{"gene":"KIFC3","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2001,"finding":"KIFC3 is a minus end-directed microtubule motor protein that localizes to Triton X-100-insoluble (lipid raft) membrane organelles beneath the apical plasma membrane of polarized epithelial cells and co-immunoprecipitates and co-localizes with annexin XIIIb on apically transported TGN-derived vesicles. Overexpression of dominant-negative (motor-domainless) KIFC3 partially inhibited apical transport of influenza hemagglutinin and annexin XIIIb, while full-length KIFC3 overexpression accelerated it.","method":"Flotation assay with detergent extraction, immunoprecipitation, GST pulldown, dominant-negative overexpression in MDCK II cells, immunoelectron microscopy","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, GST pulldown, dominant-negative functional assay, and EM localization, all in one study, replicated across in vivo and in vitro systems","pmids":["11581287"],"is_preprint":false},{"year":2002,"finding":"KIFC3 is associated with the Golgi apparatus in adrenocortical cells and is required for Golgi positioning and integration: knockout of kifC3 causes Golgi fragmentation under cholesterol-depleted conditions due to markedly reduced inward (minus-end-directed) motility of Golgi fragments. KIFC3 acts complementarily with cytoplasmic dynein in this process, and its absence exacerbates Golgi scattering caused by dynamitin overexpression even when cholesterol is present.","method":"kifC3 knockout mouse (homologous recombination), live-cell microscopy of Golgi fragment motility, dynamitin overexpression epistasis","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockout with defined cellular phenotype, epistasis with dynein pathway, cholesterol-rescue experiment, multiple orthogonal approaches in one study","pmids":["12135985"],"is_preprint":false},{"year":2001,"finding":"Mouse KifC3 is a ubiquitously expressed C-terminal (minus end-directed) kinesin. Homozygous knockout mice are viable, reproduce normally, and develop normally, indicating KifC3 is dispensable for normal development and reproduction.","method":"cDNA cloning from mouse brain library, homologous recombination knockout in embryonic stem cells, phenotypic analysis of homozygous mutants","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with phenotypic readout, single lab, negative developmental phenotype result","pmids":["11154264"],"is_preprint":false},{"year":2013,"finding":"KIFC3 localizes to the central spindle bridge during cytokinesis in a motor-dependent manner and promotes efficient cytokinesis by congressing microtubules at the central bridge. Perturbation of KIFC3 function widens and extends the central bridge and delays abscission. In interphase, KIFC3 caps microtubules released from the centrosome.","method":"Loss-of-function perturbation, live-cell microscopy, immunofluorescence localization during cell cycle stages","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined cellular phenotype with loss-of-function, localization tied to functional consequence, single lab","pmids":["24275865"],"is_preprint":false},{"year":2013,"finding":"KifC3 interacts with the peroxisomal AAA-ATPase PEX1, confirmed by co-immunoprecipitation and co-localization in cells. RNAi knockdown of KifC3 causes perinuclear clustering of peroxisomes in a microtubule-dependent manner, suggesting KifC3 regulates minus-end-directed peroxisomal transport, potentially by antagonizing dynein-driven inward movement.","method":"Yeast two-hybrid (initial identification), co-immunoprecipitation, immunofluorescence co-localization, RNAi knockdown with organelle distribution readout","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP confirmed interaction, RNAi phenotype with mechanistic interpretation, single lab, two orthogonal methods","pmids":["23954441"],"is_preprint":false},{"year":2014,"finding":"KIFC3 moves into adherens junctions (AJs) via microtubules nucleated from CAMSAP3 (Nezha) clusters and recruits the deubiquitinase USP47 to AJs. Depletion of KIFC3 or USP47 leads to increased E-cadherin ubiquitination (by Hakai E3 ligase), cleavage at a juxtamembrane region producing a 90-kDa fragment, and E-cadherin internalization. KIFC3 thus suppresses E-cadherin degradation by maintaining USP47 at AJs.","method":"Co-immunoprecipitation (KIFC3–USP47 interaction), RNAi knockdown of KIFC3/USP47, proteasome inhibitor rescue, E-cadherin ubiquitination assay, immunofluorescence","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP for interaction, RNAi phenotype with biochemical readout (ubiquitination, cleavage fragment), proteasome inhibitor rescue, multiple orthogonal methods in one study","pmids":["25253721"],"is_preprint":false},{"year":2019,"finding":"KIFC3 forms a homotetramer that provides microtubule-based centrosome cohesion during mitotic onset, pulling two centrosomes together via a specific microtubule network. KIFC3-mediated cohesion counteracts EG5-driven separation forces to prevent premature spindle formation after linker dissolution. KIFC3 is inactivated by NEK2 kinase to allow bipolar spindle assembly. Persistent centrosome cohesion in mitosis causes chromosome mis-segregation.","method":"KIFC3 knockout/depletion, biochemical characterization of homotetramer assembly, live-cell microscopy of centrosome dynamics, epistasis with EG5 and NEK2, chromosome segregation assay","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — homotetramer biochemically characterized, multiple genetic epistasis experiments, live imaging, functional assay with defined phenotype, published in high-tier journal","pmids":["31481795"],"is_preprint":false},{"year":2020,"finding":"KIFC3 has a dendrite-specific distribution in neurons and interacts with the microtubule minus-end binding protein CAMSAP2. Depletion of KIFC3 or CAMSAP2 increases microtubule dynamics during dendritic development. CAMSAP2 anchors KIFC3 at microtubule minus ends to immobilize microtubule arrays in dendrites, organizing the mixed anti-parallel microtubule polarity characteristic of dendrites.","method":"Co-immunoprecipitation (KIFC3–CAMSAP2 interaction), shRNA knockdown in neurons, live imaging of microtubule dynamics, immunofluorescence for KIFC3 dendritic distribution","journal":"Current biology : CB","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP for interaction, RNAi with live-imaging phenotype, mechanistic model with multiple orthogonal methods, single