KIF5B

UniProt ID: P33176
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

KIF5B encodes the ubiquitous kinesin-1 heavy chain, an ATP-dependent, plus-end-directed microtubule motor. Its core molecular role is to form kinesin-1 motor complexes that bind microtubules and move vesicles and organelles toward microtubule plus ends. KIF5B is recruited to many cargos through adaptors, including Arl8/SKIP-dependent lysosome positioning, lytic granule polarization in natural killer cells, mitochondrial transport, neuronal cargo transport, centrosome/nuclear positioning, and channel trafficking. Its lysosomal role is kinesin-dependent lysosome localization/positioning through adaptor-mediated cargo recruitment.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005871 kinesin complex
IBA
GO_REF:0000033 		ACCEPT
Summary: KIF5B is a heavy-chain subunit of the kinesin-1 motor complex, which contains two KIF5B heavy chains and kinesin light chains.
Reason: The cellular-component annotation reflects the canonical kinesin-1 complex architecture.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
Oligomer composed of two heavy chains and two light chains.
GO:0007411 axon guidance
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: This is a downstream neuronal phenotype or synaptic consequence inferred for kinesin-family cargo transport rather than a direct molecular or cellular core role of KIF5B.
Reason: The direct KIF5B function is motor-driven cargo transport; annotating broad neuronal outcomes as KIF5B functions overstates the evidence.
GO:0048489 synaptic vesicle transport
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: This is a plausible cargo- or cell-type-specific transport role for kinesin-1, but it is not the defining KIF5B function.
Reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core role is plus-end-directed microtubule cargo transport.
Supporting Evidence:
PMID:28426968
distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport
GO:0098971 anterograde dendritic transport of neurotransmitter receptor complex
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: This is a plausible cargo- or cell-type-specific transport role for kinesin-1, but it is not the defining KIF5B function.
Reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core role is plus-end-directed microtubule cargo transport.
Supporting Evidence:
PMID:28426968
distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport
GO:0008574 plus-end-directed microtubule motor activity
IBA
GO_REF:0000033 		ACCEPT
Summary: This is the most informative existing molecular-function annotation for KIF5B. KIF5B is the kinesin-1 heavy chain and acts as a plus-end-directed microtubule motor.
Reason: Retain as the core molecular function.
Supporting Evidence:
PMID:8606779
Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
file:human/KIF5B/KIF5B-uniprot.txt
Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.
GO:0003777 microtubule motor activity
IEA
GO_REF:0000120 		MODIFY
Summary: The annotation is correct but too broad for KIF5B, whose directional kinesin-1 activity is better captured by plus-end-directed microtubule motor activity.
Reason: Replace the generic motor term with the specific plus-end-directed microtubule motor term already present in GOA.
Supporting Evidence:
PMID:8606779
Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
file:human/KIF5B/KIF5B-uniprot.txt
Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.
GO:0005524 ATP binding
IEA
GO_REF:0000002 		MODIFY
Summary: The binding annotation is mechanistically true for kinesin-1 but less informative than the full ATP-dependent motor activity.
Reason: Use the specific plus-end-directed microtubule motor activity rather than separate generic ATP-binding or microtubule-binding terms as the reviewed molecular function.
Supporting Evidence:
PMID:1607388
the kinesin heavy chain showed both a diffuse distribution and a filamentous staining pattern that coaligned with microtubules
PMID:8606779
Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
GO:0005765 lysosomal membrane
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: KIF5B is recruited to the cytosolic face of lysosomal membranes through adaptor systems such as Arl8/SKIP to drive lysosome positioning.
Reason: Keep as a supported PN-relevant cargo-specific localization, but do not treat lysosomal membrane association as the defining location of KIF5B activity across all cargos.
Supporting Evidence:
PMID:22172677
endogenous KIF5B, the heavy chain of kinesin-1, accumulated on lysosomes in cells overexpressing Arl8b and SKIP
PMID:22172677
when KIF5B was knocked down by >85% by RNAi, lysosomes were more centrally clustered
GO:0005856 cytoskeleton
IEA
GO_REF:0000044 		ACCEPT
Summary: KIF5B is a cytoskeleton-associated microtubule motor. The term is broad but consistent with the core motor mechanism.
Reason: Retain as a core cellular context for KIF5B motor activity.
Supporting Evidence:
PMID:1607388
the kinesin heavy chain showed both a diffuse distribution and a filamentous staining pattern that coaligned with microtubules
PMID:8606779
Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
GO:0007018 microtubule-based movement
IEA
GO_REF:0000002 		MODIFY
Summary: Microtubule-based movement is correct but broad. KIF5B specifically functions as a kinesin-1 cargo motor, so vesicle transport along microtubule is the better process term.
Reason: Replace the broad process with the cargo-transport process already supported in GOA.
Supporting Evidence:
PMID:8606779
Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
file:human/KIF5B/KIF5B-uniprot.txt
Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.
GO:0008017 microtubule binding
IEA
GO_REF:0000002 		MODIFY
Summary: The binding annotation is mechanistically true for kinesin-1 but less informative than the full ATP-dependent motor activity.
Reason: Use the specific plus-end-directed microtubule motor activity rather than separate generic ATP-binding or microtubule-binding terms as the reviewed molecular function.
Supporting Evidence:
PMID:1607388
the kinesin heavy chain showed both a diffuse distribution and a filamentous staining pattern that coaligned with microtubules
PMID:8606779
Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
GO:0032839 dendrite cytoplasm
IEA
GO_REF:0000108 		KEEP AS NON CORE
Summary: This neuronal compartment annotation is consistent with kinesin cargo transport in neurons but is not a core localization for the ubiquitous KIF5B motor.
Reason: Keep as a transferred, non-core neuronal localization context.
GO:0101004 cytolytic granule membrane
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: KIF5B participates in NK-cell lytic granule polarization and cytotoxicity through an Arl8b/SKIP/kinesin-1 cargo-transport pathway.
Reason: Keep as a well-supported immune-cell cargo-specific role, secondary to the core kinesin motor function.
Supporting Evidence:
PMID:24088571
We also identified four unique peptides corresponding to KIF5B (the heavy chain of the plus-end motor protein kinesin-1 [KHC]) in the Arl8b pull down
PMID:24088571
Silencing of KIF5B expression inhibited the polarization of both the MTOC and lytic granules to the immune synapse
GO:1904115 axon cytoplasm
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: This neuronal compartment annotation is consistent with kinesin cargo transport in neurons but is not a core localization for the ubiquitous KIF5B motor.
Reason: Keep as a transferred, non-core neuronal localization context.
GO:0005515 protein binding
IPI
PMID:15161933
Comprehensive proteomic analysis of interphase and mitotic 1... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:19164528
Nesprin 4 is an outer nuclear membrane protein that can indu... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:20562859
Network organization of the human autophagy system. 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:21915095
A kinesin-1 binding motif in vaccinia virus that is widespre... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:25855459
Repeated ER-endosome contacts promote endosome translocation... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005515 protein binding
IPI
PMID:36931259
A central chaperone-like role for 14-3-3 proteins in human c... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0042802 identical protein binding
IPI
PMID:17013387
Single-molecule observations of neck linker conformational c... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0042802 identical protein binding
IPI
PMID:18004302
How kinesin waits between steps. 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0005737 cytoplasm
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005739 mitochondrion
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: KIF5B can associate with diverse organelles or cellular regions through cargo adaptors, but this term is a cargo/context-specific location rather than the core motor role.
Reason: Keep as non-core for a pleiotropic motor with many cargo associations.
GO:0030139 endocytic vesicle
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: KIF5B can associate with diverse organelles or cellular regions through cargo adaptors, but this term is a cargo/context-specific location rather than the core motor role.
Reason: Keep as non-core for a pleiotropic motor with many cargo associations.
GO:0032230 positive regulation of synaptic transmission, GABAergic
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This is a downstream neuronal phenotype or synaptic consequence inferred for kinesin-family cargo transport rather than a direct molecular or cellular core role of KIF5B.
Reason: The direct KIF5B function is motor-driven cargo transport; annotating broad neuronal outcomes as KIF5B functions overstates the evidence.
GO:0035253 ciliary rootlet
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: KIF5B can associate with diverse organelles or cellular regions through cargo adaptors, but this term is a cargo/context-specific location rather than the core motor role.
Reason: Keep as non-core for a pleiotropic motor with many cargo associations.
GO:0035617 stress granule disassembly
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This is a plausible cargo- or cell-type-specific transport role for kinesin-1, but it is not the defining KIF5B function.
Reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core role is plus-end-directed microtubule cargo transport.
Supporting Evidence:
PMID:28426968
distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport
GO:0043005 neuron projection
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This neuronal compartment annotation is consistent with kinesin cargo transport in neurons but is not a core localization for the ubiquitous KIF5B motor.
Reason: Keep as a transferred, non-core neuronal localization context.
GO:0044877 protein-containing complex binding
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0045335 phagocytic vesicle
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: KIF5B can associate with diverse organelles or cellular regions through cargo adaptors, but this term is a cargo/context-specific location rather than the core motor role.
Reason: Keep as non-core for a pleiotropic motor with many cargo associations.
GO:0098987 regulation of modification of synapse structure, modulating synaptic transmission
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This is a downstream neuronal phenotype or synaptic consequence inferred for kinesin-family cargo transport rather than a direct molecular or cellular core role of KIF5B.
Reason: The direct KIF5B function is motor-driven cargo transport; annotating broad neuronal outcomes as KIF5B functions overstates the evidence.
GO:0099524 postsynaptic cytosol
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: This seeded annotation was reviewed as a non-core KIF5B context.
Reason: KIF5B is a pleiotropic microtubule motor; this term is retained only as a secondary context.
GO:0005829 cytosol
IDA
GO_REF:0000052 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005765 lysosomal membrane
EXP
PMID:22172677
Arl8 and SKIP act together to link lysosomes to kinesin-1. 		KEEP AS NON CORE
Summary: KIF5B is recruited to the cytosolic face of lysosomal membranes through adaptor systems such as Arl8/SKIP to drive lysosome positioning.
Reason: Keep as a supported PN-relevant cargo-specific localization, but do not treat lysosomal membrane association as the defining location of KIF5B activity across all cargos.
Supporting Evidence:
PMID:22172677
endogenous KIF5B, the heavy chain of kinesin-1, accumulated on lysosomes in cells overexpressing Arl8b and SKIP
PMID:22172677
when KIF5B was knocked down by >85% by RNAi, lysosomes were more centrally clustered
GO:0005765 lysosomal membrane
EXP
PMID:24088571
Arf-like GTPase Arl8b regulates lytic granule polarization a... 		KEEP AS NON CORE
Summary: KIF5B is recruited to the cytosolic face of lysosomal membranes through adaptor systems such as Arl8/SKIP to drive lysosome positioning.
Reason: Keep as a supported PN-relevant cargo-specific localization, but do not treat lysosomal membrane association as the defining location of KIF5B activity across all cargos.
Supporting Evidence:
PMID:22172677
endogenous KIF5B, the heavy chain of kinesin-1, accumulated on lysosomes in cells overexpressing Arl8b and SKIP
PMID:22172677
when KIF5B was knocked down by >85% by RNAi, lysosomes were more centrally clustered
GO:0101004 cytolytic granule membrane
EXP
PMID:24088571
Arf-like GTPase Arl8b regulates lytic granule polarization a... 		KEEP AS NON CORE
