Affinage

KIF2B

Kinesin-like protein KIF2B · UniProt Q8N4N8

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

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIF2B is a kinesin-13 family microtubule depolymerase that drives chromosome segregation fidelity by stimulating kinetochore-microtubule (kMT) turnover specifically during early mitosis, where it corrects mal-oriented attachments before MCAK acts in a later phase (PMID:17538014, PMID:19060894). It localizes to centrosomes, midbodies, spindle microtubules, and transiently to kinetochores, and its loss produces monopolar or disorganized spindles and severely slowed chromosome movement (PMID:17538014). At kinetochores in early mitosis KIF2B forms a complex with CLASP1 that promotes kMT turnover, error correction, and spindle assembly checkpoint signalling; this complex is replaced at metaphase by an astrin-CLASP1 complex that stabilizes kMTs and silences the checkpoint (PMID:20852589). KIF2B activity and targeting are governed by phosphoregulation: Plk1 directly phosphorylates S204 (required for kinetochore localization) and T125 (required for attachment-error correction), and Plk1 phosphorylation is required for chromosome alignment (PMID:22535524, PMID:32017920), while Chk1—acting in part through Aurora-B Ser331 phosphorylation—and Mps1 control its centromere/kinetochore recruitment (PMID:23321637). Its spindle targeting is provided by a C-terminus-specific association with Cep170, which contributes a second microtubule-binding site and is itself dependent on TBK1 (PMID:23087211, PMID:26656453), and its depolymerase activity at microtubule plus-ends is temporally restrained by competitive binding of GSK3β-phosphorylated SKAP (PMID:27982129). KIF2B abundance is limited by SCF-Fbxw5-mediated polyubiquitylation, linking its turnover to ciliogenesis control (PMID:34368969). Functionally, restoring KIF2B-mediated kMT dynamics suppresses chromosomal instability, and modest overexpression in K-Ras-driven mouse lung tumors reduces segregation defects (PMID:19060894, PMID:31179849).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2007 High

    Established that KIF2B is a kinesin-13 protein required for bipolar spindle assembly and normal chromosome movement, placing it within the mitotic microtubule-dynamics machinery.

    Evidence siRNA knockdown, GFP-KIF2B live imaging, and double-knockdown epistasis with MCAK/Nuf2/NuMA/HSET in human cells

    PMID:17538014

    Open questions at the time
    • Did not resolve whether KIF2B acts at kinetochores versus poles for its primary function
    • Depolymerase biochemistry not directly reconstituted here
  2. 2008 High

    Resolved the temporal niche of KIF2B by showing it stimulates kMT turnover specifically in early mitosis to correct errors, distinct from MCAK, and that boosting this activity rescues chromosomal instability.

    Evidence kMT turnover by fluorescence dissipation after photoactivation, siRNA, and overexpression rescue in CIN tumor lines

    PMID:19060894

    Open questions at the time
    • Molecular partners conferring early-mitotic specificity not yet identified
    • Did not define how turnover defects translate to missegregation mechanistically
  3. 2010 High

    Identified the CLASP1-KIF2B complex as the early-mitotic kinetochore module for error correction and SAC maintenance, and showed a temporal switch to astrin-CLASP1 at metaphase.

    Evidence Co-immunoprecipitation, siRNA, immunofluorescence, and kMT turnover assays with temporal resolution

    PMID:20852589

    Open questions at the time
    • Mechanism of the complex switch (what displaces KIF2B) not defined here
    • Direct vs indirect KIF2B-CLASP1 binding not established
  4. 2012 High

    Defined how KIF2B activity is switched on by establishing Plk1 as a direct kinase phosphorylating distinct residues controlling localization (S204) and error-correction activity (T125).

    Evidence Phosphoproteomics, in vitro Plk1 kinase assay, phosphomutant rescue, and Plk1 inhibition (BI2536)

    PMID:22535524

    Open questions at the time
    • How S204 phosphorylation mechanistically drives kinetochore targeting unresolved
    • Structural basis of T125-dependent activity unknown
  5. 2012 High

    Explained paralog-specific spindle targeting by showing KIF2B's C-terminus binds Cep170, which provides a second microtubule-binding site absent in Kif2a/MCAK.

    Evidence Co-IP, in vitro microtubule-binding assay, and domain-swap mutants

    PMID:23087211

    Open questions at the time
    • Quantitative contribution of the second MT-binding site to depolymerase processivity not measured
    • Whether Cep170 modulates activity or only localization unclear
  6. 2013 Medium

    Placed KIF2B kinetochore recruitment downstream of mitotic checkpoint kinases by showing Chk1 (via Aurora-B Ser331) and Mps1 jointly control its centromere localization.