lab but rigorous","pmids":["32084403"],"is_preprint":false},{"year":2024,"finding":"KIFC3 is essential for spindle assembly and cytokinesis during mouse oocyte meiosis. KIFC3 localizes to centromeres at metaphase I and translocates to the midbody at telophase I. Disruption of KIFC3 causes defective polar body extrusion, aberrant meiotic spindles, chromosome misalignment, and loss of kinetochore-microtubule attachment associated with failed BubR1/Bub3 recruitment. KIFC3 interacts with Sirt2 to maintain acetylated tubulin levels and microtubule stability, and interacts with PRC1 to regulate midbody formation.","method":"Immunofluorescence localization, KIFC3 activity disruption, co-immunoprecipitation (KIFC3–Sirt2, KIFC3–PRC1), acetylated tubulin assay, polar body extrusion and spindle integrity assays","journal":"Cell communication and signaling : CCS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP for two interactions, defined meiotic phenotypes with specific molecular readouts, single lab","pmids":["38553728"],"is_preprint":false},{"year":2024,"finding":"In stressed cells undergoing senescence, KIFC3 is recruited to plus-ends of stress-induced nucleus-to-cilium microtubule arrays (sinc-MTs, which are polyglutamylated with minus-ends near the nuclear envelope) and interacts with centrosomal protein CENEXIN1. KIFC3 mediates nuclear transport of FBF1 along sinc-MTs to PML nuclear bodies. Deficiency of KIFC3 abolishes PML-NB translocation of FBF1 and CENEXIN1, and prevents senescence initiation.","method":"Immunofluorescence and live imaging of sinc-MTs, KIFC3 knockout/knockdown, co-immunoprecipitation (KIFC3–CENEXIN1), FBF1/CENEXIN1 translocation assay, senescence assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with specific molecular phenotype (failed PML-NB translocation), Co-IP interaction, live imaging, multiple orthogonal methods in one study","pmids":["39266565"],"is_preprint":false},{"year":2024,"finding":"KIFC3 physically interacts with PI3K p85α subunit, as confirmed by co-immunoprecipitation of endogenous and exogenous proteins, and promotes PI3K/AKT pathway activation to drive NSCLC cell proliferation, migration, and invasion.","method":"Co-immunoprecipitation (endogenous and exogenous KIFC3 with PI3Kp85α), western blot of pathway components, KIFC3 overexpression/knockdown with PI3K inhibitor (LY294002) rescue, xenograft tumor model","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP confirms direct interaction, inhibitor rescue confirms pathway dependency, single lab","pmids":["39227687"],"is_preprint":false},{"year":2024,"finding":"KIFC3 interacts with β-catenin phosphorylated at S47 (β-catenin p-S47), with lower binding affinity observed for S47A mutant. Knockdown of KIFC3 reduces β-catenin p-S47 at the centrosome and causes primary cilia deficiency, while β-catenin p-S47 accumulates in the Golgi. KIFC3 thus participates in transport of β-catenin p-S47 from the Golgi to the centrosome to promote primary ciliogenesis.","method":"Co-immunoprecipitation (KIFC3–β-catenin p-S47), binding affinity comparison with S47A mutant, KIFC3 knockdown with primary cilia and β-catenin localization readout","journal":"Molecules and cells","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP with mutant comparison, knockdown phenotype with localization readout, single lab","pmids":["39476973"],"is_preprint":false},{"year":2025,"finding":"In G1 phase, KIFC3 drives minus-end-directed compaction of ERES (endoplasmic reticulum exit sites) near the centrosome in a CDK1-signaling-dependent tug-of-war with plus-end-directed motors. In S/G2, kinesin-1 overcomes KIFC3 to allow ERES dispersion.","method":"Loss-of-function approaches (RNAi/knockdown), live-cell microscopy, cell cycle staging, CDK1 inhibition","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint, single lab, loss-of-function with organelle positioning readout but limited mechanistic detail in abstract","pmids":[],"is_preprint":true},{"year":2026,"finding":"In megakaryocytes, Kifc3 acts as a minus-end-directed motor for centrosomal delivery of cargos and controls centrosomal localization of Cep192. Kifc3 knockdown in neonatal megakaryocytes causes Cep192 upregulation and dispersion from the centrosome, inducing adult-type morphogenesis with augmented platelet release. A small molecule Kifc3 inhibitor identified in silico recapitulated this effect.","method":"shRNA knockdown in neonatal megakaryocytes, immunofluorescence for Cep192 localization, in silico inhibitor screening with functional validation in vitro and in vivo","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint, RNAi phenotype with localization readout, no direct binding assay for KIFC3–Cep192 interaction shown in abstract","pmids":["41929089"],"is_preprint":true}],"current_model":"KIFC3 is a minus-end-directed kinesin-14 motor that forms homotetramers and functions in multiple cellular contexts: it drives apical vesicle transport in polarized epithelial cells by associating with annexin XIIIb-containing lipid raft organelles; maintains Golgi positioning via minus-end-directed motility complementary to dynein; provides microtubule-based centrosome cohesion at mitotic onset (counteracting EG5) until inactivated by NEK2; organizes dendritic microtubule arrays by anchoring to CAMSAP2 at microtubule minus-ends; protects E-cadherin at adherens junctions by recruiting the deubiquitinase USP47 (thereby suppressing Hakai-mediated ubiquitination and degradation); regulates meiotic spindle stability and cytokinesis through interactions with Sirt2 and PRC1; and mediates nuclear transport of the senescence effector FBF1 along polyglutamylated sinc-MTs to PML nuclear bodies via interaction with CENEXIN1."