KIF2A is a kinesin-13 family protein, related to KIF2B and KIF2C/MCAK, with a centrally placed kinesin motor domain. It uses ATP to remove tubulin subunits from microtubule ends, acting as a microtubule depolymerase rather than a processive transporter. Early work on mouse KIF2 also reported plus-end-directed motility and association with axonal vesicles. KIF2A acts in the cytoplasm at centrosomes and spindle poles. In mitosis it is recruited to the spindle and its poles by DDA3/PSRC1 and is regulated by PLK1 and Aurora kinases. Its depolymerase activity at the poles balances MCAK at kinetochores to drive spindle bipolarity, spindle dynamics and chromosome movement. In neurons it depolymerizes microtubules at the growth-cone edge to suppress collateral branch extension, and loss of KIF2A causes cortical malformations (CDCBM3). In migrating cells, TTBK2-EB1/3 phosphorylation removes KIF2A from microtubule plus ends to tune microtubule dynamics. During cilium growth, TTBK2 phosphorylation restrains KIF2A at the mother centriole. In quiescent cells re-entering the cell cycle, PLK1 phosphorylates KIF2A at T554. This activates its depolymerase at the mother centriole/basal body to disassemble the primary cilium. Constitutive activation of this PLK1-KIF2A pathway impairs ciliogenesis in premature chromatid separation syndrome.
Definition: Catalysis of the removal of tubulin heterodimers from the end of a microtubule, driven by ATP hydrolysis, without translocation along the microtubule lattice.
Justification: Kinesin-13 (KIF2A, KIF2B, KIF2C/MCAK) and kinesin-8 depolymerases are annotated only with 'microtubule motor activity' and 'microtubule binding'. Neither describes their defining enzymatic activity. KIF2A catalyses MT depolymerization in vitro.
Parent term: ATP-dependent activity
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000070 mitotic sister chromatid segregation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Mitotic sister chromatid segregation (ARBA). Reason: KIF2A contributes to chromosome segregation indirectly, through spindle assembly and dynamics; its direct role is spindle-pole MT depolymerization. Supporting Evidence: PMID:15302853 RNAi-induced knockdown of Kif2a expression inhibited cell cycle progression because cells assembled monopolar spindles PMID:17538014 the microtubule depolymerase activities of Kif2a, Kif2b, and MCAK fulfill distinct functions during mitosis in human cells |
| GO:0000226 microtubule cytoskeleton organization | IGI PMID:26323690 TTBK2 with EB1/3 regulates microtubule dynamics in migrating... | ACCEPT | Summary: Microtubule cytoskeleton organization (IGI with TTBK2). Reason: KIF2A and TTBK2 genetically interact in regulating MT dynamics in migrating cells; KIF2A organizes MT arrays through depolymerization. Supporting Evidence: PMID:26323690 TTBK2 inhibits the MT-depolymerizing activity of KIF2A by reducing the interaction between KIF2A and MTs PMID:26323690 TTBK2 depletion increased the binding of KIF2A to MTs, especially at the EB3-containing MT ends |
| GO:0000922 spindle pole | IDA PMID:18411309 DDA3 recruits microtubule depolymerase Kif2a to spindle pole... | ACCEPT | Summary: Spindle pole (colocalizes_with, IDA). Reason: KIF2A is recruited to spindle poles by DDA3. Supporting Evidence: PMID:18411309 Biochemically, DDA3 directly interacted with the MT depolymerase Kif2a in an MT-dependent manner and increased the efficiency of targeting Kif2a to spindle poles PMID:15302853 we now show it localizes to centrosomes and spindle poles during mitosis in cultured cells |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: Spindle pole (UniProt subcellular location). Reason: Supported by direct data. Supporting Evidence: PMID:15302853 we now show it localizes to centrosomes and spindle poles during mitosis in cultured cells |
| GO:0003774 cytoskeletal motor activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cytoskeletal motor activity (ARBA). Reason: KIF2A's well-established activity is ATP-dependent microtubule depolymerization; kinesin-13 proteins depolymerize microtubules without motile function. Mouse KIF2 was nonetheless reported to move microtubules plus-end-directionally in a gliding assay and to associate with axonal vesicles. The motor annotation is not demonstrably wrong, but it is not the core activity. GO lacks a microtubule depolymerase MF term (see proposed_new_terms). Supporting Evidence: PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) PMID:7535303 Recombinant KIF2 exists as a dimer with a bigger head and plus-end directionally moves microtubules at a velocity of 0.47 +/- 0.11 microns/s |