    Evidence Chk1/Mps1 inhibition and siRNA, phospho-specific antibodies, Aurora-B mutagenesis, and immunofluorescence

    PMID:23321637

    Open questions at the time
    • Single-lab study
    • Direct vs indirect role of Aurora-B Ser331 phosphorylation on KIF2B not biochemically isolated
  7. 2015 Medium

    Identified TBK1 as an upstream regulator required for CEP170 centrosomal localization and CEP170-KIF2B binding, linking a kinase to KIF2B's spindle-targeting interaction.

    Evidence Co-IP, siRNA, immunofluorescence, and TBK1 inhibition

    PMID:26656453

    Open questions at the time
    • Whether TBK1 acts directly on CEP170 or KIF2B not established
    • Single-lab study
  8. 2016 Medium

    Revealed a negative-regulation mechanism in which GSK3β-phosphorylated SKAP competes with KIF2B for microtubule plus-ends to temporally restrain its depolymerase activity.

    Evidence In vitro GSK3β kinase assay, MS phosphosite mapping, Co-IP, phosphomimetic rescue, and plus-end binding competition

    PMID:27982129

    Open questions at the time
    • Single-lab study
    • In vivo timing of SKAP-mediated inhibition relative to Plk1 activation not integrated
  9. 2019 Medium

    Tested the tumor-relevance of KIF2B in vivo, showing that modest overexpression reduces segregation defects in K-Ras-driven lung tumors but increases tumor size rather than suppressing incidence.

    Evidence Transgenic Kif2b overexpression in K-Ras G12D mouse lung cancer with segregation scoring and Ki-67 staining

    PMID:31179849

    Open questions at the time
    • Mechanism linking reduced CIN to larger tumors not resolved
    • Single-lab study, overexpression rather than physiological levels
  10. 2020 Medium

    Confirmed via orthogonal chemical-genetic control that Plk1-mediated phosphorylation of KIF2B is required for chromosome alignment.

    Evidence Plk1 Ser/Thr toggle chemical-genetic system, phosphoproteomics, and live-cell chromosome alignment scoring

    PMID:32017920

    Open questions at the time
    • Single-lab study
    • Did not separate KIF2B's contribution from other Plk1 substrates in the alignment phenotype
  11. 2021 Medium

    Established that KIF2B abundance is controlled by SCF-Fbxw5-mediated polyubiquitylation, connecting its degradation to ciliogenesis.

    Evidence In vitro ubiquitylation reconstitution with neddylated SCF-Fbxw5/Cdc34 and siRNA rescue of ciliogenesis

    PMID:34368969

    Open questions at the time
    • KIF2B-specific (vs Kif2a/MCAK) contribution to ciliogenesis rescue is single-lab
    • In vivo timing of degradation across the cell cycle not defined
  12. 2025 Low

    Extended KIF2B's role to meiosis by identifying an interaction with the LINC component KASH5 in spermatocytes, implicating it in telomere force transmission during meiotic prophase.

    Evidence Co-IP and yeast two-hybrid with KASH5 bait, proteomic screen in mouse spermatocytes (preprint)

    PMID:40501626

    Open questions at the time
    • Functional role of KIF2B specifically (vs KIF5B) not tested
    • Preprint, single lab, interaction not validated reciprocally in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs (Plk1, Chk1/Aurora-B/Mps1, SKAP competition, Cep170/TBK1 targeting, Fbxw5 degradation) are integrated in space and time to switch KIF2B activity on and off at individual kinetochores remains unresolved.
  • No structural model of KIF2B or its regulated complexes
  • Quantitative hierarchy among regulators undefined
  • Physiological meiotic and ciliary roles not mechanistically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 3 GO:0008092 cytoskeletal protein binding 2 GO:0003774 cytoskeletal motor activity 1
Localization
GO:0005694 chromosome 3 GO:0005856 cytoskeleton 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 4
Partners
CEP170CLASP1KASH5PLK1SKAPTBK1
Complex memberships
CEP170-KIF2B complexKIF2B-CLASP1 kinetochore complex