},"narrative":{"mechanistic_narrative":"KIFC3 is a minus-end-directed (C-terminal) kinesin motor that uses microtubule-based transport and minus-end anchoring to position organelles, stabilize microtubule arrays, and organize the centrosome across diverse cellular contexts [PMID:11581287, PMID:11154264, PMID:31481795]. In polarized epithelial cells it associates with annexin XIIIb on lipid-raft membrane organelles to drive apical vesicle transport [PMID:11581287], and it maintains Golgi positioning by supplying inward, minus-end-directed motility that acts complementarily to cytoplasmic dynein [PMID:12135985]. At microtubule minus ends KIFC3 is anchored by CAMSAP family proteins: CAMSAP3-nucleated microtubules deliver KIFC3 to adherens junctions, where it recruits the deubiquitinase USP47 to protect E-cadherin from Hakai-mediated ubiquitination, cleavage, and degradation [PMID:25253721], while CAMSAP2 anchors KIFC3 at minus ends to immobilize and organize the mixed-polarity microtubule arrays of dendrites [PMID:32084403]. In mitosis, KIFC3 assembles into a homotetramer that generates microtubule-based centrosome cohesion counteracting EG5-driven separation, and it is inactivated by NEK2 to license bipolar spindle assembly; persistent cohesion causes chromosome mis-segregation [PMID:31481795]. KIFC3 also localizes to the central spindle to promote cytokinesis [PMID:24275865], and during oocyte meiosis it supports spindle assembly and midbody formation through interactions with Sirt2 (maintaining acetylated tubulin) and PRC1 [PMID:38553728]. In stressed cells it is recruited to polyglutamylated nucleus-to-cilium microtubule arrays and, via CENEXIN1, transports the senescence effector FBF1 to PML nuclear bodies to initiate senescence [PMID:39266565].","teleology":[{"year":2001,"claim":"Established KIFC3 as a minus-end-directed motor with a defined transport cargo, linking it to apical membrane trafficking in polarized epithelia.","evidence":"Flotation/detergent extraction, reciprocal Co-IP and GST pulldown with annexin XIIIb, dominant-negative overexpression and immuno-EM in MDCK II cells","pmids":["11581287"],"confidence":"High","gaps":["Motor velocity and processivity not measured in vitro","Mechanism coupling motor to raft organelle not defined"]},{"year":2001,"claim":"Determined that KifC3 is ubiquitously expressed yet dispensable for mouse development and reproduction, indicating functional redundancy in vivo.","evidence":"cDNA cloning and homologous-recombination knockout mice with phenotypic analysis","pmids":["11154264"],"confidence":"Medium","gaps":["No conditional/tissue-specific analysis","Redundant motors not identified"]},{"year":2002,"claim":"Showed KIFC3 supplies minus-end-directed motility for Golgi positioning, working complementarily with dynein rather than redundantly.","evidence":"kifC3 knockout mouse cells, live imaging of Golgi fragment motility, cholesterol depletion and dynamitin overexpression epistasis","pmids":["12135985"],"confidence":"High","gaps":["Direct adaptor linking KIFC3 to Golgi membranes unknown","Cholesterol-dependence mechanism not resolved"]},{"year":2013,"claim":"Extended KIFC3 function to cytokinesis, where motor-dependent localization to the central bridge promotes efficient abscission.","evidence":"Loss-of-function perturbation, live-cell microscopy and cell-cycle immunofluorescence","pmids":["24275865"],"confidence":"Medium","gaps":["Central-bridge binding partners not identified","Single-lab loss-of-function only"]},{"year":2013,"claim":"Implicated KIFC3 in peroxisome positioning via PEX1, broadening its organelle-transport roles.","evidence":"Yeast two-hybrid, Co-IP, co-localization and RNAi with peroxisome distribution readout","pmids":["23954441"],"confidence":"Medium","gaps":["Direct binding interface with PEX1 not mapped","Antagonism with dynein inferred, not demonstrated biochemically"]},{"year":2014,"claim":"Revealed a non-transport scaffolding role: KIFC3 at adherens junctions recruits USP47 to protect E-cadherin from ubiquitin-dependent degradation.","evidence":"Co-IP of KIFC3–USP47, RNAi of KIFC3/USP47, E-cadherin ubiquitination assay, proteasome inhibitor rescue, immunofluorescence","pmids":["25253721"],"confidence":"High","gaps":["Whether motor activity is required for USP47 delivery unclear","Structural basis of KIFC3–USP47 interaction unknown"]},{"year":2019,"claim":"Defined the mitotic mechanism of KIFC3 centrosome cohesion: a homotetramer generates pulling forces opposing EG5 and is switched off by NEK2 to permit spindle bipolarity.","evidence":"Knockout/depletion, biochemical homotetramer characterization, live imaging, EG5/NEK2 epistasis, chromosome segregation assay","pmids":["31481795"],"confidence":"High","gaps":["NEK2 phosphosites on KIFC3 not mapped","Structure of the cohesion microtubule network not resolved"]},{"year":2020,"claim":"Showed CAMSAP2 anchors KIFC3 at microtubule minus ends to immobilize and organize dendritic microtubule arrays, establishing a minus-end anchoring function.","evidence":"Co-IP of KIFC3–CAMSAP2, shRNA in neurons, live imaging of microtubule dynamics, dendritic immunofluorescence","pmids":["32084403"],"confidence":"High","gaps":["How KIFC3 immobilizes minus ends mechanistically not resolved","Relationship to axonal microtubules not addressed"]},{"year":2024,"claim":"Established KIFC3 as essential for meiotic spindle stability and cytokinesis through Sirt2 (tubulin acetylation) and PRC1 (midbody) interactions.","evidence":"Immunofluorescence, activity disruption, Co-IP of KIFC3–Sirt2 and KIFC3–PRC1, acetylated-tubulin and polar-body assays in mouse oocytes","pmids":["38553728"],"confidence":"Medium","gaps":["Direct vs indirect nature of Sirt2/PRC1 interactions not dissected","Single-lab study"]},{"year":2024,"claim":"Linked KIFC3 to senescence initiation by transporting FBF1 along polyglutamylated sinc-MTs to PML nuclear bodies via CENEXIN1.","evidence":"Live imaging of sinc-MTs, KIFC3 knockout/knockdown, Co-IP of KIFC3–CENEXIN1, FBF1/CENEXIN1 translocation and senescence assays","pmids":["39266565"],"confidence":"High","gaps":["How KIFC3 selects FBF1 as cargo unknown","Trigger for sinc-MT polyglutamylation not defined"]},{"year":2024,"claim":"Implicated KIFC3 in oncogenic signaling through physical interaction with PI3K p85α driving PI3K/AKT activation in NSCLC.","evidence":"Endogenous/exogenous Co-IP with p85α, pathway western blots, overexpression/knockdown with LY294002 rescue, xenograft model","pmids":["39227687"],"confidence":"Medium","gaps":["Whether interaction requires motor function unknown","Single-lab, one cancer type"]},{"year":2024,"claim":"Proposed a ciliogenesis role: KIFC3 transports phospho-S47 β-catenin from Golgi to centrosome to support primary cilia formation.","evidence":"Co-IP of KIFC3 with β-catenin p-S47, S47A binding comparison, knockdown with cilia and localization readouts","pmids":["39476973"],"confidence":"Medium","gaps":["Direct phospho-dependent binding interface not mapped","Single-lab study"]},{"year":2026,"claim":"Suggested KIFC3 controls centrosomal Cep192 localization to govern megakaryocyte maturation and platelet release, with a candidate small-molecule