{"gene":"KIF20B","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2001,"finding":"KIF20B/KRMP1 has an intrinsic ATPase activity in its N-terminal motor domain that is diminished by substituting the conserved Lys-168 with Arg; the central stalk domain forms a coiled-coil and can self-interact in vivo; the protein is phosphorylated in vivo with Thr-1604 identified as a cdc2 kinase phosphorylation site in the tail domain; KIF20B interacts with the mitotic peptidyl-prolyl isomerase Pin1 in vivo, with the tail domain binding the WW domain of Pin1 in vitro; overexpression causes G2-M arrest that is reversed by co-expression of Pin1.","method":"In vitro ATPase assay, site-directed mutagenesis (K168R), in vivo co-immunoprecipitation, in vitro pull-down (tail domain vs. WW domain), in vivo phosphorylation labeling, immunofluorescence, cell-cycle analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay with active-site mutagenesis plus multiple orthogonal binding/functional assays in a single focused study","pmids":["11470801"],"is_preprint":false},{"year":2007,"finding":"KIF20B/MPHOSPH1 physically interacts with PRC1 (protein regulator of cytokinesis 1) in bladder cancer cells; the two proteins colocalize at the midbody; knockdown of either protein by siRNA causes multinucleate cells and subsequent cell death, indicating the MPHOSPH1/PRC1 complex is required for cytokinesis.","method":"Co-immunoprecipitation, immunocytochemistry (colocalization), siRNA knockdown with phenotypic readout (multinucleation, cell death)","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP and colocalization plus functional KD phenotype, single lab","pmids":["17409436"],"is_preprint":false},{"year":2013,"finding":"KIF20B directly interacts with Shootin1 via a 57-amino-acid minimal binding domain (MBD) in its tail; binding affinity is ~10⁻⁷ M by surface plasmon resonance; the KIF20B/Shootin1 complex forms in vivo in developing brain; KIF20B is required for transport/mobilization of Shootin1 cargo to the developing axon (Shootin1 acts as a KIF20B cargo); the KIF20B/Shootin1 pathway promotes PIP3 accumulation in the growth cone and the multipolar-to-bipolar transition of migrating neurons; genetic epistasis shows Shootin1 and Kif20b act in the same pathway.","method":"Surface plasmon resonance (direct binding, Kd determination), co-immunoprecipitation, immunostaining, FRAP (Shootin1 mobilization), shRNA knockdown, dominant-negative MBD fragment, in vivo migration assay, epistasis analysis","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct binding measured by SPR with Kd, confirmed by Co-IP and functional FRAP, plus genetic epistasis; multiple orthogonal methods in single study","pmids":["23864681"],"is_preprint":false},{"year":2013,"finding":"Kif20b is required for normal cytokinesis of polarized cortical neural stem cells; in the loss-of-function (magoo) mouse mutant, midbody number, shape, and apical positioning are abnormal, indicating a role in midbody organization and abscission; disrupted abscission leads to apoptosis rather than binucleation, resulting in microcephaly.","method":"Loss-of-function mouse mutant (forward genetic screen), fixed and live imaging of midbodies, cortical cell counting, apoptosis assays","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean loss-of-function mutant with specific cellular phenotype (midbody defects, apoptosis, microcephaly) replicated across multiple analyses","pmids":["24173802"],"is_preprint":false},{"year":2014,"finding":"Knockdown of KIF20B/MPHOSPH1 in hepatocellular carcinoma cells stabilizes p53 and blocks STAT3 phosphorylation, prolonging mitotic arrest and inducing postmitotic apoptosis; these effects are associated with multinucleated polyploid cell accumulation.","method":"shRNA-mediated knockdown (Ad-shMPP1), Western blot for p53 and phospho-STAT3, flow cytometry, xenograft mouse model","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD with defined molecular readouts (p53, STAT3) plus in vivo validation, single lab","pmids":["25269478"],"is_preprint":false},{"year":2017,"finding":"KIF20B localizes to central spindle microtubules and the midbody throughout cytokinesis at sites distinct from KIF23/MKLP1 and KIF20A/MKLP2; siRNA depletion slows furrow ingression speed and delays abscission; KIF20B is not required for midbody assembly but coordinates late midbody maturation steps including anillin dispersal, ESCRT-III recruitment, and microtubule constriction site formation.","method":"siRNA knockdown in human cell line, fixed and live imaging (time-lapse), quantification of furrow ingression kinetics, immunostaining for anillin and ESCRT-III components","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean KD with quantitative live-imaging phenotype and multiple molecular markers; direct localization with functional consequence","pmids":["29167382"],"is_preprint":false},{"year":2017,"finding":"Loss of Kif20b in mouse cortical neurons causes defects in neuronal polarization, axon outgrowth, neurite branching, and axon caliber; mutant axons have increased width, longer growth cone filopodia, and abnormal microtubule organization; Shootin1 is lost from the axonal growth cone in Kif20b mutants, linking