DNAAF1 is a leucine-rich-repeat protein that supports cytoplasmic assembly of the outer and inner dynein arms needed for motile cilia. Loss of DNAAF1 disrupts dynein-arm incorporation and causes primary ciliary dyskinesia with respiratory and left–right patterning abnormalities. Human protein has also been observed in cilia and at mitotic spindle poles, and depletion in cultured renal epithelial cells impairs primary-cilium formation. Alternative transcripts encode three predicted products with different repeat or C-terminal regions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000922 spindle pole | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain observed spindle-pole localization. Reason: Human LRRC50-EGFP colocalized with gamma-tubulin at mitotic spindle poles in 293T cells (2008 Figure 5D). The UniProt location mapping has a positive target-specific basis. This ectopic localization does not establish a mitotic assembly mechanism or a second core function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0448 SUPPORTS TRANSFER The official spindle-pole location maps to GO:0000922 and is independently corroborated by the human-protein microscopy. Supporting Evidence: PMID:18385425 at the mitotic spindle poles |
| GO:0001947 heart looping | IMP PMID:19944400 Deletions and point mutations of LRRC50 cause primary ciliar... | KEEP AS NON CORE | Summary: Retain the developmental laterality consequence. Reason: Situs abnormalities accompanying DNAAF1-associated ciliary dysfunction support the existing heart-looping annotation in its developmental context. This is not evidence that DNAAF1 directly builds myocardium or supplies a distinct cardiac molecular activity. |
| GO:0001947 heart looping | IMP PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | KEEP AS NON CORE | Summary: Retain the developmental laterality consequence. Reason: Situs abnormalities accompanying DNAAF1-associated ciliary dysfunction support the existing heart-looping annotation in its developmental context. This is not evidence that DNAAF1 directly builds myocardium or supplies a distinct cardiac molecular activity. |
| GO:0003341 cilium movement | IMP PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | KEEP AS NON CORE | Summary: Retain the effect on cilium movement. Reason: Patient nasal cilia are immotile when both dynein-arm classes are lost. Protist rescue and depletion experiments connect the phenotype to arm assembly. The existing movement assertion is retained contextually; the direct functional unit is assembly, not force generation by DNAAF1 itself. Supporting Evidence: |
| GO:0003356 regulation of cilium beat frequency | IMP PMID:19944400 Deletions and point mutations of LRRC50 cause primary ciliar... | KEEP AS NON CORE | Summary: Retain the ciliary beat phenotype without a frequency-sensor mechanism. Reason: Loss of DNAAF1 produces immotile respiratory cilia and loss of arm components. This positively supports the curated effect on beating. It does not identify an acute frequency-regulating activity separate from the assembly defect. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000108 | REMOVE | Summary: Do not infer extracellular protein localization from extracellular fluid movement. Reason: The electronic row is traced to GO:0060287, a left–right-organizer cilium movement process, through GO_REF:0000108. DNAAF1 supplies intracellular dynein-arm assembly, and the human localization experiment places the protein in cytoplasm and membrane-bounded cilia. GO:0005576 denotes space outside the cell, not the cytoplasmic interior of a protruding cilium. The process-to-compartment inference conflates where fluid is moved with where this assembly factor acts; this is a mapping-specific correction, not a claim that secretion is impossible under every condition. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH ROLE CONFLATION Sources checked: GO:0060287 SUPPORTS SOURCE BUT NOT TARGET The source process is retained as a contextual ciliary/laterality role, but it does not locate this intracellular assembly factor in the extracellular region. The exact current automatic record and GO_REF method were inspected. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm is a supported assembly compartment. Reason: Human LRRC50-EGFP is diffusely cytoplasmic. Cross-species preassembly experiments support this compartment, but the greater-than-99-percent cell-body fraction measured in Chlamydomonas is not a quantitative human localization result. No more restrictive soluble-cytosol claim is required. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER The official cytoplasm location is corroborated by the human construct and the conserved preassembly mechanism. |
| GO:0005737 cytoplasm | NAS PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | ACCEPT | Summary: Cytoplasm is a supported assembly compartment. Reason: Human LRRC50-EGFP is diffusely cytoplasmic. Cross-species preassembly experiments support this compartment, but the greater-than-99-percent cell-body fraction measured in Chlamydomonas is not a quantitative human localization result. No more restrictive soluble-cytosol claim is required. |
| GO:0005929 cilium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the observed ciliary pool. Reason: Human LRRC50-EGFP was detected in the ciliary extension of canine MDCK cells (Figure 5E); the host species does not change the identity of the expressed human protein. This supports the broad cilium location while leaving endogenous abundance and structural incorporation unresolved. Predominant cytoplasmic assembly does not exclude a smaller ciliary pool. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0066 SUPPORTS TRANSFER The official cilium mapping is supported by the human-protein imaging; a constitutive motor-complex residence is not inferred. Supporting Evidence: |
