id: Q19633
gene_symbol: klp-11
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: >-
  KLP-11 is one of the two motor (heavy-chain) subunits of Caenorhabditis elegans
  heterotrimeric kinesin-II, a plus-end-directed microtubule motor of the kinesin-2
  family. The holoenzyme is a heterotrimer of the two distinct motor subunits KLP-11
  and KLP-20 together with the non-motor accessory subunit KAP-1 (kinesin-associated
  protein), and is the nematode orthologue of vertebrate KIF3A/KIF3B/KAP3 kinesin-II.
  KLP-11 is unprocessive as a homodimer; processive movement requires heterodimerization
  with its partner KLP-20, and heterodimerization is also required to bind the KAP-1
  cargo-adaptor subunit. Within the assembled motor, KLP-11 contributes microtubule
  plus-end motor and ATPase activity. Functionally, kinesin-II is one of two anterograde
  intraflagellar transport (IFT) motors in worm sensory cilia; together with the faster
  homodimeric OSM-3 (KIF17) motor it drives IFT particles along the doublet microtubules
  of the ciliary middle (initial) segment, with the two motors acting partly redundantly
  to build the cilium foundation. Kinesin-II moves comparatively slowly (~0.5 um/s) and,
  through mechanical competition with OSM-3, contributes to the tension across IFT
  particles that is regulated by BBS proteins. KLP-11 localizes to sensory cilia of
  ciliated neurons.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO terms
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000104
    title: Electronic Gene Ontology annotations created by transferring manual GO annotations
      between related proteins based on shared sequence features
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning models
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:17000880
    title: Mechanism of transport of IFT particles in C. elegans cilia by the concerted
      action of kinesin-II and OSM-3 motors.
    findings:
      - statement: Purified C. elegans kinesin-II is a heterotrimer of KLP-11, KLP-20 and KAP-1 (1:1:1, ~287 kD).
        supporting_text: consisting of 1 mol each of its subunits KLP-11, KLP-20, and KAP-1 with a native molecular mass of 287 kD
      - statement: Kinesin-II is one of two anterograde IFT motors that move IFT particles along ciliary microtubules.
        supporting_text: the IFT particles assembling these sensory cilia are moved by the coordinate action of two anterograde IFT motors called kinesin-II and OSM-3, which are both members of the kinesin-2 family
      - statement: Kinesin-II and OSM-3 act redundantly along the initial (middle) segment to build the cilium foundation.
        supporting_text: These motors function redundantly to move the same IFT particles along the initial segment and build the cilium foundation, with either motor but not both being dispensable for this function
      - statement: Kinesin-II is a slow plus-end MT motor (~0.5 um/s) relative to OSM-3.
        supporting_text: kinesin-II alone moved MTs at a maximal rate of 0.3 μm/s, and OSM-3 alone moved them at 0.7 μm/s
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: >-
        Full text cached and PubMed-verified. Directly establishes KLP-11 as a subunit
        of the purified heterotrimeric kinesin-II holoenzyme and its plus-end MT motility,
        the source of the WormBase IDA (GO:0003777, GO:0007018) and IPI (GO:0030993)
        annotations to klp-11.
  - id: PMID:20498083
    title: Regulation of a heterodimeric kinesin-2 through an unprocessive motor domain
      that is turned processive by its partner.
    findings:
      - statement: KLP11/KLP20 is the C. elegans heterodimeric kinesin-2 studied here.
        supporting_text: KLP11/KLP20 of Caenorhabditis elegans cilia
      - statement: Heterodimerization is required to bind KAP1, the motor-cargo link.
        supporting_text: heterodimerization is necessary to bind KAP1, the in vivo link between
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: >-
        Abstract-only in cache (full_text_available: false), but the abstract explicitly
        names KLP11/KLP20 of C. elegans and establishes that KLP-11 is unprocessive as a
        homodimer, is turned processive by heterodimerization with KLP-20, and that
        heterodimerization is required for KAP-1 binding. Supports the ComplexPortal NAS
        annotations for kinesin II complex membership and anterograde IFT.
existing_annotations:
  - term:
      id: GO:0003777
      label: microtubule motor activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: enables
    review:
      summary: >-
        KLP-11 is a kinesin-2 motor subunit that, as part of the KLP-11/KLP-20/KAP-1
        heterotrimer, is an active plus-end-directed microtubule motor. The phylogenetic
        (IBA) annotation is well supported and corroborated by direct C. elegans data.
      action: ACCEPT
      reason: >-
        Core molecular function. Kinesin-II motor activity is directly demonstrated for the
        purified holoenzyme containing KLP-11 (PMID:17000880). A more specific term
        (plus-end-directed microtubule motor activity) is captured in core_functions.