Summary: KIF5B participates in NK-cell lytic granule polarization and cytotoxicity through an Arl8b/SKIP/kinesin-1 cargo-transport pathway.
Reason: Keep as a well-supported immune-cell cargo-specific role, secondary to the core kinesin motor function.
Supporting Evidence:
PMID:24088571
We also identified four unique peptides corresponding to KIF5B (the heavy chain of the plus-end motor protein kinesin-1 [KHC]) in the Arl8b pull down
PMID:24088571
Silencing of KIF5B expression inhibited the polarization of both the MTOC and lytic granules to the immune synapse
GO:0005829 cytosol
TAS
Reactome:R-HSA-9700181 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005829 cytosol
TAS
Reactome:R-HSA-9712078 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005829 cytosol
TAS
Reactome:R-HSA-9712079 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005829 cytosol
TAS
Reactome:R-HSA-9712083 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005829 cytosol
TAS
Reactome:R-HSA-9712084 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005829 cytosol
TAS
Reactome:R-HSA-9712085 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005829 cytosol
TAS
Reactome:R-HSA-9850958 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0005515 protein binding
IPI
PMID:28426968
MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- v... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0042267 natural killer cell mediated cytotoxicity
IMP
PMID:24088571
Arf-like GTPase Arl8b regulates lytic granule polarization a... 		KEEP AS NON CORE
Summary: KIF5B participates in NK-cell lytic granule polarization and cytotoxicity through an Arl8b/SKIP/kinesin-1 cargo-transport pathway.
Reason: Keep as a well-supported immune-cell cargo-specific role, secondary to the core kinesin motor function.
Supporting Evidence:
PMID:24088571
We also identified four unique peptides corresponding to KIF5B (the heavy chain of the plus-end motor protein kinesin-1 [KHC]) in the Arl8b pull down
PMID:24088571
Silencing of KIF5B expression inhibited the polarization of both the MTOC and lytic granules to the immune synapse
GO:0032418 lysosome localization
IMP
PMID:22172677
Arl8 and SKIP act together to link lysosomes to kinesin-1. 		KEEP AS NON CORE
Summary: KIF5B has direct evidence for lysosome positioning/localization through Arl8/SKIP-dependent recruitment of kinesin-1 to lysosomes.
Reason: Keep as the supported Proteostasis Network-relevant cargo-specific process. This does not justify propagating the broader PN lysosomal-tubulation context to lysosome organization.
Supporting Evidence:
PMID:22172677
endogenous KIF5B, the heavy chain of kinesin-1, accumulated on lysosomes in cells overexpressing Arl8b and SKIP
PMID:22172677
when KIF5B was knocked down by >85% by RNAi, lysosomes were more centrally clustered
GO:0005829 cytosol
TAS
Reactome:R-HSA-9700179 		KEEP AS NON CORE
Summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization does not describe the specific motor function.
Reason: Keep as a correct broad location, not as a core functional annotation.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
GO:0099641 anterograde axonal protein transport
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This is a plausible cargo- or cell-type-specific transport role for kinesin-1, but it is not the defining KIF5B function.
Reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core role is plus-end-directed microtubule cargo transport.
Supporting Evidence:
PMID:28426968
distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport
GO:0045296 cadherin binding
HDA
PMID:25468996
E-cadherin interactome complexity and robustness resolved by... 		MARK AS OVER ANNOTATED
Summary: The interaction may be experimentally observed, but the GO term is generic and does not convey KIF5B biology.
Reason: Do not use generic binding terms as reviewed KIF5B function; the informative molecular function is plus-end-directed microtubule motor activity and cargo transport.
GO:0003777 microtubule motor activity
IDA
PMID:28426968
MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- v... 		MODIFY
Summary: The annotation is correct but too broad for KIF5B, whose directional kinesin-1 activity is better captured by plus-end-directed microtubule motor activity.
Reason: Replace the generic motor term with the specific plus-end-directed microtubule motor term already present in GOA.
Supporting Evidence:
PMID:8606779
Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
file:human/KIF5B/KIF5B-uniprot.txt
Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.
GO:0008017 microtubule binding
IDA
PMID:28426968
MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- v... 		MODIFY
Summary: The binding annotation is mechanistically true for kinesin-1 but less informative than the full ATP-dependent motor activity.
Reason: Use the specific plus-end-directed microtubule motor activity rather than separate generic ATP-binding or microtubule-binding terms as the reviewed molecular function.
Supporting Evidence:
PMID:1607388
the kinesin heavy chain showed both a diffuse distribution and a filamentous staining pattern that coaligned with microtubules
PMID:8606779
Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
GO:0047496 vesicle transport along microtubule
IDA
PMID:28426968
MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- v... 		ACCEPT
Summary: This process captures the core cargo-transport role of KIF5B as a kinesin-1 motor moving vesicles and organelles along microtubules.
Reason: Retain as a core biological-process abstraction for KIF5B motor function.
Supporting Evidence:
PMID:24088571
Kinesin-1 regulates long-range anterograde intracellular transport of vesicles, including lysosomes
GO:1990048 anterograde neuronal dense core vesicle transport
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This is a plausible cargo- or cell-type-specific transport role for kinesin-1, but it is not the defining KIF5B function.
Reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core role is plus-end-directed microtubule cargo transport.
Supporting Evidence:
PMID:28426968
distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport
GO:1990049 retrograde neuronal dense core vesicle transport
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This is a plausible cargo- or cell-type-specific transport role for kinesin-1, but it is not the defining KIF5B function.
Reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core role is plus-end-directed microtubule cargo transport.
Supporting Evidence:
PMID:28426968
distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport
GO:0051642 centrosome localization
IMP
PMID:20386726
Bicaudal D2, dynein, and kinesin-1 associate with nuclear po... 		KEEP AS NON CORE
Summary: KIF5B contributes to centrosome and nuclear positioning during mitotic entry through antagonism with dynein-dependent forces.
Reason: Keep as a supported cell-cycle positioning role, but not as the core function of this pleiotropic motor.
Supporting Evidence:
PMID:20386726
we show that while dynein pulls centrosomes and the nucleus together during mitotic entry, kinesin-1 pushes them apart
GO:0016020 membrane
HDA
PMID:19946888
Defining the membrane proteome of NK cells. 		MARK AS OVER ANNOTATED
Summary: Broad membrane is a high-throughput location that loses the important biology. KIF5B is a peripheral/adaptor-recruited motor on specific cargos such as lysosomes and lytic granules, not a generic membrane protein.
Reason: Retain the more specific cargo-membrane annotations where supported and avoid the uninformative broad membrane term.
GO:0042391 regulation of membrane potential
IDA
PMID:19675065
Kif5b is an essential forward trafficking motor for the Kv1.... 		MODIFY
Summary: These annotations describe downstream electrophysiological consequences of KIF5B-dependent Kv1.5 channel trafficking rather than the direct KIF5B process.
Reason: Replace membrane-potential/potassium-transport regulation with the more direct protein-localization-to-plasma-membrane process supported by the original study.
Supporting Evidence:
PMID:19675065
Thus, Kif5b is essential to anterograde trafficking of a cardiac voltage-gated potassium channel.
GO:0043268 positive regulation of potassium ion transport
IDA
PMID:19675065
Kif5b is an essential forward trafficking motor for the Kv1.... 		MODIFY
Summary: These annotations describe downstream electrophysiological consequences of KIF5B-dependent Kv1.5 channel trafficking rather than the direct KIF5B process.
Reason: Replace membrane-potential/potassium-transport regulation with the more direct protein-localization-to-plasma-membrane process supported by the original study.
Supporting Evidence:
PMID:19675065
Thus, Kif5b is essential to anterograde trafficking of a cardiac voltage-gated potassium channel.
GO:1903078 positive regulation of protein localization to plasma membrane
IDA
PMID:19675065
Kif5b is an essential forward trafficking motor for the Kv1.... 		KEEP AS NON CORE
Summary: This captures the direct mechanism in the Kv1.5 study: KIF5B promotes forward trafficking and surface localization of the channel.
Reason: Keep as a supported cargo-specific channel-trafficking role, secondary to the core microtubule motor function.
Supporting Evidence:
PMID:19675065
Thus, Kif5b is essential to anterograde trafficking of a cardiac voltage-gated potassium channel.
GO:0031982 vesicle
IDA
PMID:20682791
A protein interaction network for Ecm29 links the 26 S prote... 		KEEP AS NON CORE
Summary: KIF5B can associate with diverse organelles or cellular regions through cargo adaptors, but this term is a cargo/context-specific location rather than the core motor role.
Reason: Keep as non-core for a pleiotropic motor with many cargo associations.
GO:0035617 stress granule disassembly
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: This is a plausible cargo- or cell-type-specific transport role for kinesin-1, but it is not the defining KIF5B function.
Reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core role is plus-end-directed microtubule cargo transport.
Supporting Evidence:
PMID:28426968
distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport
GO:0003777 microtubule motor activity
ISS
GO_REF:0000024 		MODIFY
Summary: The annotation is correct but too broad for KIF5B, whose directional kinesin-1 activity is better captured by plus-end-directed microtubule motor activity.
Reason: Replace the generic motor term with the specific plus-end-directed microtubule motor term already present in GOA.
Supporting Evidence:
PMID:8606779
Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
file:human/KIF5B/KIF5B-uniprot.txt
Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.
GO:0008017 microtubule binding
ISS
GO_REF:0000024 		MODIFY
Summary: The binding annotation is mechanistically true for kinesin-1 but less informative than the full ATP-dependent motor activity.
Reason: Use the specific plus-end-directed microtubule motor activity rather than separate generic ATP-binding or microtubule-binding terms as the reviewed molecular function.
Supporting Evidence:
PMID:1607388
the kinesin heavy chain showed both a diffuse distribution and a filamentous staining pattern that coaligned with microtubules
PMID:8606779
Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
GO:0047496 vesicle transport along microtubule
ISS
GO_REF:0000024 		ACCEPT
Summary: This process captures the core cargo-transport role of KIF5B as a kinesin-1 motor moving vesicles and organelles along microtubules.
Reason: Retain as a core biological-process abstraction for KIF5B motor function.
Supporting Evidence:
PMID:24088571
Kinesin-1 regulates long-range anterograde intracellular transport of vesicles, including lysosomes
GO:0048471 perinuclear region of cytoplasm
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: KIF5B can associate with diverse organelles or cellular regions through cargo adaptors, but this term is a cargo/context-specific location rather than the core motor role.
Reason: Keep as non-core for a pleiotropic motor with many cargo associations.
GO:0003777 microtubule motor activity
TAS
PMID:8606779
Crystal structure of the kinesin motor domain reveals a stru... 		MODIFY
Summary: The annotation is correct but too broad for KIF5B, whose directional kinesin-1 activity is better captured by plus-end-directed microtubule motor activity.
Reason: Replace the generic motor term with the specific plus-end-directed microtubule motor term already present in GOA.
Supporting Evidence:
PMID:8606779
Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
file:human/KIF5B/KIF5B-uniprot.txt
Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.
GO:0005871 kinesin complex
TAS
PMID:1607388
Cloning and expression of a human kinesin heavy chain gene: ... 		ACCEPT
Summary: KIF5B is a heavy-chain subunit of the kinesin-1 motor complex, which contains two KIF5B heavy chains and kinesin light chains.
Reason: The cellular-component annotation reflects the canonical kinesin-1 complex architecture.
Supporting Evidence:
file:human/KIF5B/KIF5B-uniprot.txt
Oligomer composed of two heavy chains and two light chains.
GO:0007018 microtubule-based movement
TAS
PMID:7514426
Cloning and localization of a conventional kinesin motor exp... 		MODIFY
Summary: Microtubule-based movement is correct but broad. KIF5B specifically functions as a kinesin-1 cargo motor, so vesicle transport along microtubule is the better process term.
Reason: Replace the broad process with the cargo-transport process already supported in GOA.
Supporting Evidence:
PMID:8606779
Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
file:human/KIF5B/KIF5B-uniprot.txt
Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.

