DNAI1

Summary: Retain the spermatid manchette localization as a developmental context.

Reason: The literal mouse donor Q8C0M8 has IDA evidence from PMID:37352829. In wild-type elongating mouse spermatids, DNAI1 colocalizes with acetylated tubulin in the manchette; Cfap70 loss partly redistributes it. This supports the ortholog-based location without turning a transient spermatid pool into a separate human transport activity. The mature outer dynein arm remains the main functional setting.

Summary: Retain inherited participation in ciliary movement.

Reason: The actual IBD is at PTN000277955, the axonemal-intermediate-chain clade on the path to human leaf PTN002488192. Its descendant sources include human DNAI1 itself, mouse Dnai1 and trypanosome Q385R8. Human immotile-cilia and outer-arm-defect observations independently support the placement. Target self-evidence is legitimate experimental grounding, not circular propagation.

Summary: Retain the sequence-rule prediction of ciliary movement.

Reason: DNAI1 matches the actual ARBA00034388 condition set requiring FunFams 2.130.10.10:FF:000251 and 2.130.10.10:FF:000349 in Eutheria. The output agrees with direct human motility and arm-structure phenotypes. DNAI1 contributes as a component of the motile complex, without implying autonomous ATPase activity.

Summary: Retain ciliary movement as an established human DNAI1 role.

Reason: The accessible PMID:11231901 abstract establishes human DNAI1 mutations in PCD families; its detailed movement experiments remain inaccessible. The original PMID:10577904 directly reports immotile respiratory cilia lacking outer arms. Retain this clear gene-level function with curator deference for the particular IMP source, preserving its acts_upstream_of_or_within qualifier.

Summary: The unqualified motor-activity assertion exceeds the role established for this noncatalytic intermediate chain.

Reason: The human cloning, sequence and respiratory-ultrastructure experiments identify DNAI1 as an outer-arm intermediate chain whose loss disrupts the motor complex. The intermediate-chain identity and WD-repeat architecture support a structural interaction role in the motor complex, rather than identifying DNAI1 as the force-generating heavy chain. Refining GO:0003774 to GO:0003777 while retaining enables would preserve that excess claim. The imported qualifier remains unchanged as source metadata; the core separately records contribution to microtubule motor activity. The paper does not directly assay a human DNAI1 heavy- or light-chain interface, so those binding terms are not substituted on this source alone.

Summary: The BICD2 interaction is reported, but the identity of the assayed dynein intermediate chain remains unresolved.

Reason: The separately recovered full original uses tagged human BICD2 in SH-SY5Y cells and immunoprecipitates endogenous DIC with an Abcam mouse monoclonal antibody. Its read Methods do not give a clone or catalog number that identifies the precipitated chain as axonemal DNAI1. The official BICD2 record retains a DNAI1 interaction attribution, so the positive experiment is not discarded. Until the reagent or original target identity is resolved, neither a confident removal nor an adaptor-binding refinement is justified. The independent 74.1 identity proof for PMID:28057765 is not assumed to identify this unspecified antibody.

Summary: Refine the CFAP52 association to cytoskeletal protein binding.

Reason: The full original explicitly reports DNAI1 association with epitope-tagged CFAP52 in HEK293 cells and identifies DNAI1 in native porcine respiratory CFAP52 immunoprecipitates. CFAP52 is independently identified as a microtubule inner protein in the official Q8N1V2 record. GO:0008092 names binding to a protein component of a cytoskeleton and therefore supplies a supported partner class. These cellular co-immunoprecipitations establish association rather than a purified binary interface, and do not make DNAI1 an adenine-nucleotide enzyme or assign the CFAP45 mechanism to it. The cached UniProt Q9UI46 subunit statement independently corroborates the CFAP52 association; it does not change the assay's co-complex scope.

Proposed replacements: cytoskeletal protein binding

Summary: Refine the cytoplasmic pool to the directly observed dynein axonemal particle.

Reason: ARBA00026971 matches both DNAI1 FunFams and predicts cytoplasm. A merged mouse source also carries cytoplasm from PMID:28057765, but that donor experiment uses cytoplasmic dynein and is misassigned to Dnai1. Independent human lung-section staining in PMID:33263282 directly identifies DNAI1-positive cytoplasmic DynAPs, supporting this refinement despite the bad donor branch. Foci do not by themselves establish a diffuse soluble cytosolic pool.