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: kinesin-II alone moved MTs at a maximal rate of 0.3 μm/s, and OSM-3 alone moved them at 0.7 μm/s
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: is_active_in
    review:
      summary: >-
        Generic cytoplasmic localization inferred phylogenetically. KLP-11 is present in the
        cytoplasm of ciliated neurons (cell bodies/dendrites) before and while operating in
        cilia, consistent with kinesin motors generally.
      action: ACCEPT
      reason: >-
        Correct but low-specificity parent. The informative localization for KLP-11 is the
        cilium and the axonemal kinesin-II complex; retained as accurate context.
  - term:
      id: GO:0008017
      label: microtubule binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: enables
    review:
      summary: >-
        Microtubule binding is an intrinsic property of the kinesin motor domain (FT 13..343)
        and is required for the motor activity of KLP-11-containing kinesin-II on axonemal
        microtubules.
      action: ACCEPT
      reason: >-
        Well-supported; microtubule binding is a defining feature of kinesin motors and
        underpins the demonstrated MT gliding activity of kinesin-II (PMID:17000880).
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: the IFT particles assembling these sensory cilia are moved by the coordinate action of two anterograde IFT motors called kinesin-II and OSM-3, which are both members of the kinesin-2 family
  - term:
      id: GO:0030705
      label: cytoskeleton-dependent intracellular transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: involved_in
    review:
      summary: >-
        KLP-11 mediates microtubule-based (cytoskeleton-dependent) transport as part of
        kinesin-II. In the worm this is realized specifically as anterograde IFT within cilia.
      action: MODIFY
      reason: >-
        Correct but too general. The specific, experimentally supported process for KLP-11 is
        intraciliary anterograde transport; generalize the annotation to that term.
      proposed_replacement_terms:
        - id: GO:0035720
          label: intraciliary anterograde transport
      propagation_review:
        root_cause: TERM_SCOPING_PROBLEM
        failure_modes:
          - GRANULARITY_MISMATCH
        source_entities:
          - source_id: PANTHER:PTN009082057
            source_label: kinesin-2 / kinesin-II motor node
            source_status: SUPPORTS_TRANSFER
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: the IFT particles assembling these sensory cilia are moved by the coordinate action of two anterograde IFT motors called kinesin-II and OSM-3, which are both members of the kinesin-2 family
  - term:
      id: GO:0060271
      label: cilium assembly
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: involved_in
    review:
      summary: >-
        Kinesin-II contributes to sensory cilium assembly by delivering IFT cargo along the
        middle segment. However, klp-11 single mutants have near-full-length cilia because
        OSM-3 acts redundantly in the middle segment and builds the distal segment, so KLP-11
        is individually dispensable for ciliogenesis.
      action: KEEP_AS_NON_CORE
      reason: >-
        The annotation is correct at the pathway level, but because of OSM-3 redundancy KLP-11
        loss does not abolish cilium assembly; the sharpest core process is anterograde IFT.
        Retained as a real, non-core contribution.
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: These motors function redundantly to move the same IFT particles along the initial segment and build the cilium foundation, with either motor but not both being dispensable for this function
        - reference_id: PMID:17000880
          supporting_text: OSM-6∷GFP moves at OSM-3's fast rate in klp-11 mutants
  - term:
      id: GO:0005871
      label: kinesin complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: part_of
    review:
      summary: >-
        KLP-11 is a subunit of a kinesin complex, specifically the heterotrimeric kinesin-II
        (KLP-11/KLP-20/KAP-1). The generic kinesin complex annotation is correct.
      action: ACCEPT
      reason: >-
        Correct parent-level complex membership; the specific complex (kinesin II /
        axonemal heterotrimeric kinesin-II) is captured by the NAS/IPI annotations and
        core_functions.
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: consisting of 1 mol each of its subunits KLP-11, KLP-20, and KAP-1 with a native molecular mass of 287 kD
  - term:
      id: GO:0005874
      label: microtubule
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: is_active_in
    review:
      summary: >-
        KLP-11 is active on microtubules; as part of kinesin-II it translocates along the
        axonemal (doublet) microtubules of the ciliary middle segment.
      action: ACCEPT
      reason: >-
        Correct localization/site-of-action for a microtubule motor, consistent with the
        demonstrated MT gliding activity of the holoenzyme.
