DNAAF4, also known as DYX1C1, is a CS-domain and tetratricopeptide-repeat protein that supports cytoplasmic preassembly of outer and inner axonemal dynein arms. It associates with DNAAF2, other assembly factors and protein-folding chaperones. Tagged Xenopus ortholog experiments support localization to dynein axonemal particles, where dyneins and chaperones concentrate. Deficient assembly impairs motile-ciliary beating and causes primary ciliary dyskinesia, often with laterality defects. DNAAF4 also has context-dependent nuclear and neuronal localization; cellular experiments support association with estrogen receptors and CHIP, accompanied by reduced estrogen-receptor abundance and signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001764 neuron migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the experimentally grounded rat neuronal-migration inference as a contextual role. Reason: The literal rat donor Q5VJS5 carries IMP evidence from PMID:16989952. Two rat shRNAs impair cortical migration and full-length rat rescue restores it, with mismatch and proliferation controls. This supports the conserved contextual role without establishing a human migration mechanism or assigning it to every natural product. Later conditional mouse experiments show no gross cortical lamination abnormality under different perturbation conditions; that does not erase the earlier rat result. Dynein-arm assembly remains the central molecular role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5VJS5 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. |
| GO:0003341 cilium movement | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain ciliary motility as the physiological consequence of dynein-arm assembly. Reason: The combined InterPro/Ensembl/mouse mapping is consistent with impaired ciliary beating after DNAAF4 loss. DNAAF4 supplies assembly-factor work before motor deployment; it is not the axonemal motor itself. Retain this established physiological output, while the existing outer- and inner-arm assembly annotations describe the core contribution. Human respiratory samples show variable residual proximal outer arms and occasional reduced beating, rather than universal loss of every arm. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8R368 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. ensembl:ENSMUSP00000034734 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. InterPro:IPR037894 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. Supporting Evidence: |
| GO:0003341 cilium movement | IMP PMID:23872636 DYX1C1 is required for axonemal dynein assembly and ciliary ... | KEEP AS NON CORE | Summary: Retain ciliary motility as the physiological consequence of dynein-arm assembly. Reason: The original human, mouse and zebrafish perturbation evidence is consistent with impaired ciliary beating after DNAAF4 loss. DNAAF4 supplies assembly-factor work before motor deployment; it is not the axonemal motor itself. Retain this established physiological output, while the existing outer- and inner-arm assembly annotations describe the core contribution. Human respiratory samples show variable residual proximal outer arms and occasional reduced beating, rather than universal loss of every arm. Supporting Evidence: |
| GO:0003351 epithelial cilium movement involved in extracellular fluid movement | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the ancestral epithelial-fluid-movement context. Reason: The actual Euteleostomi node PTN002925612 is an ancestor of human DNAAF4 and carries the literal IBD. The mouse donor has direct IMP grounding: PMID:25989970 reports immotile ventricular cilia by videomicroscopy. The zebrafish donor is present in the family and currently carries related cilium-driven flow evidence, although the exact historical GO:0003351 donor row was not recovered. Human ciliary dysfunction independently supports the transfer. Fluid movement is a physiological consequence of assembly, not an extracellular location or autonomous motor activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:1914935 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. PANTHER:PTN002925612 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. ZFIN:ZDB-GENE-040426-1892 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. |