Core Functions

ATP-dependent plus-end-directed microtubule motor activity as the kinesin-1 heavy chain, driving transport of vesicles and organelles along microtubules. Cargo specificity is supplied by adaptor proteins and light-chain interactions, so cargo-specific phenotypes should be interpreted as contexts of this core motor function.

Molecular Function:
plus-end-directed microtubule motor activity
Directly Involved In:
vesicle transport along microtubule
Cellular Locations:
cytoskeleton
Supporting Evidence:
  • PMID:8606779
    Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
  • file:human/KIF5B/KIF5B-uniprot.txt
    Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes.
  • PMID:24088571
    Kinesin-1 regulates long-range anterograde intracellular transport of vesicles, including lysosomes

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000108
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:15161933
Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.
PMID:1607388
Cloning and expression of a human kinesin heavy chain gene: interaction of the COOH-terminal domain with cytoplasmic microtubules in transfected CV-1 cells.
PMID:17013387
Single-molecule observations of neck linker conformational changes in the kinesin motor protein.
PMID:18004302
How kinesin waits between steps.
PMID:19164528
Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization.
PMID:19675065
Kif5b is an essential forward trafficking motor for the Kv1.5 cardiac potassium channel.
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:20386726
Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry.
PMID:20562859
Network organization of the human autophagy system.
PMID:20682791
A protein interaction network for Ecm29 links the 26 S proteasome to molecular motors and endosomal components.
PMID:21915095
A kinesin-1 binding motif in vaccinia virus that is widespread throughout the human genome.
PMID:22172677
Arl8 and SKIP act together to link lysosomes to kinesin-1.
PMID:24088571
Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity.
PMID:25468996
E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
PMID:25855459
Repeated ER-endosome contacts promote endosome translocation and neurite outgrowth.
PMID:28426968
MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent Cargo Transport in Sensory Neurons.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:36931259
A central chaperone-like role for 14-3-3 proteins in human cells.
PMID:7514426
Cloning and localization of a conventional kinesin motor expressed exclusively in neurons.
PMID:8606779
Crystal structure of the kinesin motor domain reveals a structural similarity to myosin.
Reactome:R-HSA-9700179
Ligand-independent dimerization of ALK fusions
Reactome:R-HSA-9700181
Autophosphorylation of ALK fusions
Reactome:R-HSA-9712078
ALK mutants bind PI3KR1
Reactome:R-HSA-9712079
ALK mutants bind STAT3
Reactome:R-HSA-9712083
ALK mutants bind PI3KCA
Reactome:R-HSA-9712084
PI3K synthesizes PIP3 downstream of ALK mutants
Reactome:R-HSA-9712085
ALK mutants phosphorylate STAT3
Reactome:R-HSA-9850958
pY-STAT3 dimer translocates to the nucleus downstream of ALK mutants
file:human/KIF5B/KIF5B-uniprot.txt
UniProt record for human KIF5B
file:human/KIF5B/KIF5B-notes.md
KIF5B curation notes
file:projects/PROTEOSTASIS/mappings/autophagy_lysosome_pathway.yaml
Proteostasis Network autophagy-lysosome pathway mappings

Suggested Questions for Experts

Q: Does direct starvation-recovery or autophagic lysosome reformation evidence support annotating KIF5B to a lysosome-organization/ALR term, or should KIF5B remain annotated to lysosome localization only?

