DNAI2

Summary: Inherited participation in ciliary motility.

Reason: The literal PAINT IBD places cilium movement at PTN000278033, an ancestor of the sequence-matched human DNAI2 leaf. Human DNAI2 experimental evidence is legitimately among the descendant evidence for this node; that is not circular. The intermediate chain contributes structure to the outer-arm motor rather than independently hydrolysing ATP. Human loss-of-function and arm defects in PMID:18950741 support the retained process.

Summary: A structural motor-complex contribution supports ciliary movement.

Reason: PMID:18950741 identifies human DNAI2 loss-of-function alleles, absent axonemal DNAI2 and outer-arm ultrastructural defects in respiratory cilia. DNAI2 is an incorporated intermediate chain of the motor, so its structural contribution supplies part of the machinery producing the ciliary beat. The process annotation does not assign heavy-chain ATPase chemistry to DNAI2.

Summary: The DNAI2 patient cohort supports a role in motile cilia.

Reason: Although PMID:23261302 foregrounds CCDC114, its Results also identify three unrelated individuals homozygous for the DNAI2 nonsense allele reported as p.Trp453* with isolated outer-arm defects. Exome sequencing, segregation and Sanger confirmation concern DNAI2 directly. This supports the motor-complex contribution to ciliary movement, without transferring the separate CCDC114 functional experiments to DNAI2.

Summary: Retain the motor-complex contribution, but distinguish it from autonomous motor activity.

Reason: GO:0003777 specifically denotes movement along a microtubule driven by ATP hydrolysis. DNAI2 is the noncatalytic intermediate chain of the outer-arm motor; the heavy chains supply its motor and ATPase domains, as distinguished in PMID:18950741. Thus an unqualified intrinsic motor activity exceeds the established DNAI2 mechanism, although its contribution to that activity is real and is represented in the integrated core. The original PMID:11153919 curator assertion is preserved; this judgment rests on the verified definition and subunit mechanism, not on absence of an assay from its accessible abstract.

Summary: Retain the targeted DNAI2–DNAAF5 association.

Reason: PMID:25232951 immunoprecipitated endogenous HEATR2/DNAAF5 (Q86Y56) from terminally differentiated human bronchial epithelial cultures at day 40 after air–liquid interface induction and detected DNAI2, with an isotype-matched control. This is a specific positive association in an assembly context, not a purified binary-affinity measurement or evidence that DNAI2 itself acts as a chaperone. No more informative partner-class MF is established, so retain the interaction as non-core under the scoped project instruction.

Summary: Retain the controlled human DNAAF6–DNAI2 co-immunoprecipitation.

Reason: PMID:28176794 tested tagged human PIH1D3/DNAAF6 (Q9NQM4) and DNAI2 in HEK293-family cells, confirmed association with swapped tags, and included empty-GFP controls; several DNAAF6 disease variants disrupted the assay. Methods specify an NM_023036 DNAI2 clone, but do not resolve the two current natural products by an independently matched sequence. The result supports association, not an intrinsic chaperone activity or a measured purified binding interface. Retain positive generic binding as non-core under the scoped project instruction.

Summary: Retain the cytoplasmic preassembly pool.

Reason: The mouse Dnai2/A2AC93 donor has direct PMID:29916806 cytoplasmic localization evidence. The same paper shows endogenous human DNAI2 in the cytoplasm of immature nasal epithelial cells and in axonemes of mature cells (Figure 3A), corroborating PMID:25232951. This broad pool is biologically real and not exclusively an axonemal location. Preserve it as contextual preassembly localization rather than reducing every diffuse cytoplasmic observation to the separately inferred DynAP compartment.

Summary: Specify the outer-arm dynein complex.

Reason: The original PMID:11153919 full experimental detail remains unavailable, so its broad complex assertion is not rejected. Independent human antibody localization, mutant heavy-chain incorporation and ultrastructure in PMID:18950741 establish that DNAI2 belongs to the outer dynein arm, the supported specific subtype of axonemal dynein complex. Use the existing GO:0036157 term without implying inner-arm membership.

Proposed replacements: outer dynein arm

Summary: Specify the supported 9+2 motile-cilium compartment.

Reason: The A2AC93 mouse ortholog source includes direct ciliary localization in PMID:29916806. Human respiratory axoneme and sperm-tail localization in PMID:18950741 independently supports the 9+2 motile-cilium class. This refines the broad cilium term using the observed compartments; it does not assert that DNAI2 is absent from all other ciliary architectures.

