spindle/meiotic function distinct from cargo transport not resolved"]},{"year":2014,"claim":"Revealed lipid- and Ca2+-dependent control of KIF5B membrane association and connected its mitochondrial binding to mitophagy and metabolic inflammation.","evidence":"Liposome pull-down with C-terminal mapping, overexpression/knockdown, Ca2+ inhibitors, and mitophagy/inflammasome assays","pmids":["29033361","25462067","24812354"],"confidence":"Medium","gaps":["Molecular mechanism of KIF5B-mitochondria dissociation not directly characterized","PA-binding region structure not defined"]},{"year":2016,"claim":"Implicated KIF5B in viral pathogenesis by showing it relocalizes Nup358 to enable capsid-dependent HIV-1 nuclear entry.","evidence":"siRNA knockdown with capsid-mutant epistasis and Nup358 relocalization imaging","pmids":["27327622"],"confidence":"High","gaps":["Direct KIF5B-Nup358 binding not demonstrated","How motor activity triggers Nup358 release unresolved"]},{"year":2018,"claim":"Connected KIF5B to clathrin-mediated endocytosis, showing it binds clathrin heavy chain and promotes uncoating of large clathrin-coated vesicles required for virus entry.","evidence":"Co-IP, in vitro uncoating assay using kif5b cKO cortex, dominant-negative fragment, and VSV entry assay","pmids":["30603101","30246279"],"confidence":"High","gaps":["How a plus-end motor mechanically promotes uncoating unresolved","Mx1-KIF5B interaction is a single co-IP that cannot exclude indirect binding"]},{"year":2019,"claim":"Defined the in vivo cytokinetic requirement in chondrocytes and the synaptic D2-receptor presentation function, tying KIF5B loss to skeletal and locomotor phenotypes.","evidence":"Cell-type-specific conditional knockouts, central-spindle imaging, subcellular fractionation, and pharmacological dissection","pmids":["31636894","30664247"],"confidence":"High","gaps":["Why dopaminergic-specific deletion is insufficient for locomotor defects unexplained","Cargo adaptor for D2 receptor not identified"]},{"year":2020,"claim":"Dissected motor coordination on single vesicles and established neuron-specific functions controlled by the divergent C-terminus and its arginine methylation.","evidence":"Sub-pixel live imaging with dual-motor depletion, conditional knockout with two-photon imaging, electrophysiology, behavior, domain-swap, and PTM mapping","pmids":["33174839","38451812","31961321","33171229"],"confidence":"High","gaps":["Enzyme catalyzing KIF5B arginine methylation not identified","Mechanism by which FMRP translocation depends on KIF5B unresolved"]},{"year":2022,"claim":"Established human genetic causation, linking de novo motor-domain ATPase variants to kyphomelic skeletal dysplasia.","evidence":"Whole-exome sequencing in four individuals with structural mapping to catalytic motifs","pmids":["35342932"],"confidence":"Medium","gaps":["No in vitro biochemical confirmation of variant effect on ATPase","Tissue-specific basis of skeletal phenotype unexplained"]},{"year":2023,"claim":"Showed disease variants act dominant-negatively across organelle systems and converge on mTOR downregulation, with leucine partially rescuing patient cells.","evidence":"In vitro organelle/cilium assays, zebrafish development, CRISPR C. elegans modeling with genetic epistasis, RNA-seq/proteomics, and leucine rescue","pmids":["36018820","37934770"],"confidence":"High","gaps":["Mechanistic link between KIF5B transport defects and mTOR signaling not fully defined","Whether mTOR effect is secondary to general trafficking failure unresolved"]},{"year":2025,"claim":"Revealed a transport-independent activity—active microtubule sliding to remodel the β-cell array—and a deubiquitination pathway stabilizing KIF5B during meiotic spindle elongation.","evidence":"Live imaging with photokinetics in MIN6 cells and islets, plus Pds5A/USP14 depletion with spindle imaging and KIF5B stability analysis","pmids":["41182903","40215310"],"confidence":"High","gaps":["How glucose triggers KIF5B-mediated sliding mechanistically unresolved","USP14-KIF5B regulation shown in a single oocyte study"]},{"year":null,"claim":"It remains unresolved how KIF5B integrates its many cargo adaptors, lipid and PTM inputs, and track modifications into selective, context-dependent transport, and how motor-domain dysfunction mechanistically produces tissue-specific skeletal and metabolic disease.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model of cargo-selection hierarchy","Structural basis of allosteric activation in cells undefined","Causal chain from trafficking defect to mTOR/skeletal phenotype incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,2,27,34]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[9,14,31]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[27,30,34]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[22]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[10,12,20]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[27,30,34]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,4,19]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[7,23,27]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[26,16,35]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2,5,13,27]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,8,11,14]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[26,16,35]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[19,32]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[31,32,33]}],"complexes":["kinesin-1"],"partners":["RANBP2","KLC","SYNTABULIN","DAXX","GABARAP","BNIP-2","DESMIN","CLATHRIN HEAVY CHAIN"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P33176","full_name":"Kinesin-1 heavy chain","aliases":["Conventional kinesin heavy chain","Ubiquitous kinesin heavy chain","UKHC"],"length_aa":963,"mass_kda":109.7,"function":"Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner (By similarity). Regulates centrosome and nuclear positioning during mitotic entry. During the G2 phase of the cell cycle in a BICD2-dependent manner, antagonizes dynein function and drives the separation of nuclei and centrosomes (PubMed:20386726). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). Through binding with PLEKHM2 and ARL8B, directs lysosome movement toward microtubule plus ends (Probable). Involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571)","subcellular_location":"Cytoplasm, cytoskeleton; Cytolytic granule membrane; Lysosome membrane","url":"https://www.uniprot.org/uniprotkb/P33176/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KIF5B","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000170759","cell_line_id":"CID001426","localizations":[{"compartment":"centrosome","grade":3},{"compartment":"cytoplasmic","grade":3}],"interactors":[{"gene":"KLC2","stoichiometry":10.0},{"gene":"KLC4","stoichiometry":10.0},{"gene":"KLC1","stoichiometry":10.0},{"gene":"YWHAB","stoichiometry":4.0},{"gene":"YWHAG","stoichiometry":4.0},{"gene":"KIF5A","stoichiometry":0.2},{"gene":"NAA40","stoichiometry":0.2},{"gene":"KLC3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001426","total_profiled":1310},"omim":[{"mim_id":"621363","title":"MAP7 DOMAIN-CONTAINING PROTEIN 1; MAP7D1","url":"https://www.omim.org/entry/621363"},{"mim_id":"615562","title":"SPERM-ASSOCIATED ANTIGEN 5; SPAG5","url":"https://www.omim.org/entry/615562"},{"mim_id":"615535","title":"SPECTRIN REPEAT-CONTAINING NUCLEAR ENVELOPE PROTEIN 4; SYNE4","url":"https://www.omim.org/entry/615535"},{"mim_id":"614570","title":"KINESIN FAMILY MEMBER 18B; KIF18B","url":"https://www.omim.org/entry/614570"},{"mim_id":"611729","title":"KINESIN LIGHT CHAIN 2; KLC2","url":"https://www.omim.org/entry/611729"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centriolar satellite","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"},{"location":"End piece","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/KIF5B"},"hgnc":{"alias_symbol":["KNS","uKHC"],"prev_symbol":["KNS1"]},"alphafold":{"accession":"P33176","domains":[{"cath_id":"3.40.850.10","chopping":"5-269_295-334","consensus_level":"medium","plddt":90.2174,"start":5,"end":334},{"cath_id":"-","chopping":"337-392","consensus_level":"high","plddt":80.9484,"start":337,"end":392},{"cath_id":"1.20.5","chopping":"424-502","consensus_level":"medium","plddt":87.1813,"start":424,"end":502}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P33176","model_url":"https://alphafold.ebi.ac.uk/files/AF-P33176-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P33176-F1-predicted_aligned_error_v6.png","plddt_mean":78.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIF5B","jax_strain_url":"https://www.jax.org/strain/search?query=KIF5B"},"sequence":{"accession":"P33176","fasta_url":"https://rest.uniprot.org/uniprotkb/P33176.