Suggested experts: Sean Munro, Cleo T. Schiefermeier

Q: Should GO curation distinguish kinesin-1 heavy-chain core motor activity from cargo-specific downstream outcomes such as NK cytotoxicity, channel trafficking, and neuronal synaptic phenotypes?

Suggested experts: GO curator, kinesin-1 domain expert

Suggested Experiments

Experiment: Measure KIF5B recruitment to autolysosomes and lysosomal tubules during starvation and nutrient refeeding, using endogenous tagging plus KIF5B depletion/rescue.

Hypothesis: KIF5B contributes to lysosome positioning during recovery but requires additional evidence before annotation to autophagic lysosome reformation or lysosome organization.

Type: live-cell imaging/genetic rescue

Experiment: Compare wild-type KIF5B and motor-dead or cargo-adaptor-binding mutants for lysosome localization, lytic granule polarization, and generic vesicle transport in matched cell systems.

Hypothesis: Cargo-specific KIF5B phenotypes depend on the same core plus-end-directed motor activity but separable adaptor interactions.

Type: structure-function perturbation

📚 Additional Documentation

Notes

(KIF5B-notes.md)

KIF5B review notes

Curation scope

Falcon deep research was attempted with just deep-research-falcon human KIF5B, but the
provider timed out after 600 seconds and did not generate KIF5B-deep-research-falcon.md.
This review therefore relies on cached publications, UniProt/GOA-derived files, PN project
mappings, and these manual curation notes.

Core function

KIF5B encodes the ubiquitous kinesin-1 heavy chain. The core gene product role is
plus-end-directed, ATP-dependent movement on microtubules as part of the kinesin-1
motor complex, with broad cargo transport roles. Early cloning and localization work
showed human kinesin heavy chain coaligned with microtubules in transfected cells
PMID:1607388, and structural work on the human kinesin motor domain supports the conserved ATPase motor mechanism
PMID:8606779.

KIF5B is pleiotropic because kinesin-1 transports many cargos. The best-supported
process-level abstraction for the canonical role is vesicle/organelle transport along
microtubules rather than any one cargo-specific downstream phenotype.

Proteostasis network context

The Proteostasis Network places KIF5B under
Autophagy-Lysosome Pathway|Autophagic lysosome reformation|Lysosomal tubulation.
The PN mapping marks this row as context_only and too_broad_to_propagate to
GO:0007040 lysosome organization. That restraint is appropriate: KIF5B has strong
evidence for kinesin-dependent lysosome positioning/localization, but the current
evidence does not make KIF5B a specific autophagic lysosome reformation or lysosomal
tubulation factor in the same way as a dedicated ALR machinery component.

The direct lysosome evidence is that Arl8/SKIP recruits kinesin-1 to lysosomes and
that KIF5B knockdown causes lysosomes to cluster near the microtubule-organizing
center PMID:22172677.
In NK cells, Arl8b identifies KIF5B as a binding partner and KIF5B silencing blocks
MTOC-lytic granule polarization and reduces cytotoxicity
PMID:24088571.

Annotation decisions

  • Accept the kinesin complex and plus-end-directed microtubule motor role as core.
  • Modify generic MF annotations such as microtubule motor activity, ATP binding,
    and microtubule binding to the more informative
    GO:0008574 plus-end-directed microtubule motor activity.
  • Modify broad microtubule-based movement to
    GO:0047496 vesicle transport along microtubule where a process replacement is
    needed.
  • Keep lysosomal membrane, cytolytic granule membrane, lysosome localization,
    centrosome positioning, channel-trafficking, stress granule, mitochondrial, and
    neuronal cargo annotations as non-core cargo/context-specific roles.
  • Mark generic protein binding, identical protein binding,
    protein-containing complex binding, cadherin binding, and broad high-throughput
    membrane as over-annotated because they do not describe KIF5B's molecular role.
  • Do not add a new GO:0007040 lysosome organization annotation from the PN
    lysosomal-tubulation row; the PN project intentionally treats this row as
    context-only.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: for Proteostasis Network curation, the supported lysosomal role is kinesin-dependent lysosome localization/positioning; the PN lysosomal-tubulation row is context-only and should not be propagated to a new lysosome-organization annotation for KIF5B without more direct ALR-specific evidence.

Pn Notes

(KIF5B-pn-notes.md)

KIF5B PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: P33176
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-pr-1217 (PR 1217)
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: KIF5B encodes the ubiquitous kinesin-1 heavy chain, an ATP-dependent, plus-end-directed microtubule motor. Its core molecular role is to form kinesin-1 motor complexes that bind microtubules and move vesicles and organelles toward microtubule plus ends. KIF5B is recruited to many cargos through adaptors, including Arl8/SKIP-dependent lysosome positioning, lytic granule polarization in natural killer cells, mitochondrial transport, neuronal cargo transport, centrosome/nuclear positioning, and channel trafficking. Its lysosomal role is kinesin-dependent lysosome localization/positioning through adaptor-mediated cargo recruitment.
  • Existing/core annotation action counts: ACCEPT: 6; KEEP_AS_NON_CORE: 36; MARK_AS_OVER_ANNOTATED: 19; MODIFY: 12

PN Consistency Summary

  • Consistency: Mutually consistent. Deep research, review YAML, PN notes, and node mapping all describe a kinesin-1 heavy-chain motor recruited (Arl8/SKIP) to position lysosomes. The single projected term GO:0032418 is present in the review as IMP/KEEP_AS_NON_CORE (PMID:22172677), matching already_in_goa_exact. No contradictions.
  • PN story / NEW pressure: The PN ALR/lysosomal-tubulation story (KIF5B pulling autolysosome tubules via PI(4,5)P2) goes beyond current GO, but the node itself is context_only/too_broad and projects nothing. Review explicitly declines to add a lysosome-organization/ALR term, noting the tubulation evidence is not KIF5B-specific enough. Conclusion: already captured (lysosome localization); ALR role over-reaches for a new term now — correctly deferred to expert question.
  • Evidence alignment: PN cites Cheng/Schiefermeier-type ALR reviews + the KIF5B lysosome-distribution paper; review anchors the same biology to PMID:22172677 (Arl8/SKIP) and PMID:24088571 (Arl8b/NK granules). PN's ALR review titles are not cited as PMIDs in the review, but the substantive lysosome-positioning evidence overlaps.
  • Verdict: Consistent and well-scoped; PN ALR story noted but correctly not propagated. No edits required.

Full Consistency Review

  • UniProt: P33176 · batch: proteostasis-pr-1217 · review status: COMPLETE
  • PN placement: ALP|Autophagosome closure maturation and lysosome fusion|Localization of the lysosome (row 1) and ALP|Autophagic lysosome reformation|Lysosomal tubulation (row 2) ; PN-node mapping: row1 group mapped / ok_for_propagation / GO:0032418 lysosome localization; row2 group+class context_only / too_broad_to_propagate / GO:0007040 lysosome organization.
  • Consistency: Mutually consistent. Deep research, review YAML, PN notes, and node mapping all describe a kinesin-1 heavy-chain motor recruited (Arl8/SKIP) to position lysosomes. The single projected term GO:0032418 is present in the review as IMP/KEEP_AS_NON_CORE (PMID:22172677), matching already_in_goa_exact. No contradictions.
  • PN story / NEW pressure: The PN ALR/lysosomal-tubulation story (KIF5B pulling autolysosome tubules via PI(4,5)P2) goes beyond current GO, but the node itself is context_only/too_broad and projects nothing. Review explicitly declines to add a lysosome-organization/ALR term, noting the tubulation evidence is not KIF5B-specific enough. Conclusion: already captured (lysosome localization); ALR role over-reaches for a new term now — correctly deferred to expert question.
  • Mapping strategy: No change. The mapped lysosome-localization node and the two context_only lysosome-organization nodes are appropriately scoped; KIF5B does not push the ALR node toward propagation (parallels TOMM20/RAB7A "broader, rejected").
  • Evidence alignment: PN cites Cheng/Schiefermeier-type ALR reviews + the KIF5B lysosome-distribution paper; review anchors the same biology to PMID:22172677 (Arl8/SKIP) and PMID:24088571 (Arl8b/NK granules). PN's ALR review titles are not cited as PMIDs in the review, but the substantive lysosome-positioning evidence overlaps.
  • Verdict: Consistent and well-scoped; PN ALR story noted but correctly not propagated. No edits required.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/KIF5B/KIF5B-ai-review.yaml
  • PN workbook rows: 2

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Localization of the lysosome

  • UniProt: P33176
  • In branches: ALP
  • Notes: A kinesin. Regulates lysosome positioning in the cell, so involved in autophagosome-lysosome fusion. Knockdown leads to autophagosome accumulation near the Golgi and peripheral accumulation of lysosomes. Also drives the formation of tubules from autolysosomes during ALR by binding to PI(4,5)P2 enriched microdomains.
  • PN references (titles):
    • Membrane Trafficking in Autophagy - ScienceDirect
    • Depletion of Kinesin 5B Affects Lysosomal Distribution and Stability and Induces Peri-Nuclear Accumulation of Autophagosomes in Cancer Cells (plos.org)
  • PN-node mapping records (path + ancestors):
    • [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Localization of the lysosome
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0032418 lysosome localization]
      rationale: This group is explicitly about lysosome positioning in late autophagy. Lysosome localization is the correct propagation target rather than autophagosome-lysosome fusion.
    • [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Autophagy-Lysosome Pathway | Autophagic lysosome reformation | Lysosomal tubulation