Proposed replacements: 9+2 motile cilium

Summary: Human DNAI2 localizes along respiratory axonemes.

Reason: PMID:18950741 validates the DNAI2 antibody with an approximately 69-kDa human respiratory-cell band and detects DNAI2 throughout respiratory ciliary axonemes. Axoneme describes the anatomical location, while outer-arm complex membership is represented separately; neither implies that DNAI2 is the heavy-chain ATPase.

Summary: The ARMC4 study directly visualizes DNAI2 in human axonemes.

Reason: PMID:23849778 examines DNAI2 with DNAH5 in human respiratory cilia. ARMC4-mutant cells retain the outer-arm proteins proximally but lose them distally, whereas control axonemes show their normal distribution (Figure 5 and Figures S5/S6). These target-specific images support the DNAI2 location even though the paper investigates ARMC4 disease. They do not assign ARMC4 function to DNAI2.

Summary: The combined automated axoneme assertion is experimentally corroborated.

Reason: The official DNAI2 record contains FunFams 2.130.10.10:FF:000371 and 2.130.10.10:FF:000380; together with the eukaryotic taxon conditions these satisfy the current ARBA00028382 branch. The location vocabulary SL-0304 and mouse donor route are concordant. Direct human localization in PMID:18950741 and PMID:23849778 supports the axonemal claim independently of the rule.

Summary: Retain axonemal localization with later direct human corroboration.

Reason: PMID:11153919 provides accessible human cloning and trachea/testis expression evidence, but its full Methods were not recovered. The existing experimental assertion is nevertheless independently established by human respiratory and sperm immunofluorescence in PMID:18950741. Accept the gene-level location with curator deference while keeping the two source-access scopes distinct.

Summary: Laterality is a downstream developmental consequence of the motile-cilium defect.

Reason: Among six affected individuals with DNAI2 mutations, PMID:18950741 reports two with situs solitus and four with situs inversus. This supports the existing laterality phenotype, plausibly through altered nodal flow, but the study does not establish an additional DNAI2 patterning or signaling mechanism. Retain the process as non-core beside the direct outer-arm motility role.

Summary: The mouse oocyte-surface observation is positive, but the precise human membrane-side transfer is unresolved.

Reason: The A2AC93 donor is an IDA annotation from PMID:18547164. Its complete abstract explicitly reports mouse Dnaic2 protein at the surface of secondary and antral oocytes; this is not a negative observation. GO:0009897 requires the extracellular-facing leaflet, including peripheral association. The full localization methods and topology controls were unavailable after bounded publisher-access attempts, and the corresponding human oocyte compartment has not been established in the inspected evidence. Retain uncertainty about this specific cross-species membrane-side assertion rather than rejecting it from DNAI2's ciliary role or from abstract silence.

Summary: DNAI2 is directly detected along human sperm flagella.

Reason: PMID:18950741 shows DNAI2 immunofluorescence along normal human sperm tails, with the source describing sperm preparation and antibody controls. This is direct localization evidence. The paper separately reports infertility in one affected male but explicitly lacks that patient's sperm analysis; no disease-specific sperm experiment is inferred.

Summary: Retain the experimentally grounded ancestral outer-arm membership.

Reason: The literal PTN000278033 IBD for GO:0036157 lies on the DNAI2 lineage and includes the target's human experimental annotation as valid grounding. The exact 605-residue target sequence is represented in the family alignment. Human localization and outer-arm defects in PMID:18950741 support inheritance of this intermediate-chain role, without evidence of a target-specific loss.

Summary: DNAI2 is an outer-dynein-arm intermediate chain.

Reason: Human respiratory cells lacking DNAI2 in PMID:18950741 lose or markedly reduce the outer-arm heavy chains DNAH5 and DNAH9, with ultrastructural outer-arm defects and retained DNALI1 inner-arm staining. Combined with normal DNAI2 localization, this establishes outer-arm membership rather than merely a generic ciliary phenotype.

Summary: The literal PAINT node supports conserved outer-arm assembly participation.

Reason: PTN000278033 carries an IBD for outer dynein arm assembly grounded in human DNAI2 and fly Dnai2/FBgn0036195. The target descends from that node. PMID:18950741 directly links the incorporated human intermediate chain to correct outer-arm organization; PMID:26608786 reports loss of outer arms in fly Dmdnai2-mutant auditory cilia. The fly experiment is a distinct ciliary context, not a human assay, and target self-inclusion is legitimate evidence.