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P33176/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P33176"}},"corpus_meta":[{"pmid":"22327624","id":"PMC_22327624","title":"KIF5B-RET fusions in lung adenocarcinoma.","date":"2012","source":"Nature medicine","url":"https://pubmed.ncbi.nlm.nih.gov/22327624","citation_count":673,"is_preprint":false},{"pmid":"19383809","id":"PMC_19383809","title":"KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer.","date":"2009","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/19383809","citation_count":580,"is_preprint":false},{"pmid":"9657148","id":"PMC_9657148","title":"Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria.","date":"1998","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/9657148","citation_count":534,"is_preprint":false},{"pmid":"22194472","id":"PMC_22194472","title":"A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing.","date":"2011","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/22194472","citation_count":376,"is_preprint":false},{"pmid":"23052255","id":"PMC_23052255","title":"Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions.","date":"2012","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/23052255","citation_count":147,"is_preprint":false},{"pmid":"12743033","id":"PMC_12743033","title":"Conventional kinesin KIF5B mediates insulin-stimulated GLUT4 movements on microtubules.","date":"2003","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/12743033","citation_count":135,"is_preprint":false},{"pmid":"20505159","id":"PMC_20505159","title":"KIF5B and KIF3A/KIF3B kinesins drive MT1-MMP surface exposure, CD44 shedding, and extracellular matrix degradation in primary macrophages.","date":"2010","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/20505159","citation_count":116,"is_preprint":false},{"pmid":"30573850","id":"PMC_30573850","title":"ALK-positive histiocytosis: an expanded clinicopathologic spectrum and frequent presence of KIF5B-ALK fusion.","date":"2018","source":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/30573850","citation_count":112,"is_preprint":false},{"pmid":"17887960","id":"PMC_17887960","title":"Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function.","date":"2007","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/17887960","citation_count":107,"is_preprint":false},{"pmid":"27327622","id":"PMC_27327622","title":"KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection.","date":"2016","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/27327622","citation_count":98,"is_preprint":false},{"pmid":"17925227","id":"PMC_17925227","title":"Polarization-dependent selective transport to the apical membrane by KIF5B in MDCK cells.","date":"2007","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/17925227","citation_count":96,"is_preprint":false},{"pmid":"16498388","id":"PMC_16498388","title":"Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia.","date":"2006","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/16498388","citation_count":88,"is_preprint":false},{"pmid":"11553612","id":"PMC_11553612","title":"The docking of kinesins, KIF5B and KIF5C, to Ran-binding protein 2 (RanBP2) is mediated via a novel RanBP2 domain.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11553612","citation_count":87,"is_preprint":false},{"pmid":"32467651","id":"PMC_32467651","title":"ALK rearranged renal cell carcinoma (ALK-RCC): a multi-institutional study of twelve cases with identification of novel partner genes CLIP1, KIF5B and KIAA1217.","date":"2020","source":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/32467651","citation_count":85,"is_preprint":false},{"pmid":"19828815","id":"PMC_19828815","title":"KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons.","date":"2009","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/19828815","citation_count":85,"is_preprint":false},{"pmid":"21656749","id":"PMC_21656749","title":"A novel KIF5B-ALK variant in nonsmall cell lung cancer.","date":"2011","source":"Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/21656749","citation_count":74,"is_preprint":false},{"pmid":"25462067","id":"PMC_25462067","title":"Defective mitophagy driven by dysregulation of rheb and KIF5B contributes to mitochondrial reactive oxygen species (ROS)-induced nod-like receptor 3 (NLRP3) dependent proinflammatory response and aggravates lipotoxicity.","date":"2014","source":"Redox biology","url":"https://pubmed.ncbi.nlm.nih.gov/25462067","citation_count":74,"is_preprint":false},{"pmid":"33174839","id":"PMC_33174839","title":"Concerted action of kinesins KIF5B and KIF13B promotes efficient secretory vesicle transport to microtubule plus ends.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/33174839","citation_count":73,"is_preprint":false},{"pmid":"27496134","id":"PMC_27496134","title":"Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma.","date":"2016","source":"Molecular cancer therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/27496134","citation_count":66,"is_preprint":false},{"pmid":"18801114","id":"PMC_18801114","title":"KNS-760704 [(6R)-4,5,6,7-tetrahydro-N6-propyl-2, 6-benzothiazole-diamine dihydrochloride monohydrate] for the treatment of amyotrophic lateral sclerosis.","date":"2008","source":"CNS neuroscience & therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/18801114","citation_count":63,"is_preprint":false},{"pmid":"25982012","id":"PMC_25982012","title":"Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with brain metastases.","date":"2015","source":"Lung cancer (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/25982012","citation_count":59,"is_preprint":false},{"pmid":"17360972","id":"PMC_17360972","title":"Kif5B and Kifc1 interact and are required for motility and fission of early endocytic vesicles in mouse liver.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/17360972","citation_count":58,"is_preprint":false},{"pmid":"31961321","id":"PMC_31961321","title":"Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/31961321","citation_count":56,"is_preprint":false},{"pmid":"23378251","id":"PMC_23378251","title":"KIF5B-RET fusions in Chinese patients with non-small cell lung cancer.","date":"2013","source":"Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/23378251","citation_count":53,"is_preprint":false},{"pmid":"29033361","id":"PMC_29033361","title":"Binding of PLD2-Generated Phosphatidic Acid to KIF5B Promotes MT1-MMP Surface Trafficking and Lung Metastasis of Mouse Breast Cancer Cells.","date":"2017","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/29033361","citation_count":52,"is_preprint":false},{"pmid":"25047660","id":"PMC_25047660","title":"KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer.","date":"2014","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/25047660","citation_count":51,"is_preprint":false},{"pmid":"27494860","id":"PMC_27494860","title":"Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway.","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/27494860","citation_count":51,"is_preprint":false},{"pmid":"19305391","id":"PMC_19305391","title":"RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system.","date":"2009","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/19305391","citation_count":51,"is_preprint":false},{"pmid":"23293293","id":"PMC_23293293","title":"Kif5b controls the localization of myofibril components for their assembly and linkage to the myotendinous junctions.","date":"2013","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/23293293","citation_count":49,"is_preprint":false},{"pmid":"28877471","id":"PMC_28877471","title":"KIF5B-RET Oncoprotein Signals through a Multi-kinase Signaling Hub.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/28877471","citation_count":48,"is_preprint":false},{"pmid":"30779215","id":"PMC_30779215","title":"Macrophage ERα promoted invasion of endometrial cancer cell by mTOR/KIF5B-mediated epithelial to mesenchymal transition.","date":"2019","source":"Immunology and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/30779215","citation_count":48,"is_preprint":false},{"pmid":"22797671","id":"PMC_22797671","title":"KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung.","date":"2012","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/22797671","citation_count":47,"is_preprint":false},{"pmid":"18817524","id":"PMC_18817524","title":"Kinesin-1 (uKHC/KIF5B) is required for bidirectional motility of ER exit sites and efficient ER-to-Golgi transport.","date":"2008","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/18817524","citation_count":47,"is_preprint":false},{"pmid":"24198377","id":"PMC_24198377","title":"KIF5B promotes the forward transport and axonal function of the voltage-gated sodium channel Nav1.8.","date":"2013","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/24198377","citation_count":47,"is_preprint":false},{"pmid":"17241275","id":"PMC_17241275","title":"The role of Kif5B in axonal localization of Kv1 K(+) channels.","date":"2007","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/17241275","citation_count":43,"is_preprint":false},{"pmid":"25064355","id":"PMC_25064355","title":"A mouse model of KIF5B-RET fusion-dependent lung tumorigenesis.","date":"2014","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/25064355","citation_count":41,"is_preprint":false},{"pmid":"15184079","id":"PMC_15184079","title":"The ribosome receptor, p180, interacts with kinesin heavy chain, KIF5B.","date":"2004","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15184079","citation_count":41,"is_preprint":false},{"pmid":"23776493","id":"PMC_23776493","title":"Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23776493","citation_count":40,"is_preprint":false},{"pmid":"23932363","id":"PMC_23932363","title":"Diagnostic method for the detection of KIF5B-RET transformation in lung adenocarcinoma.","date":"2013","source":"Lung cancer (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/23932363","citation_count":40,"is_preprint":false},{"pmid":"25625428","id":"PMC_25625428","title":"Progress in Discovery of KIF5B-RET Kinase Inhibitors for the Treatment of Non-Small-Cell Lung Cancer.","date":"2015","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25625428","citation_count":39,"is_preprint":false},{"pmid":"1910150","id":"PMC_1910150","title":"The KNS1 gene of Saccharomyces cerevisiae encodes a nonessential protein kinase homologue that is distantly related to members of the CDC28/cdc2 gene family.","date":"1991","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/1910150","citation_count":33,"is_preprint":false},{"pmid":"31204277","id":"PMC_31204277","title":"A role for kinesin-1 subunits KIF5B/KLC1 in regulating epithelial mesenchymal plasticity in breast tumorigenesis.","date":"2019","source":"EBioMedicine","url":"https://pubmed.ncbi.nlm.nih.gov/31204277","citation_count":33,"is_preprint":false},{"pmid":"23342255","id":"PMC_23342255","title":"RET expression and detection of KIF5B/RET gene rearrangements in Japanese lung cancer.","date":"2012","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23342255","citation_count":32,"is_preprint":false},{"pmid":"30015159","id":"PMC_30015159","title":"Oncogenic Function of a KIF5B-MET Fusion Variant in Non-Small Cell Lung Cancer.","date":"2018","source":"Neoplasia (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/30015159","citation_count":32,"is_preprint":false},{"pmid":"25631054","id":"PMC_25631054","title":"Differential phosphorylation of a regulatory subunit of protein kinase CK2 by target of rapamycin complex 1 signaling and the Cdc-like kinase Kns1.