KIF24 is a kinesin-13 family protein with a central kinesin motor domain that binds and depolymerizes microtubules rather than walking along them (in vitro depolymerization by a KIF24 motor fragment was seen with both ATP and a non-hydrolyzable analogue). It localizes preferentially to the distal end of the mother centriole, where it interacts with CP110 and CEP97 and recruits MPHOSPH9, which in turn recruits the CP110-CEP97 distal cap. Through cap maintenance and depolymerization of centriolar microtubules, KIF24 suppresses inappropriate primary cilium formation in proliferating cells. Phosphorylation by NEK2 stimulates KIF24 depolymerizing activity, preventing cilium outgrowth or regrowth during the cell cycle and contributing to cilium resorption before mitosis. KIF24 depletion in cycling cells results in loss of CP110 from the mother centriole and promotes ciliation. Biallelic KIF24 missense variants have been reported in skeletal ciliopathy/acromesomelic dysplasia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003777 microtubule motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Microtubule motor activity (IBA) for KIF24, a kinesin-13 family member. Reason: KIF24 carries a kinesin motor domain and belongs to the kinesin-13 (internal motor) subfamily, whose motor domains depolymerize microtubule ends rather than translocate (for KIF24 a requirement for ATP hydrolysis has not been demonstrated; see deep research). GO has no separate microtubule depolymerase activity term, and kinesin-13 members are conventionally annotated with this motor activity term; the IDA shows ATP-dependent binding and depolymerization of microtubules in vitro. Accepted with the caveat that the activity is depolymerization, not cargo transport. Supporting Evidence: PMID:21620453 Kif24 is able to bind and depolymerize microtubules in vitro. PMID:30375385 KIF24, a member of the kinesin-13 family of proteins, interacts with CP110 and negatively regulates ciliogenesis file:human/KIF24/KIF24-deep-research-falcon.md However, the 2011 KIF24 fragment showed similar depolymerization in ATP and the nonhydrolyzable analogue AMP-PNP under the conditions tested. |
| GO:0003777 microtubule motor activity | IDA PMID:21620453 Centriolar kinesin Kif24 interacts with CP110 to remodel mic... | ACCEPT | Summary: Microtubule motor activity (IDA) for KIF24, a kinesin-13 family member. Reason: KIF24 carries a kinesin motor domain and belongs to the kinesin-13 (internal motor) subfamily, whose motor domains depolymerize microtubule ends rather than translocate (for KIF24 a requirement for ATP hydrolysis has not been demonstrated; see deep research). GO has no separate microtubule depolymerase activity term, and kinesin-13 members are conventionally annotated with this motor activity term; the IDA shows ATP-dependent binding and depolymerization of microtubules in vitro. Accepted with the caveat that the activity is depolymerization, not cargo transport. Supporting Evidence: PMID:21620453 Kif24 is able to bind and depolymerize microtubules in vitro. PMID:30375385 KIF24, a member of the kinesin-13 family of proteins, interacts with CP110 and negatively regulates ciliogenesis file:human/KIF24/KIF24-deep-research-falcon.md However, the 2011 KIF24 fragment showed similar depolymerization in ATP and the nonhydrolyzable analogue AMP-PNP under the conditions tested. |
| GO:0003777 microtubule motor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Microtubule motor activity (IEA) for KIF24, a kinesin-13 family member. Reason: KIF24 carries a kinesin motor domain and belongs to the kinesin-13 (internal motor) subfamily, whose motor domains depolymerize microtubule ends rather than translocate (for KIF24 a requirement for ATP hydrolysis has not been demonstrated; see deep research). GO has no separate microtubule depolymerase activity term, and kinesin-13 members are conventionally annotated with this motor activity term; the IDA shows ATP-dependent binding and depolymerization of microtubules in vitro. Accepted with the caveat that the activity is depolymerization, not cargo transport. Supporting Evidence: PMID:21620453 Kif24 is able to bind and depolymerize microtubules in vitro. PMID:30375385 KIF24, a member of the kinesin-13 family of proteins, interacts with CP110 and negatively regulates ciliogenesis file:human/KIF24/KIF24-deep-research-falcon.md However, the 2011 KIF24 fragment showed similar depolymerization in ATP and the nonhydrolyzable analogue AMP-PNP under the conditions tested. |