Summary: The intermediate chain contributes structure to outer-arm assembly.

Reason: PMID:18950741 combines human DNAI2 loss-of-function, target immunolocalization, heavy-chain incorporation and transmission electron microscopy. DNAI2 is itself a component of the arm being organized, so it supplies structural participation in this assembly process rather than being only a remote necessity factor. The evidence does not identify DNAI2 as a folding enzyme or ATPase.

Summary: The DNAI2 cohort corroborates outer-arm assembly failure.

Reason: The DNAI2 p.Trp453* cohort in PMID:23261302 has isolated outer dynein arm defects. Together with the directly characterized intermediate-chain role in PMID:18950741, this supports the existing assembly annotation. The molecular and video experiments on CCDC114 elsewhere in the paper are not treated as DNAI2 experiments.

Summary: Retain ancestral dynein light-chain binding.

Reason: The recovered IBD places light-chain binding at the deep intermediate-chain node PTN000277823, from which DNAI2 descends. Grounding includes mouse Dync1i1, fly sw and human DYNC2I2/WDR34, with direct binding studies such as PMID:11914076 and PMID:25830415; these are distinct dynein systems, not human DNAI2 assays. The conserved intermediate-chain role and Xenopus Dnai2 light-chain copurification in PMID:33263282 are compatible with the curator's ancestral placement. No target-specific loss is established, and no particular human light-chain interface or affinity is invented.

Summary: Retain ancestral dynein heavy-chain binding.

Reason: The PTN000277823 IBD is grounded in Dictyostelium dicA/P54703 experiments (PMID:10336435 and PMID:10601339), and human DNAI2 is a descendant. The donor work concerns cytoplasmic dynein and does not establish a conserved atomic contact with axonemal heavy chains. Nevertheless, human DNAI2–DNAH5 proximity and mouse co-immunoprecipitation in PMID:29916806, together with Xenopus Dnai2 heavy-chain enrichment in PMID:33263282, corroborate the relevant association and structural role. Retain the broad binding class without transferring a donor-specific interface.

Summary: Refine cilium assembly to outer dynein arm assembly.

Reason: The broad PMID:11153919 assertion is retained in essence; incomplete access to that original is not evidence against it. Human DNAI2 data in PMID:18950741 establish the specific structural assembly step, outer dynein arm assembly (GO:0036158), which is a verified descendant of cilium assembly through the current is_a/part_of graph. This preserves the performed intermediate-chain role without implying a general ciliogenesis mechanism.

Proposed replacements: outer dynein arm assembly

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

Reason: The exact FunFam pair on human DNAI2 satisfies the current ARBA00026414 eukaryotic branch. Its combined evidence also includes the mouse Dnai2 donor, whose PMID:23525783 IDA is preserved without inventing individual target details from that abstract. Direct human respiratory-cilia and sperm-tail localization in PMID:18950741 independently establishes this anatomical class.

Summary: Retain the conserved DynAP preassembly localization.

Reason: The official location mapping and the literal Xenopus laevis Q4QR00 donor lead to direct tagged-Dnai2 imaging in PMID:30561330 and PMID:33263282. Xenopus Dnai2 concentrates in DynAPs, shows limited exchange compared with assembly factors, and occupies outer-arm-rich subregions. This supports the conserved preassembly location; it is not claimed as direct imaging of human DNAI2 in those experiments. Human cytoplasmic DNAI2 intermediates in PMID:25232951 and PMID:29916806 provide compatible independent context. The protein is a dynein client/subunit in this compartment, not thereby an assembly-factor chaperone.

Summary: Retain the conserved DynAP preassembly localization.

Reason: The official location mapping and the literal Xenopus laevis Q4QR00 donor lead to direct tagged-Dnai2 imaging in PMID:30561330 and PMID:33263282. Xenopus Dnai2 concentrates in DynAPs, shows limited exchange compared with assembly factors, and occupies outer-arm-rich subregions. This supports the conserved preassembly location; it is not claimed as direct imaging of human DNAI2 in those experiments. Human cytoplasmic DNAI2 intermediates in PMID:25232951 and PMID:29916806 provide compatible independent context. The protein is a dynein client/subunit in this compartment, not thereby an assembly-factor chaperone.