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25631054","citation_count":29,"is_preprint":false},{"pmid":"25064602","id":"PMC_25064602","title":"Diabetes induces changes in KIF1A, KIF5B and dynein distribution in the rat retina: implications for axonal transport.","date":"2014","source":"Experimental eye research","url":"https://pubmed.ncbi.nlm.nih.gov/25064602","citation_count":29,"is_preprint":false},{"pmid":"19675065","id":"PMC_19675065","title":"Kif5b is an essential forward trafficking motor for the Kv1.5 cardiac potassium channel.","date":"2009","source":"The Journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/19675065","citation_count":25,"is_preprint":false},{"pmid":"36002889","id":"PMC_36002889","title":"Identification of novel early pancreatic cancer biomarkers KIF5B and SFRP2 from \"first contact\" interactions in the tumor microenvironment.","date":"2022","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/36002889","citation_count":24,"is_preprint":false},{"pmid":"31320041","id":"PMC_31320041","title":"Low Molecular Weight Chitosan (∼20 kDa) protects acrylamide induced oxidative stress in D. melanogaster by restoring dopamine and KIF5B levels.","date":"2019","source":"Carbohydrate polymers","url":"https://pubmed.ncbi.nlm.nih.gov/31320041","citation_count":20,"is_preprint":false},{"pmid":"18984674","id":"PMC_18984674","title":"KIF5B gene sequence variation and response of cardiac stroke volume to regular exercise.","date":"2008","source":"Physiological genomics","url":"https://pubmed.ncbi.nlm.nih.gov/18984674","citation_count":19,"is_preprint":false},{"pmid":"24812354","id":"PMC_24812354","title":"Phospholipase C-related catalytically inactive protein (PRIP) controls KIF5B-mediated insulin secretion.","date":"2014","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/24812354","citation_count":19,"is_preprint":false},{"pmid":"27094714","id":"PMC_27094714","title":"Hypertrophy induced KIF5B controls mitochondrial localization and function in neonatal rat cardiomyocytes.","date":"2016","source":"Journal of molecular and cellular cardiology","url":"https://pubmed.ncbi.nlm.nih.gov/27094714","citation_count":18,"is_preprint":false},{"pmid":"30664247","id":"PMC_30664247","title":"Neuronal KIF5b deletion induces striatum-dependent locomotor impairments and defects in membrane presentation of dopamine D2 receptors.","date":"2019","source":"Journal of neurochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30664247","citation_count":18,"is_preprint":false},{"pmid":"7358770","id":"PMC_7358770","title":"An epithelial cell line (KNS-62) derived from a brain metastasis of bronchial squamous cell carcinoma.","date":"1980","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/7358770","citation_count":17,"is_preprint":false},{"pmid":"18932217","id":"PMC_18932217","title":"Daxx functions as a scaffold of a protein assembly constituted by GLUT4, JNK1 and KIF5B.","date":"2009","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/18932217","citation_count":17,"is_preprint":false},{"pmid":"30591488","id":"PMC_30591488","title":"Use of ALK Immunohistochemistry for Optimal Therapeutic Strategy of Pulmonary Large-cell Neuroendocrine Carcinoma and Identification of a Novel KIF5B-ALK Fusion Oncokinase.","date":"2019","source":"Anticancer research","url":"https://pubmed.ncbi.nlm.nih.gov/30591488","citation_count":17,"is_preprint":false},{"pmid":"28242773","id":"PMC_28242773","title":"Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.","date":"2017","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/28242773","citation_count":17,"is_preprint":false},{"pmid":"31636894","id":"PMC_31636894","title":"KIF5B modulates central spindle organization in late-stage cytokinesis in chondrocytes.","date":"2019","source":"Cell & bioscience","url":"https://pubmed.ncbi.nlm.nih.gov/31636894","citation_count":17,"is_preprint":false},{"pmid":"25378581","id":"PMC_25378581","title":"KIF5B transports BNIP-2 to regulate p38 mitogen-activated protein kinase activation and myoblast differentiation.","date":"2014","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/25378581","citation_count":16,"is_preprint":false},{"pmid":"23560038","id":"PMC_23560038","title":"Kinesin 5B (KIF5B) is required for progression through female meiosis and proper chromosomal segregation in mitotic cells.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23560038","citation_count":15,"is_preprint":false},{"pmid":"31351348","id":"PMC_31351348","title":"Atypical juvenile histiocytosis with novel KIF5B-ALK gene fusion mimicking subglottic hemangioma.","date":"2019","source":"International journal of pediatric otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/31351348","citation_count":15,"is_preprint":false},{"pmid":"32903808","id":"PMC_32903808","title":"KIF5B-EGFR Fusion: A Novel EGFR Mutation in Lung Adenocarcinoma.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32903808","citation_count":14,"is_preprint":false},{"pmid":"25644797","id":"PMC_25644797","title":"Treadmill training modifies KIF5B motor protein in the STZ-induced diabetic rat spinal cord and sciatic nerve.","date":"2015","source":"Archives of Iranian medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25644797","citation_count":13,"is_preprint":false},{"pmid":"36018820","id":"PMC_36018820","title":"Dominantly acting KIF5B variants with pleiotropic cellular consequences cause variable clinical phenotypes.","date":"2023","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36018820","citation_count":12,"is_preprint":false},{"pmid":"33791222","id":"PMC_33791222","title":"Micro1278 Leads to Tumor Growth Arrest, Enhanced Sensitivity to Oxaliplatin and Vitamin D and Inhibits Metastasis via KIF5B, CYP24A1, and BTG2, Respectively.","date":"2021","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/33791222","citation_count":12,"is_preprint":false},{"pmid":"26268359","id":"PMC_26268359","title":"KIF5B-RET Fusion gene may coincide oncogenic mutations of EGFR or KRAS gene in lung adenocarcinomas.","date":"2015","source":"Diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26268359","citation_count":11,"is_preprint":false},{"pmid":"35342932","id":"PMC_35342932","title":"De novo heterozygous variants in KIF5B cause kyphomelic dysplasia.","date":"2022","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35342932","citation_count":11,"is_preprint":false},{"pmid":"33561610","id":"PMC_33561610","title":"Quantitative Proteomics Reveals Association of Neuron Projection Development Genes ARF4, KIF5B, and RAB8A With Hirschsprung Disease.","date":"2020","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/33561610","citation_count":11,"is_preprint":false},{"pmid":"37934770","id":"PMC_37934770","title":"Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.","date":"2023","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37934770","citation_count":10,"is_preprint":false},{"pmid":"33171229","id":"PMC_33171229","title":"Irreversible incorporation of L-dopa into the C-terminus of α-tubulin inhibits binding of molecular motor KIF5B to microtubules and alters mitochondrial traffic along the axon.","date":"2020","source":"Neurobiology of disease","url":"https://pubmed.ncbi.nlm.nih.gov/33171229","citation_count":10,"is_preprint":false},{"pmid":"23891510","id":"PMC_23891510","title":"KIF5B/RET fusion gene analysis in a selected series of cytological specimens of EGFR, KRAS and EML4-ALK wild-type adenocarcinomas of the lung.","date":"2013","source":"Lung cancer (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/23891510","citation_count":9,"is_preprint":false},{"pmid":"35434049","id":"PMC_35434049","title":"Effective response to crizotinib of concurrent KIF5B-MET and MET-CDR2-rearranged non-small cell lung cancer: A case report.","date":"2022","source":"World journal of clinical cases","url":"https://pubmed.ncbi.nlm.nih.gov/35434049","citation_count":9,"is_preprint":false},{"pmid":"35982724","id":"PMC_35982724","title":"Central nervous system involvement of systemic ALK-positive histiocytosis with KIF5B-ALK fusion.","date":"2022","source":"Radiology case reports","url":"https://pubmed.ncbi.nlm.nih.gov/35982724","citation_count":9,"is_preprint":false},{"pmid":"36471407","id":"PMC_36471407","title":"Partial response to pralsetinib in an advanced pulmonary sarcomatoid carcinoma patient harboring a KIF5B-RET rearrangement: a case report.","date":"2022","source":"World journal of surgical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36471407","citation_count":9,"is_preprint":false},{"pmid":"25885434","id":"PMC_25885434","title":"Analysis of Kif5b expression during mouse kidney development.