DNAAF11 is the current human symbol for LRRC6 (HGNC:16725; UniProt Q86X45). The review preserves all 53 imported annotation source objects, including their qualifiers, evidence types and supporting entities. Two raw records differing in annotation identifier/date normalize to the same final DynAP source row; no biological assertion was discarded.
The single core combines outer and inner dynein-arm assembly with correct localization of their components to motile cilia and participation in assembling the functional motile cilium. It includes the conserved cytosol assignment and directly imaged human airway DynAP location, with separate evidence for each. The evidence establishes participation in assembly and incorporation of axonemal arms, without demonstrating an autonomous LRRC6 motor, folding-chaperone, DNA-binding or transport activity. The three original short supporting quotations remain only in the YAML core. Additional short source-access anchors appear once in the appended notes.
| Primary source | Evidence and boundary |
|---|---|
| PMID:23122589(https://pubmed.ncbi.nlm.nih.gov/23122589/) | Human primary ciliary dyskinesia, dynein-arm ultrastructure and beating defects. Control nasal-brush LRRC6 staining occurs in cytoplasm and cilia; mutant loss provides a specificity control. |
| PMID:23527195(https://pubmed.ncbi.nlm.nih.gov/23527195/) | Human airway cultures and knockdown show loss of dynein arms while cilia remain. LRRC6 is cytoplasmic/basal-body-proximal and absent from axonemes in this preparation. Reduced dynein transcripts do not establish direct DNA binding by LRRC6. |
| PMID:33403504 / PMC7910352 | Separately indexed original Figure 2c supports human control sperm-flagellum staining with mutant loss. Figure 4 germ-cell cytoplasmic localization uses mouse, as stated in the Methods. The normal cache remains abstract-only. See Immunofluorescence staining Methods; Results on the loss-of-function variant and Figure 2c; and Results, Expression of LRRC6 in various germ cells, with Figure 4. These recovered text sections, not image reanalysis, supply the distinctions. A short original-only anchor appears in the notes. |
| PMID:30561330(https://elifesciences.org/articles/38497) | Results on conservation of DynAPs and the Figure 1 supplement identify endogenous human airway LRRC6/DNAI1 foci. Tagged colocalization and dynamic experiments are separately Xenopus; see the construct and immunofluorescence Methods. |
| PMID:33263282(https://elifesciences.org/articles/58662) | Tagged Xenopus LRRC6 and construct Methods corroborate DynAP organization. This is not an additional endogenous human localization experiment. |
| PMID:27353389(https://pubmed.ncbi.nlm.nih.gov/27353389/) | Complete abstract supports mouse outer-arm targeting defects despite preserved 9+2 architecture and IC1–IC2 association. Full text was not recovered. Direct MGI cytosol annotations on mouse O88978 remain curator-supported, including spermatocyte and spermatid IDA records. |
The positive human ciliary observations are preserved alongside the negative airway result. Their discrepancy does not justify deleting every ciliary annotation. Broad cilium is refined to motile cilium. Cytoplasm is refined using separate evidence for cytosol and DynAPs: germ-cell rows use the conserved cytosol assignment; broader target-level rows cover both locations without attributing a human airway condensate to the original germ-cell experiment or ancestral clade. These target-level replacements do not exhaust the cytoplasmic compartments in every original cell context. Existing cytosol transfers retain their curated mouse donor grounding. Human DynAP microscopy alone does not prove a separate soluble pool. The distributed signal in PMID:23527195 remains valid; it is not rewritten as exclusively punctate staining.
GO:0120293 is an intracellular membraneless organelle and cellular anatomical structure. It belongs in the core locations slot, not the protein-complex slot. Cytosol excludes organelles, so cytosol and DynAP are distinct locations, not an ancestor/descendant pair. The 2018 MCC-specificity experiment compares the examined mucociliary epithelial cell types; ectopic Foxj1 also induces solitary motile cilia with DynAPs. None of these experiments establishes a DynAP in the germ cells of the older papers. The extracellular-region electronic row instead conflates fluid-movement processes with the location of the gene product. Cilia move extracellular fluid without making the intracellular assembly factor extracellular. This judgment does not depend on absence of a secretion signal.
Three ZMYND10 sources remain positive with their experimental limits. PMID:23891469(https://pubmed.ncbi.nlm.nih.gov/23891469/) includes tagged human LRRC6–ZMYND10 association and CS-region interaction, with separate rat tissue and Xenopus experiments. The normal PMID:23891471(https://pmc.ncbi.nlm.nih.gov/articles/PMC3738835/) cache is abstract-only. The separately recovered primary Results beside Figure 4F/G and Figure S7 identify human cDNA two-hybrid tests and GST-ZMYND10 pull-down of in-vitro-translated Myc-LRRC6 with GST control; short exact anchors and section locators are in the follow-up notes. PMID:29601588(https://pubmed.ncbi.nlm.nih.gov/29601588/) supports ZMYND10-dependent stabilization of LRRC6. That direction is not inverted into autonomous LRRC6 folding activity.
PMID:29916806(https://elifesciences.org/articles/34389), Results on LRRC6 interaction and the cell-culture/transfection Methods, distinguishes negative endogenous mouse testis association from positive transient human LRRC6/mouse Zmynd10 assays. The proposed relay is a mechanistic model; it does not independently demonstrate LRRC6 protein folding. Failure to detect an endogenous pair in one context does not negate every positive tagged assay.
The SCRIB associations are IntAct EBI-9394895 from PMID:25036637(https://pubmed.ncbi.nlm.nih.gov/25036637/) and EBI-54631541 from PMID:33961781(https://pubmed.ncbi.nlm.nih.gov/33961781/). Both are human HEK293T anti-tag association experiments with C-terminally tagged LRRC6. They do not resolve a direct binary interface or demonstrate a polarity function for LRRC6. The available caches are marked full text but contain short extracts; this review does not claim access to every original target table or Methods section.