inhibitor.","evidence":"shRNA in neonatal megakaryocytes, Cep192 immunofluorescence, in silico inhibitor screen with in vitro/in vivo validation (preprint)","pmids":["41929089"],"confidence":"Low","gaps":["No direct KIFC3–Cep192 binding assay shown","Preprint, not peer reviewed","Inhibitor specificity not established"]},{"year":null,"claim":"How a single minus-end-directed motor is selectively targeted to its many distinct cargos and contexts (apical vesicles, Golgi, junctions, centrosomes, sinc-MTs) and how its activity is switched between transport and anchoring/scaffolding roles remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unified model of cargo-adaptor selection","Regulatory switches beyond NEK2 unknown","No high-resolution structure of motor–cargo complexes"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,1,6]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[6,7]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[0,6]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1,11]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[6,9,11]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[7,9]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,5]},{"term_id":"GO:0005777","term_label":"peroxisome","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3,6]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,1,9]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[9]}],"complexes":["KIFC3 homotetramer"],"partners":["ANXA13B","USP47","CAMSAP2","CAMSAP3","PEX1","PRC1","SIRT2","CENEXIN1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BVG8","full_name":"Kinesin-like protein KIFC3","aliases":[],"length_aa":833,"mass_kda":92.8,"function":"Minus-end microtubule-dependent motor protein. Involved in apically targeted transport (By similarity). Required for zonula adherens maintenance","subcellular_location":"Cell junction, adherens junction; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasmic vesicle membrane","url":"https://www.uniprot.org/uniprotkb/Q9BVG8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KIFC3","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KIFC3","total_profiled":1310},"omim":[{"mim_id":"612686","title":"PLECKSTRIN HOMOLOGY DOMAIN-CONTAINING PROTEIN, FAMILY A, MEMBER 7; PLEKHA7","url":"https://www.omim.org/entry/612686"},{"mim_id":"612685","title":"CALMODULIN-REGULATED SPECTRIN-ASSOCIATED PROTEIN 3; CAMSAP3","url":"https://www.omim.org/entry/612685"},{"mim_id":"604535","title":"KINESIN FAMILY MEMBER C3; KIFC3","url":"https://www.omim.org/entry/604535"},{"mim_id":"600724","title":"CYCLIC NUCLEOTIDE-GATED CHANNEL, BETA-1; CNGB1","url":"https://www.omim.org/entry/600724"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"kidney","ntpm":168.1}],"url":"https://www.proteinatlas.org/search/KIFC3"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9BVG8","domains":[{"cath_id":"3.40.850.10","chopping":"444-681_688-766","consensus_level":"medium","plddt":87.4115,"start":444,"end":766}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BVG8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BVG8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BVG8-F1-predicted_aligned_error_v6.png","plddt_mean":74.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIFC3","jax_strain_url":"https://www.jax.org/strain/search?query=KIFC3"},"sequence":{"accession":"Q9BVG8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BVG8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BVG8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BVG8"}},"corpus_meta":[{"pmid":"11581287","id":"PMC_11581287","title":"KIFC3, a microtubule minus end-directed motor for the apical transport of annexin XIIIb-associated Triton-insoluble membranes.","date":"2001","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11581287","citation_count":134,"is_preprint":false},{"pmid":"12135985","id":"PMC_12135985","title":"Role of KIFC3 motor protein in Golgi positioning and integration.","date":"2002","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12135985","citation_count":68,"is_preprint":false},{"pmid":"31481795","id":"PMC_31481795","title":"The balance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly.","date":"2019","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/31481795","citation_count":50,"is_preprint":false},{"pmid":"35812733","id":"PMC_35812733","title":"KIFC3 Promotes Proliferation, Migration, and Invasion in Colorectal Cancer via PI3K/AKT/mTOR Signaling Pathway.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35812733","citation_count":35,"is_preprint":false},{"pmid":"32084403","id":"PMC_32084403","title":"Microtubule Minus-End Binding Protein CAMSAP2 and Kinesin-14 Motor KIFC3 Control Dendritic Microtubule Organization.","date":"2020","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/32084403","citation_count":34,"is_preprint":false},{"pmid":"25253721","id":"PMC_25253721","title":"Minus end-directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions.","date":"2014","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/25253721","citation_count":28,"is_preprint":false},{"pmid":"11154264","id":"PMC_11154264","title":"Molecular cloning and functional analysis of mouse C-terminal kinesin motor KifC3.","date":"2001","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/11154264","citation_count":25,"is_preprint":false},{"pmid":"23954441","id":"PMC_23954441","title":"Identification of the kinesin KifC3 as a new player for positioning of peroxisomes and other organelles in mammalian cells.","date":"2013","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/23954441","citation_count":21,"is_preprint":false},{"pmid":"9782090","id":"PMC_9782090","title":"Cloning of a novel C-terminal kinesin (KIFC3) that maps to human chromosome 16q13-q21 and thus is a candidate gene for Bardet-Biedl syndrome.","date":"1998","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/9782090","citation_count":20,"is_preprint":false},{"pmid":"10375449","id":"PMC_10375449","title":"Characterization of a novel C-kinesin (KIFC3) abundantly expressed in vertebrate retina and RPE.","date":"1999","source":"Experimental eye research","url":"https://pubmed.ncbi.nlm.nih.gov/10375449","citation_count":18,"is_preprint":false},{"pmid":"36948354","id":"PMC_36948354","title":"KIFC3 regulates progression of hepatocellular carcinoma via EMT and the AKT/mTOR pathway.","date":"2023","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/36948354","citation_count":10,"is_preprint":false},{"pmid":"36890049","id":"PMC_36890049","title":"KIFC3 