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25885434","citation_count":8,"is_preprint":false},{"pmid":"35359354","id":"PMC_35359354","title":"Case Report: ALK-Positive Histiocytosis With KIF5B-ALK Fusion in Cerebrum-Disseminated Lesions in a Child.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35359354","citation_count":8,"is_preprint":false},{"pmid":"38451812","id":"PMC_38451812","title":"KIF5B plays important roles in dendritic spine plasticity and dendritic localization of PSD95 and FMRP in the mouse cortex in vivo.","date":"2024","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/38451812","citation_count":8,"is_preprint":false},{"pmid":"30246279","id":"PMC_30246279","title":"The large GTPase Mx1 binds Kif5B for cargo transport along microtubules.","date":"2018","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/30246279","citation_count":8,"is_preprint":false},{"pmid":"34163176","id":"PMC_34163176","title":"A Novel KIF5B-EGFR Fusion Variant in Non-Small-Cell Lung Cancer and Response to Afatinib: A Case Report.","date":"2021","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/34163176","citation_count":8,"is_preprint":false},{"pmid":"26377589","id":"PMC_26377589","title":"Cabozantinib for the treatment of non-small cell lung cancer with KIF5B-RET fusion. An example of swift repositioning.","date":"2015","source":"Archives of pharmacal research","url":"https://pubmed.ncbi.nlm.nih.gov/26377589","citation_count":7,"is_preprint":false},{"pmid":"33816604","id":"PMC_33816604","title":"A new KIF5B-ERBB4 gene fusion in a lung adenocarcinoma patient.","date":"2021","source":"ERJ open research","url":"https://pubmed.ncbi.nlm.nih.gov/33816604","citation_count":7,"is_preprint":false},{"pmid":"33832282","id":"PMC_33832282","title":"A rare KIF5B-ALK fusion variant in a lung adenocarcinoma patient who responded to crizotinib and acquired the ALK L1196M mutation after resistance: a case report.","date":"2021","source":"Annals of palliative medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33832282","citation_count":6,"is_preprint":false},{"pmid":"30603101","id":"PMC_30603101","title":"A new role of anterograde motor Kif5b in facilitating large clathrin-coated vesicle mediated endocytosis via regulating clathrin uncoating.","date":"2018","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/30603101","citation_count":6,"is_preprint":false},{"pmid":"23402760","id":"PMC_23402760","title":"Dissect Kif5b in nuclear positioning during myogenesis: the light chain binding domain and the autoinhibitory peptide are both indispensable.","date":"2013","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/23402760","citation_count":6,"is_preprint":false},{"pmid":"36895965","id":"PMC_36895965","title":"FOXA2 and STAT5A regulate oncogenic activity of KIF5B-RET fusion.","date":"2023","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/36895965","citation_count":5,"is_preprint":false},{"pmid":"41182903","id":"PMC_41182903","title":"Glucose-stimulated KIF5B-driven microtubule sliding organizes microtubule networks in mouse pancreatic β cells.","date":"2025","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/41182903","citation_count":5,"is_preprint":false},{"pmid":"38499154","id":"PMC_38499154","title":"KIF5B-mediated internalization of FMDV promotes virus infection.","date":"2024","source":"Virologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/38499154","citation_count":4,"is_preprint":false},{"pmid":"36773735","id":"PMC_36773735","title":"Correlative increasing expressions of KIF5b and Nav1.7 in DRG neurons of rats under neuropathic pain conditions.","date":"2023","source":"Physiology & behavior","url":"https://pubmed.ncbi.nlm.nih.gov/36773735","citation_count":4,"is_preprint":false},{"pmid":"33200553","id":"PMC_33200553","title":"Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk.","date":"2020","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33200553","citation_count":4,"is_preprint":false},{"pmid":"30978476","id":"PMC_30978476","title":"High intensity interval training decreases the expressions of KIF5B and Dynein in Hippocampus of Wistar male rats.","date":"2019","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/30978476","citation_count":4,"is_preprint":false},{"pmid":"40215310","id":"PMC_40215310","title":"The cohesin-associated protein Pds5A governs the meiotic spindle assembly via deubiquitination of Kif5B in oocytes.","date":"2025","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/40215310","citation_count":3,"is_preprint":false},{"pmid":"38948025","id":"PMC_38948025","title":"LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis.","date":"2024","source":"Oncology research","url":"https://pubmed.ncbi.nlm.nih.gov/38948025","citation_count":3,"is_preprint":false},{"pmid":"34002144","id":"PMC_34002144","title":"Novel intergenic KIF5B-MET fusion variant in a patient with gastric cancer: A case report.","date":"2021","source":"World journal of clinical cases","url":"https://pubmed.ncbi.nlm.nih.gov/34002144","citation_count":3,"is_preprint":false},{"pmid":"35242632","id":"PMC_35242632","title":"Use of on-therapy ctDNA monitoring in a patient with KIF5B-RET fusion positive advanced non-small cell lung cancer: a case report.","date":"2022","source":"Translational lung cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/35242632","citation_count":3,"is_preprint":false},{"pmid":"36033470","id":"PMC_36033470","title":"Case report: Salvage capmatinib therapy in KIF5B-MET fusion-positive lung adenocarcinoma with resistance to telisotuzumab vedotin.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36033470","citation_count":3,"is_preprint":false},{"pmid":"26002460","id":"PMC_26002460","title":"Stable knockdown of Kif5b in MDCK cells leads to epithelial-mesenchymal transition.","date":"2015","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/26002460","citation_count":2,"is_preprint":false},{"pmid":"27264953","id":"PMC_27264953","title":"Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes.","date":"2016","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/27264953","citation_count":2,"is_preprint":false},{"pmid":"38690167","id":"PMC_38690167","title":"Case report: Acquired resistance to crizotinib from a MET Y1230H mutation in a patient with non-small cell lung cancer and KIF5B-MET fusion.","date":"2024","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38690167","citation_count":2,"is_preprint":false},{"pmid":"17925219","id":"PMC_17925219","title":"Catch the KIF5B train to the apical surface.","date":"2007","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/17925219","citation_count":2,"is_preprint":false},{"pmid":"39590120","id":"PMC_39590120","title":"A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma.","date":"2024","source":"Current oncology (Toronto, Ont.)","url":"https://pubmed.ncbi.nlm.nih.gov/39590120","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":49971,"output_tokens":8892,"usd":0.141647,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":18898,"output_tokens":5739,"usd":0.118983,"stage2_stop_reason":"end_turn"},"total_usd":0.26063,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"KIF5B (kinesin heavy chain) is essential for mitochondrial and lysosomal dispersion in extraembryonic cells; kif5B-/- knockout mice show perinuclear clustering of mitochondria and impaired lysosomal dispersion, and this phenotype is reversed by exogenous KIF5B expression. Subcellular fractionation confirmed KIF5B associates with mitochondria.\",\n      \"method\": \"Homologous recombination knockout mouse, subcellular fractionation, rescue by exogenous expression\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined phenotype, rescue experiment, subcellular fractionation; independently foundational study with multiple orthogonal methods\",\n      \"pmids\": [\"9657148\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"RanBP2 contains a novel kinesin-binding domain (KBD) located between RBD2 and RBD3 that directly associates with KIF5B and KIF5C (but not KIF5A) both in vitro and in vivo; kinesin light chain and RanGTPase are also part of this macroassembly complex.\",\n      \"method\": \"Yeast two-hybrid, in vitro binding, co-immunoprecipitation, functional domain mapping\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct in vitro binding plus in vivo co-IP, multiple orthogonal methods in single study\",\n      \"pmids\": [\"11553612\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"KIF5B mediates insulin-stimulated long-range movement of GLUT4-containing vesicles on microtubules in adipocytes through a PI3-kinase-independent mechanism; dominant-negative kinesin light chain mutants blocked outward GLUT4 vesicle movement and GLUT4 translocation to the plasma membrane.\",\n      \"method\": \"Live-cell imaging (GLUT4-YFP/tubulin-CFP), dominant-negative expression, wortmannin inhibition\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — live imaging with defined molecular perturbation (dominant negative), multiple orthogonal methods, clear functional readout\",\n      \"pmids\": [\"12743033\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The ribosome receptor p180 binds KIF5B; the binding site is residues 1294–1413 of p180 and the C-terminal cargo-binding domain of KIF5B (residues 867–907), and the interaction is likely coiled-coil in nature; the p180 binding site on KIF5B is homologous to the kinectin-binding site.