id: Q8I7G4
gene_symbol: dyf-1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: >-
  DYF-1 is a tetratricopeptide-repeat (TPR) protein and a subunit of intraflagellar
  transport (IFT) complex B, the anterograde IFT module that builds and maintains cilia.
  It is the Caenorhabditis elegans ortholog of human TTC30A/TTC30B and of the
  ciliate/algal IFT70, and its name reflects the abnormal dye-filling (Dyf) phenotype of
  its mutants. DYF-1 is expressed in ciliated sensory neurons and localizes to the ciliary
  basal body and the axoneme, moving processively along the axoneme as part of IFT trains.
  Its central role is to act as an obligatory activator/adaptor for the homodimeric
  kinesin-2 motor OSM-3 (the KIF17 ortholog): DYF-1 is specifically required for OSM-3 to
  dock onto and move IFT particles, and in its absence OSM-3 is inactive so that IFT trains
  are carried by heterotrimeric kinesin-II alone and the distal singlet segments of amphid
  and phasmid cilia fail to form. As an IFT-B component DYF-1 is required for normal
  ciliogenesis and for delivery of ciliary cargo, and DYF-1/IFT70 is additionally required
  for polyglutamylation of the axonemal tubulin of sensory cilia.
alternative_products:
- name: a
  id: Q8I7G4-1
- name: b
  id: Q8I7G4-2
  sequence_note: VSP_033490
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Standard GO_Central IBA pipeline. The phylogenetic inferences (IFT complex B
      membership, intraciliary transport, IFT-B binding, axonemal microtubule) are all
      corroborated by C. elegans experimental data, so the IBA transfers are sound.
- 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: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Electronic mapping of the UniProt "Cilium" subcellular-location keyword to
      GO:0005929; redundant with the experimental IDA cilium annotation but not incorrect.
- id: PMID:16049494
  title: Functional coordination of intraflagellar transport motors.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Founding functional paper for dyf-1 (Ou et al. 2005, Nature). The abstract directly
      establishes that DYF-1 is specifically required for OSM-3 kinesin to dock onto and
      move IFT particles and that OSM-3 is inactive in dyf-1 mutants. Correctly supports the
      intraciliary-transport and OSM-3-activation core function. The same PMID is also the
      GOA citation for the protein-polyglutamylation and plasma-membrane-localization IMP
      rows, which its abstract does not itself address (see those annotations).
- id: PMID:17761526
  title: The zebrafish fleer gene encodes an essential regulator of cilia tubulin
    polyglutamylation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Pathak et al. 2007. Establishes the DYF-1/fleer family role in cilia tubulin
      polyglutamylation and states explicitly that C. elegans dyf-1 is also required for
      tubulin polyglutamylation in sensory-neuron cilia; also confirms fleer/DYF1 orthology.
      This is the definitive supporting reference for the protein-polyglutamylation
      annotation (which GOA cites to PMID:16049494 instead).
- id: PMID:22922713
  title: The BBSome controls IFT assembly and turnaround in cilia.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: >-
      Wei et al. 2012. A C. elegans IFT paper whose main text (cached) concerns dyf-2 and
      bbs-1 IFT turnaround; DYF-1 is not named in the cached main text (dyf-2/bbs-1 are the
      subjects). It is the assigned reference for the ciliary-basal-body IDA (assigned_by
      MGI); the basal-body localization is biologically expected for any IFT-B protein, but
      the dyf-1-specific evidence could not be verbatim-verified here (may reside in a
      supplement). Deferred to the experimental curator; retained as ACCEPT on biological
      grounds.
- id: PMID:28479320
  title: Dynein-Driven Retrograde Intraflagellar Transport Is Triphasic in C. elegans
    Sensory Cilia.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Yi et al. 2017. Identifies DYF-1 as a component of IFT complex B by mass spectrometry
      (basis of ComplexPortal CPX-1290 and the UniProt SUBUNIT list) and shows IFT-B is
      required for ciliary entry of dynein-2. Supports the IFT-B membership, intraciliary
      transport, cilium-localization and cilium-assembly (NAS) annotations.