KIF20B-dependent Shootin1 localization to proper neurite morphogenesis.","method":"Kif20b loss-of-function mouse mutant, in vivo and in vitro cortical neuron labeling and imaging, live-imaging of axon extension, immunostaining for Shootin1","journal":"Neural development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean mouse KO with specific morphological and molecular phenotypes; single lab, multiple readouts","pmids":["28359322"],"is_preprint":false},{"year":2019,"finding":"USP7 stabilizes FBXO38 via its deubiquitylase catalytic activity (protecting FBXO38 from proteasomal degradation); FBXO38 in turn stabilizes KIF20B independently of an SCF complex; depletion of USP7 or FBXO38 dramatically reduces KIF20B protein levels and KIF20B at the midbody, causing cytokinetic defects; restoring FBXO38 or KIF20B rescues cytokinetic defects caused by USP7 silencing.","method":"Affinity purification–mass spectrometry (USP7 interactome), BioID (FBXO38 interactome), co-immunoprecipitation, siRNA knockdown, Western blot, immunofluorescence of midbody, rescue experiments","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal AP-MS and BioID interaction profiling plus functional rescue experiments establishing epistatic order USP7→FBXO38→KIF20B","pmids":["30804394"],"is_preprint":false},{"year":2019,"finding":"KIF20B protein has microtubule-binding and microtubule-bundling properties as well as microtubule-stimulated ATPase activity in vitro; it functions as a slow plus-end-directed motor; during interphase it localizes to a proportion of nuclei, redistributes during metaphase to cytoplasm/perichromatin, and localizes to the midbody stem body/midzone during telophase/anaphase.","method":"In vitro microtubule-binding and bundling assays, in vitro ATPase assay, indirect immunofluorescence with monoclonal antibody (10C7) in HEp2 cells and tissue sections","journal":"Monoclonal antibodies in immunodiagnosis and immunotherapy","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical assays confirming motor and bundling activity, but single antibody characterization paper with limited mechanistic follow-up","pmids":["31260385"],"is_preprint":false},{"year":2018,"finding":"KIF20B localizes to pseudopod protrusions of colorectal cancer cells and influences invadopodia formation; KIF20B overexpression promotes EMT mediated by Gli1, and this process is modulated by intracellular actin dynamics.","method":"Immunofluorescence localization, siRNA/overexpression in CRC cell lines, migration/invasion assays, actin dynamics analysis","journal":"Molecular carcinogenesis","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization and KD/OE phenotype in cancer cells with partial pathway placement (Gli1/EMT/actin), single lab, limited mechanistic depth","pmids":["29573464"],"is_preprint":false}],"current_model":"KIF20B is a vertebrate-specific Kinesin-6 family motor with intrinsic microtubule-stimulated ATPase activity and plus-end-directed motility; it localizes to the central spindle and midbody during cytokinesis where it promotes efficient furrow ingression and coordinates late midbody maturation (anillin dispersal, ESCRT-III recruitment, microtubule constriction), and its protein levels are regulated by a USP7→FBXO38→KIF20B stabilization cascade; in neural development it transports Shootin1 cargo to the axonal growth cone to drive neuronal polarization and migration, and loss-of-function causes midbody disorganization, failed abscission, apoptosis, and microcephaly."},"narrative":{"mechanistic_narrative":"KIF20B is a Kinesin-6 family motor that drives cytokinesis and neuronal morphogenesis through plus-end-directed transport on microtubules [PMID:11470801, PMID:31260385]. Its N-terminal motor domain has intrinsic, microtubule-stimulated ATPase activity dependent on the conserved Lys-168, and the protein binds and bundles microtubules while acting as a slow plus-end-directed motor [PMID:11470801, PMID:31260385]. During cytokinesis KIF20B localizes to central spindle microtubules and the midbody at sites distinct from KIF23/MKLP1 and KIF20A/MKLP2, where it is dispensable for midbody assembly but required to promote efficient furrow ingression and to coordinate late midbody maturation—anillin dispersal, ESCRT-III recruitment, and microtubule constriction-site formation [PMID:29167382]; it cooperates with PRC1 at the midbody, and loss of either causes multinucleation and death [PMID:17409436]. KIF20B protein abundance is controlled by a USP7→FBXO38→KIF20B stabilization cascade in which the deubiquitylase USP7 protects FBXO38, which in turn stabilizes KIF20B and maintains its midbody pool [PMID:30804394]. In neural development KIF20B binds Shootin1 through a 57-residue tail domain and transports this cargo to the axonal growth cone, promoting PIP3 accumulation and the multipolar-to-bipolar transition during cortical neuron migration and axon morphogenesis [PMID:23864681, PMID:28359322]. Loss of Kif20b disrupts midbody organization and abscission in cortical neural stem cells, leading to apoptosis and microcephaly [PMID:24173802].","teleology":[{"year":2001,"claim":"Established KIF20B as a bona fide motor enzyme by demonstrating intrinsic ATPase activity in its motor