Proposed replacements: dynein axonemal particle

Summary: Remove a centrosome transfer grounded in the wrong dynein intermediate-chain experiment.

Reason: The literal mouse Q8C0M8 donor carries an IDA centrosome annotation from PMID:28057765. Its full Methods identify rat EGFP-IC1B, Santa Cruz clone 74.1 and purified bovine-brain cytoplasmic dynein; the manufacturer identifies 74.1 targets as DYNC1I1/DYNC1I2. The insulin-responsive centrosomal observations concern cytoplasmic dynein, not axonemal DNAI1. This is a source-annotation identity error, not evidence that the mouse ortholog has diverged or that all periciliary DNAI1 pools are absent.

Summary: Refine the generic cytoskeleton mapping to axoneme.

Reason: The UniProt location mapping SL-0090 is compatible with DNAI1, but the human mature motor is an outer-arm component of ciliary and sperm axonemes. The specific axoneme location is directly supported by human DNAI1 staining and structural/clinical evidence and is already represented by another source row. No new assertion is created.

Proposed replacements: axoneme

Summary: Refine the original cytoskeletal placement to axoneme.

Reason: The cited human study identifies the axonemal intermediate-chain gene and links truncating variants to absent outer arms and immotile respiratory cilia. Later human DNAI1 immunostaining directly resolves the mature axonemal location. Axoneme is more informative than generic cytoskeleton; the inference does not assign a cytoplasmic transport-motor role.

Proposed replacements: axoneme

Summary: Preserve the HPA cilium observation in its measured cell context.

Reason: The actual HPA record reports supported staining in primary cilia of serum-starved hTERT-RPE1 cells, as well as sperm mid, principal and end pieces. Preserve that measured cilium location as a contextual observation. The inspected record text and assay metadata do not independently resolve the staining to the axonemal microtubule bundle within those cells, and individual fluorescence images were not assessed. Primary cilia do contain axonemes; the limitation here is sub-ciliary localization evidence, not a claim that axoneme implies motility or that the antibody is nonspecific.

Summary: Refine the established ciliary location to axoneme using independent human evidence.

Reason: PMID:27120127 remains abstract-only after a failed publisher attempt. Its GAS8 focus is not evidence of target misattribution. The official DNAI1 UniProt record explicitly attributes cilium-axoneme localization to this PMID, and independently read human lung and sperm studies directly place DNAI1 in axonemes. Together these support the gene-level refinement to GO:0005930. The curated source attribution is corroboration, not a claim that the exact DNAI1 panel in PMID:27120127 was personally verified.

Proposed replacements: axoneme

Summary: Refine the original cilium assertion to the axonemal motor location.

Reason: The original establishes a human axonemal intermediate chain and outer-arm loss in immotile respiratory cilia. Later direct human DNAI1 staining resolves axonemes within cilia. Use the existing specific axoneme term while retaining this TAS source and its provenance.

Proposed replacements: axoneme

Summary: Retain the mature axonemal location.

Reason: The SL-0304 mapping agrees with direct human lung-section DNAI1 staining and sperm-flagellum observations. This describes the mature outer-arm pool, distinct from the cytoplasmic DynAP pool.

Summary: Retain left-right patterning as a physiological consequence of motile-cilium function.

Reason: The actual ARBA00084643 conditions match the two DNAI1 FunFams in Vertebrata. Human DNAI1-associated PCD includes laterality defects, supporting this developmental context. The core molecular contribution is the outer-arm motor subunit, rather than a separate symmetry-specifying biochemical activity.

Summary: Retain the established laterality phenotype in DNAI1-associated PCD.

Reason: The accessible original abstract describes siblings or families with human DNAI1 mutations and differing situs, consistent with disrupted motile-cilium-dependent laterality. Detailed nodal experiments were not accessible. Retain the curated developmental role while distinguishing it from the mature motor mechanism.

Summary: Retain the clinically supported laterality context.

Reason: The actual abstract reports a systematic PCD cohort with heterotaxy and enrichment of DNAI1/DNAH5 mutations among patients with situs abnormalities. Full target-resolved tables were not recovered, so no DNAI1-specific numerical estimate or isolated embryological mechanism is asserted. This supports the established gene-level developmental role alongside independent DNAI1 family evidence.