| GO:0005515 protein binding | IPI PMID:21620453 Centriolar kinesin Kif24 interacts with CP110 to remodel mic... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:21620453 Centriolar kinesin Kif24 interacts with CP110 to remodel mic... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:24421332 The CP110-interacting proteins Talpid3 and Cep290 play overl... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:24421332 The CP110-interacting proteins Talpid3 and Cep290 play overl... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:26290419 Nek2 activation of Kif24 ensures cilium disassembly during t... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:30375385 M-Phase Phosphoprotein 9 regulates ciliogenesis by modulatin... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005515 protein binding | IPI PMID:35709258 Spatial centrosome proteome of human neural cells uncovers d... | REMOVE | Summary: Generic protein binding (IPI) for KIF24. Reported partners include CP110, CEP97, Talpid3, NEK2 and MPHOSPH9 and large-scale interactome hits. Reason: GO:0005515 protein binding is uninformative about the molecular activity of the gene product. Removal does not dispute that the reported physical interaction occurs; the biologically meaningful consequences of the interaction are captured by the process, location and more specific function terms reviewed elsewhere in this document. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding (IEA, InterPro kinesin motor domain). Reason: The kinesin motor domain contains the conserved nucleotide-binding P-loop; ATP binding underlies the depolymerase activity of kinesin-13 motors. |
| GO:0005813 centrosome | IDA PMID:30375385 M-Phase Phosphoprotein 9 regulates ciliogenesis by modulatin... | ACCEPT | Summary: Centrosome localization (IDA). Reason: KIF24 localizes to centrosomes, preferentially at the distal end of the mother centriole. Supporting Evidence: PMID:21620453 Kif24 preferentially localizes to mother centrioles. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: Centrosome localization (IEA). Reason: KIF24 localizes to centrosomes, preferentially at the distal end of the mother centriole. Supporting Evidence: PMID:21620453 Kif24 preferentially localizes to mother centrioles. |
| GO:0005814 centriole | IDA PMID:21620453 Centriolar kinesin Kif24 interacts with CP110 to remodel mic... | ACCEPT | Summary: Centriole localization (IDA). Reason: KIF24 localizes to the mother centriole distal end, colocalizing with CP110, CEP97 and MPHOSPH9. Supporting Evidence: PMID:21620453 Kif24 preferentially localizes to mother centrioles. PMID:30375385 Surprisingly, MPP9 appeared as a ring-like structure surrounding the centriole distal-end marker Centrin-3 and was colocalized with other distal-end markers, such as CP110, CEP97, and KIF24 |
| GO:0005814 centriole | IDA PMID:30375385 M-Phase Phosphoprotein 9 regulates ciliogenesis by modulatin... | ACCEPT | Summary: Centriole localization (IDA). Reason: KIF24 localizes to the mother centriole distal end, colocalizing with CP110, CEP97 and MPHOSPH9. Supporting Evidence: PMID:21620453 Kif24 preferentially localizes to mother centrioles. PMID:30375385 Surprisingly, MPP9 appeared as a ring-like structure surrounding the centriole distal-end marker Centrin-3 and was colocalized with other distal-end markers, such as CP110, CEP97, and KIF24 |
| GO:0005814 centriole | IEA GO_REF:0000044 | ACCEPT | Summary: Centriole localization (IEA). Reason: KIF24 localizes to the mother centriole distal end, colocalizing with CP110, CEP97 and MPHOSPH9. Supporting Evidence: PMID:21620453 Kif24 preferentially localizes to mother centrioles. PMID:30375385 Surprisingly, MPP9 appeared as a ring-like structure surrounding the centriole distal-end marker Centrin-3 and was colocalized with other distal-end markers, such as CP110, CEP97, and KIF24 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: Reactome-derived cytosol localization (TAS) for KIF24, from pathway reactions in which KIF24 participates. Reason: Reactome places soluble, non-membrane participants of its reactions in the cytosol compartment. This is not wrong in the broad sense, but the informative location of KIF24 is the distal end of the mother centriole; cytosol is retained as a non-core, low-information location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626220 | KEEP AS NON CORE | Summary: Reactome-derived cytosol localization (TAS) for KIF24, from pathway reactions in which KIF24 participates. Reason: Reactome places soluble, non-membrane participants of its reactions in the cytosol compartment. This is not wrong in the broad sense, but the informative location of KIF24 is the distal end of the mother centriole; cytosol is retained as a non-core, low-information location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626223 | KEEP AS NON CORE | Summary: Reactome-derived cytosol localization (TAS) for KIF24, from pathway reactions in which KIF24 participates. Reason: Reactome places soluble, non-membrane participants of its reactions in the cytosol compartment. This is not wrong in the broad sense, but the informative location of KIF24 