domain and linking its mitotic behavior to phosphoregulation and Pin1.","evidence":"In vitro ATPase assay with K168R active-site mutant, co-IP and pull-down with Pin1, in vivo phospho-labeling and cell-cycle analysis","pmids":["11470801"],"confidence":"High","gaps":["No microtubule-dependent motility or directionality assessed","Functional consequence of Pin1 binding and Thr-1604 phosphorylation on motor activity unresolved"]},{"year":2007,"claim":"Placed KIF20B in the cytokinesis machinery by showing it complexes with PRC1 at the midbody and is required to complete cell division.","evidence":"Reciprocal co-IP, midbody colocalization, and siRNA knockdown causing multinucleation/death in bladder cancer cells","pmids":["17409436"],"confidence":"Medium","gaps":["Direct vs. indirect nature of the PRC1 interaction not resolved","Single cell-type context"]},{"year":2013,"claim":"Defined a distinct neurodevelopmental role by identifying Shootin1 as a direct KIF20B cargo whose transport drives neuronal polarization.","evidence":"SPR Kd determination, co-IP from developing brain, FRAP-based cargo mobilization, shRNA, dominant-negative MBD, in vivo migration and epistasis","pmids":["23864681"],"confidence":"High","gaps":["Whether motor ATPase activity drives Shootin1 transport not directly tested","Mechanism of PIP3 accumulation downstream of Shootin1 delivery unclear"]},{"year":2013,"claim":"Connected KIF20B cytokinesis function to organismal phenotype, showing abscission failure in neural stem cells causes apoptosis and microcephaly rather than binucleation.","evidence":"magoo loss-of-function mouse mutant with midbody imaging, cortical cell counting, apoptosis assays","pmids":["24173802"],"confidence":"High","gaps":["Molecular step of abscission requiring KIF20B not pinpointed in this study","Link between midbody mispositioning and apoptosis mechanistically undefined"]},{"year":2014,"claim":"Linked KIF20B loss to p53/STAT3 signaling outcomes, framing its depletion as a route to mitotic arrest and postmitotic apoptosis in cancer.","evidence":"shRNA knockdown in hepatocellular carcinoma cells, Western blot for p53/phospho-STAT3, flow cytometry, xenograft","pmids":["25269478"],"confidence":"Medium","gaps":["Whether p53/STAT3 effects are direct or secondary to cytokinesis failure unclear","No mechanistic connection between KIF20B motor activity and STAT3 phosphorylation"]},{"year":2017,"claim":"Resolved the precise cytokinetic step KIF20B serves, distinguishing it from other Kinesin-6 motors and assigning it to late midbody maturation.","evidence":"siRNA in human cells with quantitative live imaging of furrow ingression and immunostaining for anillin and ESCRT-III","pmids":["29167382"],"confidence":"High","gaps":["How KIF20B coordinates anillin dispersal and ESCRT-III recruitment mechanistically unknown","Direct binding partners at the constriction site not identified"]},{"year":2017,"claim":"Extended the Shootin1-transport model to neurite morphogenesis, showing KIF20B-dependent growth-cone Shootin1 localization shapes axon caliber and branching.","evidence":"Kif20b mouse mutant cortical neurons with in vivo/in vitro imaging, live axon-extension imaging, Shootin1 immunostaining","pmids":["28359322"],"confidence":"Medium","gaps":["Cause of abnormal microtubule organization in mutant axons not defined","Whether axon defects are cell-autonomous transport defects vs. cytokinesis history unclear"]},{"year":2019,"claim":"Identified an upstream stability pathway controlling KIF20B abundance, defining the epistatic order USP7→FBXO38→KIF20B for midbody function.","evidence":"AP-MS, BioID, co-IP, siRNA, Western blot, midbody immunofluorescence, and rescue experiments","pmids":["30804394"],"confidence":"High","gaps":["Mechanism by which FBXO38 stabilizes KIF20B independent of SCF unresolved","Whether stabilization is regulated dynamically across the cell cycle unknown"]},{"year":2019,"claim":"Confirmed KIF20B as a microtubule-binding, microtubule-bundling, slow plus-end-directed motor and described its cell-cycle-dependent redistribution.","evidence":"In vitro microtubule-binding/bundling and ATPase assays plus monoclonal-antibody immunofluorescence in HEp2 cells and tissue","pmids":["31260385"],"confidence":"Medium","gaps":["Single-antibody localization with limited mechanistic follow-up","Functional role of interphase nuclear localization undefined"]},{"year":2018,"claim":"Implicated KIF20B in cancer cell invasion via pseudopod/invadopodia localization and Gli1-mediated EMT.","evidence":"Immunofluorescence, siRNA/overexpression in colorectal cancer lines, migration/invasion assays, actin dynamics analysis","pmids":["29573464"],"confidence":"Low","gaps":["Low-confidence single-lab study with limited mechanistic depth","Connection between motor activity, actin dynamics, and Gli1 not established","Direct partners in invadopodia unidentified"]},{"year":null,"claim":"How KIF20B mechanically couples its plus-end-directed motor activity to specific late-abscission events (anillin dispersal, ESCRT-III recruitment, constriction-site formation) and whether the same motor activity powers Shootin1 cargo transport remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model linking