- id: PMID:15916950
  title: Functional genomics of the cilium, a sensory organelle.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Blacque et al. 2005 SAGE/DAF-19 ciliary-transcriptome screen; source of the UniProt
      tissue-specificity statement that dyf-1 is expressed in amphid, phasmid and
      labial-quadrant sensory neurons. Background/expression context, not an annotation
      source.
existing_annotations:
- term:
    id: GO:0030992
    label: intraciliary transport particle B
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      DYF-1 is a subunit of intraflagellar transport complex B (IFT-B). This IBA transfer is
      strongly corroborated experimentally: DYF-1 was identified in the C. elegans IFT-B
      complex by mass spectrometry (PMID:28479320; ComplexPortal CPX-1290).
    action: ACCEPT
    reason: >-
      Core cellular-component identity of DYF-1. Phylogenetically inferred and independently
      confirmed by biochemical identification of DYF-1 in worm IFT-B.
    supported_by:
    - reference_id: PMID:28479320
      supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
        localization
      reference_section_type: ABSTRACT
- term:
    id: GO:0042073
    label: intraciliary transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      DYF-1 functions in intraflagellar (intraciliary) transport as an IFT-B subunit and
      OSM-3 kinesin activator. IBA is well supported by the C. elegans experimental data.
    action: ACCEPT
    reason: >-
      Core biological process. Confirmed experimentally in worm (PMID:16049494): DYF-1 is
      required for OSM-3 to move IFT particles.
    supported_by:
    - reference_id: PMID:16049494
      supporting_text: specifically required for OSM-3 kinesin to dock onto and move IFT
        particles
      reference_section_type: ABSTRACT
- term:
    id: GO:0005879
    label: axonemal microtubule
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      DYF-1 acts along axonemal microtubules, where IFT trains move. The is_active_in
      qualifier is appropriate for an IFT motor-associated protein that translocates along
      the axoneme; corroborated by the experimental IDA localization (PMID:16049494).
    action: ACCEPT
    reason: >-
      Consistent with DYF-1's role as an axoneme-associated IFT-B component that undergoes
      IFT along ciliary microtubules.
- term:
    id: GO:0120170
    label: intraciliary transport particle B binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      DYF-1 binds the IFT-B particle as one of its subunits. This is the most informative
      molecular-function term available for DYF-1 and is preferable to generic protein
      binding.
    action: ACCEPT
    reason: >-
      Captures DYF-1's molecular function as an IFT-B-associated protein. Note this binding
      term does not express DYF-1's distinctive OSM-3-kinesin-activation activity, which has
      no dedicated GO MF term (see knowledge_gaps).
    supported_by:
    - reference_id: PMID:28479320
      supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
        localization
      reference_section_type: ABSTRACT
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      DYF-1 localizes to the cilium. Electronic mapping from the UniProt Cilium subcellular
      keyword; redundant with the experimental IDA cilium annotation.
    action: ACCEPT
    reason: >-
      Correct location, independently supported by experimental evidence (PMID:16049494).
- term:
    id: GO:0005929
    label: cilium
  evidence_type: NAS
  original_reference_id: PMID:28479320
  qualifier: located_in
  review:
    summary: >-
      DYF-1 localizes to the cilium as an IFT-B component (ComplexPortal NAS from
      PMID:28479320).
    action: ACCEPT
    reason: Correct ciliary localization; consistent with IFT-B membership and IDA evidence.
- term:
    id: GO:0030992
    label: intraciliary transport particle B
  evidence_type: NAS
  original_reference_id: PMID:28479320
  qualifier: part_of
  review:
    summary: >-
      DYF-1 is part of IFT complex B, identified by mass spectrometry in C. elegans
      (PMID:28479320) and curated by ComplexPortal (CPX-1290).
    action: ACCEPT
    reason: >-
      Direct experimental/curated support for IFT-B membership; the strongest evidence for
      this core cellular-component identity.
    supported_by:
    - reference_id: PMID:28479320
      supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
        localization
      reference_section_type: ABSTRACT
- term:
    id: GO:0042073
    label: intraciliary transport
  evidence_type: NAS
  original_reference_id: PMID:28479320
  qualifier: involved_in
  review:
    summary: >-
      DYF-1 participates in intraciliary transport as an IFT-B subunit (ComplexPortal NAS
      from PMID:28479320).
    action: ACCEPT
    reason: Core biological process; concordant with the IBA and IMP intraciliary-transport rows.