\",\n      \"method\": \"Yeast two-hybrid screen, domain mapping\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single yeast two-hybrid screen, no in vivo validation reported in abstract\",\n      \"pmids\": [\"15184079\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The kinesin-binding domain (KBD) of RanBP2 selectively interacts with KIF5B and KIF5C via a ~100-residue segment spanning a coiled-coil and globular tail cargo-binding domain; a single residue conserved in KIF5B/KIF5C but absent in KIF5A confers isoform specificity. Selective inhibition of KBD–KIF5B/KIF5C interaction causes perinuclear mitochondrial clustering, reduced mitochondrial membrane potential, and cell shrinkage.\",\n      \"method\": \"Domain mutagenesis, cell-based KBD inhibition, mitochondrial localization assay, membrane potential measurement\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mutagenesis defining single residue specificity, functional cellular phenotype upon inhibition, multiple orthogonal readouts\",\n      \"pmids\": [\"17887960\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"KIF5B mediates post-Golgi transport of the apical marker p75-GFP in polarized MDCK epithelial cells but not in subconfluent cells; immunoprecipitation demonstrates a polarity-dependent interaction between KIF5B and p75-GFP that is absent before polarization. Dominant-negative KIF5B or function-blocking antibodies selectively block apical (but not basolateral) transport.\",\n      \"method\": \"Time-lapse microscopy, dominant-negative expression, microinjection of function-blocking antibodies, co-immunoprecipitation\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — live imaging, co-IP showing polarity-dependent interaction, antibody inhibition; multiple orthogonal methods in one study\",\n      \"pmids\": [\"17925227\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"KIF5B interacts with Kv1 potassium channels via the T1 domain and mediates their axonal targeting; dominant-negative Kif5B blocks axonal localization of endogenous Kv1.1, Kv1.2, and Kv1.4 in cortical neurons, and Kv1.2 co-immunoprecipitates with Kif5B from brain lysate.\",\n      \"method\": \"Dominant-negative expression, co-immunoprecipitation from brain lysate, co-localization in cortical neurons\",\n      \"journal\": \"The European journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP from native tissue plus dominant-negative functional experiment, single lab\",\n      \"pmids\": [\"17241275\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Kif5B and the minus-end kinesin Kifc1 interact, co-localize on early endocytic vesicles (>90% of Kifc1-positive vesicles also contain Kif5B), mediate plus- and minus-end motility respectively, and both activities are required for vesicle fission; inhibition of either motor reduces fission frequency.\",\n      \"method\": \"In vitro microtubule-binding/motility assay, antibody inhibition, co-immunoprecipitation after FLAG-Kifc1 expression in 293T cells\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro motility assay with antibody inhibition and co-IP, single lab, multiple methods\",\n      \"pmids\": [\"17360972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"KIF5B (kinesin-1) is required for bidirectional positioning of COPII-coated ER exit sites (ERES) and for ER-to-Golgi transport; knockdown of KIF5B inhibits ER-to-Golgi transport and alters the morphology of transport carriers.\",\n      \"method\": \"siRNA knockdown, high-resolution 2D Gaussian localization of ERES, ER-to-Golgi trafficking assay\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA KD with quantitative localization and trafficking assay, single lab\",\n      \"pmids\": [\"18817524\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"RANBP2, through its kinesin-binding domain flanked by RBD2 and RBD3, activates the ATPase activity of KIF5B ~30-fold in the presence of microtubules and ATP in a minimal purified system; activation is biphasic and cooperative, and deletion of one RBD reduces activation threefold and abolishes cooperativity. RBD2-KBD-RBD3 also induces KIF5B unfolding in the absence of microtubules.\",\n      \"method\": \"In vitro ATPase assay with purified components, domain deletion mutagenesis\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstituted in vitro ATPase assay with purified components and systematic domain mutagenesis; first demonstration of a native allosteric activator of KIF5B\",\n      \"pmids\": [\"19305391\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Syntabulin acts as a KIF5B motor adaptor mediating anterograde axonal transport of presynaptic cargoes and mitochondria in sympathetic neurons; interference with syntabulin–KIF5B interaction delays synaptic activity, impairs transmission, reduces mitochondrial distribution, and these defects are rescued by ATP application.\",\n      \"method\": \"RNAi knockdown, dominant-negative interference with syntabulin–KIF5B interaction, electrophysiology, mitochondrial distribution assay, ATP rescue\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with specific molecular interference, electrophysiological readout, rescue experiment; multiple orthogonal methods\",\n      \"pmids\": [\"19828815\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Kif5b is essential for anterograde (forward) trafficking of the cardiac potassium channel Kv1.5 from the Golgi to the cell surface; overexpression of Kif5b increases Kv1.5 current density in a Golgi-dependent manner (blocked by Brefeldin A), and Kif5b dominant-negative blocks surface expression of newly induced Kv1.5.\",\n      \"method\": \"Patch-clamp electrophysiology, dominant-negative expression, Brefeldin A treatment, tetracycline-inducible Kv1.5 system\",\n      \"journal\": \"The Journal of physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — electrophysiological quantification combined with pharmacological and dominant-negative interventions, multiple orthogonal methods\",\n      \"pmids\": [\"19675065\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Daxx functions as a scaffold assembling a complex of GLUT4, JNK1, and KIF5B; Daxx interacts with KIF5B through the 6xTPR domain of kinesin light chain. Depletion of Daxx causes partial translocation of GLUT4 from storage compartment to endosomes.\",\n      \"method\": \"Co-immunoprecipitation, two-hybrid protein-protein interaction, Daxx depletion\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP and two-hybrid interactions plus depletion phenotype, single lab\",\n      \"pmids\": [\"18932217\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"KIF5B and KIF3A/KIF3B kinesins regulate bidirectional transport of MT1-MMP-positive vesicles along microtubules in human macrophages; siRNA knockdown of KIF5B reduces delivery of MT1-MMP to the cell surface and impairs surface-associated MT1-MMP functions including CD44 shedding and extracellular matrix degradation at podosomes.\",\n      \"method\": \"siRNA knockdown, live-cell vesicle tracking, MT1-MMP surface exposure assay, ECM degradation assay\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — siRNA KD in primary human macrophages with multiple functional readouts (surface exposure, shedding, ECM degradation), live imaging\",\n      \"pmids\": [\"20505159\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIF5B promotes anterograde transport of Nav1.8 to the plasma membrane and axons in DRG neurons; the N terminus of Nav1.8 directly interacts with the 511–620 aa stalk domain of KIF5B (co-immunoprecipitation); KIF5B mutants defective in ATP hydrolysis or cargo binding fail to increase Nav1.8 surface expression; disrupting the KIF5B–Nav1.8 interaction abolishes KIF5B-enhanced Nav1.8 current and axonal accumulation.\",\n      \"method\": \"Co-immunoprecipitation, domain mutagenesis, patch-clamp, overexpression/knockdown in DRG neurons, Brefeldin A treatment\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct interaction mapped by co-IP with domain mutants, functional electrophysiological validation, multiple orthogonal approaches\",\n      \"pmids\": [\"24198377\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Kif5b mediates anterograde transport of α-sarcomeric actin, non-muscle myosin IIB, desmin, and nestin to the growing tips of elongating myotubes; conditional Kif5b knockout in myogenic cells causes aggregation of these proteins and defective myofibril assembly and linkage to myotendinous junctions. A 64-amino acid α-helix domain in the tail region of Kif5b directly interacts with desmin.\",\n      \"method\": \"Conditional knockout (Cre-loxP), immunofluorescence, rescue by Kif5b re-expression, functional domain mapping (direct interaction with desmin)\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with clear phenotype, rescue, and direct domain–cargo interaction mapping\",\n      \"pmids\": [\"23293293\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIF5B is required for axonal localization of Kv1 channels and is required for female meiosis progression; RNAi silencing of Kif5b in mouse oocytes delays germinal vesicle breakdown and causes failure of first polar body extrusion; in mitotic cells, knockdown causes centrosome amplification and chromosomal segregation defects.\",\n      \"method\": \"RNAi silencing in mouse oocytes and mitotic cells, live imaging of meiotic progression\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi with clear meiotic and mitotic phenotypes, single lab\",\n      \"pmids\": [\"23560038\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"For nuclear positioning during myogenesis, both the kinesin light chain (KLC) binding domain and the autoinhibitory peptide in the globular tail of Kif5b are indispensable; the coiled-coil stalk/tail domain (containing KLC-binding sites) targets to the perinuclear region, while the globular tail domain alone cannot, and rescue of nuclear positioning in Kif5b-deficient myoblasts requires both regions.