| GO:0005930 axoneme | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the curated axonemal localization context. Reason: Ciliary-shaft localization of human LRRC50-EGFP and the reported axonemal Oda7 association support the existing location. Fluorescence in the shaft alone does not resolve a stable structural interface. The axonemal pool is retained without treating DNAAF1 as a mature dynein motor subunit. The inherited is_active_in qualifier is retained as the curator's axonemal activity context, rather than inferred anew from shaft fluorescence alone. The independent human IFT88 association supports a connection to ciliary delivery (PMID:29228333), but a specific DNAAF1 reaction inside the axoneme has not been isolated. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002915666 SUPPORTS TRANSFER The saved IBD and current PANTHER tree place human leaf PTN000062877 below this node. The axoneme IBD is experimentally grounded on the human target; its occurrence among the seeds is expected, not circular. No target loss or misplaced descent was identified. |
| GO:0005930 axoneme | IDA PMID:18385425 LRRC50, a conserved ciliary protein implicated in polycystic... | KEEP AS NON CORE | Summary: Retain the curated axonemal localization context. Reason: Ciliary-shaft localization of human LRRC50-EGFP and the reported axonemal Oda7 association support the existing location. Fluorescence in the shaft alone does not resolve a stable structural interface. The axonemal pool is retained without treating DNAAF1 as a mature dynein motor subunit. |
| GO:0007368 determination of left/right symmetry | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain conserved left–right patterning consequences. Reason: Human situs abnormalities and zebrafish organizer-cilium immotility provide positive support for the inherited laterality role. This developmental consequence is distinct from the direct dynein-arm assembly mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002915666 SUPPORTS TRANSFER The saved IBD and current PANTHER tree place human leaf PTN000062877 below this node. The IBD has human and zebrafish experimental grounding. Both fall within the reconstructed descendant clade; donor count and self-inclusion are not objections. |
| GO:0030324 lung development | IMP PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | UNDECIDED | Summary: Lung morphogenesis is not resolved by the inspected patient evidence. Reason: The original paper documents chronic airway disease, ciliary immotility and dynein-arm loss, which establish respiratory cilium dysfunction. GO:0030324 describes formation and maturation of the lung itself. The inspected original main text and patient table do not distinguish a developmental lung role from secondary airway pathology; the experimental assertion is retained as unresolved rather than rejected as a wrong-gene or wrong-species annotation. Supporting Evidence: |
| GO:0035082 axoneme assembly | IBA GO_REF:0000033 | MODIFY | Summary: Refine axoneme assembly to the two supported arm-assembly processes. Reason: The valid ancestral assembly assertion is consistent with human loss of both outer and inner arms. These specific arm-assembly terms describe the demonstrated contribution more precisely than general axoneme construction. This does not claim that DNAAF1 assembles the microtubule doublets themselves. Official QuickGO is_a/part_of ancestor closures place both GO:0036158 and GO:0036159 under GO:0035082; these are genuine descendant refinements, unlike the separately retained motile-cilium term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002915666 SUPPORTS TRANSFER The saved IBD and current PANTHER tree place human leaf PTN000062877 below this node. The IBD and target descent support assembly; human dynein-subunit localization supplies a narrower target-level refinement. Proposed replacements: outer dynein arm assembly inner dynein arm assembly |
| GO:0035469 determination of pancreatic left/right asymmetry | IMP PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | KEEP AS NON CORE | Summary: Retain the pancreatic laterality context. Reason: The existing pancreatic-asymmetry assertion fits the ciliary left–right patterning phenotype. Patient situs inversus and zebrafish organ-position defects support a contextual developmental effect; no pancreas-specific biochemical function is inferred. |
| GO:0036158 outer dynein arm assembly | IMP PMID:19944400 Deletions and point mutations of LRRC50 cause primary ciliar... | ACCEPT | Summary: DNAAF1 supports outer dynein arm assembly. Reason: Patient cilia lose proximal and distal ODA components DNAH5, DNAH9 and DNAI2. Together with conserved preassembly experiments, this directly supports an outer-arm assembly contribution, not motor ATPase activity. |
| GO:0036159 inner dynein arm assembly | IMP PMID:19944400 Deletions and point mutations of LRRC50 cause primary ciliar... | ACCEPT | Summary: DNAAF1 supports inner dynein arm assembly in human cilia. Reason: DNALI1 is absent from patient axonemes while remaining cytoplasmic, and ultrastructure shows IDA loss. This supports assembly or delivery of inner arms. Protist mutants chiefly lacking ODAs do not erase the broader human phenotype. |
| GO:0044458 motile cilium assembly | IMP PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | ACCEPT | Summary: Dynein-arm assembly contributes to construction of the motile cilium. Reason: Human DNAAF1 loss disrupts assembly of both dynein-arm classes within recognizable cilia. Motile-cilium assembly includes building these functional structures and does not require complete absence of a cilium. Retain this supported motile-structure assertion: the checked QuickGO is_a/part_of hierarchy places outer- and inner-arm assembly under axoneme assembly, but not under GO:0044458, so those replacements would not preserve this claim. The specific arm-assembly activities remain independently represented. |