| GO:0005515 protein binding | IPI PMID:19423554 Functional interaction of DYX1C1 with estrogen receptors sug... | MODIFY | Summary: Specify binding to a nuclear receptor. Reason: The original reports human ERalpha/DYX1C1 co-immunoprecipitation in SH-SY5Y cells and ligand-dependent cellular association, with domain-deletion and receptor controls. ESR1/P03372 is an established ligand-regulated nuclear receptor. GO:0016922 captures the partner class without assigning DNA binding or transcription-factor activity to DNAAF4. Co-immunoprecipitation supports association rather than a purified binary interface; the separate rat neurite proximity assay is not relabeled human. Proposed replacements: nuclear receptor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19423554 Functional interaction of DYX1C1 with estrogen receptors sug... | MODIFY | Summary: Specify binding to the E3 ubiquitin ligase CHIP/STUB1. Reason: PMID:19423554 reports CHIP/DYX1C1 co-immunoprecipitation in human SH-SY5Y cells: full-length and TPR-deleted DYX1C1 associate, whereas the p23-region deletion does not. The official Q9UNE7 record establishes CHIP as an E3 ubiquitin ligase, matching GO:0031625. The assay does not establish purified direct contact, DNAAF4 ubiquitin-transfer activity, or activation of CHIP itself. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | MODIFY | Summary: Specify binding to an ATG8-family ubiquitin-like protein. Reason: The exact human DNAAF4–GABARAP/O95166 record EBI-2946905 from PMID:20562859 is a positive GST pulldown of radiolabeled, reticulocyte-lysate-translated DNAAF4; it includes an ATG8 mutant annotated as decreasing interaction; separate tagged cellular associations are also present. Both participant sequence/taxon identifiers match the official records. The partner is an ATG8-family small conjugating protein, so GO:0032182 is more informative. This is not an inferred DNAAF4 autophagy-receptor, ubiquitin-ligase or conjugation activity, and the assay is not described as two purified proteins. Proposed replacements: ubiquitin-like protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | MODIFY | Summary: Specify binding to an ATG8-family ubiquitin-like protein. Reason: The exact human DNAAF4–GABARAPL2/P60520 record EBI-2947572 from PMID:20562859 is a positive GST pulldown of radiolabeled, reticulocyte-lysate-translated DNAAF4; it is complemented by a lysate-based GST pulldown. Both participant sequence/taxon identifiers match the official records. The partner is an ATG8-family small conjugating protein, so GO:0032182 is more informative. This is not an inferred DNAAF4 autophagy-receptor, ubiquitin-ligase or conjugation activity, and the assay is not described as two purified proteins. Proposed replacements: ubiquitin-like protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | MODIFY | Summary: Specify binding to an ATG8-family ubiquitin-like protein. Reason: The exact human DNAAF4–MAP1LC3C/Q9BXW4 record EBI-2948454 from PMID:20562859 is a positive GST pulldown of radiolabeled, reticulocyte-lysate-translated DNAAF4; it is complemented by a lysate-based GST pulldown. Both participant sequence/taxon identifiers match the official records. The partner is an ATG8-family small conjugating protein, so GO:0032182 is more informative. This is not an inferred DNAAF4 autophagy-receptor, ubiquitin-ligase or conjugation activity, and the assay is not described as two purified proteins. Proposed replacements: ubiquitin-like protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | MODIFY | Summary: Specify binding to an ATG8-family ubiquitin-like protein. Reason: The exact human DNAAF4–GABARAPL1/Q9H0R8 record EBI-2947293 from PMID:20562859 is a positive GST pulldown of radiolabeled, reticulocyte-lysate-translated DNAAF4; it is complemented by a tagged cellular association. Both participant sequence/taxon identifiers match the official records. The partner is an ATG8-family small conjugating protein, so GO:0032182 is more informative. This is not an inferred DNAAF4 autophagy-receptor, ubiquitin-ligase or conjugation activity, and the assay is not described as two purified proteins. Proposed replacements: ubiquitin-like protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23872636 DYX1C1 is required for axonemal dynein assembly and ciliary ... | KEEP AS NON CORE | Summary: Retain the targeted DNAAF2 assembly-factor interaction. Reason: Full-length pairwise yeast two-hybrid and tagged HEK293 co-immunoprecipitation establish the human DNAAF4–DNAAF2 interaction; PMID:29844425 independently finds strong association for experimental DYX1C1 iso-a. GO:0051087 concerns binding to a chaperone partner, not folding activity of DNAAF4. DNAAF2 is established here as an assembly factor and HSP-associated cofactor; these experiments do not establish that DNAAF2 itself recognizes nascent or unfolded clients as specified by that partner class. Retain this positive pair as non-core protein binding. Separate DNAAF4 associations with HSP70/HSP90 support the chaperone-binding core, without changing this source partner or implying a motor activity. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Specify binding to the cytoskeletal regulator SPDL1. Reason: The literal human DNAAF4–SPDL1 pair has validated two-hybrid evidence EBI-10596834 plus array/pooling records in PMID:25416956; both sequence identifiers match the official proteins. The main original specifies repeated pairwise tests and confirmed identity. SPDL1 is a dynein–dynactin activating adaptor involved in spindle orientation and kinetochore motor recruitment, supporting GO:0005519. This records qualitative binding capacity, without claiming that DNAAF4 regulates mitosis or forms an endogenous spindle complex. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28041644 Mutations in PIH1D3 Cause X-Linked Primary Ciliary Dyskinesi... | KEEP AS NON CORE | Summary: Retain the human DNAAF6/PIH1D3 interaction. Reason: PMID:28041644 tests sequence-confirmed human cDNAs by yeast two-hybrid and reciprocal tagged co-immunoprecipitation in HEK293T cells. PIH1D3/DNAAF6 precipitates DNAAF4 and vice versa. DNAAF6 participates in assembly and associates with HSP90; that does not by itself classify DNAAF6 as the nascent/unfolded-client-binding chaperone meant by GO:0051087. Retain the positive source-specific interaction as non-core protein binding. The chaperone-binding core is independently grounded in DNAAF4 association with HSP70/HSP90, not inferred from a requirement that DNAAF4 fold proteins autonomously. Supporting Evidence: PMID:28041644 PIH1D3 was consistantly able to precipitate DNAAF2/KTU and DNAAF4/DYX1C1 and vice versa |
| GO:0005515 protein binding | IPI PMID:29601588 ZMYND10 stabilizes intermediate chain proteins in the cytopl... | KEEP AS NON CORE | Summary: Retain the ZMYND10 association with its assay scope. Reason: PMID:29601588 Results and Figure S7E/F report tagged DYX1C1–ZMYND10 co-immunoprecipitation in HEK293T cells. The GST pulldowns of other network partners are not reassigned to this pair. ZMYND10-dependent client stabilization and HSC70 cooperation support an assembly/co-chaperone role, but do not resolve whether ZMYND10 recognizes nascent or unfolded clients in the sense required to classify this partner under GO:0051087. Retain the positive association as non-core protein binding, without claiming a purified direct interface. Lack of autonomous DNAAF4 folding activity is not a reason to reject chaperone binding; the core uses independently demonstrated HSP70/HSP90 associations. Supporting Evidence: |
| GO:0005576 extracellular region | IEA GO_REF:0000108 | REMOVE | Summary: Reject the process-to-extracellular-location inference. Reason: The electronic inference uses GO:0003351, which describes cilia moving extracellular fluid. The moved fluid is extracellular; that does not locate the intracellular assembly factor there. Human localization/fractionation and ortholog DynAP experiments place DNAAF4 in intracellular compartments. This source-role mismatch, rather than lack of a secretion signal or absence of literature, makes the extracellular-region assertion unsupported. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION COMPARTMENT OR COMPLEX MISMATCH Sources checked: GO:0003351 SUPPORTS SOURCE BUT NOT TARGET The extracellular fluid is the moved substrate; the process does not locate its intracellular assembly factor there. |
| GO:0005634 nucleus | EXP PMID:12954984 A candidate gene for developmental dyslexia encodes a nuclea... | KEEP AS NON CORE | Summary: Retain positive nuclear localization in the assayed human protein and tissue contexts. Reason: The separately accessed original shows full-length human DYX1C1-V5/His in monkey COS-1 nuclei and nuclear immunoreactivity in subsets of human cortical neurons and white-matter glia, with preimmune-serum controls. This is a positive context-specific location, not a demonstrated nuclear assembly function or a universal localization of all natural products. The normal publication cache remains abstract-only. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:16989952 DYX1C1 functions in neuronal migration in developing neocort... | KEEP AS NON CORE | Summary: Retain the human-construct nuclear observation with the processing caveat. Reason: The original tests full-length human DYX1C1 in COS-1 cells and reports nuclear staining in roughly half of cells with an N-terminal antibody, while C-terminal staining is cytoplasmic. Two approximately 24-kDa bands lead to a proposed cleavage model, not a resolved natural-isoform assignment. Rat tagged constructs and rat migration assays are separate. These limitations qualify the positive nuclear observation rather than proving it wrong. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:19423554 Functional interaction of DYX1C1 with estrogen receptors sug... | KEEP AS NON CORE | Summary: Retain ligand- and construct-dependent nuclear localization. Reason: The original human DYX1C1 construct is detected in nucleus and cytoplasm in COS-7 host cells; estradiol promotes nuclear punctate colocalization with estrogen receptors, whereas receptor/ligand controls change this behavior. This supports a nuclear pool in that context, without making the dynein assembly core nuclear or treating it as an endogenous human tissue experiment. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the mapped nuclear location as a secondary cellular context. Reason: The UniProt subcellular-location mapping is corroborated by human brain immunostaining and human-construct localization experiments. Their host, processing and ligand conditions differ, so nucleus is retained as a nonexclusive secondary location rather than assigned to every product or to the assembly core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. |
| GO:0005737 cytoplasm | EXP PMID:12954984 A candidate gene for developmental dyslexia encodes a nuclea... | MODIFY | Summary: Specify the supported cytosolic and DynAP locations, preserving the original context. Reason: The original detects cytoplasmic immunoreactivity in ischemic human brain and neuronal processes, with adjacent preimmune controls; no quantitative expression analysis was attempted. Independent human HPA ICC/IF explicitly supports cytosol, and tagged Xenopus DNAAF4 is localized to DynAPs in PMID:30561330. These are distinct gene-level refinements of cytoplasm, already represented by existing rows; neither the original microscopy nor DynAP foci alone is claimed to prove a diffuse soluble pool, and the ortholog experiment is not relabeled human. Proposed replacements: cytosol dynein axonemal particle |
| GO:0005737 cytoplasm | IDA PMID:16989952 DYX1C1 functions in neuronal migration in developing neocort... | MODIFY | Summary: Specify the supported cytosolic and DynAP locations, preserving the original context. Reason: The original human-construct COS-1 assays support a cytoplasmic pool, while rat tagged constructs and a proposed cleavage model have their own scope. Independent human HPA ICC/IF explicitly supports cytosol, and tagged Xenopus DNAAF4 is localized to DynAPs in PMID:30561330. These are distinct gene-level refinements of cytoplasm, already represented by existing rows; neither the original microscopy nor DynAP foci alone is claimed to prove a diffuse soluble pool, and the ortholog experiment is not relabeled human. Proposed replacements: cytosol dynein axonemal particle |
| GO:0005737 cytoplasm | IDA PMID:19423554 Functional interaction of DYX1C1 with estrogen receptors sug... | MODIFY | Summary: Specify the supported cytosolic and DynAP locations, preserving the original context. Reason: The original human DYX1C1 construct occupies cytoplasm as well as nucleus in COS-7 cells, with ligand-dependent nuclear association. Independent human HPA ICC/IF explicitly supports cytosol, and tagged Xenopus DNAAF4 is localized to DynAPs in PMID:30561330. These are distinct gene-level refinements of cytoplasm, already represented by existing rows; neither the original microscopy nor DynAP foci alone is claimed to prove a diffuse soluble pool, and the ortholog experiment is not relabeled human. Proposed replacements: cytosol dynein axonemal particle |