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: NAS
  original_reference_id: PMID:28479320
  qualifier: involved_in
  review:
    summary: >-
      As an IFT-B component required for anterograde transport, DYF-1 is required for cilium
      assembly; the distal singlet segments of amphid/phasmid cilia fail to form in dyf-1
      mutants (via loss of OSM-3 activity).
    action: ACCEPT
    reason: >-
      IFT-B is essential for ciliogenesis; this NAS annotation is well grounded in DYF-1's
      role in building the distal ciliary segment.
    supported_by:
    - reference_id: PMID:28479320
      supporting_text: essential for cilium formation and maintenance
      reference_section_type: ABSTRACT
- term:
    id: GO:0072659
    label: protein localization to plasma membrane
  evidence_type: IMP
  original_reference_id: PMID:16049494
  qualifier: involved_in
  review:
    summary: >-
      This IMP is attributed to PMID:16049494 (Ou et al. 2005), whose cached abstract is
      entirely about coordination of the kinesin-II and OSM-3 IFT motors and does not
      address localization of any plasma-membrane/ciliary-membrane protein. The generic term
      protein localization to plasma membrane is also imprecise for a ciliary IFT role
      (ciliary membrane rather than bulk plasma membrane).
    action: UNDECIDED
    reason: >-
      Cannot verify the supporting evidence: the cached publication is abstract-only and the
      abstract does not mention membrane-protein localization, and no specific mislocalized
      cargo can be identified from the accessible text. Per review guidelines, marked
      UNDECIDED rather than removed, since the curator may have used full-text/supplementary
      data not available here.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IDA
  original_reference_id: PMID:22922713
  qualifier: located_in
  review:
    summary: >-
      DYF-1 localizes to the ciliary basal body (ciliary base), the docking/loading zone
      where IFT trains assemble. Basal-body localization is a defining feature of IFT-B
      proteins, which build and load onto IFT trains at the ciliary base.
    action: ACCEPT
    reason: >-
      Experimental IDA (assigned_by MGI) consistent with DYF-1's role as an IFT-B subunit
      that docks at the ciliary base. DYF-1 is not named in the cached main text of
      PMID:22922713 (which foregrounds dyf-2/bbs-1); per review guidelines the experimental
      annotation is retained and deferred to the curator rather than removed, and the
      citation is flagged UNVERIFIED in reference_review.
- term:
    id: GO:0005879
    label: axonemal microtubule
  evidence_type: IDA
  original_reference_id: PMID:16049494
  qualifier: located_in
  review:
    summary: >-
      DYF-1::GFP localizes along the ciliary axoneme and undergoes IFT (Ou et al. 2005),
      consistent with an axonemal-microtubule location.
    action: ACCEPT
    reason: >-
      Experimental localization supporting DYF-1's presence along axonemal microtubules;
      concordant with the IBA is_active_in axonemal-microtubule row.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IDA
  original_reference_id: PMID:16049494
  qualifier: located_in
  review:
    summary: >-
      DYF-1 is directly observed in the cilium (Ou et al. 2005). UniProt records the
      subcellular location Cell projection, cilium from this study.
    action: ACCEPT
    reason: Experimental (IDA) ciliary localization; the best-supported location annotation.
- term:
    id: GO:0018095
    label: protein polyglutamylation
  evidence_type: IMP
  original_reference_id: PMID:16049494
  qualifier: involved_in
  review:
    summary: >-
      DYF-1/IFT70 is required for tubulin polyglutamylation of the ciliary axoneme. This is
      a genuine, literature-established function of dyf-1 shown directly in C. elegans by
      Pathak et al. 2007 (PMID:17761526), although GOA cites it here to PMID:16049494, whose
      abstract does not address polyglutamylation. It is a downstream/indirect role, not
      DYF-1's core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Real but non-core: DYF-1 is not itself a glutamylase; polyglutamylation loss is a
      consequence of DYF-1 dysfunction (whether via failed IFT-delivery of a glutamylase or
      via the B-tubule/axoneme structural defect is unresolved; see knowledge_gaps). Retained
      because the function is well supported; supporting text drawn from the definitive paper
      (PMID:17761526) rather than the GOA-cited PMID:16049494.