  • UniProt: P33176
  • In branches: ALP
  • Notes: A kinesin. Regulates lysosome positioning in the cell, so involved in autophagosome-lysosome fusion. Knockdown leads to autophagosome accumulation near the Golgi and peripheral accumulation of lysosomes. Also drives the formation of tubules from autolysosomes during ALR by binding to PI(4,5)P2 enriched microdomains.
  • PN references (titles):
    • Membrane Trafficking in Autophagy - ScienceDirect
    • Depletion of Kinesin 5B Affects Lysosomal Distribution and Stability and Induces Peri-Nuclear Accumulation of Autophagosomes in Cancer Cells (plos.org)
  • PN-node mapping records (path + ancestors):
    • [group] Autophagy-Lysosome Pathway|Autophagic lysosome reformation|Lysosomal tubulation
      status=context_only scope=too_broad_to_propagate GO=[GO:0007040 lysosome organization]
      rationale: This PN group specifically captures the tubulation and membrane-remodeling step that regenerates lysosomes from autolysosomes. That aligns better to lysosome organization than to generic autophagy, but the current member set mixes factors annotated in GO to lysosome localization and phagosome/lysosome fusion rather than a clean shared lysosome-organization process role, so propagation would overstate the evidence.
    • [class] Autophagy-Lysosome Pathway|Autophagic lysosome reformation
      status=context_only scope=too_broad_to_propagate GO=[GO:0007040 lysosome organization]
      rationale: Autophagic lysosome reformation is the lysosome-regeneration phase that follows autolysosome formation and cargo degradation. As a class, it is better aligned to lysosome organization than to generic autophagy, but the PN members are mechanistically mixed across membrane remodeling, tubulation, product efflux, and unknown late-stage roles, so class-level propagation would still over-annotate.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

  • GO:0032418 lysosome localization | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Localization of the lysosome