Regulates the progression and metastasis of gastric cancer via Notch1 pathway.","date":"2023","source":"Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver","url":"https://pubmed.ncbi.nlm.nih.gov/36890049","citation_count":8,"is_preprint":false},{"pmid":"38553728","id":"PMC_38553728","title":"Kinesin KIFC3 is essential for microtubule stability and cytokinesis in oocyte meiosis.","date":"2024","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/38553728","citation_count":8,"is_preprint":false},{"pmid":"24275865","id":"PMC_24275865","title":"KIFC3 promotes mitotic progression and integrity of the central spindle in cytokinesis.","date":"2013","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/24275865","citation_count":8,"is_preprint":false},{"pmid":"39266565","id":"PMC_39266565","title":"Transiently formed nucleus-to-cilium microtubule arrays mediate senescence initiation in a KIFC3-dependent manner.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39266565","citation_count":6,"is_preprint":false},{"pmid":"36051093","id":"PMC_36051093","title":"KIFC3 promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells by activating EMT and β-catenin signaling.","date":"2022","source":"World journal of gastrointestinal oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36051093","citation_count":6,"is_preprint":false},{"pmid":"39227687","id":"PMC_39227687","title":"KIFC3 promotes the proliferation, migration and invasion of non-small cell lung cancer through the PI3K/AKT signaling pathway.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39227687","citation_count":5,"is_preprint":false},{"pmid":"39476973","id":"PMC_39476973","title":"Transport of Golgi-localized β-catenin p-S47 by KIF11 or KIFC3 induces primary ciliogenesis.","date":"2024","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/39476973","citation_count":4,"is_preprint":false},{"pmid":"39390964","id":"PMC_39390964","title":"KIFC3 promotes the progression of non-small cell lung cancer cells through the PI3K/Akt pathway.","date":"2024","source":"Thoracic cancer","url":"https://pubmed.ncbi.nlm.nih.gov/39390964","citation_count":3,"is_preprint":false},{"pmid":"41786879","id":"PMC_41786879","title":"PMM2 interacts with TRIM28 to recruit E2F4 and promote KIFC3-mediated tumor glycolysis and colorectal cancer progression.","date":"2026","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/41786879","citation_count":0,"is_preprint":false},{"pmid":"40299423","id":"PMC_40299423","title":"Identification of KIFC3 as a Colorectal Cancer Biomarker and Its Regulatory Mechanism in the Immune Microenvironment Based on Integrated Analysis of Multi-Omics Databases.","date":"2025","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/40299423","citation_count":0,"is_preprint":false},{"pmid":"41929089","id":"PMC_41929089","title":"The Kifc3 Motor Protein Controls Centrosomal Factor Cep192 in Ontogenic Coordination of Megakaryocyte Development.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41929089","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.01.679872","title":"Cell cycle-regulated tug-of-war between microtubule motors positions major trafficking organelles","date":"2025-10-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.01.679872","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.11.18.624165","title":"Cancer-associated DAXX mutations reveal a critical role for ATRX localization in ALT suppression","date":"2024-11-20","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.18.624165","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14164,"output_tokens":4156,"usd":0.052416,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":12001,"output_tokens":4230,"usd":0.082878,"stage2_stop_reason":"end_turn"},"total_usd":0.135294,"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\": 2001,\n      \"finding\": \"KIFC3 is a minus end-directed microtubule motor protein that localizes to Triton X-100-insoluble (lipid raft) membrane organelles beneath the apical plasma membrane of polarized epithelial cells and co-immunoprecipitates and co-localizes with annexin XIIIb on apically transported TGN-derived vesicles. Overexpression of dominant-negative (motor-domainless) KIFC3 partially inhibited apical transport of influenza hemagglutinin and annexin XIIIb, while full-length KIFC3 overexpression accelerated it.\",\n      \"method\": \"Flotation assay with detergent extraction, immunoprecipitation, GST pulldown, dominant-negative overexpression in MDCK II cells, immunoelectron microscopy\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, GST pulldown, dominant-negative functional assay, and EM localization, all in one study, replicated across in vivo and in vitro systems\",\n      \"pmids\": [\"11581287\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"KIFC3 is associated with the Golgi apparatus in adrenocortical cells and is required for Golgi positioning and integration: knockout of kifC3 causes Golgi fragmentation under cholesterol-depleted conditions due to markedly reduced inward (minus-end-directed) motility of Golgi fragments. KIFC3 acts complementarily with cytoplasmic dynein in this process, and its absence exacerbates Golgi scattering caused by dynamitin overexpression even when cholesterol is present.\",\n      \"method\": \"kifC3 knockout mouse (homologous recombination), live-cell microscopy of Golgi fragment motility, dynamitin overexpression epistasis\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockout with defined cellular phenotype, epistasis with dynein pathway, cholesterol-rescue experiment, multiple orthogonal approaches in one study\",\n      \"pmids\": [\"12135985\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Mouse KifC3 is a ubiquitously expressed C-terminal (minus end-directed) kinesin. Homozygous knockout mice are viable, reproduce normally, and develop normally, indicating KifC3 is dispensable for normal development and reproduction.\",\n      \"method\": \"cDNA cloning from mouse brain library, homologous recombination knockout in embryonic stem cells, phenotypic analysis of homozygous mutants\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with phenotypic readout, single lab, negative developmental phenotype result\",\n      \"pmids\": [\"11154264\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIFC3 localizes to the central spindle bridge during cytokinesis in a motor-dependent manner and promotes efficient cytokinesis by congressing microtubules at the central bridge. Perturbation of KIFC3 function widens and extends the central bridge and delays abscission. In interphase, KIFC3 caps microtubules released from the centrosome.