| GO:0003774 cytoskeletal motor activity | TAS PMID:9177777 Identification of a novel human kinesin-related gene (HK2) b... | KEEP AS NON CORE | Summary: Cytoskeletal motor activity (TAS) from the HK2 cloning paper. Reason: KIF2A's well-established activity is ATP-dependent microtubule depolymerization; kinesin-13 proteins depolymerize microtubules without motile function. Mouse KIF2 was nonetheless reported to move microtubules plus-end-directionally in a gliding assay and to associate with axonal vesicles. The motor annotation is not demonstrably wrong, but it is not the core activity. GO lacks a microtubule depolymerase MF term (see proposed_new_terms). The cloning paper inferred this from homology to mouse KIF2. Supporting Evidence: PMID:9177777 The gene is > 90% homologous to the mouse KIF2, a gene belonging to the family of kinesin-related motor proteins, and we therefore named it HK2 (human kinesin 2) PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) |
| GO:0003777 microtubule motor activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Microtubule motor activity (IBA). Reason: KIF2A's well-established activity is ATP-dependent microtubule depolymerization; kinesin-13 proteins depolymerize microtubules without motile function. Mouse KIF2 was nonetheless reported to move microtubules plus-end-directionally in a gliding assay and to associate with axonal vesicles. The motor annotation is not demonstrably wrong, but it is not the core activity. GO lacks a microtubule depolymerase MF term (see proposed_new_terms). The IBA is inherited from the kinesin superfamily node. Supporting Evidence: PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) PMID:7535303 Recombinant KIF2 exists as a dimer with a bigger head and plus-end directionally moves microtubules at a velocity of 0.47 +/- 0.11 microns/s |
| GO:0003777 microtubule motor activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Microtubule motor activity (InterPro). Reason: KIF2A's well-established activity is ATP-dependent microtubule depolymerization; kinesin-13 proteins depolymerize microtubules without motile function. Mouse KIF2 was nonetheless reported to move microtubules plus-end-directionally in a gliding assay and to associate with axonal vesicles. The motor annotation is not demonstrably wrong, but it is not the core activity. GO lacks a microtubule depolymerase MF term (see proposed_new_terms). Supporting Evidence: PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) |
| GO:0005515 protein binding | IPI PMID:18411309 DDA3 recruits microtubule depolymerase Kif2a to spindle pole... | REMOVE | Summary: Interaction with DDA3/PSRC1 (Q6PGN9). Reason: Generic protein binding is uninformative. Removing GO:0005515 does not dispute the interaction. The DDA3 interaction is biologically meaningful (it recruits KIF2A to spindle poles); that role is captured by the spindle-pole location and spindle-organization terms. Supporting Evidence: PMID:18411309 Biochemically, DDA3 directly interacted with the MT depolymerase Kif2a in an MT-dependent manner and increased the efficiency of targeting Kif2a to spindle poles |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: HT Y2H interaction with LARP1B. Reason: Generic protein binding is uninformative. Removing GO:0005515 does not dispute the interaction. Screen hit; no known functional context. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: HT Y2H interaction with FAM13C. Reason: Generic protein binding is uninformative. Removing GO:0005515 does not dispute the interaction. Screen hit. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: HT Y2H interaction with MRPL53. Reason: Generic protein binding is uninformative. Removing GO:0005515 does not dispute the interaction. Screen hit. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Interaction with CEP170 (quantitative interactome). Reason: Generic protein binding is uninformative. Removing GO:0005515 does not dispute the interaction. CEP170 is a subdistal-appendage/centriolar protein, so the association fits KIF2A's mother-centriole localization. No informative MF follows from it. |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | REMOVE | Summary: Interaction with CEP170 (centrosome-cilium interface interactome). Reason: Generic protein binding is uninformative. Removing GO:0005515 does not dispute the interaction. Consistent with KIF2A at the mother centriole; still uninformative as MF. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Interaction with FAM13C (variant interaction screen). Reason: Generic protein binding is uninformative. Removing GO:0005515 does not dispute the interaction. Screen hit. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Interaction with CEP170 (OpenCell). Reason: Generic protein binding is uninformative. Removing GO:0005515 does not dispute the interaction. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding (InterPro). Reason: Kinesin-13 depolymerization is ATP-dependent. Supporting Evidence: PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) PMID:29980677 AMPPNP-bound Kif2A can form stable complexes with tubulin in solution and trigger MT depolymerization. We also demonstrate the importance of the neck in modulating ATP turnover and catalytic depolymerization of MTs |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleoplasm (HPA). Reason: HPA antibody staining reports nucleoplasm/nucleoli. No nuclear function of KIF2A is known; retained as an observed location, non-core. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm (IBA). Reason: Correct. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005737 cytoplasm | IDA PMID:26323690 TTBK2 with EB1/3 regulates microtubule dynamics in migrating... | ACCEPT | Summary: Cytoplasm (IDA). Reason: Diffuse cytoplasmic KIF2A in HeLa cells. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm (UniProt subcellular location). Reason: Correct. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005813 centrosome | IBA GO_REF:0000033 | ACCEPT | Summary: Centrosome (IBA). Reason: KIF2A localizes to centrosomes; the PTN node includes human KIF2A itself as grounding. Supporting Evidence: PMID:15302853 we now show it localizes to centrosomes and spindle poles during mitosis in cultured cells |
| GO:0005813 centrosome | IDA GO_REF:0000052 | ACCEPT | Summary: Centrosome (HPA). Reason: HPA calls centrosome (Enhanced). Supporting Evidence: PMID:15302853 we now show it localizes to centrosomes and spindle poles during mitosis in cultured cells |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: Centrosome (IDA, centrosome proteomics/localization). Reason: KIF2A is not named in the cached abstract/text; deferring to the curator. Centrosomal localization is independently supported. Supporting Evidence: PMID:21399614 We have combined protein identification and localization, using PCP-SILAC mass spectrometry, BAC transgeneOmics, and antibodies to define the constituents of human centrosomes PMID:15302853 we now show it localizes to centrosomes and spindle poles during mitosis in cultured cells |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: Centrosome (UniProt subcellular location). Reason: Correct. Supporting Evidence: PMID:15302853 we now show it localizes to centrosomes and spindle poles during mitosis in cultured cells |
| GO:0005814 centriole | IDA PMID:23213374 3D-structured illumination microscopy provides novel insight... | ACCEPT | Summary: Centriole (IDA, 3D-SIM). Reason: KIF2A is not named in the cached text (likely supplementary data); deferring to the curator. It is consistent with depolymerase activity at the mother centriole during cilium disassembly. Supporting Evidence: PMID:23213374 Appendage proteins showed rings with multiple density masses, and the number of these masses was strongly reduced during mitosis PMID:25660017 we report that kinesin superfamily protein 2A (KIF2A), phosphorylated at T554 by PLK1, exhibits microtubule-depolymerizing activity at the mother centriole to disassemble the primary cilium in a growth-signal-dependent manner |
| GO:0005819 spindle | IBA GO_REF:0000033 | ACCEPT | Summary: Spindle (IBA). Reason: KIF2A is recruited to the mitotic spindle. Supporting Evidence: PMID:18411309 Thus, DDA3 recruits Kif2a to the mitotic spindle and spindle poles and controls spindle dynamics |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: Spindle (UniProt subcellular location). Reason: Correct. Supporting Evidence: PMID:18411309 Thus, DDA3 recruits Kif2a to the mitotic spindle and spindle poles and controls spindle dynamics |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol (HPA). Reason: Correct. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141409 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141422 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141431 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141439 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638803 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638821 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2213248 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467809 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467811 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2468287 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2484822 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-375302 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666129 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666160 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666169 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6811423 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6811426 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9648114 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983259 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983266 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-990489 | ACCEPT | Summary: Cytosol (Reactome TAS, kinesin-mediated transport pathways). Reason: KIF2A is a soluble cytoplasmic protein; cytosol is correct, though the Reactome kinesin cargo-transport context is not KIF2A's core role. Supporting Evidence: PMID:26323690 KIF2A in control cells exhibited diffuse distribution and no apparent colocalization with EB3 |