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 KIF2B (kinesin-13 family) localizes predominantly to centrosomes and midbodies, but also to spindle microtubules and transiently to kinetochores. KIF2B-deficient cells assemble monopolar or disorganized spindles and show ~80% reduction in chromosome movement velocity. Bipolar spindle assembly can be restored by simultaneous depletion of MCAK, Nuf2, or treatment with low-dose nocodazole, or by perturbing NuMA/HSET pole-focusing activities, placing KIF2B function in spindle assembly and chromosome movement. siRNA knockdown, GFP-KIF2B live-cell imaging, immunofluorescence, epistasis by double-knockdown Molecular biology of the cell High 17538014
2008 KIF2B stimulates kinetochore-microtubule (kMT) dynamics specifically during early mitosis to correct mal-oriented attachments, while MCAK acts in a distinct, later phase. Few-fold reductions in kMT turnover, particularly in early mitosis, induce severe chromosome segregation defects. Overexpression of KIF2B restores kMT dynamics and chromosome segregation fidelity in chromosomally unstable tumor cell lines. siRNA knockdown, kMT turnover assay (fluorescence dissipation after photoactivation), overexpression rescue in CIN tumor lines Nature cell biology High 19060894
2010 In early mitosis, KIF2B forms a complex with CLASP1 at kinetochores to promote kMT turnover, correction of attachment errors, and maintenance of spindle assembly checkpoint (SAC) signalling. During metaphase, this KIF2B-CLASP1 complex is replaced by an astrin-CLASP1 complex that promotes kMT stability and SAC silencing. The two complexes are mutually exclusive at kinetochores. KIF18A affects kMT attachments and chromosome movement through these proteins. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, kMT turnover assay, epistasis The EMBO journal High 20852589
2012 Plk1 directly phosphorylates KIF2B at threonine 125 (T125) and serine 204 (S204). Phosphorylation of S204 is required for KIF2B kinetochore localization and activity in prometaphase; phosphorylation of T125 is required for KIF2B activity in correcting kMT attachment errors. These sites were identified by mass spectrometry and validated by mutagenesis. Mass spectrometry phosphoproteomics, in vitro kinase assay with Plk1, phosphomimetic/phosphodeficient mutagenesis, immunofluorescence, Plk1 inhibitor (BI2536) Molecular biology of the cell High 22535524
2012 The C-terminus of KIF2B mediates specific protein-protein interactions that distinguish it from other kinesin-13 paralogs. Cep170 and Cep170R (KIAA0284) specifically associate with KIF2B (not Kif2a or MCAK). Cep170 binds microtubules in vitro and provides KIF2B with a second microtubule-binding site to target it to the mitotic spindle. The N-terminus is the primary determinant of kinesin-13 localization. Co-immunoprecipitation, in vitro microtubule-binding assay, domain-swap mutants, immunofluorescence Molecular biology of the cell High 23087211
2013 Chk1 activity is required for stable localization of KIF2B (and MCAK) to centromeres/kinetochores. Decreased Chk1 activity leads to hyperstable kMTs and unstable binding of KIF2B to centromeres/kinetochores. Chk1 phosphorylates Aurora-B at Ser331, and this phosphorylation is required for optimal KIF2B localization. Mps1 inhibition also diminishes initial recruitment of KIF2B to centromeres/kinetochores, and Chk1 and Mps1 jointly regulate KIF2B localization. Chk1 inhibitor/siRNA, Mps1 inhibitor, immunofluorescence for KIF2B localization, phospho-specific antibodies, Aurora-B mutagenesis Journal of cell science Medium 23321637
2015 TBK1 is necessary for CEP170 centrosomal localization and for CEP170 binding to KIF2B. Disruption of the TBK1-CEP170 complex augments microtubule stability and triggers mitotic defects, placing TBK1 upstream of the CEP170-KIF2B interaction in regulating microtubule dynamics. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, TBK1 inhibitor Nature communications Medium 26656453
2016 GSK3β phosphorylates SKAP, and this phosphorylation promotes SKAP binding to KIF2B to regulate its microtubule depolymerase activity at microtubule plus-ends. SKAP competes with KIF2B for microtubule plus-end binding, thereby temporally inhibiting KIF2B depolymerase activity to ensure accurate kinetochore-microtubule attachment. In vitro kinase assay (GSK3β phosphorylating SKAP), mass spectrometry phosphosite mapping, co-immunoprecipitation, phosphomimetic rescue assay, microtubule plus-end binding competition assay Scientific reports Medium 27982129
2019 Modest overexpression of KIF2B in transgenic mice reduces chromosome segregation defects in K-Ras G12D-driven lung tumors but does not reduce tumor incidence; instead, tumors are significantly larger with elevated Ki-67 in KIF2B-overexpressing animals. This establishes that KIF2B-mediated reduction of CIN suppresses tumor growth in the context of K-Ras-driven lung cancer. Transgenic mouse overexpression (Kif2b), K-Ras G12D lung cancer model, chromosome segregation scoring, Ki-67 immunostaining Cell cycle Medium 31179849
2020 Plk1 phosphorylation of KIF2B at Ser/Thr sites controls chromosome alignment. Using a Ser/Thr toggle chemical-genetic system, toggling Plk1-phosphorylated Ser residues on KIF2B to Thr (placing them under orthogonal kinase control) caused sharp increases in misaligned chromosomes and prometaphase arrest upon chemical inhibition, confirming that Plk1-mediated phosphorylation of KIF2B is required for chromosome alignment. Chemical-genetic Plk1 Ser/Thr toggle system, phosphoproteomics, live-cell imaging, chromosome alignment scoring Cell chemical biology Medium 32017920
2021 SCFFbxw5 ubiquitin E3 ligase polyubiquitylates KIF2B (along with Kif2a and MCAK) in vitro via Cdc34, without requiring preceding modifications on KIF2B. Concomitant knockdown of KIF2B, Kif2a, or MCAK rescues ciliogenesis defects caused by Fbxw5 loss, indicating SCFFbxw5-mediated degradation of KIF2B contributes to regulation of ciliogenesis. In vitro ubiquitylation reconstitution assay (protein microarray screen + neddylated SCFFbxw5 + Cdc34), siRNA knockdown rescue of ciliogenesis The EMBO journal Medium 34368969
2025 KIF2B interacts with KASH5 (a LINC complex component) in mouse spermatocytes, as identified by co-immunoprecipitation and yeast two-hybrid assays using KASH5 as bait, suggesting KIF2B participates in force transmission to telomeres during meiotic prophase chromosome movements. Co-immunoprecipitation, yeast two-hybrid (KASH5 bait), proteomic screen of microtubule-associated motor proteins in mouse spermatocytes bioRxivpreprint Low 40501626

