KIF1A encodes a neuron-specific kinesin-3 (Unc-104 subfamily) motor. An N-terminal motor domain with neck coil is followed by a regulatory CC1-FHA-CC2 region that controls autoinhibition and dimerization, and a C-terminal cargo-binding region ending in a PH domain. Activated KIF1A dimers move rapidly and processively toward microtubule plus ends, carrying synaptic vesicle precursors down the axon to presynaptic sites and transporting dense core vesicles in axons and dendrites, where Ca2+/calmodulin enhances cargo binding and scaffolds such as liprin-alpha and TANC2 capture vesicles at synapses. In radial glial progenitors of the developing cortex, KIF1A acts at the nuclear surface to drive basally directed interkinetic nuclear migration, opposing dynein-driven apical movement. Heterozygous and biallelic KIF1A variants cause KIF1A-associated neurological disorder, spanning spastic paraplegia (SPG30), hereditary sensory and autonomic neuropathy (HSN2C), and NESCAV syndrome with intellectual disability, optic atrophy and cerebellar atrophy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003774 cytoskeletal motor activity | IEA GO_REF:0000117 | ACCEPT | Summary: Cytoskeletal motor activity is a correct, broad parent of KIF1A plus-end-directed microtubule motor activity. Reason: KIF1A is a kinesin-3 (Unc-104 subfamily) motor that moves processively toward microtubule plus ends as a dimer; disease variants in the motor domain reduce microtubule binding, velocity and processivity. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Kinesin motor with a plus-end-directed microtubule motor activity PMID:33880452 a gene that encodes an anterograde neuronal microtubule (MT) motor protein |
| GO:0003774 cytoskeletal motor activity | TAS PMID:7539720 The neuron-specific kinesin superfamily protein KIF1A is a u... | ACCEPT | Summary: Okada et al. characterized KIF1A as a fast anterograde axonal motor; cytoskeletal motor activity is a correct parent of its plus-end-directed microtubule motor activity. Reason: Correct but general; the precise child term plus-end-directed microtubule motor activity (GO:0008574) is separately annotated and used in core_functions. Supporting Evidence: PMID:7539720 a novel neuron-specific kinesin superfamily motor that was discovered to be a monomeric, globular molecule file:human/KIF1A/KIF1A-uniprot.txt Kinesin motor with a plus-end-directed microtubule motor activity |
| GO:0003777 microtubule motor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Microtubule motor activity from the kinesin motor domain (InterPro). Reason: KIF1A is a kinesin-3 (Unc-104 subfamily) motor that moves processively toward microtubule plus ends as a dimer; disease variants in the motor domain reduce microtubule binding, velocity and processivity. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Kinesin family. Unc-104 subfamily. file:human/KIF1A/KIF1A-uniprot.txt Kinesin motor with a plus-end-directed microtubule motor activity |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Binary interaction with a KIF1B isoform from a neurodegenerative-disease interactome screen; protein binding is uninformative. Reason: Generic protein binding from a high-throughput neurodegenerative-disease interactome screen is uninformative about KIF1A function; the interaction is not disputed, but it neither defines a motor or cargo-adaptor activity nor has been followed up functionally. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Binary interaction from a neurodegenerative-disease interactome screen (Haenig et al. 2020); protein binding is uninformative. Reason: Generic protein binding from a high-throughput neurodegenerative-disease interactome screen is uninformative about KIF1A function; the interaction is not disputed, but it neither defines a motor or cargo-adaptor activity nor has been followed up functionally. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Binary interaction from a neurodegenerative-disease interactome screen (Haenig et al. 2020); protein binding is uninformative. Reason: Generic protein binding from a high-throughput neurodegenerative-disease interactome screen is uninformative about KIF1A function; the interaction is not disputed, but it neither defines a motor or cargo-adaptor activity nor has been followed up functionally. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Binary interaction from a neurodegenerative-disease interactome screen (Haenig et al. 2020); protein binding is uninformative. Reason: Generic protein binding from a high-throughput neurodegenerative-disease interactome screen is uninformative about KIF1A function; the interaction is not disputed, but it neither defines a motor or cargo-adaptor activity nor has been followed up functionally. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Binary interaction from a neurodegenerative-disease interactome screen (Haenig et al. 2020); protein binding is uninformative. Reason: Generic protein binding from a high-throughput neurodegenerative-disease interactome screen is uninformative about KIF1A function; the interaction is not disputed, but it neither defines a motor or cargo-adaptor activity nor has been followed up functionally. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Binary interaction from a neurodegenerative-disease interactome screen (Haenig et al. 2020); protein binding is uninformative. Reason: Generic protein binding from a high-throughput neurodegenerative-disease interactome screen is uninformative about KIF1A function; the interaction is not disputed, but it neither defines a motor or cargo-adaptor activity nor has been followed up functionally. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: The kinesin motor domain binds ATP, which powers stepping. Reason: Intrinsic to kinesin motor mechanism. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Dimeric motor; dimerization is required for ATP-driven processive motility file:human/KIF1A/KIF1A-uniprot.txt Kinesin family. Unc-104 subfamily. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: KIF1A is a cytoplasmic motor. Reason: Well supported. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: KIF1A associates with the microtubule cytoskeleton. Reason: Well supported. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Cytoplasm, cytoskeleton |
| GO:0005871 kinesin complex | IBA GO_REF:0000033 | ACCEPT | Summary: KIF1A functions as a (homo)dimeric kinesin motor complex. Reason: Dimerization via CC1-FHA is required for processive motility; the PAINT kinesin complex placement is appropriate. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Dimeric motor; dimerization is required for ATP-driven processive motility PMID:22863567 KIF1A adopts a monomeric form in vitro but acts as a processive dimer in vivo |
| GO:0005874 microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: KIF1A acts on microtubules. Reason: Motor-domain microtubule binding is established by disease-variant biophysics. Supporting Evidence: PMID:33880452 reduced MT binding, reduced velocity and processivity, and increased non-motile rigor MT binding |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000002 | ACCEPT | Summary: Microtubule-based movement is the process driven by the KIF1A motor. Reason: KIF1A is a kinesin-3 (Unc-104 subfamily) motor that moves processively toward microtubule plus ends as a dimer; disease variants in the motor domain reduce microtubule binding, velocity and processivity. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Kinesin motor with a plus-end-directed microtubule motor activity PMID:33880452 reduced MT binding, reduced velocity and processivity, and increased non-motile rigor MT binding |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | ACCEPT | Summary: Microtubule binding is intrinsic to the kinesin motor domain. Reason: KAND variants that reduce microtubule binding directly assay this activity. Supporting Evidence: PMID:33880452 reduced MT binding, reduced velocity and processivity, and increased non-motile rigor MT binding |
| GO:0008017 microtubule binding | IEA GO_REF:0000002 | ACCEPT | Summary: Microtubule binding from the kinesin motor domain signature. Reason: As above. Supporting Evidence: PMID:33880452 reduced MT binding, reduced velocity and processivity, and increased non-motile rigor MT binding |
| GO:0008089 anterograde axonal transport | TAS PMID:7539720 The neuron-specific kinesin superfamily protein KIF1A is a u... | ACCEPT | Summary: KIF1A is the anterograde axonal motor for synaptic vesicle precursors. Reason: Okada 1995 and the Kif1a knockout (Yonekawa 1998) establish KIF1A-driven anterograde axonal transport of synaptic vesicle precursors. Supporting Evidence: PMID:7539720 KIF1A was associated with organelles that contained synaptic vesicle proteins such as synaptotagmin, synaptophysin, and Rab3A PMID:9548721 In the nervous systems of these mutants, the transport of synaptic vesicle precursors showed a specific and significant decrease file:human/KIF1A/KIF1A-uniprot.txt It is required for anterograde axonal transport of synaptic vesicle precursors |
| GO:0008574 plus-end-directed microtubule motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Plus-end-directed microtubule motor activity is the core KIF1A activity (IBA). Reason: KIF1A moves toward microtubule plus ends; this is its core molecular function. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Kinesin motor with a plus-end-directed microtubule motor activity PMID:33880452 a gene that encodes an anterograde neuronal microtubule (MT) motor protein PMID:33880452 reduced MT binding, reduced velocity and processivity, and increased non-motile rigor MT binding |
| GO:0008574 plus-end-directed microtubule motor activity | IEA GO_REF:0000003 | ACCEPT | Summary: Plus-end-directed microtubule motor activity via EC 5.6.1.3 mapping. Reason: KIF1A moves toward microtubule plus ends; this is its core molecular function. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Kinesin motor with a plus-end-directed microtubule motor activity |
| GO:0008574 plus-end-directed microtubule motor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Plus-end-directed microtubule motor activity transferred from mouse Kif1a. Reason: KIF1A moves toward microtubule plus ends; this is its core molecular function. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Kinesin motor with a plus-end-directed microtubule motor activity PMID:7539720 a novel neuron-specific kinesin superfamily motor that was discovered to be a monomeric, globular molecule |