is the distal end of the mother centriole; cytosol is retained as a non-core, low-information location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626227 | KEEP AS NON CORE | Summary: Reactome-derived cytosol localization (TAS) for KIF24, from pathway reactions in which KIF24 participates. Reason: Reactome places soluble, non-membrane participants of its reactions in the cytosol compartment. This is not wrong in the broad sense, but the informative location of KIF24 is the distal end of the mother centriole; cytosol is retained as a non-core, low-information location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626228 | KEEP AS NON CORE | Summary: Reactome-derived cytosol localization (TAS) for KIF24, from pathway reactions in which KIF24 participates. Reason: Reactome places soluble, non-membrane participants of its reactions in the cytosol compartment. This is not wrong in the broad sense, but the informative location of KIF24 is the distal end of the mother centriole; cytosol is retained as a non-core, low-information location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | KEEP AS NON CORE | Summary: Reactome-derived cytosol localization (TAS) for KIF24, from pathway reactions in which KIF24 participates. Reason: Reactome places soluble, non-membrane participants of its reactions in the cytosol compartment. This is not wrong in the broad sense, but the informative location of KIF24 is the distal end of the mother centriole; cytosol is retained as a non-core, low-information location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626699 | KEEP AS NON CORE | Summary: Reactome-derived cytosol localization (TAS) for KIF24, from pathway reactions in which KIF24 participates. Reason: Reactome places soluble, non-membrane participants of its reactions in the cytosol compartment. This is not wrong in the broad sense, but the informative location of KIF24 is the distal end of the mother centriole; cytosol is retained as a non-core, low-information location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | KEEP AS NON CORE | Summary: Reactome-derived cytosol localization (TAS) for KIF24, from pathway reactions in which KIF24 participates. Reason: Reactome places soluble, non-membrane participants of its reactions in the cytosol compartment. This is not wrong in the broad sense, but the informative location of KIF24 is the distal end of the mother centriole; cytosol is retained as a non-core, low-information location. |
| GO:0005874 microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: Microtubule (IBA). Reason: KIF24 acts on microtubules, specifically centriolar microtubules at the mother centriole; the phylogenetic location inference for kinesin-13 family members is consistent. Supporting Evidence: PMID:21620453 ectopically expressed Kif24 specifically remodels centriolar microtubules without significantly altering cytoplasmic microtubules |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Microtubule-based movement (IEA, InterPro kinesin motor domain). Reason: Kinesin-13 family members, including KIF24, are not translocating motors; their motor domain acts at microtubule ends to depolymerize them. There is no evidence that KIF24 moves cargo along microtubules, so this generic kinesin mapping over-states the process. Supporting Evidence: PMID:21620453 We have identified a protein, Kif24, that shares homology with the kinesin-13 subfamily of motor proteins |
| GO:0007019 microtubule depolymerization | IBA GO_REF:0000033 | ACCEPT | Summary: Microtubule depolymerization (IBA). Reason: Core activity of KIF24: in vitro depolymerization and specific remodeling of centriolar microtubules in cells; NEK2 phosphorylation stimulates this activity. Supporting Evidence: PMID:21620453 ectopically expressed Kif24 specifically remodels centriolar microtubules without significantly altering cytoplasmic microtubules PMID:26290419 Kif24 is a physiological substrate of Nek2, which regulates cilia disassembly through a concerted mechanism involving Kif24-mediated microtubule depolymerization. |
| GO:0007019 microtubule depolymerization | IDA PMID:21620453 Centriolar kinesin Kif24 interacts with CP110 to remodel mic... | ACCEPT | Summary: Microtubule depolymerization (IDA). Reason: Core activity of KIF24: in vitro depolymerization and specific remodeling of centriolar microtubules in cells; NEK2 phosphorylation stimulates this activity. Supporting Evidence: PMID:21620453 ectopically expressed Kif24 specifically remodels centriolar microtubules without significantly altering cytoplasmic microtubules PMID:26290419 Kif24 is a physiological substrate of Nek2, which regulates cilia disassembly through a concerted mechanism involving Kif24-mediated microtubule depolymerization. |