| GO:0005871 kinesin complex | IBA GO_REF:0000033 | ACCEPT | Summary: Kinesin complex (IBA). Reason: KIF2/KIF2A forms a homodimeric kinesin without light chains. Supporting Evidence: PMID:7535303 Recombinant KIF2 exists as a dimer with a bigger head and plus-end directionally moves microtubules at a velocity of 0.47 +/- 0.11 microns/s |
| GO:0005874 microtubule | IDA PMID:26323690 TTBK2 with EB1/3 regulates microtubule dynamics in migrating... | ACCEPT | Summary: Microtubule (colocalizes_with, IDA). Reason: KIF2A binds microtubules, especially EB3-marked ends when TTBK2 is depleted. Supporting Evidence: PMID:26323690 TTBK2 depletion increased the binding of KIF2A to MTs, especially at the EB3-containing MT ends |
| GO:0005876 spindle microtubule | IDA PMID:18411309 DDA3 recruits microtubule depolymerase Kif2a to spindle pole... | ACCEPT | Summary: Spindle microtubule (colocalizes_with, IDA). Reason: Supported. Supporting Evidence: PMID:18411309 Thus, DDA3 recruits Kif2a to the mitotic spindle and spindle poles and controls spindle dynamics |
| GO:0007018 microtubule-based movement | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Microtubule-based movement (IBA). Reason: KIF2A's well-established activity is ATP-dependent microtubule depolymerization; kinesin-13 proteins depolymerize microtubules without motile function. Mouse KIF2 was nonetheless reported to move microtubules plus-end-directionally in a gliding assay and to associate with axonal vesicles. The motor annotation is not demonstrably wrong, but it is not the core activity. GO lacks a microtubule depolymerase MF term (see proposed_new_terms). Supporting Evidence: PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) PMID:7535303 Recombinant KIF2 exists as a dimer with a bigger head and plus-end directionally moves microtubules at a velocity of 0.47 +/- 0.11 microns/s |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Microtubule-based movement (InterPro). Reason: KIF2A's well-established activity is ATP-dependent microtubule depolymerization; kinesin-13 proteins depolymerize microtubules without motile function. Mouse KIF2 was nonetheless reported to move microtubules plus-end-directionally in a gliding assay and to associate with axonal vesicles. The motor annotation is not demonstrably wrong, but it is not the core activity. GO lacks a microtubule depolymerase MF term (see proposed_new_terms). Supporting Evidence: PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) |
| GO:0007019 microtubule depolymerization | IEA GO_REF:0000117 | ACCEPT | Summary: Microtubule depolymerization (ARBA). Reason: Core activity of KIF2A. Supporting Evidence: PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) PMID:26323690 Phosphorylation by TTBK2 decreased the MT-depolymerizing activity of KIF2A PMID:29980677 AMPPNP-bound Kif2A can form stable complexes with tubulin in solution and trigger MT depolymerization. We also demonstrate the importance of the neck in modulating ATP turnover and catalytic depolymerization of MTs |
| GO:0007019 microtubule depolymerization | TAS PMID:26323690 TTBK2 with EB1/3 regulates microtubule dynamics in migrating... | ACCEPT | Summary: Microtubule depolymerization (TAS, TTBK2 paper). Reason: Purified KIF2A depolymerizes GMPCPP microtubules, and TTBK2 phosphorylation inhibits this activity. This is direct evidence for the core activity. Supporting Evidence: PMID:26323690 Phosphorylation by TTBK2 decreased the MT-depolymerizing activity of KIF2A PMID:26323690 TTBK2 inhibits the MT-depolymerizing activity of KIF2A by reducing the interaction between KIF2A and MTs PMID:29980677 AMPPNP-bound Kif2A can form stable complexes with tubulin in solution and trigger MT depolymerization. We also demonstrate the importance of the neck in modulating ATP turnover and catalytic depolymerization of MTs |
| GO:0007052 mitotic spindle organization | IDA PMID:18411309 DDA3 recruits microtubule depolymerase Kif2a to spindle pole... | ACCEPT | Summary: Mitotic spindle organization (IDA, DDA3 paper). Reason: KIF2A knockdown was analyzed directly for spindle morphology and dynamics; DDA3-recruited KIF2A controls spindle dynamics. Supporting Evidence: PMID:18411309 To directly determine the effect of Kif2a on spindle dynamics, we analyzed the spindle morphology and dynamics in Kif2a knockdown cells PMID:18411309 Thus, DDA3 recruits Kif2a to the mitotic spindle and spindle poles and controls spindle dynamics |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | ACCEPT | Summary: Microtubule binding (IBA). Reason: Supported by direct data. Supporting Evidence: PMID:26323690 TTBK2 inhibits the MT-depolymerizing activity of KIF2A by reducing the interaction between KIF2A and MTs |
