DNAAF4 is the approved human symbol for DYX1C1 (HGNC:21493; UniProt Q8WXU2). Its central contribution is cytoplasmic preassembly of outer and inner axonemal dynein arms. Ciliary beating, extracellular-fluid movement and laterality are physiological consequences of that assembly work. The core includes binding to protein-folding chaperones, supported by controlled human HSP70/HSP90 associations. No autonomous motor ATPase or protein-folding reaction is assigned to DNAAF4.
Tarkar et al., PMID:23872636, selected Results and Methods, establishes dynein-arm defects despite preserved cilia and other axonemal structures. Human respiratory fractionation enriches DYX1C1 in cytoplasm; the paper's respiratory immunofluorescence of the target itself is mouse. Human outer-arm defects vary along the axoneme, with residual proximal arms in some samples. Full-length yeast two-hybrid and tagged HEK293 co-immunoprecipitation support the DNAAF2 interaction. The Results describe a mouse tracheal chaperone interactome, while the immunoprecipitation Methods specify mouse brain lysates; neither is a human tissue assay. HSP70/HSP90/CCT co-immunoprecipitation supports chaperone association, without establishing purified contact or an autonomous folding reaction.
Maurizy et al., PMID:29844425, Figure 4, Results and Methods, distinguishes DYX1C1 iso-a/DNAAF2 from iso-c/PIH1D3 associations. Its R2SD model contains SPAG1, DNAAF2 and RUVBL proteins and remains hypothetical; it is not the DYX1C1/DNAAF2 pair. PIH1D2 client-stabilization experiments are not transferred to DNAAF4.
Huizar et al., PMID:30561330, Table 1 explicitly lists Dyx1C1/Dnaaf4 in DynAPs and Table 2 reports its fluorescence recovery. The plasmid Methods identify Xenopus cDNA-derived fluorescent constructs. The normal publication text omits these table rows, which were checked in the original article XML. Human LRRC6 imaging in that paper is separate evidence and is not called human DNAAF4 imaging. DynAP is a membraneless cellular structure, so it is represented as a location, not a protein-containing complex.
The human HPA record independently reports supported cytosol localization. That evidence supports a cytosolic pool separately from DynAPs; the word cytoplasmic alone would not prove soluble cytosol. The broad cytoplasm annotations are refined to these two supported locations without claiming that every cited microscopy experiment resolved both.
Taipale et al., PMID:12954984, localization Methods and Figures 2–4, reports human DYX1C1 in transfected COS-1 nuclei and nuclear staining in subsets of human neurons and glia. Ischemic human brain also shows cytoplasmic and neuronal-process staining, with preimmune controls. These positive findings are retained; the genetic association study is not itself a molecular-function assay.
Wang et al., PMID:16989952, Results and Figure 3, distinguishes rat neuronal RNAi/rescue from human full-length protein expressed in COS-1. The latter produces different N- and C-terminal staining patterns and approximately 24-kDa bands. Cleavage is proposed rather than mapped to natural isoforms, and the authors could not resolve endogenous brain localization. Selected original text was accessed through the author-uploaded article; the normal cache remains abstract-only.
Massinen et al., PMID:19423554, Figures 1–4 and the construct, co-immunoprecipitation, reporter and proximity-assay Methods, supports estrogen-receptor/CHIP association and reduced receptor abundance and signaling. MG132 blocks the measured receptor loss. Human expression constructs in COS-7, MCF-7 and SH-SY5Y experiments are distinguished from endogenous rat neurite proximity signals. The separately accessed author-uploaded original supplies these sections while the normal cache remains abstract-only. This is a secondary regulatory role, not proof of DNAAF4 ubiquitin catalysis, DNA binding or an endogenous neuronal signaling mechanism.
Current GO:0030331 is obsolete and advises nuclear receptor binding, GO:0016922, with the estrogen receptor identified as input. Imported term IDs are preserved, with the replacement recorded in review fields. Direction-resolved reporter and MG132 experiments support negative estrogen-receptor signaling and positive proteasomal protein breakdown, respectively.
| Source | DNAAF4 partner | Evidence and interpretation |
|---|---|---|
| PMID:19423554(https://doi.org/10.1093/hmg/ddp215) | ESR1; CHIP/STUB1 | Controlled cellular association supports nuclear-receptor and E3-ligase binding classes. It is not purified binary-contact or DNAAF4 catalytic evidence. |
| PMID:20562859(https://doi.org/10.1038/nature09204) | GABARAP, GABARAPL2, MAP1LC3C, GABARAPL1 | Targeted GST pulldowns use radiolabeled reticulocyte-lysate-translated DNAAF4. Exact IntAct records EBI-2946905, EBI-2947572, EBI-2948454 and EBI-2947293 distinguish these tests from additional cellular associations. The partner class supports ubiquitin-like protein binding, not autophagy-receptor or conjugating activity. |
| PMID:25416956(https://doi.org/10.1016/j.cell.2014.10.050) | SPDL1 | EBI-10596834 is validated two-hybrid evidence, with array/pooling stages. The primary main text describes repeated pairwise testing and identity confirmation. Binding a cytoskeletal regulator does not establish a DNAAF4 mitotic role. |
| PMID:23872636(https://doi.org/10.1038/ng.2707) | DNAAF2 | Full-length pairwise yeast two-hybrid plus tagged human-host co-immunoprecipitation. Positive assembly-factor binding is retained. DNAAF2 participation and HSP association do not by themselves establish the nascent/unfolded-client-binding partner class in GO:0051087. |
| PMID:28041644(https://doi.org/10.1016/j.ajhg.2016.11.019) | DNAAF6/PIH1D3 | Target-resolved Figure 4 and Methods describe sequence-confirmed human cDNAs, yeast two-hybrid and reciprocal tagged co-immunoprecipitation. |
| PMID:29601588(https://doi.org/10.1371/journal.pgen.1007316) | ZMYND10 | Results and Figure S7E/F support tagged DYX1C1 association. GST validations of other partners are not assigned to this pair. |
The 13 available target-selected IntAct records match both participants' current sequence/taxon identifiers. An absent database record for another pair is not evidence against a positive original experiment. Supported generic interactions without a justified more specific class remain non-core under the project's standing curation instruction.
