DNAH11 (dynein axonemal heavy chain 11) is a beta-type heavy chain of the outer dynein arm (ODA), the ATPase motor that powers ciliary beating by sliding outer doublet microtubules towards their minus ends. In human respiratory cilia DNAH11 is found only in the proximal part of the axoneme, where it forms proximal (type 1) ODAs with the gamma chain DNAH5; its paralog DNAH9 takes this place in distal ODAs. Its mouse orthologue, left-right dynein (lrd, Dnah11), is present in the motile monocilia of the embryonic node and is needed for the leftward nodal flow that breaks left-right symmetry; iv/iv mice carrying lrd mutations show randomized situs. DNAH11 interacts with CFAP45, which joins a proximal axonemal module with CFAP52 and adenylate kinase AK8 that is thought to regulate local adenine nucleotide levels. Biallelic loss-of-function variants cause primary ciliary dyskinesia 7 (CILD7). This is one of the commonest forms of PCD with normal ciliary ultrastructure on standard electron microscopy: tomography reveals only a partial proximal ODA loss, and cilia beat in a stiff, hyperkinetic pattern with reduced amplitude. Situs abnormalities are frequent. DNAH11 is not detected in the human sperm axoneme, and male fertility can be preserved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003356 regulation of cilium beat frequency | IMP PMID:18022865 Primary ciliary dyskinesia associated with normal axoneme ul... | MODIFY | Summary: DNAH11-mutant respiratory cilia have normal ultrastructure but a stiff, hyperkinetic beat with reduced bending. Reason: The phenotype is real and distinctive, but it reflects loss of the proximal ODA motor rather than a regulatory activity of DNAH11: DNAH11 is a force-generating motor subunit, not a regulator of beat frequency. The process these IMP data actually support is the motility itself, so the term is replaced with epithelial cilium movement involved in extracellular fluid movement, the same replacement used for the GO:0060294 row and the process in core_functions. DNAH11 has no cilium movement row in GOA, so this replacement carries the real process onto the gene. Proposed replacements: epithelial cilium movement involved in extracellular fluid movement Supporting Evidence: PMID:18022865 Respiratory ciliated cells from the affected individuals showed an abnormal nonflexible beating pattern with a reduced cilium bending capacity and a hyperkinetic beat. |
| GO:0003356 regulation of cilium beat frequency | IMP PMID:22184204 Mutations of DNAH11 in patients with primary ciliary dyskine... | MODIFY | Summary: All tested patients with biallelic DNAH11 mutations had a hyperkinetic beat with reduced waveform amplitude. Reason: As for the PMID:18022865 row: a characteristic loss-of-function phenotype of the respiratory-cilium motor, not evidence that DNAH11 regulates beat frequency. Replaced with epithelial cilium movement involved in extracellular fluid movement, the process the data support. Proposed replacements: epithelial cilium movement involved in extracellular fluid movement Supporting Evidence: PMID:22184204 Each of the 14 patients (11 families) with biallelic mutations in DNAH11 that were tested by videomicroscopy had the characteristic hyperkinetic beating pattern and reduced waveform amplitude, as previously reported |
| GO:0003356 regulation of cilium beat frequency | IMP PMID:22499950 High prevalence of respiratory ciliary dysfunction in congen... | MODIFY | Summary: A heterotaxy patient with two DNAH11 mutations had a hyperkinetic ciliary beat. Reason: Single case consistent with the larger studies. The hyperkinetic beat is a loss-of-function phenotype of the ODA motor, not a regulatory activity, so the term is replaced with epithelial cilium movement involved in extracellular fluid movement, as for the other GO:0003356 rows. Proposed replacements: epithelial cilium movement involved in extracellular fluid movement Supporting Evidence: PMID:22499950 Another with hyperkinetic ciliary beat had 2 mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based ATP binding from the dynein heavy chain AAA+ motor domain. Reason: Correct: the DNAH11 motor head carries the AAA1 P-loop that binds and hydrolyses ATP, but ATP binding is a generic part of the motor activity captured by the microtubule motor activity annotations. Supporting Evidence: file:human/DNAH11/DNAH11-uniprot.txt Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function. |
