CFAP43 is a conserved axonemal protein with an N-terminal WD-repeat region and an extended C-terminal coiled-coil region. Together with CFAP44 it forms the tether/tether-head complex associated with inner dynein arm f and the doublet microtubule surface. Its structural integration links axonemal organization to coordinated ciliary beating. Human respiratory axoneme structures identify CFAP43 in this machinery, while human infertility and mouse loss-of-function studies establish a requirement for normal sperm flagellar architecture and motility. Respiratory cilia can remain assembled while their beat frequency and fluid transport are altered. The relative requirements for this complex vary across tissues and organisms, and the functional differences among the five human alternative products remain unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003341 cilium movement | IEA GO_REF:0000117 | ACCEPT | Summary: CFAP43 participates in the structural machinery that supports ciliary movement. Reason: The ARBA inference agrees with independent human axonemal structure and mammalian/protist functional evidence. In PMID:31884020, mouse tracheal loss of Cfap43 changes beating and reduces bead transport; PMID:29687140 shows altered Tetrahymena waveform despite retained cilia. CFAP43 contributes axonemal structure rather than supplying dynein ATPase activity. The historical ARBA rule was not reconstructed. |
| GO:0003356 regulation of cilium beat frequency | IEA GO_REF:0000107 | ACCEPT | Summary: The beat-frequency inference has an experimentally grounded mouse donor. Reason: The exact E9Q7R9 mouse donor carries the PMID:31884020 IMP for this term. Selected primary tracheal-imaging Methods and Movie S4/S5 legends report increased frequency but reduced fluid transport after Cfap43 loss in respiratory cilia that retain gross structure. The assignment has a structural basis beyond that phenotype: Tetrahymena fap43 disruption displaces retained I1 motor domains in PMID:29514928 Figure 4, and the native human structure identifies the conserved CFAP43-containing tether machinery. Together these support a conserved structural contribution to beat-frequency control within the motility core. The human assignment remains an ortholog inference; neither a direct human frequency assay nor a defined human frequency-setting interface was demonstrated. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:E9Q7R9 SUPPORTS TRANSFER Mouse Cfap43 identity and source annotations inspected; its Ensembl cross-reference is ENSMUSP00000125007.2. The original unversioned donor is preserved. Supporting Evidence: PMID:31884020 beating frequency of tracheal cilia PMID:29514928 stabilizing the position and assembly |
| GO:0003356 regulation of cilium beat frequency | ISS GO_REF:0000024 | ACCEPT | Summary: The manually transferred beat-frequency role is consistent with the mouse experiment. Reason: Mouse E9Q7R9 provides the original experimental grounding: PMID:31884020 measures altered tracheal frequency and flow after Cfap43 loss. Retain the curator's ISS assignment as a core facet of the conserved axonemal structural role, supported by the independent I1 positional-stability experiment and human tether structure. This synthesis links performed structural work to frequency modulation without claiming that the proposed algal powerstroke mechanism was directly tested in human. The electronic and manual transfer rows share the same mouse experiment and are not independent replications. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:E9Q7R9 SUPPORTS TRANSFER Mouse Cfap43 identity and source annotations inspected; its Ensembl cross-reference is ENSMUSP00000125007.2. The original unversioned donor is preserved. |
| GO:0005930 axoneme | IBA GO_REF:0000033 | ACCEPT | Summary: Axonemal structural activity is consistent with the ancestral inference. Reason: Human native respiratory-axoneme reconstruction in PMID:37258679 identifies CFAP43 in the conserved tether/tether-head docking machinery; the official 8J07 entity-81 mapping is to Q8NDM7. This provides target evidence for structural activity at the axoneme beyond localization alone. The original PAINT node and all WITH entities remain unchanged. Its historical node placement was not reconstructed, and donor count is not used to question the inference. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008557012 UNRESOLVED Historical PAINT node placement, alignment and complete IBD history were not reconstructed. No loss or misplaced-node claim is made. UniProtKB:E9Q7R9 SUPPORTS TRANSFER Mouse Cfap43 identity and source annotations inspected; its Ensembl cross-reference is ENSMUSP00000125007.2. The original unversioned donor is preserved. UniProtKB:Q580P9 SUPPORTS TRANSFER Exact Trypanosoma CFAP43 identity Tb927.4.5380 and endogenous tagged axonemal localization in PMID:29449551 were checked. UniProtKB:Q57YQ1 UNRESOLVED Current Tb927.8.6940 identity and axoneme annotation were checked; its exact relationship to the historical PAINT node was not reconstructed. |
