dyf-3 (C. elegans) research notes

UniProt: Q6I6D4 (CLUA1_CAEEL). WormBase: WBGene00001119 / C04C3.5. Gene: dyf-3.
Human ortholog: CLUAP1 (clusterin-associated protein 1); also known as IFT38 / qilin.
PANTHER family: PTHR21547 "CLUSTERIN ASSOCIATED PROTEIN 1". Pfam: PF10234 (Cluap1).
InterPro: IPR019366 (Clusterin-associated protein-1).

Note: the flagship project doc projects/CAEEL_CILIOPATHY.md lists dyf-3 as an
"IFT54 ortholog" — this is incorrect. dyf-3 is the CLUAP1/IFT38 ortholog (PANTHER
PTHR21547, Pfam Cluap1). dyf-11 is the true IFT54/TRAF3IP1 ortholog.

Identity / orthology

• UniProt names the protein "Clusterin-associated protein 1 homolog" and states it
  "Belongs to the CLUAP1 family." 404 aa (isoform 1), 3 alternatively spliced isoforms
  (dyf-3a/b/c differing at the N-terminus).
• Structural features (UniProt): a long coiled-coil region (residues 176-306) and a
  C-terminal disordered, acidic region (328-382). No catalytic domain; no enzyme
  classification.
• Named "qilin" in some IFT literature: PMID:25443296.

KNOWN (well supported)

1. Required for sensory cilium formation / ciliogenesis (C. elegans, experimental)

• dyf-3 mutants are Dyf (dye-filling defective) and have structurally abnormal cilia.
  PMID:15713455.
• Loss of dyf-3 stunts cilia and causes ectopic posterior neuronal projections.
  PMID:15713455.
• UniProt DISRUPTION PHENOTYPE: "Cilia of at least eight pairs of amphid neurons from
  mutant dyf(m185) animals are truncated at a middle segment, and empty amphidial
  sockets were seen indicating cilium structural abnormalities."
• GOA: cilium assembly (GO:0060271) IDA from PMID:15713455.

2. Component of the intraflagellar transport (IFT) complex B

• The dyf-3 gene product was predicted early on to act in IFT: PMID:15713455.
• UniProt FUNCTION/SUBUNIT (from PMID:28479320): "Component of the intraflagellar
  transport (IFT) complex B ... IFT complex B composed of at least che-2, che-13,
  dyf-1, dyf-3, dyf-6, dyf-11, dyf-13, ift-20, ift-74, ift-81, ifta-2, osm-1, osm-5
  and osm-6."
• Vertebrate ortholog IFT38/CLUAP1 is an integral component of the IFT-B peripheral
  subcomplex: PMID:26980730.
• Function depends on binding to other IFT-B subunits: PMID:26980730.
• Co-purifies with the IFT-B complex: PMID:25443296.
• GOA: intraciliary transport particle B (GO:0030992), intraciliary transport
  (GO:0042073), cilium (GO:0005929) — IBA and NAS/ComplexPortal.

3. Role in ciliary entry/retrograde transport of dynein-2 cargo (che-3)

• PMID:28479320 (Yi et al 2017) shows IFT-B is required for ciliary entry of dynein-2:
  PMID:28479320.
• UniProt FUNCTION (from PMID:28479320): "May be required for ciliary entrance and
  transport of specific ciliary cargo proteins such as che-3 which are related to
  motility." (che-3 = cytoplasmic dynein heavy chain / dynein-2). Note UniProt says
  "motile cilium" in the generic family sentence; C. elegans cilia are non-motile
  sensory cilia — the "motile" wording is generic CLUAP1-family text.

4. Localization: ciliated sensory neurons (dendrite, cell body, axon, cilium)

• Expressed in a defined set of ciliated chemosensory neurons: PMID:15713455.
• UniProt SUBCELLULAR LOCATION: axon, cilium, dendrite (all IDA from PMID:15713455).
• GOA IDA (PMID:15713455): axon (GO:0030424), dendrite (GO:0030425), cell projection
  (GO:0042995), neuronal cell body (GO:0043025). These reflect the pan-neuronal
  distribution of an IFT protein en route to/along the cilium; the cilium/ciliary base
  is the site of function.