\",\n      \"method\": \"Domain truncation rescue experiments in Kif5b-deficient myoblasts, immunofluorescence localization\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain deletion rescue in null cells, single lab, clear functional readout\",\n      \"pmids\": [\"23402760\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KIF5B directly interacts with BNIP-2 via its BCH domain at both the motor and tail domains of KIF5B; KIF5B mediates microtubule-dependent anterograde transport of BNIP-2 to endosomes in C2C12 cells. KIF5B modulates p38MAPK activity through BNIP-2 transport, promoting myogenic differentiation; disruption of anterograde transport by dominant-negative KIF5B abolishes BNIP-2's promyogenic effects.\",\n      \"method\": \"Co-immunoprecipitation, far-Western blot, live microscopy with organelle markers, dominant-negative KIF5B, knockdown/gain-of-function\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct interaction confirmed by far-Western and co-IP, live transport imaging, pathway placement via gain/loss-of-function with signaling readout\",\n      \"pmids\": [\"25378581\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Palmitate causes dissociation of KIF5B from mitochondria via Ca2+-dependent effects, disrupting mitophagy; Rheb and KIF5B interact with the mitochondrial outer membrane, and their disruption blocks mitochondrial degradation and promotes NLRP3 inflammasome activation and IL-1β-dependent insulin resistance; Rheb/KIF5B overexpression attenuates these effects.\",\n      \"method\": \"Overexpression/knockdown, Ca2+ signaling inhibitors, mitophagy assays, ROS measurement\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — functional rescue by overexpression, Ca2+ dependence shown, but mechanism of KIF5B–mitochondria interaction not directly characterized at molecular level\",\n      \"pmids\": [\"25462067\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PRIP and GABARAP function in a complex to regulate KIF5B-mediated insulin secretory vesicle transport; GABARAP knockdown reduces co-localization of insulin vesicles with KIF5B and decreases insulin secretion; free GABARAP (released by PRIP silencing or interference peptide) enhances co-localization of vesicles with microtubules and promotes mobility.\",\n      \"method\": \"siRNA knockdown, co-immunofluorescence, density step-gradient fractionation, live-cell vesicle tracking\",\n      \"journal\": \"Biology open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA KD with co-localization and functional secretion readout, single lab\",\n      \"pmids\": [\"24812354\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KIF5B induces relocalization of the nuclear pore component Nup358 into the cytoplasm during HIV-1 infection in a capsid-dependent manner; cytoplasmic Nup358 then directly associates with viral cores. KIF5B knockdown prevents nuclear entry and infection by HIV-1 but not by N74D or P90A capsid mutants that do not rely on Nup358.\",\n      \"method\": \"siRNA knockdown, fluorescence microscopy of Nup358 relocalization, infection assays with capsid mutants\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KD phenotype confirmed by capsid-mutant epistasis, multiple orthogonal readouts (localization + infectivity), mechanistic pathway placement\",\n      \"pmids\": [\"27327622\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PLD2-generated phosphatidic acid (PA) directly and specifically binds to the C-terminus of KIF5B in vitro (liposome pull-down); this PA–KIF5B interaction is required for vesicular association of KIF5B, surface localization of MT1-MMP, invadopodia formation, and invasion in breast cancer cells.\",\n      \"method\": \"Liposome pull-down screen, in vitro binding assay, KIF5B C-terminal domain mapping, MT1-MMP surface localization assay, invasion assay\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct in vitro lipid binding with domain mapping, functional cellular consequence (MT1-MMP trafficking, invasion) linked to the interaction\",\n      \"pmids\": [\"29033361\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Kif5b directly interacts with clathrin heavy chain (CHC) and preferentially localizes to relatively large clathrin-coated vesicles (CCVs); Kif5b promotes uncoating of large CCVs in vitro (uncoating decreased in cortex CCVs from kif5b cKO mice, increased by adding Kif5b fragments containing the CHC-binding site). Kif5b depletion inhibits cellular entry of vesicular stomatitis virus via large CCV, linking anterograde transport to clathrin-mediated endocytosis.\",\n      \"method\": \"Co-immunoprecipitation, in vitro CCV uncoating assay with kif5b cKO cortex, dominant-negative fragment, virus entry assay\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct interaction, in vitro uncoating assay with KO tissue, dominant-negative, virus entry functional readout; multiple orthogonal methods\",\n      \"pmids\": [\"30603101\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The dynamin-related GTPase Mx1 interacts (directly or indirectly) with Kif5B and α-tubulin as assessed by co-immunoprecipitation; Mx1 aids in vesicle fission and stabilizes the interaction between Kif5B, microtubules, and apical transport carriers in MDCK cells.\",\n      \"method\": \"Co-immunoprecipitation, live-cell microscopy, nocodazole disruption, Mx1 knockout/mutant\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP, indirect interaction not excluded, single lab\",\n      \"pmids\": [\"30246279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Neuronal deletion of Kif5b reduces dopamine D2 receptor in synaptic plasma membranes (subcellular fractionation) causing D2-dependent movement initiation defects and hypo-locomotion; dopamine metabolism is impaired in neuronal Kif5b-KO. Deletion of Kif5b only in dopaminergic neurons is not sufficient to produce locomotor defects.\",\n      \"method\": \"Conditional knockout (neuronal and dopaminergic-specific), HPLC dopamine measurement, subcellular fractionation, pharmacological receptor agonist/antagonist testing\",\n      \"journal\": \"Journal of neurochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — cell-type-specific conditional KO, subcellular fractionation linking KIF5B to D2R membrane presentation, epistatic pharmacological dissection\",\n      \"pmids\": [\"30664247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"KIF5B is concentrated in the central spindle during cytokinesis in chondrocytes; KIF5B null chondrocytes fail cytokinesis, leading to incomplete cell rotation, disrupted proliferation and differentiation, and disorganized growth plate.\",\n      \"method\": \"Conditional knockout in chondrocytes, immunofluorescence of central spindle during cytokinesis, growth plate histology\",\n      \"journal\": \"Cell & bioscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with clear cytokinesis phenotype and subcellular localization; single lab\",\n      \"pmids\": [\"31636894\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF5B and KIF13B jointly transport Rab6-positive secretory vesicles from the Golgi to the cell periphery; KIF5B plays the dominant role while KIF13B helps vesicles reach freshly polymerized microtubule plus ends where KIF5B binds poorly (due to slow MAP7 family protein recruitment). Sub-pixel localization showed both motors localize to the vesicle front during plus-end transport; when vesicles reverse direction, KIF5B shifts to the back while KIF13B moves to the middle, suggesting KIF5B undergoes tug-of-war with a minus-end motor.\",\n      \"method\": \"siRNA depletion, live-cell imaging with sub-pixel localization, TIRF microscopy, co-localization of dual motors on same vesicle\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — quantitative sub-pixel live imaging, dual-motor depletion, mechanistic dissection of motor positioning; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"33174839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF5B conditional knockout in CaMKIIα-positive neurons causes heightened turnover and lower stability of dendritic spines, reduced PSD95 acquisition, and abolishes the preceding FMRP translocation to the proximity of newly forming spines (both basally and after fear extinction learning).\",\n      \"method\": \"In vivo two-photon imaging, conditional knockout (CaMKIIα-Cre), spine morphogenesis quantification, FMRP localization tracking\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo two-photon imaging in conditional KO mice with learning-dependent functional readout; multiple orthogonal in vivo measurements\",\n      \"pmids\": [\"38451812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIF5B conditional knockout in hippocampal neurons causes deficits in dendritic spine morphogenesis, synaptic plasticity, and memory formation; these functional specificities relative to KIF5A are determined by their divergent carboxyl-termini, where arginine methylation of KIF5B regulates its function.\",\n      \"method\": \"Conditional knockout mouse, dendritic transport assays, electrophysiology (LTP), behavioral memory tests, domain-swap and arginine methylation experiments\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with multiple orthogonal readouts (morphology, electrophysiology, behavior), PTM mapping, domain-swap experiment\",\n      \"pmids\": [\"31961321\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"L-dopa incorporated post-translationally into the C-terminus of α-tubulin reduces KIF5B binding affinity for microtubules; in L-dopa-treated neuronal cells, mitochondrial anterograde transport velocity is reduced, mitochondria spend more time paused, and fewer reach the distal axon segment.