    supported_by:
    - reference_id: PMID:17761526
      supporting_text: dyf-1, is also required for tubulin polyglutamylation in sensory
        neuron cilia
      reference_section_type: ABSTRACT
- term:
    id: GO:0042073
    label: intraciliary transport
  evidence_type: IMP
  original_reference_id: PMID:16049494
  qualifier: involved_in
  review:
    summary: >-
      Direct experimental evidence (IMP): in dyf-1 mutants OSM-3 is inactive and IFT
      particles are moved by kinesin-II alone, so distal singlet ciliary segments are not
      built. This is the primary experimental support for DYF-1's role in intraciliary
      transport.
    action: ACCEPT
    reason: >-
      Strongest experimental evidence for DYF-1's core function in anterograde IFT via
      OSM-3 activation.
    supported_by:
    - reference_id: PMID:16049494
      supporting_text: specifically required for OSM-3 kinesin to dock onto and move IFT
        particles
      reference_section_type: ABSTRACT
    - reference_id: PMID:16049494
      supporting_text: an OSM-3 kinesin activator in the formation of two IFT pathways
      reference_section_type: ABSTRACT
- term:
    id: GO:0035720
    label: intraciliary anterograde transport
  evidence_type: IMP
  original_reference_id: PMID:16049494
  qualifier: involved_in
  review:
    summary: >-
      NEW (proposed, more specific). DYF-1 acts specifically in ANTEROGRADE intraciliary
      transport: it is required for the anterograde kinesin-2 motor OSM-3 to dock onto and
      move IFT particles, building the distal singlet segment of amphid/phasmid cilia. The
      current GOA rows use the generic parent term intraciliary transport (GO:0042073); the
      anterograde-specific child term more precisely captures DYF-1's role.
    action: NEW
    reason: >-
      DYF-1's function is anterograde-specific (OSM-3 activation), so intraciliary anterograde
      transport (GO:0035720) is more informative than the generic GO:0042073 already annotated
      by GOA.
    supported_by:
    - reference_id: PMID:16049494
      supporting_text: specifically required for OSM-3 kinesin to dock onto and move IFT
        particles
      reference_section_type: ABSTRACT
core_functions:
- description: >-
    DYF-1 is a tetratricopeptide-repeat subunit of intraflagellar transport complex B that
    acts as the obligatory activator/adaptor coupling the homodimeric kinesin-2 motor OSM-3
    to anterograde IFT trains. DYF-1 is specifically required for OSM-3 to dock onto and move
    IFT particles; in its absence OSM-3 is inactive, IFT trains are moved by heterotrimeric
    kinesin-II alone, and the distal singlet segments of amphid/phasmid sensory cilia fail to
    form. It functions at the ciliary basal body (train assembly/loading) and along axonemal
    microtubules, and is required for ciliogenesis of sensory cilia.
  molecular_function:
    id: GO:0120170
    label: intraciliary transport particle B binding
  in_complex:
    id: GO:0030992
    label: intraciliary transport particle B
  directly_involved_in:
  - id: GO:0035720
    label: intraciliary anterograde transport
  - id: GO:0060271
    label: cilium assembly
  locations:
  - id: GO:0036064
    label: ciliary basal body
  - id: GO:0005879
    label: axonemal microtubule
  supported_by:
  - reference_id: PMID:16049494
    supporting_text: specifically required for OSM-3 kinesin to dock onto and move IFT
      particles
    reference_section_type: ABSTRACT
  - reference_id: PMID:28479320
    supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
      localization
    reference_section_type: ABSTRACT
knowledge_gaps:
- gap_statement: >-
    How DYF-1 activates OSM-3 kinesin at the molecular level is unknown: whether it binds the
    motor directly, relieves OSM-3 autoinhibition, or bridges OSM-3 to the IFT-B core, and
    which OSM-3 surface it engages, are undetermined. There is also no GO molecular-function
    term that expresses a kinesin-2 docking/activation-factor activity, so the gene reads as
    MF-dark despite a well-defined cellular role.
  boundary: >-
    DYF-1 is an IFT complex B subunit localizing to the ciliary base and axoneme that is
    genetically and specifically required for OSM-3 to dock onto and move IFT particles;
    loss inactivates OSM-3 and prevents assembly of the distal singlet ciliary segment. Its
    only informative MF term is intraciliary transport particle B binding (GO:0120170).