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: kinesin-II alone moved MTs at a maximal rate of 0.3 μm/s, and OSM-3 alone moved them at 0.7 μm/s
  - term:
      id: GO:0007018
      label: microtubule-based movement
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: involved_in
    review:
      summary: >-
        As a kinesin motor, KLP-11 drives microtubule-based movement. In the worm this is the
        anterograde movement of IFT particles within cilia.
      action: ACCEPT
      reason: >-
        Correct general process; the specific term (intraciliary anterograde transport) is
        also annotated (NAS) and captured in core_functions.
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: the IFT particles assembling these sensory cilia are moved by the coordinate action of two anterograde IFT motors called kinesin-II and OSM-3, which are both members of the kinesin-2 family
  - term:
      id: GO:0016887
      label: ATP hydrolysis activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: enables
    review:
      summary: >-
        KLP-11 contains a P-loop kinesin motor domain (ATP-binding site residues 99..106) and,
        as part of kinesin-II, hydrolyzes ATP to power motility; the holoenzyme uses Mg-ATP
        with Michaelis-Menten kinetics.
      action: ACCEPT
      reason: >-
        ATP hydrolysis is essential for kinesin motor function and is directly evidenced by
        the ATP-dependent MT gliding kinetics of purified kinesin-II (PMID:17000880).
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: indicating that Mg-ATP is the preferred substrate for kinesin-2 motors
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000104
    qualifier: enables
    review:
      summary: >-
        Broad nucleotide-binding parent inferred from the kinesin P-loop motif. KLP-11 binds
        ATP/ADP during its mechanochemical cycle.
      action: ACCEPT
      reason: >-
        Correct but non-specific; the informative child (ATP binding) is separately annotated.
  - term:
      id: GO:0003774
      label: cytoskeletal motor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000104
    qualifier: enables
    review:
      summary: >-
        Parent of microtubule motor activity; correct for KLP-11 as a cytoskeletal (kinesin)
        motor.
      action: ACCEPT
      reason: >-
        Correct but less specific than microtubule motor activity, which is separately
        annotated and refined in core_functions.
  - term:
      id: GO:0003777
      label: microtubule motor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    qualifier: enables
    review:
      summary: >-
        InterPro/ARBA electronic assignment of microtubule motor activity based on the kinesin
        motor domain. Consistent with the IBA and IDA annotations.
      action: ACCEPT
      reason: >-
        Correct; duplicates the well-supported microtubule motor activity from an electronic
        pipeline.
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    qualifier: enables
    review:
      summary: >-
        ATP binding at the kinesin motor domain P-loop (BINDING 99..106) is required for the
        ATPase-driven motor cycle of KLP-11.
      action: ACCEPT
      reason: >-
        Correct and specific; supported by the conserved P-loop and the Mg-ATP kinetics of the
        holoenzyme (PMID:17000880).
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: indicating that Mg-ATP is the preferred substrate for kinesin-2 motors
  - term:
      id: GO:0005856
      label: cytoskeleton
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    qualifier: located_in
    review:
      summary: >-
        KLP-11 localizes to the microtubule cytoskeleton (the ciliary axoneme). Broad but
        accurate.
      action: ACCEPT
      reason: >-
        Correct low-specificity localization for a microtubule motor; the informative site is
        the cilium/axoneme.
  - term:
      id: GO:0005929
      label: cilium
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    qualifier: located_in
    review:
      summary: >-
        KLP-11 localizes to sensory cilia, where kinesin-II performs anterograde IFT along the
        middle segment.
      action: ACCEPT
      reason: >-
        Core localization, consistent with UniProt subcellular location and the cilia IFT role
        of kinesin-II (PMID:17000880).
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: the IFT particles assembling these sensory cilia are moved by the coordinate action of two anterograde IFT motors called kinesin-II and OSM-3, which are both members of the kinesin-2 family
  - term:
      id: GO:0007018
      label: microtubule-based movement
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    qualifier: involved_in
    review:
      summary: >-
        Electronic assignment of microtubule-based movement, duplicating the IBA/IDA process
        annotation.
      action: ACCEPT
      reason: >-
        Correct; the more specific process (intraciliary anterograde transport) is also
        annotated.