\",\n      \"method\": \"Loss-of-function perturbation, live-cell microscopy, immunofluorescence localization during cell cycle stages\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined cellular phenotype with loss-of-function, localization tied to functional consequence, single lab\",\n      \"pmids\": [\"24275865\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KifC3 interacts with the peroxisomal AAA-ATPase PEX1, confirmed by co-immunoprecipitation and co-localization in cells. RNAi knockdown of KifC3 causes perinuclear clustering of peroxisomes in a microtubule-dependent manner, suggesting KifC3 regulates minus-end-directed peroxisomal transport, potentially by antagonizing dynein-driven inward movement.\",\n      \"method\": \"Yeast two-hybrid (initial identification), co-immunoprecipitation, immunofluorescence co-localization, RNAi knockdown with organelle distribution readout\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP confirmed interaction, RNAi phenotype with mechanistic interpretation, single lab, two orthogonal methods\",\n      \"pmids\": [\"23954441\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KIFC3 moves into adherens junctions (AJs) via microtubules nucleated from CAMSAP3 (Nezha) clusters and recruits the deubiquitinase USP47 to AJs. Depletion of KIFC3 or USP47 leads to increased E-cadherin ubiquitination (by Hakai E3 ligase), cleavage at a juxtamembrane region producing a 90-kDa fragment, and E-cadherin internalization. KIFC3 thus suppresses E-cadherin degradation by maintaining USP47 at AJs.\",\n      \"method\": \"Co-immunoprecipitation (KIFC3–USP47 interaction), RNAi knockdown of KIFC3/USP47, proteasome inhibitor rescue, E-cadherin ubiquitination assay, immunofluorescence\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP for interaction, RNAi phenotype with biochemical readout (ubiquitination, cleavage fragment), proteasome inhibitor rescue, multiple orthogonal methods in one study\",\n      \"pmids\": [\"25253721\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"KIFC3 forms a homotetramer that provides microtubule-based centrosome cohesion during mitotic onset, pulling two centrosomes together via a specific microtubule network. KIFC3-mediated cohesion counteracts EG5-driven separation forces to prevent premature spindle formation after linker dissolution. KIFC3 is inactivated by NEK2 kinase to allow bipolar spindle assembly. Persistent centrosome cohesion in mitosis causes chromosome mis-segregation.\",\n      \"method\": \"KIFC3 knockout/depletion, biochemical characterization of homotetramer assembly, live-cell microscopy of centrosome dynamics, epistasis with EG5 and NEK2, chromosome segregation assay\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — homotetramer biochemically characterized, multiple genetic epistasis experiments, live imaging, functional assay with defined phenotype, published in high-tier journal\",\n      \"pmids\": [\"31481795\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"KIFC3 has a dendrite-specific distribution in neurons and interacts with the microtubule minus-end binding protein CAMSAP2. Depletion of KIFC3 or CAMSAP2 increases microtubule dynamics during dendritic development. CAMSAP2 anchors KIFC3 at microtubule minus ends to immobilize microtubule arrays in dendrites, organizing the mixed anti-parallel microtubule polarity characteristic of dendrites.\",\n      \"method\": \"Co-immunoprecipitation (KIFC3–CAMSAP2 interaction), shRNA knockdown in neurons, live imaging of microtubule dynamics, immunofluorescence for KIFC3 dendritic distribution\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP for interaction, RNAi with live-imaging phenotype, mechanistic model with multiple orthogonal methods, single lab but rigorous\",\n      \"pmids\": [\"32084403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KIFC3 is essential for spindle assembly and cytokinesis during mouse oocyte meiosis. KIFC3 localizes to centromeres at metaphase I and translocates to the midbody at telophase I. Disruption of KIFC3 causes defective polar body extrusion, aberrant meiotic spindles, chromosome misalignment, and loss of kinetochore-microtubule attachment associated with failed BubR1/Bub3 recruitment. KIFC3 interacts with Sirt2 to maintain acetylated tubulin levels and microtubule stability, and interacts with PRC1 to regulate midbody formation.\",\n      \"method\": \"Immunofluorescence localization, KIFC3 activity disruption, co-immunoprecipitation (KIFC3–Sirt2, KIFC3–PRC1), acetylated tubulin assay, polar body extrusion and spindle integrity assays\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP for two interactions, defined meiotic phenotypes with specific molecular readouts, single lab\",\n      \"pmids\": [\"38553728\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In stressed cells undergoing senescence, KIFC3 is recruited to plus-ends of stress-induced nucleus-to-cilium microtubule arrays (sinc-MTs, which are polyglutamylated with minus-ends near the nuclear envelope) and interacts with centrosomal protein CENEXIN1. KIFC3 mediates nuclear transport of FBF1 along sinc-MTs to PML nuclear bodies. Deficiency of KIFC3 abolishes PML-NB translocation of FBF1 and CENEXIN1, and prevents senescence initiation.\",\n      \"method\": \"Immunofluorescence and live imaging of sinc-MTs, KIFC3 knockout/knockdown, co-immunoprecipitation (KIFC3–CENEXIN1), FBF1/CENEXIN1 translocation assay, senescence assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with specific molecular phenotype (failed PML-NB translocation), Co-IP interaction, live imaging, multiple orthogonal methods in one study\",\n      \"pmids\": [\"39266565\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KIFC3 physically interacts with PI3K p85α subunit, as confirmed by co-immunoprecipitation of endogenous and exogenous proteins, and promotes PI3K/AKT pathway activation to drive NSCLC cell proliferation, migration, and invasion.