motor cycle to midbody maturation steps","Direct effectors recruited by KIF20B at the constriction site unknown","Motor-dependence of Shootin1 transport not directly demonstrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[0,8]},{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[8]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[8]},{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[8,5]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[8]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,3,5,7]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2,6,3]}],"complexes":[],"partners":["PRC1","SHOOTIN1","PIN1","FBXO38","USP7"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96Q89","full_name":"Kinesin-like protein KIF20B","aliases":["Cancer/testis antigen 90","CT90","Kinesin family member 20B","Kinesin-related motor interacting with PIN1","M-phase phosphoprotein 1","MPP1"],"length_aa":1820,"mass_kda":210.6,"function":"Plus-end-directed motor enzyme that is required for completion of cytokinesis (PubMed:11470801, PubMed:12740395). Required for proper midbody organization and abscission in polarized cortical stem cells. Plays a role in the regulation of neuronal polarization by mediating the transport of specific cargos. Participates in the mobilization of SHTN1 and in the accumulation of PIP3 in the growth cone of primary hippocampal neurons in a tubulin and actin-dependent manner. In the developing telencephalon, cooperates with SHTN1 to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in cerebral cortex growth (By similarity). Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436)","subcellular_location":"Nucleus; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Nucleus, nucleolus; Nucleus, nucleoplasm; Cytoplasm, cytoskeleton, spindle; Cytoplasm, cytoskeleton, spindle pole; Midbody; Cell projection, axon; Cell projection, growth cone","url":"https://www.uniprot.org/uniprotkb/Q96Q89/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KIF20B","classification":"Not Classified","n_dependent_lines":146,"n_total_lines":1208,"dependency_fraction":0.12086092715231789},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"KPNA4","stoichiometry":0.2},{"gene":"KPNB1","stoichiometry":0.2},{"gene":"NCAPH","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KIF20B","total_profiled":1310},"omim":[{"mim_id":"605498","title":"KINESIN FAMILY MEMBER 20B; KIF20B","url":"https://www.omim.org/entry/605498"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytokinetic bridge","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Midbody","reliability":"Additional"},{"location":"Centrosome","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"},{"location":"Perinuclear theca","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":9.6},{"tissue":"lymphoid tissue","ntpm":9.1}],"url":"https://www.proteinatlas.org/search/KIF20B"},"hgnc":{"alias_symbol":["MPP1","KRMP1","CT90"],"prev_symbol":["MPHOSPH1"]},"alphafold":{"accession":"Q96Q89","domains":[{"cath_id":"3.40.850.10","chopping":"61-96_108-228_263-478","consensus_level":"medium","plddt":86.4295,"start":61,"end":478},{"cath_id":"1.10.287","chopping":"1355-1423_1442-1552","consensus_level":"medium","plddt":75.4898,"start":1355,"end":1552}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96Q89","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96Q89-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96Q89-F1-predicted_aligned_error_v6.png","plddt_mean":62.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KIF20B","jax_strain_url":"https://www.jax.org/strain/search?query=KIF20B"},"sequence":{"accession":"Q96Q89","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96Q89.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96Q89/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96Q89"}},"corpus_meta":[{"pmid":"17409436","id":"PMC_17409436","title":"Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer.","date":"2007","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/17409436","citation_count":91,"is_preprint":false},{"pmid":"25269478","id":"PMC_25269478","title":"MPHOSPH1: a potential therapeutic target for hepatocellular carcinoma.","date":"2014","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/25269478","citation_count":46,"is_preprint":false},{"pmid":"23864681","id":"PMC_23864681","title":"Shootin1 acts in concert with KIF20B to promote polarization of migrating neurons.","date":"2013","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/23864681","citation_count":44,"is_preprint":false},{"pmid":"24173802","id":"PMC_24173802","title":"The vertebrate-specific Kinesin-6, Kif20b, is required for normal cytokinesis of polarized cortical stem cells and cerebral cortex size.","date":"2013","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/24173802","citation_count":43,"is_preprint":false},{"pmid":"29167382","id":"PMC_29167382","title":"Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely abscission in human cells.","date":"2017","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/29167382","citation_count":37,"is_preprint":false},{"pmid":"28359322","id":"PMC_28359322","title":"Mutation of Kinesin-6 Kif20b causes defects in cortical neuron polarization and morphogenesis.","date":"2017","source":"Neural development","url":"https://pubmed.ncbi.nlm.nih.gov/28359322","citation_count":35,"is_preprint":false},{"pmid":"30804394","id":"PMC_30804394","title":"USP7 Regulates Cytokinesis through FBXO38 and KIF20B.