  - term:
      id: GO:0008017
      label: microtubule binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    qualifier: enables
    review:
      summary: >-
        InterPro electronic assignment of microtubule binding via the kinesin motor domain;
        duplicates the IBA annotation.
      action: ACCEPT
      reason: >-
        Correct; microtubule binding is intrinsic to the kinesin motor domain.
  - term:
      id: GO:0032991
      label: protein-containing complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    qualifier: part_of
    review:
      summary: >-
        Generic complex-membership assignment. KLP-11 is specifically a subunit of the
        heterotrimeric kinesin-II complex.
      action: MODIFY
      reason: >-
        Too general. Replace with the specific kinesin II complex to convey the actual
        assembly KLP-11 belongs to.
      proposed_replacement_terms:
        - id: GO:0016939
          label: kinesin II complex
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: consisting of 1 mol each of its subunits KLP-11, KLP-20, and KAP-1 with a native molecular mass of 287 kD
  - term:
      id: GO:0007018
      label: microtubule-based movement
    evidence_type: NAS
    original_reference_id: PMID:20498083
    qualifier: involved_in
    review:
      summary: >-
        ComplexPortal NAS annotation. KLP-11 (as the KLP-11/KLP-20 heterodimer, and within the
        kinesin-II holoenzyme) drives microtubule-based movement; heterodimerization confers
        the processivity needed for transport.
      action: ACCEPT
      reason: >-
        Author-stated (NAS) and consistent with the biochemistry: KLP-11 becomes a processive
        MT motor upon heterodimerization with KLP-20 (PMID:20498083).
      supported_by:
        - reference_id: PMID:20498083
          supporting_text: KLP11/KLP20 of Caenorhabditis elegans cilia
  - term:
      id: GO:0016939
      label: kinesin II complex
    evidence_type: NAS
    original_reference_id: PMID:20498083
    qualifier: part_of
    review:
      summary: >-
        KLP-11 is a subunit of kinesin II. The heterodimer of the two motor subunits
        (KLP-11/KLP-20) plus KAP-1 constitutes the kinesin-II complex; heterodimerization is
        required for KAP-1 binding.
      action: ACCEPT
      reason: >-
        Core complex membership. Supported by both the ComplexPortal NAS record and the
        biochemistry of the KLP-11/KLP-20/KAP-1 assembly (PMID:20498083, PMID:17000880).
      supported_by:
        - reference_id: PMID:20498083
          supporting_text: heterodimerization is necessary to bind KAP1, the in vivo link between
        - reference_id: PMID:17000880
          supporting_text: consisting of 1 mol each of its subunits KLP-11, KLP-20, and KAP-1 with a native molecular mass of 287 kD
  - term:
      id: GO:0035720
      label: intraciliary anterograde transport
    evidence_type: NAS
    original_reference_id: PMID:20498083
    qualifier: involved_in
    review:
      summary: >-
        KLP-11-containing kinesin-II is an anterograde IFT motor of C. elegans cilia; the
        heterodimeric motor drives anterograde transport of IFT particles.
      action: ACCEPT
      reason: >-
        Core biological process for KLP-11. Author-stated (NAS) and corroborated by the
        cooperative anterograde IFT role of kinesin-II with OSM-3 (PMID:17000880).
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: the IFT particles assembling these sensory cilia are moved by the coordinate action of two anterograde IFT motors called kinesin-II and OSM-3, which are both members of the kinesin-2 family
  - term:
      id: GO:0003777
      label: microtubule motor activity
    evidence_type: IDA
    original_reference_id: PMID:17000880
    qualifier: enables
    review:
      summary: >-
        Direct assay: purified recombinant C. elegans kinesin-II containing KLP-11 is an active
        microtubule motor in gliding assays, moving MTs at ~0.5 um/s.
      action: ACCEPT
      reason: >-
        Direct experimental evidence (IDA) for KLP-11's core molecular function as a component
        of the kinesin-II motor holoenzyme.
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: kinesin-II alone moved MTs at a maximal rate of 0.3 μm/s, and OSM-3 alone moved them at 0.7 μm/s
  - term:
      id: GO:0007018
      label: microtubule-based movement
    evidence_type: IDA
    original_reference_id: PMID:17000880
    qualifier: involved_in
    review:
      summary: >-
        Direct in vitro demonstration that KLP-11-containing kinesin-II generates
        microtubule-based movement (MT gliding), the biochemical basis of its IFT role.
      action: ACCEPT
      reason: >-
        Direct experimental evidence (IDA). The specific process (intraciliary anterograde
        transport) is also annotated (NAS) and captured in core_functions.