| GO:0005737 cytoplasm | IDA PMID:23872636 DYX1C1 is required for axonemal dynein assembly and ciliary ... | MODIFY | Summary: Specify the supported cytosolic and DynAP locations, preserving the original context. Reason: The original human respiratory-cell fractionation enriches DYX1C1 in cytoplasm with little axonemal signal; the respiratory imaging of Dyx1c1 itself is mouse. Independent human HPA ICC/IF explicitly supports cytosol, and tagged Xenopus DNAAF4 is localized to DynAPs in PMID:30561330. These are distinct gene-level refinements of cytoplasm, already represented by existing rows; neither the original microscopy nor DynAP foci alone is claimed to prove a diffuse soluble pool, and the ortholog experiment is not relabeled human. Proposed replacements: cytosol dynein axonemal particle |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Specify the supported cytosolic and DynAP locations, preserving the original context. Reason: The literal ARBA00026971 rule matches both target FunFam conditions and asserts cytoplasm; the combined mouse/Ensembl and UniProt location sources also support that broad intracellular placement. Independent human HPA ICC/IF explicitly supports cytosol, and tagged Xenopus DNAAF4 is localized to DynAPs in PMID:30561330. These are distinct gene-level refinements of cytoplasm, already represented by existing rows; neither the original microscopy nor DynAP foci alone is claimed to prove a diffuse soluble pool, and the ortholog experiment is not relabeled human. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00026971 SUPPORTS TRANSFER The underlying transfer or mapping is biologically supported; current term scope and independent compartment evidence justify the stated refinement. UniProtKB:Q8R368 SUPPORTS TRANSFER The underlying transfer or mapping is biologically supported; current term scope and independent compartment evidence justify the stated refinement. ensembl:ENSMUSP00000034734 SUPPORTS TRANSFER The underlying transfer or mapping is biologically supported; current term scope and independent compartment evidence justify the stated refinement. UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER The underlying transfer or mapping is biologically supported; current term scope and independent compartment evidence justify the stated refinement. Proposed replacements: cytosol dynein axonemal particle |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Accept the human HPA cytosol observation. Reason: The current HPA record for ENSG00000256061/DNAAF4 gives supported ICC/IF localization with cytosol as a main location. This directly supports the imported HPA source. It is nonexclusive: other cell-type-specific locations are recorded, and it does not collapse the membrane-free DynAP organelle into cytosol. Supporting Evidence: GO_REF:0000052 |
| GO:0007368 determination of left/right symmetry | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain left/right determination as a developmental consequence of motile-cilia assembly. Reason: The actual PTN002925612 ancestral IBD includes human, mouse and zebrafish evidence; the target is correctly within that clade, and target self-inclusion is legitimate. These data support a conserved contribution to laterality through properly functioning cilia, not a separate direct patterning, transcriptional or cardiac molecular activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:1914935 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. PANTHER:PTN002925612 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. UniProtKB:Q8WXU2 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. ZFIN:ZDB-GENE-040426-1892 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. |
| GO:0007368 determination of left/right symmetry | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain left/right determination as a developmental consequence of motile-cilia assembly. Reason: The mapped mouse ortholog Q8R368 has direct IMP laterality evidence, including PMID:23872636. These data support a conserved contribution to laterality through properly functioning cilia, not a separate direct patterning, transcriptional or cardiac molecular activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8R368 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. ensembl:ENSMUSP00000034734 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. |
| GO:0007368 determination of left/right symmetry | IMP PMID:23872636 DYX1C1 is required for axonemal dynein assembly and ciliary ... | KEEP AS NON CORE | Summary: Retain left/right determination as a developmental consequence of motile-cilia assembly. Reason: The cited original reports human situs abnormalities and mouse/zebrafish laterality effects alongside ciliary dysfunction. These data support a conserved contribution to laterality through properly functioning cilia, not a separate direct patterning, transcriptional or cardiac molecular activity. |