| GO:0008017 microtubule binding | IDA PMID:26323690 TTBK2 with EB1/3 regulates microtubule dynamics in migrating... | ACCEPT | Summary: Microtubule binding (IDA). Reason: KIF2A binds MTs in vitro and in cells; TTBK2 reduces this binding. Supporting Evidence: PMID:26323690 TTBK2 inhibits the MT-depolymerizing activity of KIF2A by reducing the interaction between KIF2A and MTs PMID:26323690 TTBK2 depletion increased the binding of KIF2A to MTs, especially at the EB3-containing MT ends |
| GO:0008017 microtubule binding | IEA GO_REF:0000120 | ACCEPT | Summary: Microtubule binding (ARBA). Reason: Correct. Supporting Evidence: PMID:26323690 TTBK2 inhibits the MT-depolymerizing activity of KIF2A by reducing the interaction between KIF2A and MTs |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Membrane (HDA, NK cell membrane proteome). Reason: KIF2A has no transmembrane segment. Detection in a membrane-enriched proteomic fraction most likely reflects peripheral or vesicle association (cf. KIF2-associated vesicles), so a bare membrane location is uninformative. Supporting Evidence: PMID:7535303 Our results strongly suggest that KIF2 functions as a new anterograde motor, being specialized for a particular group of membranous organelles involved in fast axonal transport |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP hydrolysis activity (IBA). Reason: ATP hydrolysis powers kinesin-13 depolymerization. Supporting Evidence: PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) PMID:29980677 AMPPNP-bound Kif2A can form stable complexes with tubulin in solution and trigger MT depolymerization. We also demonstrate the importance of the neck in modulating ATP turnover and catalytic depolymerization of MTs |
| GO:0030334 regulation of cell migration | IGI PMID:26323690 TTBK2 with EB1/3 regulates microtubule dynamics in migrating... | KEEP AS NON CORE | Summary: Regulation of cell migration (IGI with TTBK2). Reason: KIF2A depolymerase activity, regulated by TTBK2/EB, modulates MT dynamics in migrating cells. This is a context-specific downstream effect. Supporting Evidence: PMID:26323690 TTBK2 inhibits the MT-depolymerizing activity of KIF2A by reducing the interaction between KIF2A and MTs |
| GO:0030425 dendrite | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Dendrite (IEA, inferred from dendritic transport). Reason: Neuronal localization is plausible given KIF2A's neuronal roles; non-core. Supporting Evidence: PMID:12887924 we propose that KIF2A regulates microtubule dynamics at the growth cone edge by depolymerizing microtubules and that it plays an important role in the suppression of collateral branch extension |
| GO:0030705 cytoskeleton-dependent intracellular transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cytoskeleton-dependent intracellular transport (IBA). Reason: Mouse KIF2 was proposed as an anterograde vesicle motor. This is not KIF2A's established core role. Supporting Evidence: PMID:7535303 Our results strongly suggest that KIF2 functions as a new anterograde motor, being specialized for a particular group of membranous organelles involved in fast axonal transport PMID:15302853 Kif2a has been shown to catalyze microtubule depolymerization in the absence of motile function (Desai et al., 1999) file:human/KIF2A/KIF2A-deep-research-falcon.md KIF2A is not established as a transporter of a particular vesicle or soluble cargo. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | MODIFY | Summary: Cilium assembly (IBA, kinesin-13 node). Reason: The kinesin-13 node conveys a role in organizing ciliary/centriolar microtubules. For human KIF2A the demonstrated role is cilium disassembly: PLK1-phosphorylated KIF2A depolymerizes microtubules at the mother centriole, and its loss impairs serum-induced disassembly. Defective ciliogenesis in PCS syndrome is due to constitutive (excess) KIF2A activity. That is not evidence that KIF2A builds cilia. Comparator: AURKA, NEDD9 and HDAC6 carry GO:0061523 for this pathway, and KIF2A, as the enzyme that depolymerizes, does the work of the step. Vyslouzil et al. 2025 show that excess KIF2A activity at the mother centriole (when TTBK2 restraint is lost) impairs cilium elongation. This again points to KIF2A as a negative (disassembling) factor, not a positive assembly factor. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002380633 · PTN002380633 SUPPORTS SOURCE BUT NOT TARGET Kinesin-13 node with Drosophila kinesin-13 members among its sources. A role in organizing ciliary/centriolar microtubule length is plausibly ancestral. For human KIF2A the experimentally supported role is depolymerase-driven cilium disassembly, not assembly. Proposed replacements: cilium disassembly Supporting Evidence: PMID:25660017 we report that kinesin superfamily protein 2A (KIF2A), phosphorylated at T554 by PLK1, exhibits microtubule-depolymerizing activity at the mother centriole to disassemble the primary cilium in a growth-signal-dependent manner PMID:25660017 KIF2A-deficient hTERT-RPE1 cells showed the impairment of primary cilia disassembly following growth stimulation PMID:25660017 the PLK1-KIF2A pathway is constitutively active in cells from patients with premature chromatid separation (PCS) syndrome and is responsible for defective ciliogenesis in this syndrome PMID:39930500 we link the defects in cilia growth to aberrant turnover of a microtubule-depolymerizing kinesin KIF2A, which we find restrained by TTBK2 phosphorylation |
| GO:0090307 mitotic spindle assembly | IMP PMID:15843429 Functional analysis of human microtubule-based motor protein... | ACCEPT | Summary: Mitotic spindle assembly (IMP, esiRNA screen). Reason: KIF2A depletion produces monopolar spindles; it is required for bipolar spindle assembly. The requirement varies by cell line (largely normal bipolar spindles in RPE1 cells), plausibly because of kinesin-13 compensation. Supporting Evidence: PMID:15843429 Eg5 (a member of the kinesin-5 family), Kif2A (a member of the kinesin-13 family), and KifC1 (a member of the kinesin-14 family) are crucial for spindle formation PMID:15302853 RNAi-induced knockdown of Kif2a expression inhibited cell cycle progression because cells assembled monopolar spindles file:human/KIF2A/KIF2A-deep-research-falcon.md Another human-cell study found largely normal bipolar spindles after KIF2A loss in hTERT-RPE1 cells. |
| GO:0097228 sperm principal piece | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sperm principal piece (IEA from mouse). Reason: Electronic transfer from mouse. It is plausible as a tissue-specific location but unrelated to KIF2A's core functions. |
| GO:0098935 dendritic transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dendritic transport (IEA from mouse). Reason: Based on the historical view of KIF2 as a neuronal transport motor. KIF2A's established neuronal role is MT depolymerization in growth cones. Supporting Evidence: PMID:7535303 Our results strongly suggest that KIF2 functions as a new anterograde motor, being specialized for a particular group of membranous organelles involved in fast axonal transport PMID:12887924 we propose that KIF2A regulates microtubule dynamics at the growth cone edge by depolymerizing microtubules and that it plays an important role in the suppression of collateral branch extension file:human/KIF2A/KIF2A-deep-research-falcon.md KIF2A is not established as a transporter of a particular vesicle or soluble cargo. |
| GO:0098982 GABA-ergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GABA-ergic synapse (IEA from mouse). Reason: Electronic transfer of a mouse synaptic localization; non-core. |
| GO:0120103 centriolar subdistal appendage | IDA PMID:23213374 3D-structured illumination microscopy provides novel insight... | ACCEPT | Summary: Centriolar subdistal appendage (IDA, 3D-SIM). Reason: KIF2A is not named in the cached text; deferring to the curator. Localization to the mother-centriole appendages fits its role in cilium disassembly and its association with CEP170. Supporting Evidence: PMID:23213374 Appendage proteins showed rings with multiple density masses, and the number of these masses was strongly reduced during mitosis PMID:25660017 we report that kinesin superfamily protein 2A (KIF2A), phosphorylated at T554 by PLK1, exhibits microtubule-depolymerizing activity at the mother centriole to disassemble the primary cilium in a growth-signal-dependent manner |
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Download this section (compressed HTML)Q: Does PLK1-activated KIF2A depolymerize axonemal microtubules directly, or centriolar/basal-body microtubules that anchor the axoneme? How does this relate to AURKA-HDAC6-driven disassembly?
Q: Is the reported plus-end-directed motility of mouse KIF2 (1995) reproducible for human KIF2A? If not, should kinesin-13 motor-activity annotations be revisited?
Q: Should GO add an MF term for ATP-dependent microtubule depolymerase activity to capture kinesin-13/kinesin-8 enzymology?
Q: Is KIF2A restraint by TTBK2 (S137/S140) during cilium growth and its activation by PLK1 (T554) during resorption a single switch at the mother centriole?
Experiment: Rescue KIF2A-knockout RPE1 cells with T554A, T554E and depolymerase-dead KIF2A. Measure serum-induced cilium disassembly kinetics, separating this from mitotic effects.
Experiment: Single-molecule TIRF of purified human KIF2A to test for directional motility versus lattice diffusion and end depolymerization.
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