\",\n      \"method\": \"Co-immunoprecipitation (endogenous and exogenous KIFC3 with PI3Kp85α), western blot of pathway components, KIFC3 overexpression/knockdown with PI3K inhibitor (LY294002) rescue, xenograft tumor model\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP confirms direct interaction, inhibitor rescue confirms pathway dependency, single lab\",\n      \"pmids\": [\"39227687\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KIFC3 interacts with β-catenin phosphorylated at S47 (β-catenin p-S47), with lower binding affinity observed for S47A mutant. Knockdown of KIFC3 reduces β-catenin p-S47 at the centrosome and causes primary cilia deficiency, while β-catenin p-S47 accumulates in the Golgi. KIFC3 thus participates in transport of β-catenin p-S47 from the Golgi to the centrosome to promote primary ciliogenesis.\",\n      \"method\": \"Co-immunoprecipitation (KIFC3–β-catenin p-S47), binding affinity comparison with S47A mutant, KIFC3 knockdown with primary cilia and β-catenin localization readout\",\n      \"journal\": \"Molecules and cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP with mutant comparison, knockdown phenotype with localization readout, single lab\",\n      \"pmids\": [\"39476973\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In G1 phase, KIFC3 drives minus-end-directed compaction of ERES (endoplasmic reticulum exit sites) near the centrosome in a CDK1-signaling-dependent tug-of-war with plus-end-directed motors. In S/G2, kinesin-1 overcomes KIFC3 to allow ERES dispersion.\",\n      \"method\": \"Loss-of-function approaches (RNAi/knockdown), live-cell microscopy, cell cycle staging, CDK1 inhibition\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint, single lab, loss-of-function with organelle positioning readout but limited mechanistic detail in abstract\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In megakaryocytes, Kifc3 acts as a minus-end-directed motor for centrosomal delivery of cargos and controls centrosomal localization of Cep192. Kifc3 knockdown in neonatal megakaryocytes causes Cep192 upregulation and dispersion from the centrosome, inducing adult-type morphogenesis with augmented platelet release. A small molecule Kifc3 inhibitor identified in silico recapitulated this effect.\",\n      \"method\": \"shRNA knockdown in neonatal megakaryocytes, immunofluorescence for Cep192 localization, in silico inhibitor screening with functional validation in vitro and in vivo\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint, RNAi phenotype with localization readout, no direct binding assay for KIFC3–Cep192 interaction shown in abstract\",\n      \"pmids\": [\"41929089\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"KIFC3 is a minus-end-directed kinesin-14 motor that forms homotetramers and functions in multiple cellular contexts: it drives apical vesicle transport in polarized epithelial cells by associating with annexin XIIIb-containing lipid raft organelles; maintains Golgi positioning via minus-end-directed motility complementary to dynein; provides microtubule-based centrosome cohesion at mitotic onset (counteracting EG5) until inactivated by NEK2; organizes dendritic microtubule arrays by anchoring to CAMSAP2 at microtubule minus-ends; protects E-cadherin at adherens junctions by recruiting the deubiquitinase USP47 (thereby suppressing Hakai-mediated ubiquitination and degradation); regulates meiotic spindle stability and cytokinesis through interactions with Sirt2 and PRC1; and mediates nuclear transport of the senescence effector FBF1 along polyglutamylated sinc-MTs to PML nuclear bodies via interaction with CENEXIN1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIFC3 is a minus-end-directed (C-terminal) kinesin motor that uses microtubule-based transport and minus-end anchoring to position organelles, stabilize microtubule arrays, and organize the centrosome across diverse cellular contexts [#0, #2, #6]. In polarized epithelial cells it associates with annexin XIIIb on lipid-raft membrane organelles to drive apical vesicle transport [#0], and it maintains Golgi positioning by supplying inward, minus-end-directed motility that acts complementarily to cytoplasmic dynein [#1]. At microtubule minus ends KIFC3 is anchored by CAMSAP family proteins: CAMSAP3-nucleated microtubules deliver KIFC3 to adherens junctions, where it recruits the deubiquitinase USP47 to protect E-cadherin from Hakai-mediated ubiquitination, cleavage, and degradation [#5], while CAMSAP2 anchors KIFC3 at minus ends to immobilize and organize the mixed-polarity microtubule arrays of dendrites [#7]. In mitosis, KIFC3 assembles into a homotetramer that generates microtubule-based centrosome cohesion counteracting EG5-driven separation, and it is inactivated by NEK2 to license bipolar spindle assembly; persistent cohesion causes chromosome mis-segregation [#6]. KIFC3 also localizes to the central spindle to promote cytokinesis [#3], and during oocyte meiosis it supports spindle assembly and midbody formation through interactions with Sirt2 (maintaining acetylated tubulin) and PRC1 [#8]. In stressed cells it is recruited to polyglutamylated nucleus-to-cilium microtubule arrays and, via CENEXIN1, transports the senescence effector FBF1 to PML nuclear bodies to initiate senescence [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established KIFC3 as a minus-end-directed motor with a defined transport cargo, linking it to apical membrane trafficking in polarized epithelia.\",\n      \"evidence\": \"Flotation/detergent extraction, reciprocal Co-IP and GST pulldown with annexin XIIIb, dominant-negative overexpression and immuno-EM in MDCK II cells\",\n      \"pmids\": [\"11581287\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Motor velocity and processivity not measured in vitro\", \"Mechanism coupling motor to raft organelle not defined\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Determined that KifC3 is ubiquitously expressed yet dispensable for mouse development and reproduction, indicating functional redundancy in vivo.\",\n      \"evidence\": \"cDNA cloning and homologous-recombination knockout mice with phenotypic analysis\",\n      \"pmids\": [\"11154264\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No conditional/tissue-specific analysis\", \"Redundant motors not identified\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Showed KIFC3 supplies minus-end-directed motility for Golgi positioning, working complementarily with dynein rather than redundantly.