The actual PTHR46492 tree places human Q8WXU2 below the Euteleostomi IBD node PTN002925612 and the eukaryotic node PTN002925607. Six source IBDs were reconstructed. Human self-evidence and a single experimentally grounded donor are legitimate; neither is treated as circular or weak by itself.
Mouse PMID:25807483(https://doi.org/10.1038/nature14269), extended-data tables and phenotyping Methods, grounds the cardiac/laterality donor context. Mouse PMID:25989970(https://doi.org/10.1016/j.bandl.2015.04.008), Results section 3.1, directly reports immotile ventricular cilia after conditional forebrain loss, alongside preserved gross cortical lamination. These developmental observations do not require a separate cardiac or neuronal molecular core. The current zebrafish Q6P010 record contains related ciliary-flow evidence; the exact historical GO:0003351 donor row was not recovered, and is not invented.
ARBA00026971's actual target-matching condition set requires the two recorded FunFam assignments and supports cytoplasm. The extracellular-region inference is different: its source is the process of moving extracellular fluid, which does not locate the assembly factor outside the plasma membrane. Positive intracellular observations and the incorrect process/location role explain that removal.
Official sequences give Q8WXU2-1 at 420 residues, Q8WXU2-2 at 381 and Q8WXU2-3 at 376. All retain the N-terminal CS domain; shorter products alter the later TPR region and tail. Figure 4 of PMID:29844425 labels experimental iso-a420, iso-b376 and iso-c381. Thus the length/domain correspondence is a→1, c→2 and b→3; complete experimental-clone sequence authentication was not available. Co-immunoprecipitation efficiencies are not affinities, and no universal alternate-product inactivity is inferred.
Machine source files and cache availability flags are preserved. Normal caches for 12954984, 16989952 and 19423554 remain abstract-only despite separate original-section access. Publication 25807483's fresh normal cache exactly matches the existing source. The central 29844425 and DynAP 30561330 caches are reused unchanged from genuine prior fetches. Automated Falcon research and its configured fallback failed authentication/quota checks; the manual assessments above are not presented as provider-generated output.
GO:0051087 protein-folding chaperone binding describes binding to the chaperone partner. It does not assert that DNAAF4 itself performs folding. Human DYX1C1 constructs associate with HSP70/HSP90 in the controlled LUMIER experiments of PMID:29844425(https://doi.org/10.1038/s41467-018-04431-1), Results/Figure 4b and the cloning/LUMIER Methods. The cDNAs are human except the separate RUVBL1/2 constructs. Low co-IP efficiencies do not erase positive association, and they are not dissociation constants. Experimental iso-a is 420 residues; correspondence to the official canonical product is supported by length/domain organization rather than complete recovered clone sequence.
This chaperone-binding function belongs to the existing assembly core. It is grounded in the actual HSP partners, not obtained by relabeling the DNAAF2, DNAAF6 or ZMYND10 source pairs. Those assembly/co-chaperone partners are not automatically equivalent to the defined nascent/unfolded-client-binding class. A residual biological gap remains over direct client recognition, chaperone-cycle modulation and the step that enables productive dynein assembly. The review pairs that gap with a reconstitution and airway-cell rescue experiment; it does not borrow the PIH1D2/R2SP client assays as DNAAF4 evidence.
The original-section locators above remain applicable when the normal cache is abstract-only. This guide is retained for navigation and is not cited as experimental support. Original notes are preserved, with the superseding binding rationale appended separately.
One authored IPI annotation now records GO:0051087 from the human LUMIER evidence in PMID:29844425(https://doi.org/10.1038/s41467-018-04431-1), Results/Figure 4b and cloning/LUMIER Methods. This makes the established core claim available as an annotation while retaining its cellular-association and construct limits. The 42 imported assertions, core and three products are preserved. No partner from another experiment is substituted into those source records.
The DNAAF2, DNAAF6 and ZMYND10 generic-binding rows follow the project's explicit user instruction: supported interactions remain non-core when no evidence-backed more informative class is established. The general validator still reports advisory warnings for that deliberate project-level choice. The original notes and source provenance remain intact.