DNAAF3 is a cytoplasmic dynein assembly factor required for maturation of outer and inner dynein arms before their deployment in motile cilia. Deficiency disrupts respiratory ciliary beating and can alter leftβright organ patterning, causing primary ciliary dyskinesia. The conserved protein concentrates in dynein assembly particles in multiciliated cells. Ortholog genetics, dynein mass spectrometry and structural comparisons support a candidate role in arginine methylation during dynein maturation; intrinsic human methyltransferase activity and its separation from noncatalytic assembly functions remain unresolved. Alternative transcripts encode five predicted products with distinct sequence boundaries.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic assembly factor with enrichment in DynAPs. Reason: The official SL-0086 assertion maps exactly to cytoplasm. DNAAF3 acts before axonemal deployment of dynein motors, and the Xenopus DNAAF3 fusion in PMID:30561330 Figure 2C occupies cytoplasmic foci with a surrounding cytoplasmic pool. Retain the general cytoplasmic location alongside the specifically supported DynAP enrichment; neither assertion makes DNAAF3 a mature axonemal motor. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER Exact SL-0086 to GO:0005737 mapping verified. Conserved preassembly and Xenopus localization support the cytoplasmic compartment. Supporting Evidence: GO_REF:0000044 file:human/DNAAF3/DNAAF3-evidence-guide.md |
| GO:0044458 motile cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited participation in motile-cilium assembly through maturation of its dynein-arm components. Reason: The human leaf PTN002502984 descends from PTN001858482 in PTHR22118, and the literal IBD grounding includes genuine human experimental evidence. DNAAF3 promotes maturation of the outer and inner dynein arms that form part of a functional motile cilium. Human patient cilia lack these arms, while ortholog rescue and biochemical experiments identify a cytoplasmic assembly defect: abnormal heavy/intermediate-chain complexes form but fail to become assembly competent. Persistent ciliary projections therefore do not negate participation in their constituent assembly. This is a core role. GO:0036158 and GO:0036159 are not current is_a/part_of descendants of GO:0044458, so those separately represented arm-assembly processes do not replace this inherited claim. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001858482 SUPPORTS TRANSFER Valid root-to-human descent and both IBD annotations verified. The saved IBD snapshot contains fly and human seeds, while current QuickGO also lists zebrafish; no donor-count objection or target circularity is inferred. |
| GO:0044458 motile cilium assembly | IMP PMID:22387996 Mutations in axonemal dynein assembly factor DNAAF3 cause pr... | ACCEPT | Summary: DNAAF3 contributes to assembly of functional motile cilia by maturing their axonemal dynein arms. Reason: PMID:22387996 directly shows loss of both dynein-arm classes in human patient respiratory cilia; zebrafish knockdown leaves ciliary morphology and number largely intact while disrupting arms and motility. In Chlamydomonas, rescue and cytoplasmic heavy/intermediate-chain assays show that PF22/DNAAF3 supports maturation into assembly-competent motors. The performed work is dynein-component assembly, not merely an effect on beating or a claim that DNAAF3 builds the ciliary membrane. GO:0044458 encompasses arrangement of components into a motile cilium, making this core participation despite persistence of projections. The specific arm terms are retained separately because neither is an is_a/part_of descendant of GO:0044458. Supporting Evidence: PMID:22387996 cilia that lack both outer and inner dynein arms file:human/DNAAF3/DNAAF3-evidence-guide.md |
| GO:0070286 axonemal dynein complex assembly | IBA GO_REF:0000033 | MODIFY | Summary: Inherited axonemal dynein assembly includes both outer and inner arms. Reason: PTHR22118 places the human target beneath the stated PTN001858482 ancestral node, whose GO:0070286 IBD is experimentally grounded. Refine the broader assembly term to its verified outer-arm and inner-arm assembly children using the target-specific evidence in PMID:22387996. This preserves the positive phylogenetic judgment and does not infer catalytic motor activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001858482 SUPPORTS TRANSFER Node placement, current GO:0070286 annotation and human target descent are verified; the change supplies target-level specificity rather than rejecting inheritance. Proposed replacements: outer dynein arm assembly inner dynein arm assembly |
| GO:0070286 axonemal dynein complex assembly | IEA GO_REF:0000002 | MODIFY | Summary: Correct family mapping can be refined to outer and inner dynein-arm assembly. Reason: IPR039304 is the DNAAF3 family, with an actual human target match over canonical residues 1β470 and an explicit GO:0070286 mapping. The InterPro entry cites PMID:22387996 and describes preassembly of both inner and outer arms. Refine the correct broad mapping to those two specific assembly processes without assigning an independent chaperone or motor activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR039304 SUPPORTS TRANSFER Official family, target match and exact InterPro2GO mapping verified. Source biology supports both proposed child processes. Proposed replacements: outer dynein arm assembly inner dynein arm assembly |
| GO:0070286 axonemal dynein complex assembly | IMP PMID:22387996 Mutations in axonemal dynein assembly factor DNAAF3 cause pr... | MODIFY | Summary: Experimental assembly phenotype resolved to outer and inner dynein arms. Reason: The human and ortholog findings in PMID:22387996 support DNAAF3-dependent dynein-arm preassembly. Outer dynein arm assembly and inner dynein arm assembly are verified is_a children of the existing term and express the two supported target-level components. Preserve the original experimental assertion while making its biological scope more specific. Proposed replacements: outer dynein arm assembly inner dynein arm assembly Supporting Evidence: PMID:22387996 Its loss prevents correct assembly of inner and outer dynein arms file:human/DNAAF3/DNAAF3-evidence-guide.md |
| GO:0120293 dynein axonemal particle | IEA GO_REF:0000044 | ACCEPT | Summary: DynAP localization from a correctly mapped, experimentally grounded ortholog inference. Reason: SL-0542 maps exactly to dynein axonemal particle. The human UniProt location traces to Xenopus laevis DNAAF3 Q32NQ7, whose direct IDA evidence is PMID:30561330. The original Figure 2C shows tagged Xenopus DNAAF3 co-localizing with Ktu in cytoplasmic DynAPs. Retain the conserved location, while distinguishing it from direct imaging of endogenous human DNAAF3 or demonstrated localization of every predicted human isoform. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0542 SUPPORTS TRANSFER Exact mapping to GO:0120293 verified; human UniProt explicitly cites the experimentally localized Xenopus Q32NQ7 donor. |
| GO:0120293 dynein axonemal particle | ISS GO_REF:0000024 | ACCEPT | Summary: Experimentally localized Xenopus ortholog supports the human DynAP transfer. Reason: The literal donor Q32NQ7 is Xenopus laevis dnaaf3 and carries direct IDA to GO:0120293 from PMID:30561330. Methods identify DNAAF3 cloned from a Xenopus cDNA library, and Figure 2C shows the DNAAF3 fluorescent fusion in Ktu-positive DynAPs. This positive source evidence supports the curator's ortholog transfer. Human staining in the same paper assays LRRC6 and DNAI1, so it is not presented as direct human DNAAF3 imaging. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q32NQ7 SUPPORTS TRANSFER Verified Xenopus DNAAF3 with direct IDA30561330 localization. Its separate assembly ISS to human does not make this independently measured localization circular. Supporting Evidence: PMID:30561330 all tested DNAAFs co-localized significantly in cytosolic foci GO_REF:0000024 file:human/DNAAF3/DNAAF3-evidence-guide.md |
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