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: kinesin-II alone moved MTs at a maximal rate of 0.3 μm/s, and OSM-3 alone moved them at 0.7 μm/s
  - term:
      id: GO:0030993
      label: axonemal heterotrimeric kinesin-II complex
    evidence_type: IPI
    original_reference_id: PMID:17000880
    qualifier: part_of
    review:
      summary: >-
        KLP-11 physically assembles into the axonemal heterotrimeric kinesin-II complex with
        KLP-20 (WBGene00002230) and KAP-1 (WBGene00002182), demonstrated as a monodisperse
        1:1:1 (~287 kD) heterotrimer by sucrose gradients and gel filtration.
      action: ACCEPT
      reason: >-
        Direct physical-interaction evidence (IPI) for the most specific, experimentally
        grounded cellular-component annotation for KLP-11. This is a core annotation.
      supported_by:
        - reference_id: PMID:17000880
          supporting_text: consisting of 1 mol each of its subunits KLP-11, KLP-20, and KAP-1 with a native molecular mass of 287 kD
core_functions:
  - description: >-
      As a motor subunit of the heterotrimeric kinesin-II holoenzyme (KLP-11/KLP-20/KAP-1),
      KLP-11 contributes plus-end-directed microtubule motor and ATPase activity. KLP-11 is
      unprocessive on its own (as a homodimer); processive plus-end movement is generated only
      by heterodimerization with the partner motor subunit KLP-20. The assembled motor drives
      relatively slow (~0.5 um/s) plus-end transport along axonemal microtubules.
    molecular_function:
      id: GO:0003777
      label: microtubule motor activity
    contributes_to_molecular_function:
      id: GO:0008574
      label: plus-end-directed microtubule motor activity
    directly_involved_in:
      - id: GO:0035720
        label: intraciliary anterograde transport
    locations:
      - id: GO:0005929
        label: cilium
      - id: GO:0005874
        label: microtubule
    in_complex:
      id: GO:0030993
      label: axonemal heterotrimeric kinesin-II complex
    supported_by:
      - reference_id: PMID:17000880
        supporting_text: consisting of 1 mol each of its subunits KLP-11, KLP-20, and KAP-1 with a native molecular mass of 287 kD
      - reference_id: PMID:20498083
        supporting_text: KLP11/KLP20 of Caenorhabditis elegans cilia
  - description: >-
      KLP-11-containing kinesin-II hydrolyzes ATP to power its motor cycle; the purified
      holoenzyme uses Mg-ATP as its preferred substrate with Michaelis-Menten kinetics,
      coupling ATP hydrolysis to microtubule-based movement.
    molecular_function:
      id: GO:0016887
      label: ATP hydrolysis activity
    directly_involved_in:
      - id: GO:0007018
        label: microtubule-based movement
    in_complex:
      id: GO:0030993
      label: axonemal heterotrimeric kinesin-II complex
    supported_by:
      - reference_id: PMID:17000880
        supporting_text: indicating that Mg-ATP is the preferred substrate for kinesin-2 motors
  - description: >-
      Kinesin-II (with KLP-11) is one of two anterograde IFT motors that, together with the
      homodimeric OSM-3 motor, move IFT particles along the doublet microtubules of the ciliary
      middle segment. The two motors act partly redundantly to build the cilium foundation, and
      their mechanical competition contributes to IFT-particle tension regulated by BBS proteins.
    molecular_function:
      id: GO:0003777
      label: microtubule motor activity
    directly_involved_in:
      - id: GO:0035720
        label: intraciliary anterograde transport
    locations:
      - id: GO:0005929
        label: cilium
    in_complex:
      id: GO:0030993
      label: axonemal heterotrimeric kinesin-II complex
    supported_by:
      - reference_id: PMID:17000880
        supporting_text: These motors function redundantly to move the same IFT particles along the initial segment and build the cilium foundation, with either motor but not both being dispensable for this function
knowledge_gaps:
  - gap_statement: >-
      No KLP-11 subunit-resolved in vivo molecular function is established independently of its
      partners: all motility, IFT and localization data are for the intact KLP-11/KLP-20/KAP-1
      heterotrimer (or the KLP-11/KLP-20 heterodimer), and KLP-11 is unprocessive as a homodimer,
      so it has no demonstrated autonomous processive motor activity.