| GO:0005930 axoneme | IEA GO_REF:0000120 | ACCEPT | Summary: The combined axoneme-location mapping agrees with human structural evidence. Reason: The selected UniProt subcellular mapping and mouse Cfap43 source are concordant with the native human Q8NDM7 structure in axonemal preparation 8J07. Retain located_in without converting it to a new qualifier or claiming purified microtubule binding from location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:E9Q7R9 SUPPORTS TRANSFER Mouse Cfap43 identity and source annotations inspected; its Ensembl cross-reference is ENSMUSP00000125007.2. The original unversioned donor is preserved. |
| GO:0005930 axoneme | ISS GO_REF:0000024 | ACCEPT | Summary: Axoneme localization is correct, although the preserved donor accession names CFAP44. Reason: Official UniProt Q57WH1 is Trypanosoma CFAP44/Tb927.7.3560, whereas the same paper identifies CFAP43 as Q580P9/Tb927.4.5380. PMID:29449551 directly localizes both tagged proteins to the axoneme; its target CFAP43 result and independent native human Q8NDM7 structure support the retained location. Preserve the original Q57WH1 field and disclose this donor-identity mismatch rather than silently repairing it or rejecting correct target biology. The historical transfer decision is unresolved; no claim is made that the paper omitted CFAP43. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q57WH1 SUPPORTS SOURCE BUT NOT TARGET Verified CFAP44 identity and source axoneme location. It is not the CFAP43 accession assayed in the same paper; the historical reason for its use in this ISS assertion was not established. |
| GO:0007288 sperm axoneme assembly | IBA GO_REF:0000033 | ACCEPT | Summary: The phylogenetic sperm-axoneme-assembly assertion agrees with target evidence. Reason: The original human CFAP43 IMP and mouse disruption experiments in PMID:29449551 establish defective sperm axonemal organization. Direct structural integration in the tether/tether-head complex provides a performed structural role. GO:0007288 includes assembly and organization, so the term is not limited to the first initiation step. Human Q8NDM7 in the WITH list is legitimate target evidence used by PAINT, not circularity. The ancestral node history remains uninspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008557012 UNRESOLVED Historical PAINT node placement, alignment and complete IBD history were not reconstructed. No loss or misplaced-node claim is made. UniProtKB:Q8NDM7 SUPPORTS TRANSFER The target itself has the preserved PMID:29449551 IMP; self-evidence can ground an ancestral inference. UniProtKB:Q96MT7 UNRESOLVED CFAP44 is a neighboring complex component; its presence in the original PAINT evidence is preserved without reconstructing every ancestral placement. |
| GO:0007288 sperm axoneme assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse Cfap43 provides direct experimental grounding for this assembly transfer. Reason: The E9Q7R9 source carries experimental sperm-axoneme-assembly annotations, including PMID:29449551. Mouse loss disrupts flagellar organization, while the same paper directly studies a human CFAP43-mutated patient. The transferred process is additionally coherent with CFAP43 structural incorporation; it does not imply that every axonemal subcomplex fails to assemble. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:E9Q7R9 SUPPORTS TRANSFER Mouse Cfap43 identity and source annotations inspected; its Ensembl cross-reference is ENSMUSP00000125007.2. The original unversioned donor is preserved. Supporting Evidence: |
| GO:0007288 sperm axoneme assembly | IMP PMID:29449551 Mutations in CFAP43 and CFAP44 cause male infertility and fl... | ACCEPT | Summary: The original human IMP supports sperm axoneme assembly and organization. Reason: PMID:29449551 Figure 2 examines sperm from a CFAP43-mutated patient by TEM and reports profound axonemal/periaxonemal disorganization and central-pair defects. Mouse Cfap43 disruption corroborates the architectural role in Figures 4–5. The paper does not establish that CFAP43 directly polymerizes tubulin or that every dynein arm is absent; those narrower activities are not inferred. Supporting Evidence: PMID:29449551 severe axonemal disorganization |
| GO:0007288 sperm axoneme assembly | ISS GO_REF:0000024 | ACCEPT | Summary: The curator-transferred assembly role agrees with mouse and human evidence. Reason: The exact mouse Cfap43 donor has experimental support, and the original human IMP is retained separately. Keep this source-specific ISS assertion as a conserved structural role; it is not an additional human experiment and does not imply uniform ciliogenesis failure in all cell types. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:E9Q7R9 SUPPORTS TRANSFER Mouse Cfap43 identity and source annotations inspected; its Ensembl cross-reference is ENSMUSP00000125007.2. The original unversioned donor is preserved. |