5. Cell-autonomous, DAF-19/RFX–regulated ciliary gene

• PMID:15713455.
• PMID:15713455. (X-box/RFX ciliary
  gene battery — consistent with a dedicated ciliary component.)

6. Required for cilia-dependent sensory behaviors (downstream/indirect)

• GOA IMP (PMID:23664973): chemotaxis (GO:0006935), chemosensory behavior (GO:0007635),
  response to alkaline pH (GO:0010446). PMID:23664973's abstract is about the guanylyl
  cyclase GCY-14 and does not name dyf-3; dyf-3 was assayed in the full text (as a
  Dyf/cilium-defective strain) — dye-filling/ciliary integrity is required for these
  amphid-mediated behaviors. These behaviors are downstream consequences of the loss
  of functional cilia, not a distinct molecular activity of DYF-3. Treat as NON-CORE.

NOT known / knowledge gaps

• Molecular/biochemical activity is undefined. DYF-3/CLUAP1 has no catalytic
  activity and no assigned GO molecular function (GOA carries GO:0003674 ND). It is a
  structural/scaffold subunit of IFT-B; the exact interaction partners within IFT-B in
  C. elegans, and which specific cargo it adapts, are not established. The mouse work
  shows it must bind other IFT-B components to function but does not define a discrete
  molecular activity (PMID:26980730).
• Which ciliary cargoes DYF-3 specifically adapts is uncertain. UniProt hedges "May
  be required for ciliary entrance and transport of specific ciliary cargo proteins
  such as che-3" (PMID:28479320) — the "May" and single-cargo example show the cargo
  spectrum is not defined.
• Core vs peripheral placement / stoichiometry in the worm IFT-B is inferred from
  vertebrate biochemistry (PMID:26980730), not directly measured in C. elegans.
• No GO MF term exists for "IFT-B structural subunit" — an ontology gap; the gene
  reads MF-dark despite a well-defined cellular role (mirrors CFAP300 exemplar).

Existing-annotation review plan (20 GOA annotations)

• cilium assembly (GO:0060271) IDA/IBA/NAS → ACCEPT (core). IDA is the strongest.
• intraciliary transport particle B (GO:0030992) IBA/NAS → ACCEPT (core CC / complex).
• intraciliary transport (GO:0042073) NAS → ACCEPT (core BP).
• cilium (GO:0005929) IBA/IEA/NAS → ACCEPT (site of function; is_active_in/located_in).
• microtubule organizing center (GO:0005815) IBA → KEEP_AS_NON_CORE or MODIFY. IFT
  proteins concentrate at the ciliary base (basal body region). The MTOC IBA is a
  broad phylogenetic call; basal body is the more specific/appropriate location.
• axon (GO:0030424) IDA/IEA, dendrite (GO:0030425) IDA/IEA, cell projection
  (GO:0042995) IDA, neuronal cell body (GO:0043025) IDA → KEEP_AS_NON_CORE. These
  reflect the neuronal distribution of the protein in transit; not the functional site.
• chemotaxis (GO:0006935), chemosensory behavior (GO:0007635), response to alkaline pH
  (GO:0010446) IMP → KEEP_AS_NON_CORE. Downstream cilia-dependent behaviors; do not
  REMOVE (experimental IMP, full text not in cache).
• molecular_function (GO:0003674) ND → ACCEPT as a genuine MF knowledge gap (do not
  invent an MF).

Provenance policy

All supporting_text quotes above are verbatim substrings of the cached abstracts/
full-text in publications/. PMID:15713455, 23664973, 28479320 are abstract-only
(full_text_available: false); PMID:26980730 abstract-only; PMID:25443296 full text.