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30804394","citation_count":29,"is_preprint":false},{"pmid":"11470801","id":"PMC_11470801","title":"Identification of a novel kinesin-related protein, KRMP1, as a target for mitotic peptidyl-prolyl isomerase Pin1.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11470801","citation_count":29,"is_preprint":false},{"pmid":"30805928","id":"PMC_30805928","title":"KIF20B promotes the progression of clear cell renal cell carcinoma by stimulating cell proliferation.","date":"2019","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30805928","citation_count":27,"is_preprint":false},{"pmid":"29573464","id":"PMC_29573464","title":"Pseudopod-associated protein KIF20B promotes Gli1-induced epithelial-mesenchymal transition modulated by pseudopodial actin dynamic in human colorectal cancer.","date":"2018","source":"Molecular carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/29573464","citation_count":23,"is_preprint":false},{"pmid":"34539784","id":"PMC_34539784","title":"KIF20B Promotes Cell Proliferation and May Be a Potential Therapeutic Target in Pancreatic Cancer.","date":"2021","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/34539784","citation_count":12,"is_preprint":false},{"pmid":"31260385","id":"PMC_31260385","title":"A Monoclonal Antibody to M-Phase Phosphoprotein 1/Kinesin-Like Protein KIF20B.","date":"2019","source":"Monoclonal antibodies in immunodiagnosis and immunotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/31260385","citation_count":10,"is_preprint":false},{"pmid":"38599670","id":"PMC_38599670","title":"Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus.","date":"2024","source":"Lupus science & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38599670","citation_count":4,"is_preprint":false},{"pmid":"38305288","id":"PMC_38305288","title":"KIF20B Correlates with LUAD Progression and Is an Independent Risk Factor.","date":"2024","source":"Critical reviews in eukaryotic gene expression","url":"https://pubmed.ncbi.nlm.nih.gov/38305288","citation_count":2,"is_preprint":false},{"pmid":"30519350","id":"PMC_30519350","title":"Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor.","date":"2018","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30519350","citation_count":1,"is_preprint":false},{"pmid":"40229707","id":"PMC_40229707","title":"Inhibition of miR-325 inhibits KIF20B expression and the colorectal cancer cells' invasion & proliferation.","date":"2025","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/40229707","citation_count":1,"is_preprint":false},{"pmid":"37102216","id":"PMC_37102216","title":"Anti-KIF20B autoantibodies in systemic autoimmune rheumatic diseases: Their high prevalence in systemic lupus erythematosus.","date":"2023","source":"The Journal of dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/37102216","citation_count":1,"is_preprint":false},{"pmid":"40435336","id":"PMC_40435336","title":"RETRACTION: KIF20B Promotes Cell Proliferation and May Be a Potential Therapeutic Target in Pancreatic Cancer.","date":"2025","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40435336","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10715,"output_tokens":2933,"usd":0.03807,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10228,"output_tokens":3505,"usd":0.069382,"stage2_stop_reason":"end_turn"},"total_usd":0.107452,"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\": \"KIF20B/KRMP1 has an intrinsic ATPase activity in its N-terminal motor domain that is diminished by substituting the conserved Lys-168 with Arg; the central stalk domain forms a coiled-coil and can self-interact in vivo; the protein is phosphorylated in vivo with Thr-1604 identified as a cdc2 kinase phosphorylation site in the tail domain; KIF20B interacts with the mitotic peptidyl-prolyl isomerase Pin1 in vivo, with the tail domain binding the WW domain of Pin1 in vitro; overexpression causes G2-M arrest that is reversed by co-expression of Pin1.\",\n      \"method\": \"In vitro ATPase assay, site-directed mutagenesis (K168R), in vivo co-immunoprecipitation, in vitro pull-down (tail domain vs. WW domain), in vivo phosphorylation labeling, immunofluorescence, cell-cycle analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay with active-site mutagenesis plus multiple orthogonal binding/functional assays in a single focused study\",\n      \"pmids\": [\"11470801\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"KIF20B/MPHOSPH1 physically interacts with PRC1 (protein regulator of cytokinesis 1) in bladder cancer cells; the two proteins colocalize at the midbody; knockdown of either protein by siRNA causes multinucleate cells and subsequent cell death, indicating the MPHOSPH1/PRC1 complex is required for cytokinesis.