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: P33176
gene_symbol: KIF5B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  KIF5B encodes the ubiquitous kinesin-1 heavy chain, an ATP-dependent, plus-end-directed microtubule
  motor. Its core molecular role is to form kinesin-1 motor complexes that bind microtubules and move
  vesicles and organelles toward microtubule plus ends. KIF5B is recruited to many cargos through
  adaptors, including Arl8/SKIP-dependent lysosome positioning, lytic granule polarization in natural
  killer cells, mitochondrial transport, neuronal cargo transport, centrosome/nuclear positioning, and
  channel trafficking. Its lysosomal role is kinesin-dependent lysosome localization/positioning
  through adaptor-mediated cargo recruitment.
existing_annotations:
- term:
    id: GO:0005871
    label: kinesin complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: KIF5B is a heavy-chain subunit of the kinesin-1 motor complex, which
      contains two KIF5B heavy chains and kinesin light chains.
    action: ACCEPT
    reason: The cellular-component annotation reflects the canonical kinesin-1 complex
      architecture.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Oligomer composed of two heavy chains and two light chains.
- term:
    id: GO:0007411
    label: axon guidance
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: This is a downstream neuronal phenotype or synaptic consequence inferred
      for kinesin-family cargo transport rather than a direct molecular or cellular core
      role of KIF5B.
    action: MARK_AS_OVER_ANNOTATED
    reason: The direct KIF5B function is motor-driven cargo transport; annotating broad
      neuronal outcomes as KIF5B functions overstates the evidence.
    proposed_replacement_terms:
    - id: GO:0047496
      label: vesicle transport along microtubule
- term:
    id: GO:0048489
    label: synaptic vesicle transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: This is a plausible cargo- or cell-type-specific transport role for
      kinesin-1, but it is not the defining KIF5B function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core
      role is plus-end-directed microtubule cargo transport.
    supported_by:
    - reference_id: PMID:28426968
      supporting_text: 'distinct kinesins differentially regulate cargo velocity: kinesin-3
        drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport'
- term:
    id: GO:0098971
    label: anterograde dendritic transport of neurotransmitter receptor complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: This is a plausible cargo- or cell-type-specific transport role for
      kinesin-1, but it is not the defining KIF5B function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core
      role is plus-end-directed microtubule cargo transport.
    supported_by:
    - reference_id: PMID:28426968
      supporting_text: 'distinct kinesins differentially regulate cargo velocity: kinesin-3
        drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport'
- term:
    id: GO:0008574
    label: plus-end-directed microtubule motor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: This is the most informative existing molecular-function annotation for
      KIF5B. KIF5B is the kinesin-1 heavy chain and acts as a plus-end-directed
      microtubule motor.
    action: ACCEPT
    reason: Retain as the core molecular function.
    supported_by:
    - reference_id: PMID:8606779
      supporting_text: Kinesin is the founding member of a superfamily of microtubule
        based motor proteins that perform force-generating tasks such as organelle
        transport and chromosome segregation.
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Microtubule-dependent motor required for normal distribution of
        mitochondria and lysosomes.
- term:
    id: GO:0003777
    label: microtubule motor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: The annotation is correct but too broad for KIF5B, whose directional
      kinesin-1 activity is better captured by plus-end-directed microtubule motor
      activity.
    action: MODIFY
    reason: Replace the generic motor term with the specific plus-end-directed
      microtubule motor term already present in GOA.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
    supported_by:
    - reference_id: PMID:8606779
      supporting_text: Kinesin is the founding member of a superfamily of microtubule
        based motor proteins that perform force-generating tasks such as organelle
        transport and chromosome segregation.
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Microtubule-dependent motor required for normal distribution of
        mitochondria and lysosomes.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: The binding annotation is mechanistically true for kinesin-1 but less
      informative than the full ATP-dependent motor activity.
    action: MODIFY
    reason: Use the specific plus-end-directed microtubule motor activity rather than
      separate generic ATP-binding or microtubule-binding terms as the reviewed
      molecular function.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
    supported_by:
    - reference_id: PMID:1607388
      supporting_text: the kinesin heavy chain showed both a diffuse distribution and a
        filamentous staining pattern that coaligned with microtubules
    - reference_id: PMID:8606779
      supporting_text: Here, we report the crystal structure of the human kinesin motor
        domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: KIF5B is recruited to the cytosolic face of lysosomal membranes through
      adaptor systems such as Arl8/SKIP to drive lysosome positioning.
    action: KEEP_AS_NON_CORE
    reason: Keep as a supported PN-relevant cargo-specific localization, but do not
      treat lysosomal membrane association as the defining location of KIF5B activity
      across all cargos.
    supported_by:
    - reference_id: PMID:22172677
      supporting_text: endogenous KIF5B, the heavy chain of kinesin-1, accumulated on
        lysosomes in cells overexpressing Arl8b and SKIP
    - reference_id: PMID:22172677
      supporting_text: when KIF5B was knocked down by >85% by RNAi, lysosomes were more
        centrally clustered
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: KIF5B is a cytoskeleton-associated microtubule motor. The term is broad but
      consistent with the core motor mechanism.
    action: ACCEPT
    reason: Retain as a core cellular context for KIF5B motor activity.
    supported_by:
    - reference_id: PMID:1607388
      supporting_text: the kinesin heavy chain showed both a diffuse distribution and a
        filamentous staining pattern that coaligned with microtubules
    - reference_id: PMID:8606779
      supporting_text: Here, we report the crystal structure of the human kinesin motor
        domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
- term:
    id: GO:0007018
    label: microtubule-based movement
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Microtubule-based movement is correct but broad. KIF5B specifically
      functions as a kinesin-1 cargo motor, so vesicle transport along microtubule is
      the better process term.
    action: MODIFY
    reason: Replace the broad process with the cargo-transport process already supported
      in GOA.
    proposed_replacement_terms:
    - id: GO:0047496
      label: vesicle transport along microtubule
    supported_by:
    - reference_id: PMID:8606779
      supporting_text: Kinesin is the founding member of a superfamily of microtubule
        based motor proteins that perform force-generating tasks such as organelle
        transport and chromosome segregation.
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Microtubule-dependent motor required for normal distribution of
        mitochondria and lysosomes.
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: The binding annotation is mechanistically true for kinesin-1 but less
      informative than the full ATP-dependent motor activity.
    action: MODIFY
    reason: Use the specific plus-end-directed microtubule motor activity rather than
      separate generic ATP-binding or microtubule-binding terms as the reviewed
      molecular function.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
    supported_by:
    - reference_id: PMID:1607388
      supporting_text: the kinesin heavy chain showed both a diffuse distribution and a
        filamentous staining pattern that coaligned with microtubules
    - reference_id: PMID:8606779
      supporting_text: Here, we report the crystal structure of the human kinesin motor
        domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
- term:
    id: GO:0032839
    label: dendrite cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: located_in
  review:
    summary: This neuronal compartment annotation is consistent with kinesin cargo
      transport in neurons but is not a core localization for the ubiquitous KIF5B
      motor.
    action: KEEP_AS_NON_CORE
    reason: Keep as a transferred, non-core neuronal localization context.
- term:
    id: GO:0101004
    label: cytolytic granule membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: KIF5B participates in NK-cell lytic granule polarization and cytotoxicity
      through an Arl8b/SKIP/kinesin-1 cargo-transport pathway.
    action: KEEP_AS_NON_CORE
    reason: Keep as a well-supported immune-cell cargo-specific role, secondary to the
      core kinesin motor function.
    supported_by:
    - reference_id: PMID:24088571
      supporting_text: We also identified four unique peptides corresponding to KIF5B
        (the heavy chain of the plus-end motor protein kinesin-1 [KHC]) in the Arl8b
        pull down
    - reference_id: PMID:24088571
      supporting_text: Silencing of KIF5B expression inhibited the polarization of both
        the MTOC and lytic granules to the immune synapse
- term:
    id: GO:1904115
    label: axon cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: This neuronal compartment annotation is consistent with kinesin cargo
      transport in neurons but is not a core localization for the ubiquitous KIF5B
      motor.
    action: KEEP_AS_NON_CORE
    reason: Keep as a transferred, non-core neuronal localization context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15161933
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19164528
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20562859
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21915095
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25855459
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36931259
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:17013387
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18004302
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: KIF5B can associate with diverse organelles or cellular regions through
      cargo adaptors, but this term is a cargo/context-specific location rather than the
      core motor role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core for a pleiotropic motor with many cargo associations.
- term:
    id: GO:0030139
    label: endocytic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: KIF5B can associate with diverse organelles or cellular regions through
      cargo adaptors, but this term is a cargo/context-specific location rather than the
      core motor role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core for a pleiotropic motor with many cargo associations.
- term:
    id: GO:0032230
    label: positive regulation of synaptic transmission, GABAergic
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This is a downstream neuronal phenotype or synaptic consequence inferred
      for kinesin-family cargo transport rather than a direct molecular or cellular core
      role of KIF5B.
    action: MARK_AS_OVER_ANNOTATED
    reason: The direct KIF5B function is motor-driven cargo transport; annotating broad
      neuronal outcomes as KIF5B functions overstates the evidence.
    proposed_replacement_terms:
    - id: GO:0047496
      label: vesicle transport along microtubule
- term:
    id: GO:0035253
    label: ciliary rootlet
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: KIF5B can associate with diverse organelles or cellular regions through
      cargo adaptors, but this term is a cargo/context-specific location rather than the
      core motor role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core for a pleiotropic motor with many cargo associations.
- term:
    id: GO:0035617
    label: stress granule disassembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This is a plausible cargo- or cell-type-specific transport role for
      kinesin-1, but it is not the defining KIF5B function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core
      role is plus-end-directed microtubule cargo transport.
    supported_by:
    - reference_id: PMID:28426968
      supporting_text: 'distinct kinesins differentially regulate cargo velocity: kinesin-3
        drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport'
- term:
    id: GO:0043005
    label: neuron projection
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: This neuronal compartment annotation is consistent with kinesin cargo
      transport in neurons but is not a core localization for the ubiquitous KIF5B
      motor.
    action: KEEP_AS_NON_CORE
    reason: Keep as a transferred, non-core neuronal localization context.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: KIF5B can associate with diverse organelles or cellular regions through
      cargo adaptors, but this term is a cargo/context-specific location rather than the