Summary: Retain the laterality association without overstating the genetic evidence in this cohort.

Reason: The recovered original identifies heterotaxy patient 9002 with ciliary dysfunction and a single heterozygous DNAI1 founder variant; it explicitly reports no heterotaxy patient with two known PCD mutations and proposes a multigenic model. This study is contextual corroboration, not proof that one DNAI1 allele alone causes heterotaxy. Independent biallelic DNAI1 family evidence supports retaining the established laterality role.

Summary: Remove an insulin-pathway transfer based on cytoplasmic dynein identity.

Reason: The mouse Q8C0M8 donor IDA cites PMID:28057765, whose insulin/GSK3beta organelle-transport experiments use cytoplasmic dynein, rat EGFP-IC1B and the 74.1 cytoplasmic-intermediate-chain reagent. The manufacturer names DYNC1I1/DYNC1I2 as its targets. The experiment does not establish an insulin receptor signaling role for axonemal DNAI1, so the wrong source assignment should not propagate to human DNAI1.

Summary: Refine microtubule cytoskeleton to the directly supported axoneme.

Reason: ARBA00029268 genuinely matches both DNAI1 FunFams and outputs this broad cytoskeletal term. Human localization and outer-arm membership specify the mature axonemal compartment. The replacement does not convert a component of a microtubule-associated motor into an autonomous microtubule motor or infer centrosomal transport.

Proposed replacements: axoneme

Summary: Retain participation in flagellated sperm motility.

Reason: The particular PMID:11231901 sperm experiments remain inaccessible, but the curated assertion is consistent with DNAI1 outer-arm membership, independent human sperm localization and the clinical asthenozoospermia literature. Retain the clear gene-level motility role with source-specific curator deference, without claiming that the accessible abstract documents a purified sperm-motor assay.

Summary: Retain the established sperm-motility role while limiting this association study.

Reason: The abstract reports screening 90 men with isolated asthenozoospermia and 200 controls, with possible associations involving DNAI1, DNAH5 and DNAH11 and no detected axonemal ultrastructural anomaly. Full original access failed. This is not sufficient to establish a dominant DNAI1 mechanism, but it is compatible with the independently established axonemal role and direct human sperm localization. Retain the curated motility assertion without transferring the pooled three-gene counts to DNAI1.

Summary: Refine the supported motile-cilium location to 9+2 motile cilium.

Reason: The SL-0117 mapping correctly places DNAI1 in motile cilia. Human respiratory ultrastructure and direct DNAI1 staining in multiciliated airway-cell axonemes support the 9+2 motile-cilium type. GO:0097729 is a descendant of GO:0031514, whereas axoneme specifies the internal microtubule structure without retaining the motile-cilium type. Use GO:0097729 here and retain the separately supported axoneme annotation. This identifies the established respiratory pool without asserting that every DNAI1-positive cell compartment has that architecture.

Proposed replacements: 9+2 motile cilium

Summary: Retain direct human sperm-flagellum localization.

Reason: Although the paper centers on DNAH3, its full Results and Figure 5 supplement explicitly assay DNAI1 in human sperm and detect it along flagella in both controls and DNAH3-variant patients. Methods specify anti-DNAI1 Proteintech 12756-1-AP and fixed/permeabilized sperm immunofluorescence. The separately reported mouse experiment is not substituted for this human result.

Summary: Retain inherited outer-dynein-arm membership.

Reason: The IBD for GO:0036157 is on axonemal-intermediate-chain node PTN000277955, a verified ancestor of human DNAI1. Its human descendant evidence is legitimate and agrees with the original clinical/structural data. This is not circular merely because DNAI1 is listed in WITH/FROM.

Summary: Retain outer-arm membership with curator deference for the original source.

Reason: The source cache exposes only the PMID:11231901 abstract, but the gene-level claim is well established by the original human cloning study and subsequent mutation/ultrastructure studies. Retain the curated membership assertion; no isolated catalytic role follows from belonging to the complex.

Summary: Retain the outer-arm component assignment supported by human mutation/ultrastructure evidence.

Reason: The full original genotypes human PCD families and examines nasal epithelial ciliary ultrastructure. DNAI1 mutations occur with outer-arm defects, supporting the intermediate-chain assignment in combination with sequence and localization evidence. Uncertain monoallelic variants are discussed separately in the paper and do not define all DNAI1 biology.