\",\n      \"method\": \"Co-immunoprecipitation, immunocytochemistry (colocalization), siRNA knockdown with phenotypic readout (multinucleation, cell death)\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP and colocalization plus functional KD phenotype, single lab\",\n      \"pmids\": [\"17409436\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KIF20B directly interacts with Shootin1 via a 57-amino-acid minimal binding domain (MBD) in its tail; binding affinity is ~10⁻⁷ M by surface plasmon resonance; the KIF20B/Shootin1 complex forms in vivo in developing brain; KIF20B is required for transport/mobilization of Shootin1 cargo to the developing axon (Shootin1 acts as a KIF20B cargo); the KIF20B/Shootin1 pathway promotes PIP3 accumulation in the growth cone and the multipolar-to-bipolar transition of migrating neurons; genetic epistasis shows Shootin1 and Kif20b act in the same pathway.\",\n      \"method\": \"Surface plasmon resonance (direct binding, Kd determination), co-immunoprecipitation, immunostaining, FRAP (Shootin1 mobilization), shRNA knockdown, dominant-negative MBD fragment, in vivo migration assay, epistasis analysis\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct binding measured by SPR with Kd, confirmed by Co-IP and functional FRAP, plus genetic epistasis; multiple orthogonal methods in single study\",\n      \"pmids\": [\"23864681\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Kif20b is required for normal cytokinesis of polarized cortical neural stem cells; in the loss-of-function (magoo) mouse mutant, midbody number, shape, and apical positioning are abnormal, indicating a role in midbody organization and abscission; disrupted abscission leads to apoptosis rather than binucleation, resulting in microcephaly.\",\n      \"method\": \"Loss-of-function mouse mutant (forward genetic screen), fixed and live imaging of midbodies, cortical cell counting, apoptosis assays\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean loss-of-function mutant with specific cellular phenotype (midbody defects, apoptosis, microcephaly) replicated across multiple analyses\",\n      \"pmids\": [\"24173802\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Knockdown of KIF20B/MPHOSPH1 in hepatocellular carcinoma cells stabilizes p53 and blocks STAT3 phosphorylation, prolonging mitotic arrest and inducing postmitotic apoptosis; these effects are associated with multinucleated polyploid cell accumulation.\",\n      \"method\": \"shRNA-mediated knockdown (Ad-shMPP1), Western blot for p53 and phospho-STAT3, flow cytometry, xenograft mouse model\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD with defined molecular readouts (p53, STAT3) plus in vivo validation, single lab\",\n      \"pmids\": [\"25269478\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KIF20B localizes to central spindle microtubules and the midbody throughout cytokinesis at sites distinct from KIF23/MKLP1 and KIF20A/MKLP2; siRNA depletion slows furrow ingression speed and delays abscission; KIF20B is not required for midbody assembly but coordinates late midbody maturation steps including anillin dispersal, ESCRT-III recruitment, and microtubule constriction site formation.\",\n      \"method\": \"siRNA knockdown in human cell line, fixed and live imaging (time-lapse), quantification of furrow ingression kinetics, immunostaining for anillin and ESCRT-III components\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with quantitative live-imaging phenotype and multiple molecular markers; direct localization with functional consequence\",\n      \"pmids\": [\"29167382\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Loss of Kif20b in mouse cortical neurons causes defects in neuronal polarization, axon outgrowth, neurite branching, and axon caliber; mutant axons have increased width, longer growth cone filopodia, and abnormal microtubule organization; Shootin1 is lost from the axonal growth cone in Kif20b mutants, linking KIF20B-dependent Shootin1 localization to proper neurite morphogenesis.\",\n      \"method\": \"Kif20b loss-of-function mouse mutant, in vivo and in vitro cortical neuron labeling and imaging, live-imaging of axon extension, immunostaining for Shootin1\",\n      \"journal\": \"Neural development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean mouse KO with specific morphological and molecular phenotypes; single lab, multiple readouts\",\n      \"pmids\": [\"28359322\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"USP7 stabilizes FBXO38 via its deubiquitylase catalytic activity (protecting FBXO38 from proteasomal degradation); FBXO38 in turn stabilizes KIF20B independently of an SCF complex; depletion of USP7 or FBXO38 dramatically reduces KIF20B protein levels and KIF20B at the midbody, causing cytokinetic defects; restoring FBXO38 or KIF20B rescues cytokinetic defects caused by USP7 silencing.\",\n      \"method\": \"Affinity purification–mass spectrometry (USP7 interactome), BioID (FBXO38 interactome), co-immunoprecipitation, siRNA knockdown, Western blot, immunofluorescence of midbody, rescue experiments\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal AP-MS and BioID interaction profiling plus functional rescue experiments establishing epistatic order USP7→FBXO38→KIF20B\",\n      \"pmids\": [\"30804394\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"KIF20B protein has microtubule-binding and microtubule-bundling properties as well as microtubule-stimulated ATPase activity in vitro; it functions as a slow plus-end-directed motor; during interphase it localizes to a proportion of nuclei, redistributes during metaphase to cytoplasm/perichromatin, and localizes to the midbody stem body/midzone during telophase/anaphase.