| GO:0030317 flagellated sperm motility | IEA GO_REF:0000107 | ACCEPT | Summary: CFAP43 supports motility of structurally organized sperm flagella. Reason: The mouse donor carries experimental sperm-motility evidence. PMID:29449551 reports immotile Cfap43-null sperm with severe flagellar architecture defects, alongside human multiple morphological abnormalities of sperm flagella. CFAP43 is part of the force-transmitting axonemal structure itself, so its assembly-dependent contribution to sperm movement is part of the structural motility core rather than merely a distant consequence. These sperm experiments do not isolate a beat-specific defect from the architecture defect or demonstrate intrinsic motor activity. GO:0030317 is a typed descendant of the core cilium-movement term GO:0003341; the core summary covers this sperm-specific manifestation without repeating that narrower process. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:E9Q7R9 SUPPORTS TRANSFER Mouse Cfap43 identity and source annotations inspected; its Ensembl cross-reference is ENSMUSP00000125007.2. The original unversioned donor is preserved. Supporting Evidence: |
| GO:0031514 motile cilium | IEA GO_REF:0000044 | ACCEPT | Summary: The motile-cilium mapping is consistent with the respiratory axonemal protein. Reason: Native human respiratory-axoneme reconstruction identifies Q8NDM7 in motile ciliary machinery, supporting the selected UniProt SL-0117 mapping. The motile cilium is the enclosing core compartment in which the more precise axonemal structural function operates. Retain this original broad CC assertion as ACCEPT alongside the axoneme and 9+2 location assertions: overlapping source granularity does not make a correctly localized core protein non-core. The compact core location uses axoneme, not an assertion that the enclosing motile cilium is peripheral. |
| GO:0097729 9+2 motile cilium | IEA GO_REF:0000107 | ACCEPT | Summary: Localization in 9+2 motile cilia has a verified mouse source and human corroboration. Reason: The exact E9Q7R9 donor carries PMID:31884020 IDA for this location. Human respiratory axonemes in PMID:37258679 independently identify CFAP43 in the corresponding motile-ciliary structure. Retain the ortholog-transfer evidence code and original donor rather than recasting the row as a human IDA. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:E9Q7R9 SUPPORTS TRANSFER Mouse Cfap43 identity and source annotations inspected; its Ensembl cross-reference is ENSMUSP00000125007.2. The original unversioned donor is preserved. |
| GO:0005200 structural constituent of cytoskeleton | IDA PMID:37258679 Axonemal structures reveal mechanoregulatory and disease mec... | NEW | Summary: CFAP43 contributes the structure of the axonemal tether/tether-head apparatus. Reason: The native human respiratory-axoneme structure identifies CFAP43 as part of the conserved tether/tether-head docking apparatus. Official PDBe 8J07 entity 81 maps to the 1665-residue Q8NDM7 canonical sequence (chains i6/i8); this is an experimentally constrained, AlphaFold-assisted structural model, not a purified binary-binding assay or proof that every residue is resolved. The detailed algal complex map and Tetrahymena fap43 loss of the tether/tether-head corroborate performed structural work. GO:0005200 directly describes that contribution. No equivalent MF is present in the 13-source seed, and no new process is proposed. Other human alternative products were not independently tested by this structure. Retain enables because GO:0005200 describes the structural contribution made by the CFAP43 molecule itself within the assembled complex; this does not assert autonomous assembly or transfer the dynein motor activity to CFAP43. |
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Download this section (compressed HTML)Q: How do the five human CFAP43 products differ in tether/tether-head incorporation and in respiratory versus sperm axonemes?
Q: Which CFAP43 surfaces couple tether deformation to dynein coordination, and which interactions are conserved between human cilia and protist models?
Q: Why does CFAP43 loss cause severe sperm axoneme disorganization while respiratory axonemes can retain gross structure but beat at an altered frequency?
Q: Should GO represent the structurally defined CFAP43-CFAP44 tether/tether-head apparatus with its own cellular-component complex term, and how should its relationship to inner dynein arm f and species-specific components be delimited?
Experiment: Introduce sequence-defined, expression-matched CFAP43 product rescues in human airway cultures, measuring axonemal incorporation, cryo-electron-tomographic architecture, ciliary waveform, beat frequency and bead transport separately.
Experiment: Test structure-guided CFAP43 interface substitutions that retain overall expression and ciliary entry, then measure tether/tether-head incorporation and dynein coordination. Compare these separation-of-function mutants with complete loss rather than inferring a motor mechanism from immotility alone.
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