    boundary: >-
      It is firmly established that KLP-11 is a subunit of the purified heterotrimeric kinesin-II
      holoenzyme, that the holoenzyme is an active plus-end MT motor, and that heterodimerization
      with KLP-20 is what confers processivity and enables KAP-1 binding.
    gap_kind:
      - BIOLOGY
    dark_aspect: MF_DARK
    significance: >-
      Distinguishing the specific mechanochemical contribution of the KLP-11 head from that of
      KLP-20 is needed to understand why kinesin-II uses two distinct, asymmetric motor subunits.
    resolution: >-
      Single-molecule and structural analysis of engineered KLP-11 vs KLP-20 heads and chimeras,
      building on the finding that KLP-11 mediates asymmetric autoregulation of the heterodimer.
    provenance:
      - reference_id: PMID:20498083
        supporting_text: heterodimerization is necessary to bind KAP1, the in vivo link between
  - gap_statement: >-
      The identity of the IFT cargo(es) directly engaged by KLP-11-containing kinesin-II via
      KAP-1 in C. elegans, and how cargo loading/unloading is regulated along the middle segment,
      are not resolved by the primary literature reviewed here.
    boundary: >-
      Kinesin-II is established as an anterograde IFT motor that moves IFT particles (IFT-A/IFT-B
      subcomplexes) along the middle segment, and heterodimerization is required for KAP-1 (the
      motor-cargo link) binding.
    gap_kind:
      - BIOLOGY
    dark_aspect: BP_DARK
    significance: >-
      Defining the kinesin-II-specific cargo interface would clarify the division of labor
      between kinesin-II and OSM-3 and the handoff of IFT trains between motors.
    resolution: >-
      Proximity-labeling / cross-linking mass spectrometry of KAP-1 and KLP-11 in cilia, and
      cargo-selective transport assays.
    provenance:
      - reference_id: PMID:17000880
        supporting_text: the IFT particles assembling these sensory cilia are moved by the coordinate action of two anterograde IFT motors called kinesin-II and OSM-3, which are both members of the kinesin-2 family
  - gap_statement: >-
      The atomic structure of the fully assembled C. elegans kinesin-II heterotrimer and the
      structural basis of KLP-11-mediated asymmetric autoregulation of motor activity are unsolved.
    boundary: >-
      Only a partial X-ray structure of the stalk/tail region (residues 537-782, PDB 9IKB, 3.54 A)
      of heterotrimeric kinesin-2 is available; the motor-domain interface and regulatory
      conformations are not resolved.
    gap_kind:
      - BIOLOGY
    dark_aspect: MF_DARK
    significance: >-
      A full structure would explain how an unprocessive subunit is converted to a processive
      heterodimer and how autoregulation is imposed asymmetrically.
    resolution: >-
      Cryo-EM / higher-resolution crystallography of the intact KLP-11/KLP-20/KAP-1 holoenzyme in
      defined nucleotide states.
    provenance:
      - reference_id: PMID:20498083
        supporting_text: KLP11/KLP20 of Caenorhabditis elegans cilia
suggested_questions:
  - question: >-
      What is the distinct mechanochemical role of the KLP-11 motor head versus the KLP-20 head
      within the heterodimer, and why is an unprocessive subunit retained?
    experts: []
  - question: >-
      Which IFT-particle cargoes are engaged by kinesin-II via KAP-1 in C. elegans cilia, and how
      is the kinesin-II-to-OSM-3 handoff regulated along the middle segment?
    experts: []
suggested_experiments:
  - hypothesis: >-
      KLP-11's head contributes asymmetric autoregulation but little autonomous processivity to
      kinesin-II.
    description: >-
      Reconstitute KLP-11/KLP-20 heterodimers and KLP-11 or KLP-20 homodimers and chimeras, and
      compare single-molecule processivity, velocity, and ATPase to dissect each head's contribution.
    experiment_type: single-molecule motility / biochemistry
  - hypothesis: >-
      Full-length assembled kinesin-II adopts nucleotide-dependent conformations that impose
      asymmetric autoregulation.
    description: >-
      Determine the cryo-EM structure of the intact KLP-11/KLP-20/KAP-1 heterotrimer in different
      nucleotide states and on microtubules.
    experiment_type: structural biology (cryo-EM)
tags:
  - caeel-ciliopathy