\",\n      \"method\": \"Biochemical binding assay (KIF5B affinity for dopa-tubulin microtubules), live-cell mitochondrial transport imaging in neuronal cell lines and primary hippocampal neurons\",\n      \"journal\": \"Neurobiology of disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical binding assay plus live-cell transport imaging, single lab\",\n      \"pmids\": [\"33171229\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"De novo heterozygous KIF5B variants at conserved amino acids in the ATPase activity-related motifs of the motor domain cause kyphomelic dysplasia in humans, establishing that KIF5B motor domain function is required for normal skeletal development.\",\n      \"method\": \"Whole-exome sequencing, de novo variant identification in four individuals, structural mapping to catalytic motifs\",\n      \"journal\": \"Clinical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — genetic identification of de novo loss-of-function variants at catalytic residues in multiple unrelated individuals; no in vitro biochemical confirmation in abstract\",\n      \"pmids\": [\"35342932\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Dominant-negative KIF5B variants (p.Asn255del, p.Leu498Pro, p.Leu537Pro) disrupt lysosomal, autophagosome, and mitochondrial organization, and impact cilium biogenesis in vitro; all variants affect multiple developmental processes in zebrafish. One previously reported variant also showed these effects.\",\n      \"method\": \"In vitro cell microscopy (lysosomal/autophagosome/mitochondrial distribution), cilium biogenesis assay, zebrafish developmental analysis\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro and in vivo (zebrafish) analysis of multiple variants with organelle distribution phenotypes; single lab\",\n      \"pmids\": [\"36018820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Dominant-negative KIF5B variants (modeled in C. elegans unc-116 Thr90Ile by CRISPR) cause defective mitochondria transport in neurons (time-lapse GFP-mitochondria imaging), abnormal body length and motility suppressed by extra wild-type allele; in human cells, the corresponding p.Thr87Ile variant causes dilated ER, intracellular vacuoles, Golgi maldistribution, and down-regulation of mTOR signaling (RNA-seq, proteomics, bone IHC); leucine supplementation partially rescues mTOR pathway in patient cells.\",\n      \"method\": \"CRISPR/Cas9 modeling in C. elegans, time-lapse GFP-mitochondria imaging, dominant negative suppression genetics, RNA-seq, proteomics, leucine rescue\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — CRISPR model organism with live transport imaging and genetic epistasis, human cell and patient tissue molecular analysis with multiple omics methods, rescue experiment\",\n      \"pmids\": [\"37934770\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"KIF5B actively slides existing microtubules to the β-cell periphery in a glucose-stimulated manner, aligning the sub-membrane microtubule array in pancreatic β cells; this microtubule sliding is part of glucose-triggered microtubule remodeling that regulates insulin secretory granule positioning.\",\n      \"method\": \"Real-time live imaging, photokinetics (FRAP-like approaches), KIF5B manipulation in MIN6 cells and intact mouse islets\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — live imaging with photokinetics demonstrating active microtubule sliding by KIF5B, validated in both cell line and intact islets\",\n      \"pmids\": [\"41182903\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cohesin-associated protein Pds5A recruits the deubiquitinase USP14 to the spindle apparatus, which stabilizes KIF5B by deubiquitination, regulating meiotic spindle elongation and chromosome segregation in mouse oocytes.\",\n      \"method\": \"Morpholino depletion, genetic ablation of Pds5A, spindle organization imaging, USP14 interaction assay, KIF5B ubiquitination/stability analysis\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic depletion with spindle phenotype, deubiquitinase–KIF5B pathway mechanistically defined, single lab\",\n      \"pmids\": [\"40215310\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KIF5B is the heavy chain of kinesin-1, a plus-end-directed microtubule motor that transports a diverse array of cargoes (mitochondria, lysosomes, GLUT4 vesicles, MT1-MMP vesicles, Rab6 secretory vesicles, insulin granules, Nav1.8, Nav1.7, Kv1 channels, Kv1.5, BNIP-2, and microtubules themselves) through direct or adaptor-mediated interactions at its cargo-binding C-terminal stalk/tail domain; its ATPase motor activity is allosterically activated ~30-fold by the RanBP2 kinesin-binding domain in vitro, and its activity is regulated by lipid binding (phosphatidic acid), post-translational arginine methylation, interaction with adaptor proteins (syntabulin, RanBP2/KBD, GABARAP/PRIP, Daxx), and by the state of its microtubule track (e.g., L-dopa–modified tubulin reduces binding); loss of KIF5B causes perinuclear mitochondrial clustering, lysosomal and autophagosomal disorganization, impaired ER-to-Golgi transport, disrupted apical epithelial trafficking, defective dendritic spine plasticity and synaptic transmission, failed meiotic spindle elongation, cytokinesis failure in chondrocytes, reduced dopamine D2 receptor presentation at synapses, and skeletal dysplasia.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIF5B is the heavy chain of the kinesin-1 plus-end-directed microtubule motor that powers anterograde, long-range positioning of organelles and membrane cargoes throughout the cell, with loss of function producing perinuclear mitochondrial clustering and impaired lysosomal dispersion [#0, #4]. Its C-terminal stalk/tail region serves as a versatile cargo-binding hub, engaging cargoes directly or through adaptors and light-chain interactions: it transports GLUT4 vesicles in adipocytes [#2], apical post-Golgi carriers in polarized epithelia [#5], MT1-MMP vesicles supporting matrix degradation and invasion [#13, #22], Rab6 secretory vesicles to the cell periphery [#27], voltage-gated Nav1.8 and Kv1.5 channels to neuronal and cardiac surfaces [#14, #11], desmin and sarcomeric components to elongating myotube tips [#15], BNIP-2 toward endosomes to modulate p38MAPK-driven myogenesis [#18], and dopamine D2 receptor to synaptic membranes [#25]. Motor output is allosterically controlled: the RanBP2 kinesin-binding domain activates KIF5B ATPase ~30-fold and induces motor unfolding [#9, #1, #4], phosphatidic acid binds the C-terminus to license vesicular association [#22], divergent C-terminal arginine methylation tunes neuronal specificity [#29], and L-dopa-modified tubulin lowers track affinity [#30]. Adaptors including syntabulin, Daxx/kinesin light chain, and the PRIP/GABARAP complex couple the motor to specific cargoes [#10, #12, #20]. Beyond cargo hauling, KIF5B slides microtubules themselves to remodel the sub-membrane array in glucose-stimulated β cells [#34] and concentrates at the central spindle to drive cytokinesis and meiotic/mitotic spindle function [#26, #16, #35]. De novo heterozygous variants in the ATPase motifs of the motor domain cause kyphomelic/skeletal dysplasia in humans, with dominant-negative alleles disrupting lysosomal, autophagosomal, mitochondrial, and ciliary organization and downregulating mTOR signaling [#31, #32, #33].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established that KIF5B is required in vivo for organelle positioning, defining its core cellular function as anterograde dispersion of mitochondria and lysosomes.\",\n      \"evidence\": \"Homologous-recombination knockout mice, subcellular fractionation, and rescue by exogenous expression\",\n      \"pmids\": [\"9657148\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the adaptors linking KIF5B to mitochondria or lysosomes\", \"Did not address cargo selectivity among KIF5 paralogs\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identified RanBP2 as a direct binding partner with isoform selectivity for KIF5B/KIF5C, introducing a defined regulatory interaction at the motor.\",\n      \"evidence\": \"Yeast two-hybrid, in vitro binding, co-IP, and domain mapping\",\n      \"pmids\": [\"11553612\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of the RanBP2 interaction not yet established\", \"Did not determine effect on motor activity\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrated KIF5B drives a hormone-stimulated trafficking event, transporting GLUT4 vesicles for insulin-responsive glucose uptake.\",\n      \"evidence\": \"Live-cell imaging with dominant-negative kinesin light chain and wortmannin in adipocytes\",\n      \"pmids\": [\"12743033\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct cargo receptor for GLUT4 vesicles not defined here\", \"Regulation linking insulin signaling to motor engagement unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Mapped the molecular basis of KIF5B isoform-selective regulation and showed disrupting the RanBP2-KIF5B interaction phenocopies organelle mislocalization, linking the partner to function.\",\n      \"evidence\": \"Domain mutagenesis defining a single specificity residue plus cell-based KBD inhibition with mitochondrial readouts\",\n      \"pmids\": [\"17887960\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not quantify effect on intrinsic motor ATPase\", \"In vivo relevance of selectivity residue untested\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Extended KIF5B cargo range to ion channels and endocytic vesicle dynamics, establishing roles in neuronal channel targeting and bidirectional vesicle fission alongside an opposing motor.