      core motor role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core for a pleiotropic motor with many cargo associations.
- term:
    id: GO:0098987
    label: regulation of modification of synapse structure, modulating synaptic
      transmission
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This is a downstream neuronal phenotype or synaptic consequence inferred
      for kinesin-family cargo transport rather than a direct molecular or cellular core
      role of KIF5B.
    action: MARK_AS_OVER_ANNOTATED
    reason: The direct KIF5B function is motor-driven cargo transport; annotating broad
      neuronal outcomes as KIF5B functions overstates the evidence.
    proposed_replacement_terms:
    - id: GO:0047496
      label: vesicle transport along microtubule
- term:
    id: GO:0099524
    label: postsynaptic cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: This seeded annotation was reviewed as a non-core KIF5B context.
    action: KEEP_AS_NON_CORE
    reason: KIF5B is a pleiotropic microtubule motor; this term is retained only as a
      secondary context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: EXP
  original_reference_id: PMID:22172677
  qualifier: located_in
  review:
    summary: KIF5B is recruited to the cytosolic face of lysosomal membranes through
      adaptor systems such as Arl8/SKIP to drive lysosome positioning.
    action: KEEP_AS_NON_CORE
    reason: Keep as a supported PN-relevant cargo-specific localization, but do not
      treat lysosomal membrane association as the defining location of KIF5B activity
      across all cargos.
    supported_by:
    - reference_id: PMID:22172677
      supporting_text: endogenous KIF5B, the heavy chain of kinesin-1, accumulated on
        lysosomes in cells overexpressing Arl8b and SKIP
    - reference_id: PMID:22172677
      supporting_text: when KIF5B was knocked down by >85% by RNAi, lysosomes were more
        centrally clustered
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: EXP
  original_reference_id: PMID:24088571
  qualifier: located_in
  review:
    summary: KIF5B is recruited to the cytosolic face of lysosomal membranes through
      adaptor systems such as Arl8/SKIP to drive lysosome positioning.
    action: KEEP_AS_NON_CORE
    reason: Keep as a supported PN-relevant cargo-specific localization, but do not
      treat lysosomal membrane association as the defining location of KIF5B activity
      across all cargos.
    supported_by:
    - reference_id: PMID:22172677
      supporting_text: endogenous KIF5B, the heavy chain of kinesin-1, accumulated on
        lysosomes in cells overexpressing Arl8b and SKIP
    - reference_id: PMID:22172677
      supporting_text: when KIF5B was knocked down by >85% by RNAi, lysosomes were more
        centrally clustered
- term:
    id: GO:0101004
    label: cytolytic granule membrane
  evidence_type: EXP
  original_reference_id: PMID:24088571
  qualifier: located_in
  review:
    summary: KIF5B participates in NK-cell lytic granule polarization and cytotoxicity
      through an Arl8b/SKIP/kinesin-1 cargo-transport pathway.
    action: KEEP_AS_NON_CORE
    reason: Keep as a well-supported immune-cell cargo-specific role, secondary to the
      core kinesin motor function.
    supported_by:
    - reference_id: PMID:24088571
      supporting_text: We also identified four unique peptides corresponding to KIF5B
        (the heavy chain of the plus-end motor protein kinesin-1 [KHC]) in the Arl8b
        pull down
    - reference_id: PMID:24088571
      supporting_text: Silencing of KIF5B expression inhibited the polarization of both
        the MTOC and lytic granules to the immune synapse
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9700181
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712078
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712079
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712083
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712084
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9712085
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9850958
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28426968
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0042267
    label: natural killer cell mediated cytotoxicity
  evidence_type: IMP
  original_reference_id: PMID:24088571
  qualifier: involved_in
  review:
    summary: KIF5B participates in NK-cell lytic granule polarization and cytotoxicity
      through an Arl8b/SKIP/kinesin-1 cargo-transport pathway.
    action: KEEP_AS_NON_CORE
    reason: Keep as a well-supported immune-cell cargo-specific role, secondary to the
      core kinesin motor function.
    supported_by:
    - reference_id: PMID:24088571
      supporting_text: We also identified four unique peptides corresponding to KIF5B
        (the heavy chain of the plus-end motor protein kinesin-1 [KHC]) in the Arl8b
        pull down
    - reference_id: PMID:24088571
      supporting_text: Silencing of KIF5B expression inhibited the polarization of both
        the MTOC and lytic granules to the immune synapse
- term:
    id: GO:0032418
    label: lysosome localization
  evidence_type: IMP
  original_reference_id: PMID:22172677
  qualifier: involved_in
  review:
    summary: KIF5B has direct evidence for lysosome positioning/localization through
      Arl8/SKIP-dependent recruitment of kinesin-1 to lysosomes.
    action: KEEP_AS_NON_CORE
    reason: Keep as the supported Proteostasis Network-relevant cargo-specific process.
      This does not justify propagating the broader PN lysosomal-tubulation context to
      lysosome organization.
    supported_by:
    - reference_id: PMID:22172677
      supporting_text: endogenous KIF5B, the heavy chain of kinesin-1, accumulated on
        lysosomes in cells overexpressing Arl8b and SKIP
    - reference_id: PMID:22172677
      supporting_text: when KIF5B was knocked down by >85% by RNAi, lysosomes were more
        centrally clustered
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9700179
  qualifier: located_in
  review:
    summary: KIF5B is a cytosolic/cytoplasmic motor protein, but this broad localization
      does not describe the specific motor function.
    action: KEEP_AS_NON_CORE
    reason: Keep as a correct broad location, not as a core functional annotation.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton'
- term:
    id: GO:0099641
    label: anterograde axonal protein transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This is a plausible cargo- or cell-type-specific transport role for
      kinesin-1, but it is not the defining KIF5B function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core
      role is plus-end-directed microtubule cargo transport.
    supported_by:
    - reference_id: PMID:28426968
      supporting_text: 'distinct kinesins differentially regulate cargo velocity: kinesin-3
        drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport'
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: HDA
  original_reference_id: PMID:25468996
  qualifier: enables
  review:
    summary: The interaction may be experimentally observed, but the GO term is generic
      and does not convey KIF5B biology.
    action: MARK_AS_OVER_ANNOTATED
    reason: Do not use generic binding terms as reviewed KIF5B function; the informative
      molecular function is plus-end-directed microtubule motor activity and cargo
      transport.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
- term:
    id: GO:0003777
    label: microtubule motor activity
  evidence_type: IDA
  original_reference_id: PMID:28426968
  qualifier: enables
  review:
    summary: The annotation is correct but too broad for KIF5B, whose directional
      kinesin-1 activity is better captured by plus-end-directed microtubule motor
      activity.
    action: MODIFY
    reason: Replace the generic motor term with the specific plus-end-directed
      microtubule motor term already present in GOA.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
    supported_by:
    - reference_id: PMID:8606779
      supporting_text: Kinesin is the founding member of a superfamily of microtubule
        based motor proteins that perform force-generating tasks such as organelle
        transport and chromosome segregation.
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Microtubule-dependent motor required for normal distribution of
        mitochondria and lysosomes.
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IDA
  original_reference_id: PMID:28426968
  qualifier: enables
  review:
    summary: The binding annotation is mechanistically true for kinesin-1 but less
      informative than the full ATP-dependent motor activity.
    action: MODIFY
    reason: Use the specific plus-end-directed microtubule motor activity rather than
      separate generic ATP-binding or microtubule-binding terms as the reviewed
      molecular function.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
    supported_by:
    - reference_id: PMID:1607388
      supporting_text: the kinesin heavy chain showed both a diffuse distribution and a
        filamentous staining pattern that coaligned with microtubules
    - reference_id: PMID:8606779
      supporting_text: Here, we report the crystal structure of the human kinesin motor
        domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
- term:
    id: GO:0047496
    label: vesicle transport along microtubule
  evidence_type: IDA
  original_reference_id: PMID:28426968
  qualifier: involved_in
  review:
    summary: This process captures the core cargo-transport role of KIF5B as a kinesin-1
      motor moving vesicles and organelles along microtubules.
    action: ACCEPT
    reason: Retain as a core biological-process abstraction for KIF5B motor function.
    supported_by:
    - reference_id: PMID:24088571
      supporting_text: Kinesin-1 regulates long-range anterograde intracellular
        transport of vesicles, including lysosomes
- term:
    id: GO:1990048
    label: anterograde neuronal dense core vesicle transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This is a plausible cargo- or cell-type-specific transport role for
      kinesin-1, but it is not the defining KIF5B function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core
      role is plus-end-directed microtubule cargo transport.
    supported_by:
    - reference_id: PMID:28426968
      supporting_text: 'distinct kinesins differentially regulate cargo velocity: kinesin-3
        drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport'
- term:
    id: GO:1990049
    label: retrograde neuronal dense core vesicle transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This is a plausible cargo- or cell-type-specific transport role for
      kinesin-1, but it is not the defining KIF5B function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core
      role is plus-end-directed microtubule cargo transport.
    supported_by:
    - reference_id: PMID:28426968
      supporting_text: 'distinct kinesins differentially regulate cargo velocity: kinesin-3
        drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport'
- term:
    id: GO:0051642
    label: centrosome localization
  evidence_type: IMP
  original_reference_id: PMID:20386726
  qualifier: involved_in
  review:
    summary: KIF5B contributes to centrosome and nuclear positioning during mitotic
      entry through antagonism with dynein-dependent forces.
    action: KEEP_AS_NON_CORE
    reason: Keep as a supported cell-cycle positioning role, but not as the core
      function of this pleiotropic motor.
    supported_by:
    - reference_id: PMID:20386726
      supporting_text: we show that while dynein pulls centrosomes and the nucleus
        together during mitotic entry, kinesin-1 pushes them apart
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: Broad membrane is a high-throughput location that loses the important
      biology. KIF5B is a peripheral/adaptor-recruited motor on specific cargos such as
      lysosomes and lytic granules, not a generic membrane protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: Retain the more specific cargo-membrane annotations where supported and
      avoid the uninformative broad membrane term.
    proposed_replacement_terms:
    - id: GO:0005765
      label: lysosomal membrane
    - id: GO:0101004
      label: cytolytic granule membrane
- term:
    id: GO:0042391
    label: regulation of membrane potential
  evidence_type: IDA
  original_reference_id: PMID:19675065
  qualifier: involved_in
  review:
    summary: These annotations describe downstream electrophysiological consequences of
      KIF5B-dependent Kv1.5 channel trafficking rather than the direct KIF5B process.
    action: MODIFY
    reason: Replace membrane-potential/potassium-transport regulation with the more
      direct protein-localization-to-plasma-membrane process supported by the original
      study.
    proposed_replacement_terms:
    - id: GO:1903078
      label: positive regulation of protein localization to plasma membrane
    supported_by:
    - reference_id: PMID:19675065
      supporting_text: Thus, Kif5b is essential to anterograde trafficking of a cardiac
        voltage-gated potassium channel.
- term:
    id: GO:0043268
    label: positive regulation of potassium ion transport
  evidence_type: IDA
  original_reference_id: PMID:19675065
  qualifier: involved_in
  review:
    summary: These annotations describe downstream electrophysiological consequences of
      KIF5B-dependent Kv1.5 channel trafficking rather than the direct KIF5B process.
    action: MODIFY