| GO:0007507 heart development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the phylogenetically supported cardiac-development context. Reason: PTN002925612 is the actual ancestral IBD node, with the mouse MGI donor carrying IMP evidence from PMID:25807483. The original genetic screen places Dyx1c1 among motile-cilia laterality/CHD genes. This supports a developmental contribution associated with ciliary laterality, without claiming a distinct cardiomyocyte mechanism. One well-grounded donor is not intrinsically weak evidence and the human lineage is within the annotated clade. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:1914935 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. PANTHER:PTN002925612 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. |
| GO:0030331 obsolete nuclear estrogen receptor binding | IBA GO_REF:0000033 | MODIFY | Summary: Replace the obsolete receptor-specific term with current nuclear receptor binding. Reason: The actual PTN002925612 IBD is on the human lineage and includes human and rat experimental grounding. Current official GO marks GO:0030331 obsolete and explicitly recommends GO:0016922, with estrogen receptor identified as the input. This is an ontology update, not a rejection of the observed biology or failed orthology. Preserve the imported source identifier; human co-immunoprecipitation and rat neurite proximity have different assay scopes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002925612 SUPPORTS TRANSFER The underlying transfer or mapping is biologically supported; current term scope and independent compartment evidence justify the stated refinement. RGD:1549760 SUPPORTS TRANSFER The underlying transfer or mapping is biologically supported; current term scope and independent compartment evidence justify the stated refinement. UniProtKB:Q8WXU2 SUPPORTS TRANSFER The underlying transfer or mapping is biologically supported; current term scope and independent compartment evidence justify the stated refinement. Proposed replacements: nuclear receptor binding Supporting Evidence: |
| GO:0030331 obsolete nuclear estrogen receptor binding | IDA PMID:19423554 Functional interaction of DYX1C1 with estrogen receptors sug... | MODIFY | Summary: Replace the obsolete receptor-specific term with current nuclear receptor binding. Reason: The cited original reports receptor association, domain dependence and reduced receptor abundance/signaling in the assayed cells. Current official GO marks GO:0030331 obsolete and explicitly recommends GO:0016922, with estrogen receptor identified as the input. This is an ontology update, not a rejection of the observed biology or failed orthology. Preserve the imported source identifier; human co-immunoprecipitation and rat neurite proximity have different assay scopes. Proposed replacements: nuclear receptor binding Supporting Evidence: |
| GO:0033146 regulation of intracellular estrogen receptor signaling pathway | IDA PMID:19423554 Functional interaction of DYX1C1 with estrogen receptors sug... | MODIFY | Summary: Specify negative regulation of estrogen-receptor signaling. Reason: The original shows that DYX1C1 overexpression lowers ERalpha/ERbeta protein and reduces estrogen-responsive reporter activity in human cell assays, with ligand/receptor and domain-deletion controls. These direction-resolved results support GO:0033147. They are retained as a contextual regulatory activity; they do not establish that DNAAF4 itself binds DNA, acts as a receptor, or physiologically controls all estrogen responses. Proposed replacements: negative regulation of intracellular estrogen receptor signaling pathway Supporting Evidence: PMID:19423554 resulting in decreased transcriptional responses to 17beta-estradiol. |
| GO:0036158 outer dynein arm assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Accept outer dynein-arm assembly as a core contribution. Reason: The literal eukaryotic IBD at PTN002925607 is on the human path and is grounded by mouse and target experimental annotations. DNAAF4 associates with other assembly factors in the cytoplasm and contributes to formation of outer arms before their axonemal deployment. Human outer-arm loss can vary by proximal/distal region; this does not weaken the assembly conclusion. No autonomous motor ATPase or intrinsic folding chemistry is inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:1914935 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. PANTHER:PTN002925607 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. UniProtKB:Q8WXU2 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. Supporting Evidence: |