| GO:0007019 microtubule depolymerization | IEA GO_REF:0000117 | ACCEPT | Summary: Microtubule depolymerization (IEA). Reason: Core activity of KIF24: in vitro depolymerization and specific remodeling of centriolar microtubules in cells; NEK2 phosphorylation stimulates this activity. Supporting Evidence: PMID:21620453 ectopically expressed Kif24 specifically remodels centriolar microtubules without significantly altering cytoplasmic microtubules PMID:26290419 Kif24 is a physiological substrate of Nek2, which regulates cilia disassembly through a concerted mechanism involving Kif24-mediated microtubule depolymerization. |
| GO:0008017 microtubule binding | IEA GO_REF:0000002 | ACCEPT | Summary: Microtubule binding (IEA, InterPro). Reason: Supported experimentally: KIF24 binds and depolymerizes microtubules in vitro. Supporting Evidence: PMID:21620453 Kif24 is able to bind and depolymerize microtubules in vitro. |
| GO:0032991 protein-containing complex | IDA PMID:24421332 The CP110-interacting proteins Talpid3 and Cep290 play overl... | KEEP AS NON CORE | Summary: Protein-containing complex (IDA) from the Talpid3/CEP290 study, reflecting association of KIF24 with CP110-containing complexes. Reason: The generic complex term is correct but uninformative; KIF24 associates with CP110-CEP97-Talpid3-containing complexes at the distal centriole. No specific GO complex term exists for the CP110 cap complex. Supporting Evidence: PMID:24421332 Collectively, these data indicate that Talpid3 robustly binds to CP110 and more weakly associates with Cep97, Cep290, and Kif24. |
| GO:0042802 identical protein binding | IPI PMID:26290419 Nek2 activation of Kif24 ensures cilium disassembly during t... | MARK AS OVER ANNOTATED | Summary: Identical protein binding (IPI) from the NEK2-KIF24 study, which reports interaction between the amino- and carboxy-terminal regions of KIF24. Reason: The cited study describes an intramolecular interaction between N- and C-terminal fragments that is proposed to keep KIF24 in a closed, autoinhibited conformation relieved by NEK2 phosphorylation. This is not evidence for a homo-oligomeric binding function and adds no functional information beyond the regulation already captured. Supporting Evidence: PMID:26290419 Taken together with our observation that the amino- and carboxy-terminal regions of Kif24 can interact, these data suggest that Kif24 undergoes a conformational change in response to Nek2-mediated phosphorylation at T621/S622 |
| GO:0060271 cilium assembly | IMP PMID:21620453 Centriolar kinesin Kif24 interacts with CP110 to remodel mic... | MODIFY | Summary: Cilium assembly (IMP) from the original KIF24 study. Reason: KIF24 depletion causes aberrant cilia assembly in cycling cells, i.e. KIF24 restrains cilium formation. The positive process term mis-states the direction of the effect; the regulatory term negative regulation of cilium assembly correctly captures this phenotype. Proposed replacements: negative regulation of cilium assembly Supporting Evidence: PMID:21620453 Loss of Kif24 from cycling cells resulted in aberrant cilia assembly PMID:26290419 Consistent with our previous studies, we observed a dramatic increase in ciliation in cycling RPE1 cells depleted of Kif24, as compared with controls |
| GO:1902018 negative regulation of cilium assembly | IMP PMID:30375385 M-Phase Phosphoprotein 9 regulates ciliogenesis by modulatin... | ACCEPT | Summary: Negative regulation of cilium assembly (IMP). Reason: Core role of KIF24: it suppresses ciliogenesis in cycling cells by recruiting MPHOSPH9 and thereby the CP110-CEP97 cap, and by depolymerizing centriolar microtubules. Supporting Evidence: PMID:30375385 KIF24, a member of the kinesin-13 family of proteins, interacts with CP110 and negatively regulates ciliogenesis in two different ways: by controlling ciliary axoneme elongation through the depolymerization of centriolar microtubules and by recruiting the CP110-CEP97 complex to the distal end of the mother centriole |
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Download this section (compressed HTML)Q: Does NEK2-activated KIF24 actively depolymerize axonemal microtubules during G2/M cilium resorption, or does it act only at the centriole to prevent regrowth? This determines whether a cilium disassembly process annotation is warranted.
Q: Is the CP110-loss phenotype after KIF24 depletion fully explained by loss of MPHOSPH9 recruitment, or does KIF24 depolymerase activity contribute separately to cap retention?
Experiment: Rescue KIF24-null RPE1 cells with motor-dead (ATPase-deficient) versus MPHOSPH9-binding-deficient KIF24 to separate depolymerase and cap-recruitment contributions to ciliogenesis suppression.
Experiment: Live imaging of axoneme length in cells expressing NEK2-phosphomimetic KIF24 to test direct axonemal depolymerization during cilium resorption.
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