\",\n      \"evidence\": \"kifC3 knockout mouse cells, live imaging of Golgi fragment motility, cholesterol depletion and dynamitin overexpression epistasis\",\n      \"pmids\": [\"12135985\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct adaptor linking KIFC3 to Golgi membranes unknown\", \"Cholesterol-dependence mechanism not resolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Extended KIFC3 function to cytokinesis, where motor-dependent localization to the central bridge promotes efficient abscission.\",\n      \"evidence\": \"Loss-of-function perturbation, live-cell microscopy and cell-cycle immunofluorescence\",\n      \"pmids\": [\"24275865\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Central-bridge binding partners not identified\", \"Single-lab loss-of-function only\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Implicated KIFC3 in peroxisome positioning via PEX1, broadening its organelle-transport roles.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, co-localization and RNAi with peroxisome distribution readout\",\n      \"pmids\": [\"23954441\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding interface with PEX1 not mapped\", \"Antagonism with dynein inferred, not demonstrated biochemically\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Revealed a non-transport scaffolding role: KIFC3 at adherens junctions recruits USP47 to protect E-cadherin from ubiquitin-dependent degradation.\",\n      \"evidence\": \"Co-IP of KIFC3–USP47, RNAi of KIFC3/USP47, E-cadherin ubiquitination assay, proteasome inhibitor rescue, immunofluorescence\",\n      \"pmids\": [\"25253721\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether motor activity is required for USP47 delivery unclear\", \"Structural basis of KIFC3–USP47 interaction unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined the mitotic mechanism of KIFC3 centrosome cohesion: a homotetramer generates pulling forces opposing EG5 and is switched off by NEK2 to permit spindle bipolarity.\",\n      \"evidence\": \"Knockout/depletion, biochemical homotetramer characterization, live imaging, EG5/NEK2 epistasis, chromosome segregation assay\",\n      \"pmids\": [\"31481795\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"NEK2 phosphosites on KIFC3 not mapped\", \"Structure of the cohesion microtubule network not resolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Showed CAMSAP2 anchors KIFC3 at microtubule minus ends to immobilize and organize dendritic microtubule arrays, establishing a minus-end anchoring function.\",\n      \"evidence\": \"Co-IP of KIFC3–CAMSAP2, shRNA in neurons, live imaging of microtubule dynamics, dendritic immunofluorescence\",\n      \"pmids\": [\"32084403\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How KIFC3 immobilizes minus ends mechanistically not resolved\", \"Relationship to axonal microtubules not addressed\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established KIFC3 as essential for meiotic spindle stability and cytokinesis through Sirt2 (tubulin acetylation) and PRC1 (midbody) interactions.\",\n      \"evidence\": \"Immunofluorescence, activity disruption, Co-IP of KIFC3–Sirt2 and KIFC3–PRC1, acetylated-tubulin and polar-body assays in mouse oocytes\",\n      \"pmids\": [\"38553728\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect nature of Sirt2/PRC1 interactions not dissected\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Linked KIFC3 to senescence initiation by transporting FBF1 along polyglutamylated sinc-MTs to PML nuclear bodies via CENEXIN1.\",\n      \"evidence\": \"Live imaging of sinc-MTs, KIFC3 knockout/knockdown, Co-IP of KIFC3–CENEXIN1, FBF1/CENEXIN1 translocation and senescence assays\",\n      \"pmids\": [\"39266565\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How KIFC3 selects FBF1 as cargo unknown\", \"Trigger for sinc-MT polyglutamylation not defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Implicated KIFC3 in oncogenic signaling through physical interaction with PI3K p85α driving PI3K/AKT activation in NSCLC.\",\n      \"evidence\": \"Endogenous/exogenous Co-IP with p85α, pathway western blots, overexpression/knockdown with LY294002 rescue, xenograft model\",\n      \"pmids\": [\"39227687\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether interaction requires motor function unknown\", \"Single-lab, one cancer type\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Proposed a ciliogenesis role: KIFC3 transports phospho-S47 β-catenin from Golgi to centrosome to support primary cilia formation.\",\n      \"evidence\": \"Co-IP of KIFC3 with β-catenin p-S47, S47A binding comparison, knockdown with cilia and localization readouts\",\n      \"pmids\": [\"39476973\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct phospho-dependent binding interface not mapped\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Suggested KIFC3 controls centrosomal Cep192 localization to govern megakaryocyte maturation and platelet release, with a candidate small-molecule inhibitor.\",\n      \"evidence\": \"shRNA in neonatal megakaryocytes, Cep192 immunofluorescence, in silico inhibitor screen with in vitro/in vivo validation (preprint)\",\n      \"pmids\": [\"41929089\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct KIFC3–Cep192 binding assay shown\", \"Preprint, not peer reviewed\", \"Inhibitor specificity not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single minus-end-directed motor is selectively targeted to its many distinct cargos and contexts (apical vesicles, Golgi, junctions, centrosomes, sinc-MTs) and how its activity is switched between transport and anchoring/scaffolding roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No unified model of cargo-adaptor selection\", \"Regulatory switches beyond NEK2 unknown\", \"No high-resolution structure of motor–cargo complexes\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 1, 6]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [6, 7]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1, 11]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [6, 9, 11]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [7, 9]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0005777\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3, 6]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 1, 9]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"complexes\": [\"KIFC3 homotetramer\"],\n    \"partners\": [\"ANXA13B\", \"USP47\", \"CAMSAP2\", \"CAMSAP3\", \"PEX1\", \"PRC1\", \"SIRT2\", \"CENEXIN1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}