| GO:0036158 outer dynein arm assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Accept outer dynein-arm assembly as a core contribution. Reason: The mouse ortholog transfer is corroborated by direct human and mouse loss-of-function evidence. DNAAF4 associates with other assembly factors in the cytoplasm and contributes to formation of outer arms before their axonemal deployment. Human outer-arm loss can vary by proximal/distal region; this does not weaken the assembly conclusion. No autonomous motor ATPase or intrinsic folding chemistry is inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8R368 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. ensembl:ENSMUSP00000034734 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. Supporting Evidence: |
| GO:0036158 outer dynein arm assembly | IMP PMID:23872636 DYX1C1 is required for axonemal dynein assembly and ciliary ... | ACCEPT | Summary: Accept outer dynein-arm assembly as a core contribution. Reason: The original directly connects DNAAF4 loss to defective dynein-arm formation while cilia and other axonemal structures remain. DNAAF4 associates with other assembly factors in the cytoplasm and contributes to formation of outer arms before their axonemal deployment. Human outer-arm loss can vary by proximal/distal region; this does not weaken the assembly conclusion. No autonomous motor ATPase or intrinsic folding chemistry is inferred. Supporting Evidence: |
| GO:0036159 inner dynein arm assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inner dynein-arm assembly as a core contribution. Reason: The literal eukaryotic IBD at PTN002925607 is on the human path and is grounded by mouse and target experimental annotations. DNAAF4 associates with other assembly factors in the cytoplasm and contributes to formation of inner arms before their axonemal deployment. Human outer-arm loss can vary by proximal/distal region; this does not weaken the assembly conclusion. No autonomous motor ATPase or intrinsic folding chemistry is inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:1914935 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. PANTHER:PTN002925607 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. UniProtKB:Q8WXU2 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. Supporting Evidence: |
| GO:0036159 inner dynein arm assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Accept inner dynein-arm assembly as a core contribution. Reason: The mouse ortholog transfer is corroborated by direct human and mouse loss-of-function evidence. DNAAF4 associates with other assembly factors in the cytoplasm and contributes to formation of inner arms before their axonemal deployment. Human outer-arm loss can vary by proximal/distal region; this does not weaken the assembly conclusion. No autonomous motor ATPase or intrinsic folding chemistry is inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8R368 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. ensembl:ENSMUSP00000034734 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. Supporting Evidence: |
| GO:0036159 inner dynein arm assembly | IMP PMID:23872636 DYX1C1 is required for axonemal dynein assembly and ciliary ... | ACCEPT | Summary: Accept inner dynein-arm assembly as a core contribution. Reason: The original directly connects DNAAF4 loss to defective dynein-arm formation while cilia and other axonemal structures remain. DNAAF4 associates with other assembly factors in the cytoplasm and contributes to formation of inner arms before their axonemal deployment. Human outer-arm loss can vary by proximal/distal region; this does not weaken the assembly conclusion. No autonomous motor ATPase or intrinsic folding chemistry is inferred. Supporting Evidence: |
| GO:0043005 neuron projection | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain contextual neuronal-process localization. Reason: The UniProt location mapping is independently compatible with human ischemic-brain neuronal-process staining in PMID:12954984 and endogenous rat neurite proximity signals in PMID:19423554. These observations support the broad neuronal projection location without identifying every process as axon or dendrite, proving a neuronal molecular mechanism, or transferring the result to all products. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0518 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. |