| GO:0005929 cilium | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of cilium. Reason: Correct but general; more specific terms are annotated. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia |
| GO:0005930 axoneme | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT annotation (node PTN000073047) placing the axonemal outer-arm beta heavy chains in the axoneme. Reason: Consistent with direct immunofluorescence of DNAH11 in respiratory ciliary axonemes. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia |
| GO:0005930 axoneme | IDA PMID:31178125 Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Oute... | ACCEPT | Summary: DNAH11 is found along the respiratory ciliary axoneme but not along the sperm axoneme. Reason: Direct localization in respiratory cilia. Supporting Evidence: PMID:31178125 We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with Ξ±-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia |
| GO:0005930 axoneme | IEA GO_REF:0000120 | ACCEPT | Summary: Combined electronic annotation of axoneme. Reason: Agrees with the IDA annotations. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia |
| GO:0007017 microtubule-based process | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA prediction of microtubule-based process. Reason: True but uninformative: microtubule-based process is entailed by the cilium movement process asserted elsewhere in this review, which is the specific process this motor drives. Supporting Evidence: PMID:31178125 the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro mapping to microtubule-based movement. Reason: True but very general: the movement produced by this motor is microtubule sliding within the axoneme, and microtubule-based movement is entailed by the cilium movement process asserted elsewhere in this review. Supporting Evidence: PMID:31178125 the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating |
| GO:0007368 determination of left/right symmetry | IMP PMID:12142464 Mutations in the DNAH11 (axonemal heavy chain dynein type 11... | ACCEPT | Summary: A homozygous DNAH11 nonsense mutation in a patient with situs inversus totalis; DNAH11 is the human orthologue of mouse lrd (Dnah11), mutated in iv/iv mice. Reason: Left-right determination is a defining role of DNAH11, mediated by motile nodal cilia (lrd is required for nodal flow in mouse). acts_upstream_of_or_within is the correct qualifier. Supporting Evidence: PMID:12142464 We conclude that mutations in the coding region of DNAH11 account for situs inversus totalis and probably a minority of cases of PCD. PMID:12859898 Nodal flow is generated by motile node cell monocilia and requires the axonemal dynein, left-right dynein (lrd). |
| GO:0007368 determination of left/right symmetry | IMP PMID:18022865 Primary ciliary dyskinesia associated with normal axoneme ul... | ACCEPT | Summary: Family with DNAH11 compound heterozygous truncating mutations including a member with Kartagener syndrome (situs inversus). Reason: Consistent with the laterality role of DNAH11. Supporting Evidence: PMID:18022865 In conclusion, our findings support the view that DNAH11 mutations indeed cause PCD and KS |
| GO:0007368 determination of left/right symmetry | IMP PMID:22184204 Mutations of DNAH11 in patients with primary ciliary dyskine... | ACCEPT | Summary: Most families with biallelic DNAH11 mutations include a patient with situs abnormalities. Reason: Supports the laterality role. Supporting Evidence: PMID:22184204 Most of the 15 families with biallelic mutations had a PCD patient with situs abnormalities (13/15) |
| GO:0007368 determination of left/right symmetry | IMP PMID:22499950 High prevalence of respiratory ciliary dysfunction in congen... | ACCEPT | Summary: A heterotaxy patient with congenital heart disease carried two DNAH11 mutations. Reason: Consistent with the laterality role. Supporting Evidence: PMID:22499950 Another with hyperkinetic ciliary beat had 2 mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. |
| GO:0008569 minus-end-directed microtubule motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT places minus-end-directed motor activity at the deep dynein heavy chain node PTN000743491, grounded in experimental data for cytoplasmic and axonemal dyneins from yeast, Dictyostelium and C. elegans. Reason: DNAH11 sits inside this clade and retains an intact motor domain, so there is no reason to think the inherited activity was lost. This is the core molecular function of an outer dynein arm heavy chain. Supporting Evidence: file:human/DNAH11/DNAH11-uniprot.txt Produces force towards the minus ends of microtubules PMID:31178125 the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating |
| GO:0008569 minus-end-directed microtubule motor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping of the dynein heavy chain motor domain to minus-end-directed microtubule motor activity. Reason: DNAH11 is a full-length outer dynein arm heavy chain with all six AAA modules and a stalk ending in a microtubule-binding domain. Axonemal dyneins walk towards microtubule minus ends, which is what drives sliding of adjacent doublets. Consistent with the IBA and with the ODA-loss phenotypes. Supporting Evidence: file:human/DNAH11/DNAH11-uniprot.txt Produces force towards the minus ends of microtubules PMID:31178125 the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating |
| GO:0030286 dynein complex | IBA GO_REF:0000033 | MODIFY | Summary: PAINT annotation of dynein complex at the deep dynein heavy chain node. Reason: Correct but too general. The PAINT tree places the outer-arm gamma heavy chain (DNAH5) under an outer dynein arm node, but the beta heavy chains DNAH9 and DNAH11 receive only the generic dynein complex term. The specific complex for DNAH11 is the outer dynein arm. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000743491 Β· PTN000743491 SUPPORTS TRANSFER Dynein complex membership is correct for all descendants but less specific than outer dynein arm. Proposed replacements: outer dynein arm Supporting Evidence: PMID:31178125 However, the contribution of the different HCs (Ξ³-type: DNAH5 and DNAH8 and Ξ²-type: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. |
| GO:0030286 dynein complex | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to the generic dynein complex. Reason: Correct but too general. DNAH11 is a heavy chain of the axonemal outer dynein arm. Proposed replacements: outer dynein arm Supporting Evidence: PMID:31178125 However, the contribution of the different HCs (Ξ³-type: DNAH5 and DNAH8 and Ξ²-type: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. |
| GO:0030317 flagellated sperm motility | IMP PMID:18492703 Mutations in dynein genes in patients affected by isolated n... | MARK AS OVER ANNOTATED | Summary: A heterozygous, maternally inherited DNAH11 variant was associated with isolated asthenozoospermia. Reason: Weak genetic evidence (single heterozygous variants, no functional test). DNAH11 is not detected along the human sperm axoneme, and men with biallelic truncating DNAH11 mutations can be fertile, so a role in sperm motility is unlikely. Supporting Evidence: PMID:18492703 We found three mutations (one in each gene) specifically associated with AZS in seven patients (7.8%). PMID:18022865 the reported DNAH11 nonsense mutations are associated with a normal axonemal ultrastructure and are compatible with normal male fertility PMID:31178125 We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with Ξ±-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia |
| GO:0031514 motile cilium | IDA PMID:31178125 Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Oute... | ACCEPT | Summary: DNAH11 is present in respiratory motile cilia. Reason: Correct; more specific terms also apply. Supporting Evidence: PMID:31178125 We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with Ξ±-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia |
| GO:0031514 motile cilium | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of motile cilium. Reason: Correct but general. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia |
| GO:0045505 dynein intermediate chain binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT annotation at node PTN000743491, grounded in Dictyostelium cytoplasmic dynein heavy chain data. Reason: The axonemal ODA heavy chains also assemble with intermediate chains (DNAI1/DNAI2), so placing the function at the shared dynein heavy chain node is defensible for this branch. Kept as a structural, non-core binding activity. Supporting Evidence: file:human/DNAH11/DNAH11-uniprot.txt Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains |
| GO:0045505 dynein intermediate chain binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro (IPR026983, dynein heavy chain family) mapping to dynein intermediate chain binding. Reason: Outer dynein arms contain the intermediate chains DNAI1 and DNAI2 bound to the heavy-chain tails, so the binding is plausible. It is a structural interaction within the complex rather than the protein's primary activity. Supporting Evidence: file:human/DNAH11/DNAH11-uniprot.txt Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains |
| GO:0051959 dynein light intermediate chain binding | IBA GO_REF:0000033 | REMOVE | Summary: PAINT places light intermediate chain binding at the deep dynein heavy chain node PTN000743491. All the descendant experimental evidence comes from cytoplasmic dynein 1 heavy chain (human DYNC1H1, mouse and rat Dync1h1). Reason: Premise: the outer dynein arm contains no light intermediate chain subunit. It is built from heavy, intermediate and light chains (UniProt SUBUNIT, quoted below), whereas light intermediate chains (DYNC1LI1/2, DYNC2LI1) are subunits of cytoplasmic dyneins. An ODA heavy chain therefore has no light intermediate chain partner to bind, so the claim is not merely under-evidenced but unlikely to be correct. The PAINT node is too deep for this function: every WITH/FROM donor is a cytoplasmic dynein 1 heavy chain, and the axonemal ODA heavy-chain branch should not inherit the activity. This is an electronic inference contradicted on structural grounds, so REMOVE rather than MARK_AS_OVER_ANNOTATED. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000743491 Β· PTN000743491 SUPPORTS SOURCE BUT NOT TARGET Deep dynein heavy chain node; light intermediate chain binding is grounded only in cytoplasmic dynein 1 heavy chains. UniProtKB:Q14204 Β· DYNC1H1 SUPPORTS SOURCE BUT NOT TARGET Cytoplasmic dynein 1 heavy chain binds DYNC1LI1/2; axonemal outer arm dyneins have no LIC subunit. Supporting Evidence: file:human/DNAH11/DNAH11-uniprot.txt Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains |
| GO:0051959 dynein light intermediate chain binding | IEA GO_REF:0000002 | REMOVE | Summary: InterPro family mapping to dynein light intermediate chain binding. Reason: Premise: the outer dynein arm contains no light intermediate chain subunit. It is built from heavy, intermediate and light chains (UniProt SUBUNIT, quoted below), whereas light intermediate chains (DYNC1LI1/2, DYNC2LI1) are subunits of cytoplasmic dyneins. The InterPro family mapping therefore transfers a cytoplasmic-dynein interaction to an axonemal heavy chain that has no light intermediate chain partner; the claim is unlikely to be correct, not merely under-supported, so it is removed. Supporting Evidence: file:human/DNAH11/DNAH11-uniprot.txt Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains |
| GO:0060294 cilium movement involved in cell motility | IBA GO_REF:0000033 | MODIFY | Summary: PAINT annotation of cilium movement involved in cell motility at node PTN000743491, grounded largely in sperm-flagellar and protist dynein heavy chains. Reason: The node placement is reasonable for the dynein family as a whole, but DNAH11 is a respiratory-type outer dynein arm heavy chain. It is absent from the human sperm axoneme, where DNAH8 and DNAH17 replace it, so in humans it drives cilia that move fluid (airway, and nodal cilia for left-right patterning) rather than cells. Cilium movement that moves extracellular fluid is the accurate process. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000743491 Β· PTN000743491 SUPPORTS SOURCE BUT NOT TARGET Function holds for sperm-flagellar and protist dynein heavy chains; the human respiratory ODA heavy chains act in fluid-moving cilia. Proposed replacements: epithelial cilium movement involved in extracellular fluid movement Supporting Evidence: PMID:31178125 We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with Ξ±-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia |
| GO:0097728 9+0 motile cilium | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of 9+0 motile cilium from mouse Dnah11 (lrd). Reason: lrd protein localizes to a central subset of motile node monocilia, which generate the nodal flow. Supporting Evidence: PMID:12859898 We show that lrd localizes to a centrally located subset of node monocilia |
| GO:0097729 9+2 motile cilium | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT annotation placing dynein heavy chains in 9+2 motile cilia. Reason: Consistent with immunofluorescence of DNAH11 in the axonemes of 9+2 respiratory cilia. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia |
| GO:0097729 9+2 motile cilium | IDA PMID:26909801 DNAH11 Localization in the Proximal Region of Respiratory Ci... | ACCEPT | Summary: DNAH11 detected in the proximal region of human respiratory (9+2) cilia. Reason: Correct. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia |
| GO:0097729 9+2 motile cilium | IEA GO_REF:0000120 | ACCEPT | Summary: Combined electronic annotation of 9+2 motile cilium. Reason: Correct. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia |
| GO:0120134 proximal portion of axoneme | IDA PMID:26909801 DNAH11 Localization in the Proximal Region of Respiratory Ci... | ACCEPT | Summary: A validated monoclonal antibody places DNAH11 only in the proximal region of respiratory cilia (confirmed in GFP-lrd mouse trachea). Reason: Core location; DNAH11 defines the proximal ODA type. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia PMID:26909801 GFP-left-right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. |
| GO:0120134 proximal portion of axoneme | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of proximal portion of axoneme. Reason: Agrees with the experimental data. Supporting Evidence: PMID:26909801 IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia |
| GO:0120229 protein localization to motile cilium | IMP PMID:33139725 CFAP45 deficiency causes situs abnormalities and asthenosper... | MARK AS OVER ANNOTATED | Summary: In the CFAP45 study, CFAP45 (and CFAP52) localization in respiratory cilia was abnormal or undetectable in several DNAH11-mutant subtypes; CFAP45 co-immunoprecipitates DNAH11. Reason: The cached record of PMID:33139725 is abstract-only and does not mention DNAH11, so no cached quote supports this annotation. The full text (Europe PMC, PMC7606486) reports that CFAP45 ciliary localization is abnormal or undetectable in DNAH11-mutant respiratory cilia, and that CFAP45 co-immunoprecipitates DNAH11; that sentence is recorded below as full-text support. The observation shows that a binding partner of the proximal ODA depends on DNAH11 for its axonemal position, which fits DNAH11 acting as a structural anchor within the ODA. It does not show that DNAH11 takes part in a protein localization process (targeting or transport to the cilium); DNAH11 itself is a motor subunit. The term therefore goes beyond what the evidence supports for this gene. Supporting Evidence: |
| GO:0036157 outer dynein arm | IDA PMID:26909801 DNAH11 Localization in the Proximal Region of Respiratory Ci... | NEW | Summary: DNAH11 is a beta-type heavy chain of the proximal outer dynein arm in respiratory cilia, but it carries no outer dynein arm annotation, only the generic dynein complex. Reason: Proximal ODAs are partially lost in DNAH11-deficient cilia, DNAH11 co-fractionates with ODA components, and it is the beta heavy chain paralog of DNAH9 (distal ODA) and DNAH17 (sperm ODA). Its paralogs DNAH9 and DNAH17 and the gamma chain DNAH5 all carry this term, and the comparator check fits: DNAH11 stands in the same structural role. PAINT gives the beta heavy chains only the generic dynein complex term, which explains the gap. Supporting Evidence: PMID:26909801 TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. PMID:26909801 DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography. PMID:31178125 However, the contribution of the different HCs (Ξ³-type: DNAH5 and DNAH8 and Ξ²-type: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. |
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Download this section (compressed HTML)Q: How does loss of a proximal ODA beta heavy chain produce a faster (hyperkinetic) rather than slower beat? Does DNAH11 normally impose a load or regulatory brake on proximal bending?
Q: DNAH11 lacks an outer dynein arm annotation in GOA; should PAINT propagate outer dynein arm membership to the beta heavy chain clade (DNAH9/DNAH11/DNAH17)?
Q: Is the CFAP45-CFAP52-AK8 nucleotide homeostasis module specifically anchored through DNAH11-containing proximal ODAs, and does DNAH11 itself bind CFAP45 directly?
Experiment: Measure single-cilium waveform and beat frequency in DNAH11-null airway cells with optical tweezers or high-speed imaging under varying viscosity to explain the hyperkinetic phenotype mechanistically.
Type: biophysical ciliary beat analysis
Experiment: Cryo-ET of proximal versus distal segments of DNAH11-deficient airway cilia to determine which ODA heavy chains and associated proteins (CFAP45, CFAP52, AK8) are lost proximally.
Type: cryo-electron tomography
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