| GO:0060271 cilium assembly | IMP PMID:18385425 LRRC50, a conserved ciliary protein implicated in polycystic... | KEEP AS NON CORE | Summary: Retain broader ciliogenesis evidence from human renal cells. Reason: Two knockdown constructs in human HK-2 cells reduced ciliation; cilia that remained were shorter (Figure 6). This primary-cilium setting is broader than motile dynein-arm assembly, so replacing it with motile-cilium assembly would discard evidence. Its precise molecular mechanism remains unresolved. Supporting Evidence: |
| GO:0060287 epithelial cilium movement involved in determination of left/right asymmetry | IC PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | KEEP AS NON CORE | Summary: Retain the organizer-cilium laterality role. Reason: The curator combines ciliary movement and heart-looping evidence; human situs abnormalities and zebrafish organizer-cilium defects make this developmental connection coherent. It is retained as context rather than an additional core or a secreted-protein location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: GO:0003341 SUPPORTS TRANSFER The source movement assertion, together with GO:0001947 heart looping, supports the inferred organizer-cilium context; it does not establish an extracellular protein pool. |
| GO:0060972 left/right pattern formation | IMP PMID:19944400 Deletions and point mutations of LRRC50 cause primary ciliar... | KEEP AS NON CORE | Summary: Retain left–right pattern formation as a consequence of ciliary function. Reason: Laterality abnormalities in patients with dynein-arm defects support the existing process annotation. The mechanistic contribution remains dynein-arm assembly rather than a separate patterning signal or transcriptional program. |
| GO:0070286 axonemal dynein complex assembly | IMP PMID:19944400 Deletions and point mutations of LRRC50 cause primary ciliar... | MODIFY | Summary: Refine the dynein-complex assembly parent to both arm classes. Reason: Human observations resolve outer- and inner-arm defects. GO:0036158 and GO:0036159 are checked is_a children of GO:0070286; using both preserves the parent claim while adding supported specificity. The existing source identity is retained, and no duplicate NEW assertion is added. Proposed replacements: outer dynein arm assembly inner dynein arm assembly Supporting Evidence: |
| GO:0070286 axonemal dynein complex assembly | IMP PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | MODIFY | Summary: Refine the dynein-complex assembly parent to both arm classes. Reason: Human observations resolve outer- and inner-arm defects. GO:0036158 and GO:0036159 are checked is_a children of GO:0070286; using both preserves the parent claim while adding supported specificity. The existing source identity is retained, and no duplicate NEW assertion is added. Proposed replacements: outer dynein arm assembly inner dynein arm assembly Supporting Evidence: |
| GO:0070840 dynein complex binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain conserved dynein association without fixing a human binding mechanism. Reason: The 2008 Discussion cites positive Chlamydomonas Oda7 association with outer and I1 inner dyneins; the 2009 original independently discusses that association. The human and fish experiments in the cited 2008 study establish localization and assembly phenotypes, not a purified target interface. The curated inherited association remains biologically plausible and is retained; an exact dynein-binding mechanism is not required as the assembly core MF. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002915666 SUPPORTS TRANSFER The saved IBD and current PANTHER tree place human leaf PTN000062877 below this node. The dynein-binding IBD dated 2024-11-21 is grounded in human and zebrafish source annotations. Descent is valid; the positive ortholog association supports contextual retention, without interpreting perturbation data as a mapped human interface. |
| GO:0070840 dynein complex binding | IMP PMID:18385425 LRRC50, a conserved ciliary protein implicated in polycystic... | KEEP AS NON CORE | Summary: Retain conserved dynein association without fixing a human binding mechanism. Reason: The 2008 Discussion cites positive Chlamydomonas Oda7 association with outer and I1 inner dyneins; the 2009 original independently discusses that association. The human and fish experiments in the cited 2008 study establish localization and assembly phenotypes, not a purified target interface. The curated inherited association remains biologically plausible and is retained; an exact dynein-binding mechanism is not required as the assembly core MF. |
| GO:0071907 determination of digestive tract left/right asymmetry | IMP PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | KEEP AS NON CORE | Summary: Retain digestive tract laterality as developmental context. Reason: Human situs inversus and the zebrafish left–right phenotype support the existing digestive tract asymmetry assertion in a ciliary developmental context. This does not establish a distinct organ-specific molecular activity of DNAAF1. |
| GO:0071910 determination of liver left/right asymmetry | IMP PMID:19944405 Loss-of-function mutations in the human ortholog of Chlamydo... | KEEP AS NON CORE | Summary: Retain liver laterality as developmental context. Reason: Human situs inversus and the zebrafish left–right phenotype support the existing liver asymmetry assertion in a ciliary developmental context. This does not establish a distinct organ-specific molecular activity of DNAAF1. |
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Q: How does the human renal primary-cilium phenotype relate mechanistically to the established motile dynein-arm assembly function?
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