\",\n      \"evidence\": \"Co-IP from brain lysate, dominant-negative expression, and in vitro motility/antibody-inhibition assays\",\n      \"pmids\": [\"17241275\", \"17360972\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct Kv1-KIF5B binding interface not mapped\", \"Coordination mechanism between KIF5B and KIFC1 on shared vesicles unresolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Placed KIF5B in early secretory trafficking, showing it positions ER exit sites and supports ER-to-Golgi transport.\",\n      \"evidence\": \"siRNA knockdown with quantitative ERES localization and trafficking assays\",\n      \"pmids\": [\"18817524\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cargo adaptor for ERES positioning not identified\", \"Single-lab knockdown without rescue\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Provided the first reconstituted demonstration of a native allosteric activator, showing RanBP2 activates KIF5B ATPase ~30-fold and unfolds the motor.\",\n      \"evidence\": \"In vitro ATPase assay with purified components and systematic domain deletion\",\n      \"pmids\": [\"19305391\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological contexts where RanBP2 activates KIF5B in cells not fully defined\", \"Structural basis of cooperative activation unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identified syntabulin and Daxx as cargo adaptors and extended channel transport to Kv1.5, establishing adaptor-mediated coupling of KIF5B to presynaptic, mitochondrial, GLUT4, and channel cargoes.\",\n      \"evidence\": \"RNAi, dominant-negative interference, co-IP, electrophysiology, and ATP rescue across neuronal and cardiac systems\",\n      \"pmids\": [\"19828815\", \"18932217\", \"19675065\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Selectivity rules governing which adaptor engages which cargo unclear\", \"Daxx scaffold interaction rests on co-IP/two-hybrid in a single lab\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Linked KIF5B-driven trafficking to extracellular matrix remodeling by delivering MT1-MMP to the macrophage surface for ECM degradation.\",\n      \"evidence\": \"siRNA knockdown with surface-exposure, CD44 shedding, and ECM degradation assays plus live tracking in primary macrophages\",\n      \"pmids\": [\"20505159\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Adaptor coupling KIF5B to MT1-MMP vesicles not yet identified\", \"Coordination with KIF3A/KIF3B mechanism unresolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Mapped direct cargo-binding interfaces (Nav1.8, desmin, BNIP-2) and defined dual roles in cell division, advancing KIF5B from a generic motor to one with cargo-specific tail contacts and spindle functions.\",\n      \"evidence\": \"Co-IP with domain mutants, far-Western, conditional knockout with rescue, patch-clamp, and RNAi in oocytes/mitotic cells\",\n      \"pmids\": [\"24198377\", \"23293293\", \"23402760\", \"25378581\", \"23560038\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How motor versus tail binding to BNIP-2 is coordinated unclear\", \"Mechanism of central-spindle/meiotic function distinct from cargo transport not resolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Revealed lipid- and Ca2+-dependent control of KIF5B membrane association and connected its mitochondrial binding to mitophagy and metabolic inflammation.\",\n      \"evidence\": \"Liposome pull-down with C-terminal mapping, overexpression/knockdown, Ca2+ inhibitors, and mitophagy/inflammasome assays\",\n      \"pmids\": [\"29033361\", \"25462067\", \"24812354\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of KIF5B-mitochondria dissociation not directly characterized\", \"PA-binding region structure not defined\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Implicated KIF5B in viral pathogenesis by showing it relocalizes Nup358 to enable capsid-dependent HIV-1 nuclear entry.\",\n      \"evidence\": \"siRNA knockdown with capsid-mutant epistasis and Nup358 relocalization imaging\",\n      \"pmids\": [\"27327622\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct KIF5B-Nup358 binding not demonstrated\", \"How motor activity triggers Nup358 release unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected KIF5B to clathrin-mediated endocytosis, showing it binds clathrin heavy chain and promotes uncoating of large clathrin-coated vesicles required for virus entry.\",\n      \"evidence\": \"Co-IP, in vitro uncoating assay using kif5b cKO cortex, dominant-negative fragment, and VSV entry assay\",\n      \"pmids\": [\"30603101\", \"30246279\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How a plus-end motor mechanically promotes uncoating unresolved\", \"Mx1-KIF5B interaction is a single co-IP that cannot exclude indirect binding\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined the in vivo cytokinetic requirement in chondrocytes and the synaptic D2-receptor presentation function, tying KIF5B loss to skeletal and locomotor phenotypes.\",\n      \"evidence\": \"Cell-type-specific conditional knockouts, central-spindle imaging, subcellular fractionation, and pharmacological dissection\",\n      \"pmids\": [\"31636894\", \"30664247\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why dopaminergic-specific deletion is insufficient for locomotor defects unexplained\", \"Cargo adaptor for D2 receptor not identified\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Dissected motor coordination on single vesicles and established neuron-specific functions controlled by the divergent C-terminus and its arginine methylation.\",\n      \"evidence\": \"Sub-pixel live imaging with dual-motor depletion, conditional knockout with two-photon imaging, electrophysiology, behavior, domain-swap, and PTM mapping\",\n      \"pmids\": [\"33174839\", \"38451812\", \"31961321\", \"33171229\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Enzyme catalyzing KIF5B arginine methylation not identified\", \"Mechanism by which FMRP translocation depends on KIF5B unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Established human genetic causation, linking de novo motor-domain ATPase variants to kyphomelic skeletal dysplasia.\",\n      \"evidence\": \"Whole-exome sequencing in four individuals with structural mapping to catalytic motifs\",\n      \"pmids\": [\"35342932\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vitro biochemical confirmation of variant effect on ATPase\", \"Tissue-specific basis of skeletal phenotype unexplained\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed disease variants act dominant-negatively across organelle systems and converge on mTOR downregulation, with leucine partially rescuing patient cells.\",\n      \"evidence\": \"In vitro organelle/cilium assays, zebrafish development, CRISPR C. elegans modeling with genetic epistasis, RNA-seq/proteomics, and leucine rescue\",\n      \"pmids\": [\"36018820\", \"37934770\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanistic link between KIF5B transport defects and mTOR signaling not fully defined\", \"Whether mTOR effect is secondary to general trafficking failure unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed a transport-independent activity—active microtubule sliding to remodel the β-cell array—and a deubiquitination pathway stabilizing KIF5B during meiotic spindle elongation.\",\n      \"evidence\": \"Live imaging with photokinetics in MIN6 cells and islets, plus Pds5A/USP14 depletion with spindle imaging and KIF5B stability analysis\",\n      \"pmids\": [\"41182903\", \"40215310\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How glucose triggers KIF5B-mediated sliding mechanistically unresolved\", \"USP14-KIF5B regulation shown in a single oocyte study\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how KIF5B integrates its many cargo adaptors, lipid and PTM inputs, and track modifications into selective, context-dependent transport, and how motor-domain dysfunction mechanistically produces tissue-specific skeletal and metabolic disease.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model of cargo-selection hierarchy\", \"Structural basis of allosteric activation in cells undefined\", \"Causal chain from trafficking defect to mTOR/skeletal phenotype incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 2, 27, 34]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [9, 14, 31]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [27, 30, 34]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [22]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [10, 12, 20]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [27, 30, 34]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 4, 19]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [7, 23, 27]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [26, 16, 35]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2, 5, 13, 27]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 8, 11, 14]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [26, 16, 35]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [19, 32]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [31, 32, 33]}\n    ],\n    \"complexes\": [\"kinesin-1\"],\n    \"partners\": [\"RANBP2\", \"KLC\", \"syntabulin\", \"Daxx\", \"GABARAP\", \"BNIP-2\", \"desmin\", \"clathrin heavy chain\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}