| GO:0010970 transport along microtubule | IEA GO_REF:0000117 | ACCEPT | Summary: Transport along microtubule is the process KIF1A drives. Reason: Correct, somewhat general. Supporting Evidence: PMID:25265257 KIF1A is a neuron-specific motor protein that plays important roles in cargo transport along neurites |
| GO:0016192 vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: KIF1A transports synaptic vesicle precursors and dense core vesicles. Reason: Vesicle-mediated transport is broad but accurate for a vesicle-transporting kinesin; the more specific transport terms are also annotated. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt It is required for anterograde axonal transport of synaptic vesicle precursors file:human/KIF1A/KIF1A-uniprot.txt Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: Kinesin motor domains hydrolyse ATP to power movement. Reason: Intrinsic kinesin activity (IBA). Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Dimeric motor; dimerization is required for ATP-driven processive motility |
| GO:0030424 axon | IBA GO_REF:0000033 | ACCEPT | Summary: KIF1A is concentrated in axons. Reason: Consistent with its axonal transport role. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Within neuronal cells concentrated in the axon, with smaller amounts in the perinuclear and synaptic regions PMID:25265257 Transfection studies suggested that at least five of these mutations affect the transport of the MD along axons |
| GO:0030424 axon | IEA GO_REF:0000044 | ACCEPT | Summary: KIF1A is concentrated in axons. Reason: As above. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Within neuronal cells concentrated in the axon, with smaller amounts in the perinuclear and synaptic regions |
| GO:0030425 dendrite | IBA GO_REF:0000033 | ACCEPT | Summary: KIF1A traffics dense core vesicles in dendrites. Reason: Supported by rat hippocampal neuron data (Stucchi et al. 2018). Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons PMID:30021165 we decided to further investigate the role of KIF1A in DCV trafficking in dendrites |
| GO:0042802 identical protein binding | IPI PMID:22863567 The CC1-FHA tandem as a central hub for controlling the dime... | ACCEPT | Summary: The CC1-FHA tandem of KIF1A forms a stable dimer, promoting KIF1A homodimerization and activation. Reason: Self-association is mechanistically important for processive KIF1A motility. Supporting Evidence: PMID:22863567 KIF1A adopts a monomeric form in vitro but acts as a processive dimer in vivo PMID:22863567 we find that the CC1-FHA tandem of KIF1A exists as a stable dimer |
| GO:0043005 neuron projection | IEA GO_REF:0000044 | ACCEPT | Summary: KIF1A localizes to neuron projections and accumulates at neurite tips. Reason: Human experimental data (UniProt). Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Accumulates at the distal tip of growing neurites |
| GO:0045202 synapse | IEA GO_REF:0000044 | ACCEPT | Summary: KIF1A is present at synaptic regions where it delivers cargo. Reason: Location consistent with cargo delivery; non-motor function not implied. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Within neuronal cells concentrated in the axon, with smaller amounts in the perinuclear and synaptic regions |
| GO:0045202 synapse | ISS GO_REF:0000024 | ACCEPT | Summary: Synapse localization transferred from mouse Kif1a. Reason: As above. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Within neuronal cells concentrated in the axon, with smaller amounts in the perinuclear and synaptic regions |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: KIF1A is found in the perinuclear region, including the nuclear surface of radial glial progenitors. Reason: Consistent with UniProt and with its action from the nuclear surface during interkinetic nuclear migration. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Within neuronal cells concentrated in the axon, with smaller amounts in the perinuclear and synaptic regions PMID:21037580 Based on similar arguments, KIF1A most likely acts from the nuclear surface. |
| GO:0060998 regulation of dendritic spine development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: KIF1A-driven DCV delivery to spines affects dendritic spine development (rat). Reason: Downstream consequence of cargo delivery; retained as non-core. Supporting Evidence: PMID:30021165 liprin-Ξ± and TANC2 are not part of the KIF1A-cargo complex but capture DCVs at dendritic spines |
| GO:0061001 regulation of dendritic spine morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: KIF1A-driven DCV delivery to spines affects dendritic spine morphology (rat). Reason: As above. Supporting Evidence: PMID:30021165 liprin-Ξ± and TANC2 are not part of the KIF1A-cargo complex but capture DCVs at dendritic spines |
| GO:0098992 neuronal dense core vesicle | ISS GO_REF:0000024 | ACCEPT | Summary: KIF1A associates with neuronal dense core vesicles. Reason: Ca2+/CaM enhances KIF1A binding to DCVs. Supporting Evidence: PMID:30021165 We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility file:human/KIF1A/KIF1A-uniprot.txt neuronal dense core vesicle membrane |
