DNAL1

Summary: The source-specific ZMYND10–DNAL1 interaction remains unresolved.

Reason: The imported partner is ZMYND10 (O75800), and the current curated protein record also attributes a DNAL1 association to this reference. However, the inspected original Results, Figure 4, supplementary Figure S7 captions and expression/co-immunoprecipitation methods name DNAI1 for the relevant ZMYND10 binding and stability experiments. DNAL1 is mentioned in the background. The current IntAct and MINT queries did not recover this exact pair for this PMID, which is a retrieval limitation rather than evidence of nonbinding. Retain uncertainty about the DNAL1-specific experimental provenance; neither reject the positive curator assertion nor transfer the DNAI1 experiments to DNAL1.

Summary: HuRI supports a DNAL1–LRRC40 binary association.

Reason: Three literal HuRI records join human DNAL1 (Q4LDG9) to LRRC40 (Q9H9A6) for this PMID, including the validated two-hybrid record. Sequence hashes match the displayed 190-residue DNAL1 and 602-residue LRRC40 sequences. The target feature identifies residues 40–190 as sufficient for the tested association; this does not establish that the natural 151-residue isoform was tested. Retain the positive binding result as non-core under the scoped project policy. The screen does not establish an endogenous ciliary complex or a more informative functional role for this pair.

Summary: The axonemal location can be resolved to the outer dynein arm.

Reason: The UniProt SL-0304 mapping correctly places DNAL1 in the axoneme. The ortholog assignment, human dynein-heavy-chain association and outer-arm loss in DNAL1-associated primary ciliary dyskinesia support the more precise outer dynein arm location. That term is a verified part-of descendant of axoneme. This refinement retains the electronic source and does not assert exclusive localization or motor catalysis by the light chain. The replacement outer-dynein-arm term is already independently accepted in this review.

Proposed replacements: outer dynein arm

Summary: DNAL1 is an outer-arm dynein light-chain component.

Reason: The literal donor is Chlamydomonas reinhardtii LC1 (Q9XHH2), whose current experimental record supports outer-arm localization with this reference. The original establishes human DNAL1 association with DNAH5 using human EGFP-DNAL1 lysate and pig tracheal axonemal extract. Human disease-associated outer-arm defects independently corroborate the conserved structural role. Accept the orthology-based component assignment without presenting the mixed-species co-immunoprecipitation as direct human ultrastructural localization.

Summary: The inherited outer-arm assembly role is supported.

Reason: The actual PTHR15454 tree places human DNAL1 below the asserted Eumetazoa node PTN000833961, and the literal IBD record assigns outer dynein arm assembly there. The human sequence in the alignment exactly matches the displayed product. Human N150S disease, outer-arm loss and impaired heavy-chain association ground the structural assembly/stability role. The human target in WITH/FROM is legitimate experimental grounding of the ancestral assertion, not circular evidence.

Summary: DNAL1 helps establish a stable outer dynein arm.

Reason: The homozygous human N150S allele is associated with primary ciliary dyskinesia and loss of outer arms in the examined respiratory cilia. The same substitution reduces DNAL1 stability and its association with heavy-chain-containing axonemal material. Together with DNAL1 being an arm component, these observations support a structural contribution to assembly or stability rather than only a downstream motility phenotype. The experiment does not identify the temporal order of assembly steps.

Summary: The ancestral alpha-tubulin association is supported.

Reason: The literal alpha-tubulin-binding IBD is at PTN000833961 on the verified human lineage, with human experimental evidence among its descendant grounding. In the human-protein/rat-axoneme assay, alpha-tubulin co-precipitates with wild-type DNAL1 and substantially less with matched amounts of N150S DNAL1. Accept the conserved binding assertion while distinguishing association in axonemal extract from a purified binary interface or a measured human tether mechanism.

Summary: Wild-type DNAL1 associates with alpha-tubulin-containing axonemal material.

Reason: Human wild-type or N150S DNAL1-Myc expressed in HEK293T cells was mixed with rat tracheal high-salt axonemal extracts. After matching DNAL1 amounts, the mutant showed approximately 80% less co-precipitated alpha-tubulin and dynein heavy chain. These controlled data support the curated alpha-tubulin-binding role. They do not establish purified human binary affinity, simultaneous ternary bridging, or mechanosensing by human DNAL1. Alpha-tubulin identity is established by the anti-alpha-tubulin B-5-1-2 antibody (Abcam ab11304) in the original Figure 4C and associated Methods, rather than by the abstract's generic tubulin wording alone.

Summary: Conserved dynein-heavy-chain association is supported.

Reason: The dynein-heavy-chain-binding IBD at PTN000833961 lies on the reconstructed human lineage and is grounded by human experimental records. Independent human DNAL1 constructs associate with heavy chains in pig or rat axonemal extracts, with EGFP/background controls and an N150S-dependent reduction. This supports the inherited light-chain interaction role; it does not assign the heavy chain’s ATPase or motor activity to DNAL1.

Summary: Human DNAL1 associates with axonemal DNAH5.

Reason: The original uses the 190-residue human DNAL1 fused to EGFP and expressed in HEK293T cells. Its lysate was mixed with pig tracheal high-salt axonemal extract; anti-GFP precipitation recovered DNAH5 relative to the EGFP control. Accept specific heavy-chain binding at this assay scope. The experiment is neither a purified human pair nor a measurement of DNAL1 motor activity.

Summary: N150S impairs association with axonemal dynein heavy chain.

Reason: Wild-type human DNAL1-Myc co-precipitates a dynein heavy chain from rat tracheal axonemal extract, while the N150S construct gives markedly reduced recovery despite matching DNAL1 amounts. This supports a functional heavy-chain interaction relevant to outer-arm stability. The pathogenic substitution is not an experiment on either natural N-terminally shortened product, and the assay does not resolve a purified binding interface.