| GO:0061136 regulation of proteasomal protein catabolic process | IDA PMID:19423554 Functional interaction of DYX1C1 with estrogen receptors sug... | MODIFY | Summary: Specify positive regulation of proteasomal protein breakdown. Reason: The original reports DYX1C1-dependent reduction of ERalpha protein in human MCF-7 cells, with blockade by MG132 and loss of the effect after deleting the p23 region. These controlled results establish the positive direction for the measured proteasome-dependent breakdown. GO:1901800 is appropriate; direct ubiquitination catalysis by DNAAF4, CHIP activation and general proteasome activation are not established. Proposed replacements: positive regulation of proteasomal protein catabolic process Supporting Evidence: |
| GO:0120293 dynein axonemal particle | IEA GO_REF:0000044 | ACCEPT | Summary: Accept DynAP localization with explicit ortholog and construct scope. Reason: The UniProt subcellular-location mapping is consistent with the independently inspected ortholog experiment. Original Table 1 explicitly lists Dyx1C1/Dnaaf4 in DynAPs, and Table 2 reports its fluorescence recovery; Methods identify Xenopus cDNA-derived fluorescent constructs. This supports the conserved assembly compartment, not endogenous human DNAAF4 imaging or equivalence of every natural human product. GO:0120293 is a cellular anatomical entity and belongs in locations rather than in_complex. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0542 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. Supporting Evidence: |
| GO:0120293 dynein axonemal particle | ISS GO_REF:0000024 | ACCEPT | Summary: Accept DynAP localization with explicit ortholog and construct scope. Reason: The literal Q6AZN0 donor is Xenopus laevis dnaaf4 and carries direct IDA evidence from PMID:30561330. Original Table 1 explicitly lists Dyx1C1/Dnaaf4 in DynAPs, and Table 2 reports its fluorescence recovery; Methods identify Xenopus cDNA-derived fluorescent constructs. This supports the conserved assembly compartment, not endogenous human DNAAF4 imaging or equivalence of every natural human product. GO:0120293 is a cellular anatomical entity and belongs in locations rather than in_complex. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q6AZN0 SUPPORTS TRANSFER The actual source placement and experimental grounding are compatible with this core or contextual claim; the source-specific limits remain in the reason. Supporting Evidence: |
| GO:0051087 protein-folding chaperone binding | IPI PMID:29844425 The RPAP3-Cterminal domain identifies R2TP-like quaternary c... | NEW | Summary: Controlled human-cell experiments support DNAAF4 association with protein-folding chaperones. Reason: Human DYX1C1 constructs were tested with HSP70 and HSP90 in pairwise LUMIER co-immunoprecipitation assays in HEK293 cells. Unrelated-protein and no-antibody controls support specific association despite low co-IP efficiencies. This supplies the chaperone-binding assertion represented in the existing assembly core; it does not establish a purified direct interface, DNAAF4 folding activity or chaperone ATPase regulation. The assayed isoform labels are not assigned to official accessions without complete clone-sequence authentication. The imported DNAAF2, DNAAF6 and ZMYND10 source pairs remain distinct. Supporting Evidence: PMID:29844425 all the TPR-containing proteins interacted with HSP70, HSP90 and STIP1 |
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Download this section (compressed HTML)Q: Which endogenous cell types use DNAAF4-dependent estrogen-receptor regulation, and is that role mechanistically separate from dynein preassembly?
Q: How do the natural 381- and 376-residue products differ in dynein assembly, localization and stability beyond the paper-specific interaction assays?
Q: Does endogenous human DNAAF4 partition into DynAPs with the same dynamics as the tagged Xenopus protein?
Q: How do cell context, protein processing and perturbation timing explain the different nuclear-localization and neuronal-migration observations?
Experiment: Reconstitute human DNAAF4 with DNAAF2, HSP70/HSP90 and defined dynein clients. Measure direct association, chaperone ATP turnover, client solubility/folding and assembly as separate outputs, with no-DNAAF4 and chaperone-only controls. Compare contact-selective CS/TPR variants while checking their abundance and folding. Test whether the same variants rescue dynein-arm incorporation and beating in DNAAF4-deficient human airway cultures; a change in one output should not be assumed to establish the others.
Hypothesis: Specific DNAAF4 contacts with chaperones and assembly factors promote productive dynein preassembly.
Type: Defined biochemical reconstitution followed by human airway-cell rescue
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