| GO:0099012 neuronal dense core vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: KIF1A is a peripheral protein on the cytoplasmic face of DCV membranes. Reason: Consistent with DCV cargo binding. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt neuronal dense core vesicle membrane |
| GO:0099519 dense core granule cytoskeletal transport | ISS GO_REF:0000024 | ACCEPT | Summary: KIF1A drives cytoskeletal transport of dense core vesicles. Reason: Rat knockdown/motility data transferred by similarity. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons PMID:30021165 We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Axon cytoplasm, inferred from axonal transport roles. Reason: Logical inference. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Within neuronal cells concentrated in the axon, with smaller amounts in the perinuclear and synaptic regions |
| GO:1990048 anterograde neuronal dense core vesicle transport | ISS GO_REF:0000024 | ACCEPT | Summary: KIF1A drives anterograde DCV transport. Reason: Plus-end motor transporting DCVs in axons. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons |
| GO:1990049 retrograde neuronal dense core vesicle transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retrograde DCV transport is primarily dynein-driven; KIF1A depletion affects bidirectional DCV motility. Reason: A plus-end motor contributes to 'retrograde' DCV movement only in mixed-polarity dendrites or indirectly via coupled bidirectional transport; the PAINT placement is retained but this is not a core KIF1A process. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons PMID:30021165 we decided to further investigate the role of KIF1A in DCV trafficking in dendrites |
| GO:1990049 retrograde neuronal dense core vesicle transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retrograde DCV transport transferred from rat Kif1a. Reason: As above. Supporting Evidence: file:human/KIF1A/KIF1A-uniprot.txt Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons |
| GO:0022027 interkinetic nuclear migration | ISS PMID:21037580 Kinesin 3 and cytoplasmic dynein mediate interkinetic nuclea... | NEW | Summary: KIF1A is the plus-end motor that drives basal (G1) interkinetic nuclear migration in radial glial progenitors; human KIF1A rescues the rat knockdown. Reason: KIF1A performs the step itself (participation test passed): it acts from the nuclear surface and moves the nucleus toward microtubule plus ends, complementing dynein-driven apical movement. Rat Kif1a carries this term by IMP from the same paper; human KIF1A lacks it only because the transfer has not been made. Rescue with human KIF1A cDNA supports direct transfer. Supporting Evidence: PMID:21037580 An RNAi screen of kinesin genes identified Kif1a, a member of the kinesin-3 family, as the motor for basally directed nuclear movement PMID:21037580 Our results, therefore, suggest that KIF1A in particular is required for radial glial nuclear migration. PMID:21037580 Rescue of basally directed nuclear movement in KIF1A shRNA-/DsRed-human KIF1A-co-expressing radial glial progenitor cell. PMID:21037580 Based on similar arguments, KIF1A most likely acts from the nuclear surface. |
| GO:0048490 anterograde synaptic vesicle transport | ISS PMID:9548721 Defect in synaptic vesicle precursor transport and neuronal ... | NEW | Summary: KIF1A is the principal anterograde motor for synaptic vesicle precursors (Kif1a knockout mouse; human UniProt function). Reason: KIF1A binds and moves synaptic vesicle precursor organelles; Kif1a-null mice show a specific decrease in synaptic vesicle precursor transport. The existing anterograde axonal transport TAS row is correct but does not name the cargo. Supporting Evidence: PMID:9548721 In the nervous systems of these mutants, the transport of synaptic vesicle precursors showed a specific and significant decrease PMID:9548721 our results demonstrate that KIF1A transports a synaptic vesicle precursor file:human/KIF1A/KIF1A-uniprot.txt It is required for anterograde axonal transport of synaptic vesicle precursors |
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Download this section (compressed HTML)Q: How is KIF1A anchored to the nuclear envelope of radial glial progenitors during basal interkinetic nuclear migration (LINC/nesprin, PH-domain lipid binding, or another adaptor)?
Suggested experts: neural progenitor cell biologists, kinesin-3 cargo-adaptor researchers
Q: Should GO represent KIF1A's role in retrograde dense core vesicle transport, given that it is a plus-end motor?
Suggested experts: PAINT curators, neuronal trafficking experts
Experiment: Test KIF1A PH-domain and cargo-binding mutants for rescue of basal nuclear migration after Kif1a knockdown in embryonic cortex.
Hypothesis: Nuclear attachment of KIF1A requires its C-terminal cargo-recognition region, not only motor activity.
Type: in utero electroporation rescue with live imaging
Experiment: Correlate single-molecule motility of KAND variants with synaptic vesicle precursor flux in human iPSC-derived neurons.
Hypothesis: Rigor/non-motile variants dominantly impair synaptic vesicle precursor transport more than reduced-binding variants.
Type: TIRF motility plus live-cell cargo imaging
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