  gap_kind:
  - BIOLOGY
  - ONTOLOGY
  dark_aspect: MF_DARK
  status: OPEN
  significance: >-
    This is the step that selectively couples the OSM-3/KIF17 motor to anterograde IFT and
    builds the distal ciliary segment; the mechanism is conserved to human TTC30A/TTC30B and
    the ciliate/algal IFT70, and is central to how two anterograde kinesins are coordinated
    on a shared IFT train.
  resolution: >-
    Reconstitute OSM-3 motility with purified DYF-1 and IFT-B in vitro; determine a
    DYF-1-OSM-3 structure/interface; isolate separation-of-function dyf-1 alleles that
    uncouple IFT-B binding from OSM-3 activation; propose a molecular-function term for
    kinesin docking/activation-factor activity.
  provenance:
  - reference_id: PMID:16049494
    supporting_text: specifically required for OSM-3 kinesin to dock onto and move IFT
      particles
    reference_section_type: ABSTRACT
  - reference_id: PMID:16049494
    supporting_text: an OSM-3 kinesin activator in the formation of two IFT pathways
    reference_section_type: ABSTRACT
- gap_statement: >-
    Whether DYF-1/IFT70 promotes axonemal tubulin polyglutamylation directly (for example by
    IFT-dependent delivery of a TTLL glutamylase or its tubulin substrate) or indirectly as a
    downstream consequence of the B-tubule/axoneme structural defect is unresolved, and the
    responsible glutamylase in the dyf-1 pathway is not identified.
  boundary: >-
    Loss of the DYF-1/fleer ortholog dramatically reduces ciliary polyglutamylated tubulin
    and causes B-tubule ultrastructural defects, and C. elegans dyf-1 is likewise required
    for tubulin polyglutamylation in sensory-neuron cilia; the mechanistic link between IFT-B
    function and the polyglutamylation machinery has not been defined.
  gap_kind:
  - BIOLOGY
  dark_aspect: RESIDUAL_SUBGAP
  status: OPEN
  significance: >-
    Tubulin polyglutamylation is required for cilium structure and, in motile cilia,
    motility across species; distinguishing a direct IFT-transport role from an indirect
    structural consequence would clarify how IFT-B controls axonemal post-translational
    modification.
  resolution: >-
    Test whether a TTLL glutamylase or its substrate is an IFT-B/DYF-1 cargo (IFT
    co-transport imaging, proximity proteomics); quantify polyglutamylation vs axonemal
    ultrastructure across a dyf-1 allelic series to separate cause from consequence.
  provenance:
  - reference_id: PMID:17761526
    supporting_text: novel modulator of tubulin polyglutamylation
    reference_section_type: ABSTRACT
  - reference_id: PMID:17761526
    supporting_text: dyf-1, is also required for tubulin polyglutamylation in sensory neuron
      cilia
    reference_section_type: ABSTRACT
suggested_questions:
- question: >-
    Does DYF-1 bind OSM-3 directly, and does it activate the motor by relieving OSM-3
    autoinhibition or by tethering OSM-3 to the IFT-B core?
  experts: []
- question: >-
    Is the polyglutamylation defect in dyf-1 mutants a direct consequence of failed IFT
    delivery of a tubulin glutamylase, or an indirect result of the B-tubule structural
    defect?
  experts: []
suggested_experiments:
- hypothesis: >-
    DYF-1 activates OSM-3 by direct binding that relieves OSM-3 motor autoinhibition and
    docks it onto IFT-B.
  description: >-
    Reconstitute purified OSM-3 with DYF-1 and IFT-B and measure single-molecule motility and
    ATPase activity +/- DYF-1; map the DYF-1-OSM-3 interaction by crosslinking/MS or
    cryo-EM, and test separation-of-function dyf-1 alleles in vivo for IFT-B binding vs
    OSM-3 activation.
  experiment_type: in vitro reconstitution / single-molecule motility / structural biology
- hypothesis: >-
    DYF-1/IFT-B is required to transport a tubulin polyglutamylase (or its substrate) into
    the cilium.
  description: >-
    Image candidate TTLL glutamylases for IFT-dependent ciliary transport and co-movement
    with DYF-1/IFT-B; test whether glutamylase ciliary entry and axonemal polyglutamylation
    are lost in dyf-1 mutants while scoring axonemal ultrastructure across an allelic series.
  experiment_type: live-cell IFT imaging / genetics