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Genome stability is ensured by temporal control of kinetochore-microtubule dynamics. Nature cell biology 376 19060894
2007 The kinesin-13 proteins Kif2a, Kif2b, and Kif2c/MCAK have distinct roles during mitosis in human cells. Molecular biology of the cell 201 17538014
2010 CLASP1, astrin and Kif2b form a molecular switch that regulates kinetochore-microtubule dynamics to promote mitotic progression and fidelity. The EMBO journal 108 20852589
2015 Tank binding kinase 1 is a centrosome-associated kinase necessary for microtubule dynamics and mitosis. Nature communications 87 26656453
2012 Plk1 regulates the kinesin-13 protein Kif2b to promote faithful chromosome segregation. Molecular biology of the cell 50 22535524
2012 The microtubule-binding protein Cep170 promotes the targeting of the kinesin-13 depolymerase Kif2b to the mitotic spindle. Molecular biology of the cell 47 23087211
2014 STAG2 promotes error correction in mitosis by regulating kinetochore-microtubule attachments. Journal of cell science 37 25074805
2022 Omics and Male Infertility: Highlighting the Application of Transcriptomic Data. Life (Basel, Switzerland) 30 35207567
2013 Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity. PloS one 28 23554873
2013 Chk1 and Mps1 jointly regulate correction of merotelic kinetochore attachments. Journal of cell science 25 23321637
2015 Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study. Oncology letters 20 26870257
2016 Expression of dynein, cytoplasmic 2, heavy chain 1 (DHC2) associated with glioblastoma cell resistance to temozolomide. Scientific reports 17 27375225
2014 Mutational landscape of candidate genes in familial prostate cancer. The Prostate 15 25111073
2021 SCFFbxw5 targets kinesin-13 proteins to facilitate ciliogenesis. The EMBO journal 13 34368969
2015 Kif2a depletion generates chromosome segregation and pole coalescence defects in animal caps and inhibits gastrulation of the Xenopus embryo. Molecular biology of the cell 13 25568341
2019 Chromosomal instability suppresses the growth of K-Ras-induced lung adenomas. Cell cycle (Georgetown, Tex.) 11 31179849
2022 KIF26B Is Overexpressed in Medulloblastoma and Promotes Malignant Progression by Activating the PI3K/AKT Pathway. Analytical cellular pathology (Amsterdam) 7 35866054
2016 Phosphorylation of SKAP by GSK3β ensures chromosome segregation by a temporal inhibition of Kif2b activity. Scientific reports 6 27982129
2020 A Genetic Toggle for Chemical Control of Individual Plk1 Substrates. Cell chemical biology 3 32017920
2018 Expression analysis of a panel of cancer-testis antigens in bladder cancer. Personalized medicine 3 30362892
2025 KIF2C is essential for meiosis and manchette dynamics in male mice. Frontiers in cell and developmental biology 1 40213390
2021 α-Fodrin in Cytoskeletal Organization and the Activity of Certain Key Microtubule Kinesins. Genes 1 34067543
2025 Kinesin drive meiotic chromosome dynamics via interaction with the KASH5-LINC complex. bioRxiv : the preprint server for biology 0 40501626

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