The nine HuRI pairs, PMID:32296183 were resolved against the literal IntAct records and exact protein sequence/taxon signatures. Each has positive validated two-hybrid evidence (MI:1356) plus pooled and array screen records. These are stages of one study. The main text reports quadruplicate retesting and sequence confirmation; no supplementary threshold or pair-specific orthogonal validation is assumed. Records can be retrieved through the IntAct PSICQUIC target query.
| Literal partner | Disposition and scope |
|---|---|
| P26196, DDX6, 483 aa | The validated EBI-24771467 pair supports DEAD/H-box RNA helicase binding. DDX6 identity and helicase domains establish the partner class; no RNA-helicase activity is transferred to LRRC6. |
| P54274-2, TERF1, 419 aa | Retain non-core binding. Telomeric-DNA and spindle roles do not supply a specific LRRC6 binding-function term; no absolute compartment incompatibility is asserted. |
| Q6FHY5, MEOX2 clone, 303 aa | The validated EBI-24407380 pair supports DNA-binding transcription factor binding. Exact comparison of the Q6FHY5 sequence with P50222 finds only deletion of canonical Q81, outside the homeobox at residues 187–246. The reviewed record distinguishes DNA-dependent CDKN1A activation from DNA-independent CDKN2A activation. The source accession remains Q6FHY5; no native LRRC6 transcriptional pathway is inferred. |
| Q6PF05, TTC23L, 361 aa | Retain non-core binding; TPR domains and centrosomal/spindle localization do not establish a more informative activity class. |
| Q7RTT5, SSX7, 188 aa | Retain non-core binding; proposed transcription modulation does not establish a DNA-binding transcription-factor class. |
| Q7Z5L7-3, podocan isoform 3, 661 aa | Retain non-core binding. This tested product is cytoplasmic; the secreted isoform 1 cannot be substituted to claim a compartment mismatch or extracellular-matrix function. |
| Q96II8-3, LRCH3 isoform 3, 712 aa | Retain non-core binding. Complex association supports a possible cytoskeletal role, but the partner's own activity remains tentative; a regulator-binding refinement would exceed that class evidence. |
| Q9H8W4, PLEKHF2, 249 aa | Retain non-core binding. PH/FYVE domains and endosomal trafficking do not establish an LRRC6 adaptor or receptor-regulatory activity. |
| Q9Y333, LSM2, 95 aa | Retain non-core binding. Association with an RNA-related complex does not itself establish RNA binding by LRRC6 or a more specific pair function. |
The exact current binding definitions describe the partner class, without requiring a demonstrated LRRC6 regulatory effect. The two class refinements describe qualitative capacity to bind the demonstrated partner class. TERF1 telomeric-DNA binding does not establish sequence-specific transcriptional regulation, while the tentative SSX7 transcription-modulator description does not establish a DNA-binding transcription-factor class. The MEOX2 clone classification is inferred from its exact sequence correspondence and preserved homeobox; no clone-specific transcription assay is claimed. These binding-class refinements do not require an established native pathway, and they do not prove that the interaction occurs in motile cilia. Positive associations without a supported finer term follow the project's generic-binding instruction.
The PANTHER PTHR18849 reconstruction places the human leaf below the cytoplasm IBD at PTN007663797 and the outer-arm-assembly IBD at PTN007663798. Both ancestral placements are valid. Human target evidence appearing among descendants is legitimate experimental grounding, not circularity; donor count is not used to grade the inference.
The explicit matching condition sets were checked for ARBA00026971, ARBA00028703, ARBA00047243, ARBA00090010, ARBA00091170 and ARBA00091714 through the UniProt ARBA rule service. The sequence/family matches do not turn infertility into proof of a direct reproductive-development mechanism. The combined electronic reference GO_REF:0000120 describes combined annotation methods; each source row is assessed for its biological role separately.
The two official products are 466 and 414 residues. The short product retains canonical residues 1–408, including the CS domain at 301–396; residues 409–414 are replaced and 415–466 are absent. It is not CS-deficient, and it is not equivalent to an experimental premature-stop construct. No assay here establishes equivalent function of both natural products.
PMID:10775177(https://pubmed.ncbi.nlm.nih.gov/10775177/) remains abstract-only: it identifies human and mouse cDNAs and reports mouse meiotic expression. Male-gonad and reproductive-development claims remain unresolved because expression and infertility do not resolve the molecular participation being asserted. PMID:37328841(https://pmc.ncbi.nlm.nih.gov/articles/PMC10273532/) reports mouse organoid and tagged HeLa evidence for FOXJ1 nuclear accumulation; its discussion leaves the direct connection unresolved. This is retained as mechanistic context, without adding a transport activity or a new process annotation.
The replacement of establishment of localization in cell (GO:0051649) by protein localization to motile cilium (GO:0120229) is lateral under current is_a/part_of ancestry. Human dynein-component mislocalization and the mouse targeting study support this process within the same assembly/incorporation core, without proving an autonomous transport mechanism. The FOXJ1 observations qualify the wider biogenesis context but leave the direct LRRC6 mechanism unresolved. A new molecular-function name is not proposed by merely relabeling that process as an assembly-factor activity.
Motile-cilium assembly (GO:0044458) is retained as ACCEPT and represented in the core alongside the arm-assembly processes. Its definition covers arranging components into a motile cilium; a projection lacking dynein arms does not negate LRRC6 participation. Current typed ancestry does not make it an ancestor of GO:0036158 or GO:0036159. The FOXJ1 study provides additional, mechanistically bounded biogenesis context rather than a reason to remove this existing process.