\",\n      \"method\": \"In vitro microtubule-binding and bundling assays, in vitro ATPase assay, indirect immunofluorescence with monoclonal antibody (10C7) in HEp2 cells and tissue sections\",\n      \"journal\": \"Monoclonal antibodies in immunodiagnosis and immunotherapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical assays confirming motor and bundling activity, but single antibody characterization paper with limited mechanistic follow-up\",\n      \"pmids\": [\"31260385\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KIF20B localizes to pseudopod protrusions of colorectal cancer cells and influences invadopodia formation; KIF20B overexpression promotes EMT mediated by Gli1, and this process is modulated by intracellular actin dynamics.\",\n      \"method\": \"Immunofluorescence localization, siRNA/overexpression in CRC cell lines, migration/invasion assays, actin dynamics analysis\",\n      \"journal\": \"Molecular carcinogenesis\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization and KD/OE phenotype in cancer cells with partial pathway placement (Gli1/EMT/actin), single lab, limited mechanistic depth\",\n      \"pmids\": [\"29573464\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KIF20B is a vertebrate-specific Kinesin-6 family motor with intrinsic microtubule-stimulated ATPase activity and plus-end-directed motility; it localizes to the central spindle and midbody during cytokinesis where it promotes efficient furrow ingression and coordinates late midbody maturation (anillin dispersal, ESCRT-III recruitment, microtubule constriction), and its protein levels are regulated by a USP7→FBXO38→KIF20B stabilization cascade; in neural development it transports Shootin1 cargo to the axonal growth cone to drive neuronal polarization and migration, and loss-of-function causes midbody disorganization, failed abscission, apoptosis, and microcephaly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KIF20B is a Kinesin-6 family motor that drives cytokinesis and neuronal morphogenesis through plus-end-directed transport on microtubules [#0, #8]. Its N-terminal motor domain has intrinsic, microtubule-stimulated ATPase activity dependent on the conserved Lys-168, and the protein binds and bundles microtubules while acting as a slow plus-end-directed motor [#0, #8]. During cytokinesis KIF20B localizes to central spindle microtubules and the midbody at sites distinct from KIF23/MKLP1 and KIF20A/MKLP2, where it is dispensable for midbody assembly but required to promote efficient furrow ingression and to coordinate late midbody maturation—anillin dispersal, ESCRT-III recruitment, and microtubule constriction-site formation [#5]; it cooperates with PRC1 at the midbody, and loss of either causes multinucleation and death [#1]. KIF20B protein abundance is controlled by a USP7→FBXO38→KIF20B stabilization cascade in which the deubiquitylase USP7 protects FBXO38, which in turn stabilizes KIF20B and maintains its midbody pool [#7]. In neural development KIF20B binds Shootin1 through a 57-residue tail domain and transports this cargo to the axonal growth cone, promoting PIP3 accumulation and the multipolar-to-bipolar transition during cortical neuron migration and axon morphogenesis [#2, #6]. Loss of Kif20b disrupts midbody organization and abscission in cortical neural stem cells, leading to apoptosis and microcephaly [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established KIF20B as a bona fide motor enzyme by demonstrating intrinsic ATPase activity in its motor domain and linking its mitotic behavior to phosphoregulation and Pin1.\",\n      \"evidence\": \"In vitro ATPase assay with K168R active-site mutant, co-IP and pull-down with Pin1, in vivo phospho-labeling and cell-cycle analysis\",\n      \"pmids\": [\"11470801\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No microtubule-dependent motility or directionality assessed\", \"Functional consequence of Pin1 binding and Thr-1604 phosphorylation on motor activity unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Placed KIF20B in the cytokinesis machinery by showing it complexes with PRC1 at the midbody and is required to complete cell division.\",\n      \"evidence\": \"Reciprocal co-IP, midbody colocalization, and siRNA knockdown causing multinucleation/death in bladder cancer cells\",\n      \"pmids\": [\"17409436\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs. indirect nature of the PRC1 interaction not resolved\", \"Single cell-type context\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined a distinct neurodevelopmental role by identifying Shootin1 as a direct KIF20B cargo whose transport drives neuronal polarization.