Summary: Retain the inherited outer-arm assembly contribution.

Reason: The exact IBD at PTN000277955 lies on the DNAI1 lineage and is experimentally grounded in human DNAI1. The protein is a structural participant incorporated into the mature outer arm, and human variants impair arm-component assembly. Retain the existing process assertion without inventing a separate assembly-enzyme activity.

Summary: Retain the established structural contribution to outer-arm assembly.

Reason: Detailed PMID:11231901 experiments remain inaccessible, but independent human mutation studies demonstrate defective assembly/localization of outer-arm components. Curator deference is appropriate for this clear gene-level contribution; it is not an inference of chaperone or ATPase activity from disease necessity alone.

Summary: Retain source-specific disruption of outer-arm assembly.

Reason: The full original examines human respiratory cells from UNC119 with compound-heterozygous DNAI1 variants. DNAH5 remains proximally but is absent distally, and DNAH9 is absent from ciliary axonemes. These controlled localization observations support defective outer-arm assembly/deployment in the assayed context; they do not show that every DNAI1 variant abolishes all proximal arms.

Summary: Retain human evidence connecting DNAI1 to outer-arm assembly.

Reason: The full study combines DNAI1 genotyping, transcript analysis and nasal ciliary ultrastructure; disease-causing variants are associated with outer-arm defects. The structural subunit contributes to assembly of its own motor complex. This does not imply that DNAI1 is an autonomous folding factor or that every candidate missense variant is pathogenic.

Summary: Retain the demonstrated spatially restricted outer-arm assembly defect.

Reason: The full original analyzes human OP121-II1 cells carrying homozygous DNAI1 IVS1+2_3insT: DNAI2 signal is moderately retained proximally and lost distally. The explicit Results, Discussion and Figure 7 caption support this pattern; the abstract reverses proximal/distal disruption and a type-number label is inconsistent. Follow the measured spatial description without asserting uniform arm loss.

Summary: Retain the phylogenetically inferred light-chain-binding role.

Reason: The actual light-chain-binding IBD is at root node PTN000277823, a verified ancestor of DNAI1. Its mouse cytoplasmic-intermediate-chain, fly short-wing and human DYNC2I2 sources have direct experimental binding annotations. These sources span related dynein complexes, and the curator places the conserved intermediate-chain interaction role before their diversification. No target-specific loss or contrary axonemal interface evidence was found. Retain the class-level inference without claiming a particular human DNAI1 light-chain pair was measured here.

Summary: Retain the ancestral heavy-chain-binding role of the intermediate-chain family.

Reason: The exact IBD is at PTN000277823 on the human path. The literal Dictyostelium donor dicA/P54703 has experimental heavy-chain-binding annotations and is a cytoplasmic dynein intermediate chain. A different dynein compartment alone does not refute the ancient subunit-contact function placed at this ancestor. Human DNAI1 outer-arm membership is compatible with that role, and no target-specific divergence was established. This is a phylogenetic binding inference, not a newly measured human binary interaction.

Summary: Retain the supported 9+2 motile-cilium location.

Reason: The inspected ARBA00026414 condition set matches the two DNAI1 FunFams and the relevant taxonomic conditions, and the mouse ortholog mappings support the same ciliary context. Independently read human respiratory ultrastructure and DNAI1 axonemal staining substantiate the 9+2 motile-cilium location. Axoneme and 9+2 motile cilium describe different localization features; the separate axoneme assertion does not make this cilium-type assertion incorrect or redundant. Preserve the rule and ortholog provenance without treating their predictions as direct human assays.

Summary: Retain directly observed human DynAP localization.

Reason: Figure 7A text/caption and human-imaging Methods report DNAI1 antibody staining in primary human lung/tracheal sections, labeling both axonemes and cytoplasmic DynAPs. The Xenopus tagged Dnai1/Dnai2 experiments establish a separate sub-DynAP context. The human observation directly supports this EXP row, while assembly, storage and deployment roles of the condensate remain distinguished from a proven catalytic reaction inside it.

Summary: Retain the UniProt DynAP mapping.

Reason: SL-0542 maps the dynein axonemal particle, and the original human DNAI1 immunostaining independently supports that cytoplasmic compartment. It is an anatomical condensate location, not a new protein-complex membership or a separate molecular activity.