    reason: Replace membrane-potential/potassium-transport regulation with the more
      direct protein-localization-to-plasma-membrane process supported by the original
      study.
    proposed_replacement_terms:
    - id: GO:1903078
      label: positive regulation of protein localization to plasma membrane
    supported_by:
    - reference_id: PMID:19675065
      supporting_text: Thus, Kif5b is essential to anterograde trafficking of a cardiac
        voltage-gated potassium channel.
- term:
    id: GO:1903078
    label: positive regulation of protein localization to plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:19675065
  qualifier: involved_in
  review:
    summary: 'This captures the direct mechanism in the Kv1.5 study: KIF5B promotes forward
      trafficking and surface localization of the channel.'
    action: KEEP_AS_NON_CORE
    reason: Keep as a supported cargo-specific channel-trafficking role, secondary to
      the core microtubule motor function.
    supported_by:
    - reference_id: PMID:19675065
      supporting_text: Thus, Kif5b is essential to anterograde trafficking of a cardiac
        voltage-gated potassium channel.
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IDA
  original_reference_id: PMID:20682791
  qualifier: located_in
  review:
    summary: KIF5B can associate with diverse organelles or cellular regions through
      cargo adaptors, but this term is a cargo/context-specific location rather than the
      core motor role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core for a pleiotropic motor with many cargo associations.
- term:
    id: GO:0035617
    label: stress granule disassembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This is a plausible cargo- or cell-type-specific transport role for
      kinesin-1, but it is not the defining KIF5B function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because KIF5B is a pleiotropic motor whose conserved core
      role is plus-end-directed microtubule cargo transport.
    supported_by:
    - reference_id: PMID:28426968
      supporting_text: 'distinct kinesins differentially regulate cargo velocity: kinesin-3
        drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport'
- term:
    id: GO:0003777
    label: microtubule motor activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: The annotation is correct but too broad for KIF5B, whose directional
      kinesin-1 activity is better captured by plus-end-directed microtubule motor
      activity.
    action: MODIFY
    reason: Replace the generic motor term with the specific plus-end-directed
      microtubule motor term already present in GOA.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
    supported_by:
    - reference_id: PMID:8606779
      supporting_text: Kinesin is the founding member of a superfamily of microtubule
        based motor proteins that perform force-generating tasks such as organelle
        transport and chromosome segregation.
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Microtubule-dependent motor required for normal distribution of
        mitochondria and lysosomes.
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: The binding annotation is mechanistically true for kinesin-1 but less
      informative than the full ATP-dependent motor activity.
    action: MODIFY
    reason: Use the specific plus-end-directed microtubule motor activity rather than
      separate generic ATP-binding or microtubule-binding terms as the reviewed
      molecular function.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
    supported_by:
    - reference_id: PMID:1607388
      supporting_text: the kinesin heavy chain showed both a diffuse distribution and a
        filamentous staining pattern that coaligned with microtubules
    - reference_id: PMID:8606779
      supporting_text: Here, we report the crystal structure of the human kinesin motor
        domain with bound ADP determined to 1.8-A resolution by X-ray crystallography.
- term:
    id: GO:0047496
    label: vesicle transport along microtubule
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: This process captures the core cargo-transport role of KIF5B as a kinesin-1
      motor moving vesicles and organelles along microtubules.
    action: ACCEPT
    reason: Retain as a core biological-process abstraction for KIF5B motor function.
    supported_by:
    - reference_id: PMID:24088571
      supporting_text: Kinesin-1 regulates long-range anterograde intracellular
        transport of vesicles, including lysosomes
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: KIF5B can associate with diverse organelles or cellular regions through
      cargo adaptors, but this term is a cargo/context-specific location rather than the
      core motor role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core for a pleiotropic motor with many cargo associations.
- term:
    id: GO:0003777
    label: microtubule motor activity
  evidence_type: TAS
  original_reference_id: PMID:8606779
  qualifier: enables
  review:
    summary: The annotation is correct but too broad for KIF5B, whose directional
      kinesin-1 activity is better captured by plus-end-directed microtubule motor
      activity.
    action: MODIFY
    reason: Replace the generic motor term with the specific plus-end-directed
      microtubule motor term already present in GOA.
    proposed_replacement_terms:
    - id: GO:0008574
      label: plus-end-directed microtubule motor activity
    supported_by:
    - reference_id: PMID:8606779
      supporting_text: Kinesin is the founding member of a superfamily of microtubule
        based motor proteins that perform force-generating tasks such as organelle
        transport and chromosome segregation.
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Microtubule-dependent motor required for normal distribution of
        mitochondria and lysosomes.
- term:
    id: GO:0005871
    label: kinesin complex
  evidence_type: TAS
  original_reference_id: PMID:1607388
  qualifier: part_of
  review:
    summary: KIF5B is a heavy-chain subunit of the kinesin-1 motor complex, which
      contains two KIF5B heavy chains and kinesin light chains.
    action: ACCEPT
    reason: The cellular-component annotation reflects the canonical kinesin-1 complex
      architecture.
    supported_by:
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Oligomer composed of two heavy chains and two light chains.
- term:
    id: GO:0007018
    label: microtubule-based movement
  evidence_type: TAS
  original_reference_id: PMID:7514426
  qualifier: involved_in
  review:
    summary: Microtubule-based movement is correct but broad. KIF5B specifically
      functions as a kinesin-1 cargo motor, so vesicle transport along microtubule is
      the better process term.
    action: MODIFY
    reason: Replace the broad process with the cargo-transport process already supported
      in GOA.
    proposed_replacement_terms:
    - id: GO:0047496
      label: vesicle transport along microtubule
    supported_by:
    - reference_id: PMID:8606779
      supporting_text: Kinesin is the founding member of a superfamily of microtubule
        based motor proteins that perform force-generating tasks such as organelle
        transport and chromosome segregation.
    - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
      supporting_text: Microtubule-dependent motor required for normal distribution of
        mitochondria and lysosomes.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on
    inter-ontology links
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:15161933
  title: Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding
    proteins.
  findings: []
- id: PMID:1607388
  title: 'Cloning and expression of a human kinesin heavy chain gene: interaction of the COOH-terminal
    domain with cytoplasmic microtubules in transfected CV-1 cells.'
  findings: []
- id: PMID:17013387
  title: Single-molecule observations of neck linker conformational changes in the
    kinesin motor protein.
  findings: []
- id: PMID:18004302
  title: How kinesin waits between steps.
  findings: []
- id: PMID:19164528
  title: Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated
    cell polarization.
  findings: []
- id: PMID:19675065
  title: Kif5b is an essential forward trafficking motor for the Kv1.5 cardiac potassium
    channel.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:20386726
  title: Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and
    regulate centrosome and nuclear positioning during mitotic entry.
  findings: []
- id: PMID:20562859
  title: Network organization of the human autophagy system.
  findings: []
- id: PMID:20682791
  title: A protein interaction network for Ecm29 links the 26 S proteasome to molecular
    motors and endosomal components.
  findings: []
- id: PMID:21915095
  title: A kinesin-1 binding motif in vaccinia virus that is widespread throughout the
    human genome.
  findings: []
- id: PMID:22172677
  title: Arl8 and SKIP act together to link lysosomes to kinesin-1.
  findings: []
- id: PMID:24088571
  title: Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer
    cell-mediated cytotoxicity.
  findings: []
- id: PMID:25468996
  title: E-cadherin interactome complexity and robustness resolved by quantitative
    proteomics.
  findings: []
- id: PMID:25855459
  title: Repeated ER-endosome contacts promote endosome translocation and neurite
    outgrowth.
  findings: []
- id: PMID:28426968
  title: MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus
    KIF5-Dependent Cargo Transport in Sensory Neurons.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36931259
  title: A central chaperone-like role for 14-3-3 proteins in human cells.
  findings: []
- id: PMID:7514426
  title: Cloning and localization of a conventional kinesin motor expressed exclusively
    in neurons.
  findings: []
- id: PMID:8606779
  title: Crystal structure of the kinesin motor domain reveals a structural similarity
    to myosin.
  findings: []
- id: Reactome:R-HSA-9700179
  title: Ligand-independent dimerization of ALK fusions
  findings: []
- id: Reactome:R-HSA-9700181
  title: Autophosphorylation of ALK fusions
  findings: []
- id: Reactome:R-HSA-9712078
  title: ALK mutants bind PI3KR1
  findings: []
- id: Reactome:R-HSA-9712079
  title: ALK mutants bind STAT3
  findings: []
- id: Reactome:R-HSA-9712083
  title: ALK mutants bind PI3KCA
  findings: []
- id: Reactome:R-HSA-9712084
  title: PI3K synthesizes PIP3 downstream of ALK mutants
  findings: []
- id: Reactome:R-HSA-9712085
  title: ALK mutants phosphorylate STAT3
  findings: []
- id: Reactome:R-HSA-9850958
  title: pY-STAT3 dimer translocates to the nucleus downstream of ALK mutants
  findings: []
- id: file:human/KIF5B/KIF5B-uniprot.txt
  title: UniProt record for human KIF5B
  findings: []
- id: file:human/KIF5B/KIF5B-notes.md
  title: KIF5B curation notes
  findings: []
- id: file:projects/PROTEOSTASIS/mappings/autophagy_lysosome_pathway.yaml
  title: Proteostasis Network autophagy-lysosome pathway mappings
  findings: []
core_functions:
- description: ATP-dependent plus-end-directed microtubule motor activity as the
    kinesin-1 heavy chain, driving transport of vesicles and organelles along
    microtubules. Cargo specificity is supplied by adaptor proteins and light-chain
    interactions, so cargo-specific phenotypes should be interpreted as contexts of this
    core motor function.
  molecular_function:
    id: GO:0008574
    label: plus-end-directed microtubule motor activity
  directly_involved_in:
  - id: GO:0047496
    label: vesicle transport along microtubule
  locations:
  - id: GO:0005856
    label: cytoskeleton
  supported_by:
  - reference_id: PMID:8606779
    supporting_text: Kinesin is the founding member of a superfamily of microtubule
      based motor proteins that perform force-generating tasks such as organelle
      transport and chromosome segregation.
  - reference_id: file:human/KIF5B/KIF5B-uniprot.txt
    supporting_text: Microtubule-dependent motor required for normal distribution of
      mitochondria and lysosomes.
  - reference_id: PMID:24088571
    supporting_text: Kinesin-1 regulates long-range anterograde intracellular transport
      of vesicles, including lysosomes
proposed_new_terms: []
suggested_questions:
- question: Does direct starvation-recovery or autophagic lysosome reformation evidence
    support annotating KIF5B to a lysosome-organization/ALR term, or should KIF5B remain
    annotated to lysosome localization only?
  experts:
  - Sean Munro
  - Cleo T. Schiefermeier
- question: Should GO curation distinguish kinesin-1 heavy-chain core motor activity
    from cargo-specific downstream outcomes such as NK cytotoxicity, channel
    trafficking, and neuronal synaptic phenotypes?
  experts:
  - GO curator
  - kinesin-1 domain expert
suggested_experiments:
- description: Measure KIF5B recruitment to autolysosomes and lysosomal tubules during
    starvation and nutrient refeeding, using endogenous tagging plus KIF5B
    depletion/rescue.
  experiment_type: live-cell imaging/genetic rescue
  hypothesis: KIF5B contributes to lysosome positioning during recovery but requires
    additional evidence before annotation to autophagic lysosome reformation or lysosome
    organization.
- description: Compare wild-type KIF5B and motor-dead or cargo-adaptor-binding mutants
    for lysosome localization, lytic granule polarization, and generic vesicle transport
    in matched cell systems.
  experiment_type: structure-function perturbation
  hypothesis: Cargo-specific KIF5B phenotypes depend on the same core plus-end-directed
    motor activity but separable adaptor interactions.