\",\n      \"evidence\": \"SPR Kd determination, co-IP from developing brain, FRAP-based cargo mobilization, shRNA, dominant-negative MBD, in vivo migration and epistasis\",\n      \"pmids\": [\"23864681\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether motor ATPase activity drives Shootin1 transport not directly tested\", \"Mechanism of PIP3 accumulation downstream of Shootin1 delivery unclear\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Connected KIF20B cytokinesis function to organismal phenotype, showing abscission failure in neural stem cells causes apoptosis and microcephaly rather than binucleation.\",\n      \"evidence\": \"magoo loss-of-function mouse mutant with midbody imaging, cortical cell counting, apoptosis assays\",\n      \"pmids\": [\"24173802\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular step of abscission requiring KIF20B not pinpointed in this study\", \"Link between midbody mispositioning and apoptosis mechanistically undefined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Linked KIF20B loss to p53/STAT3 signaling outcomes, framing its depletion as a route to mitotic arrest and postmitotic apoptosis in cancer.\",\n      \"evidence\": \"shRNA knockdown in hepatocellular carcinoma cells, Western blot for p53/phospho-STAT3, flow cytometry, xenograft\",\n      \"pmids\": [\"25269478\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether p53/STAT3 effects are direct or secondary to cytokinesis failure unclear\", \"No mechanistic connection between KIF20B motor activity and STAT3 phosphorylation\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Resolved the precise cytokinetic step KIF20B serves, distinguishing it from other Kinesin-6 motors and assigning it to late midbody maturation.\",\n      \"evidence\": \"siRNA in human cells with quantitative live imaging of furrow ingression and immunostaining for anillin and ESCRT-III\",\n      \"pmids\": [\"29167382\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How KIF20B coordinates anillin dispersal and ESCRT-III recruitment mechanistically unknown\", \"Direct binding partners at the constriction site not identified\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Extended the Shootin1-transport model to neurite morphogenesis, showing KIF20B-dependent growth-cone Shootin1 localization shapes axon caliber and branching.\",\n      \"evidence\": \"Kif20b mouse mutant cortical neurons with in vivo/in vitro imaging, live axon-extension imaging, Shootin1 immunostaining\",\n      \"pmids\": [\"28359322\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cause of abnormal microtubule organization in mutant axons not defined\", \"Whether axon defects are cell-autonomous transport defects vs. cytokinesis history unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified an upstream stability pathway controlling KIF20B abundance, defining the epistatic order USP7→FBXO38→KIF20B for midbody function.\",\n      \"evidence\": \"AP-MS, BioID, co-IP, siRNA, Western blot, midbody immunofluorescence, and rescue experiments\",\n      \"pmids\": [\"30804394\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which FBXO38 stabilizes KIF20B independent of SCF unresolved\", \"Whether stabilization is regulated dynamically across the cell cycle unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Confirmed KIF20B as a microtubule-binding, microtubule-bundling, slow plus-end-directed motor and described its cell-cycle-dependent redistribution.\",\n      \"evidence\": \"In vitro microtubule-binding/bundling and ATPase assays plus monoclonal-antibody immunofluorescence in HEp2 cells and tissue\",\n      \"pmids\": [\"31260385\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-antibody localization with limited mechanistic follow-up\", \"Functional role of interphase nuclear localization undefined\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Implicated KIF20B in cancer cell invasion via pseudopod/invadopodia localization and Gli1-mediated EMT.\",\n      \"evidence\": \"Immunofluorescence, siRNA/overexpression in colorectal cancer lines, migration/invasion assays, actin dynamics analysis\",\n      \"pmids\": [\"29573464\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Low-confidence single-lab study with limited mechanistic depth\", \"Connection between motor activity, actin dynamics, and Gli1 not established\", \"Direct partners in invadopodia unidentified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KIF20B mechanically couples its plus-end-directed motor activity to specific late-abscission events (anillin dispersal, ESCRT-III recruitment, constriction-site formation) and whether the same motor activity powers Shootin1 cargo transport remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model linking motor cycle to midbody maturation steps\", \"Direct effectors recruited by KIF20B at the constriction site unknown\", \"Motor-dependence of Shootin1 transport not directly demonstrated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0, 8]},\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [5, 8]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [8, 5]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 3, 5, 7]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [2, 6, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PRC1\", \"Shootin1\", \"Pin1\", \"FBXO38\", \"USP7\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}