DNAH10 (dynein axonemal heavy chain 10) is a 4471-residue axonemal dynein heavy chain. With DNAH2 it forms the two heavy chains of the two-headed inner dynein arm f (I1 dynein; DNAH10 corresponds to the Chlamydomonas 1-alpha subspecies). The arm also contains the intermediate chains DNAI3, DNAI4 and DNAI7 and several light chains. It has an N-terminal stem and a motor head of six AAA modules with ATP-binding P-loops and a coiled-coil stalk with a microtubule-binding domain. Like other axonemal dyneins it is expected to generate minus-end-directed force that drives doublet sliding. DNAH10 is expressed mainly in testis and trachea and lies along the whole sperm flagellum and in respiratory cilia, where it localizes independently of the light intermediate chain DNALI1. Biallelic DNAH10 variants cause asthenoteratozoospermia with multiple morphological abnormalities of the sperm flagella (MMAF; spermatogenic failure 56), with loss of inner dynein arms and reduced DNAH2, DNAH6 and DNAH1 in sperm. Other families have primary ciliary dyskinesia with chronic respiratory infection, situs inversus and disordered respiratory axonemes. Dnah10 knockout and knock-in mice reproduce male infertility and PCD-like airway disease with hydrocephalus. Zebrafish dnah10 mutants have slower-beating ependymal monocilia and spinal curvature. Later reports link DNAH10 to manchette function during spermiogenesis, through bridging of the UCHL3-PACRG complex, and to primary cilia in skeletal development, but these roles are less well established.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based ATP binding; the motor head carries ATP-binding P-loops. Reason: Correct but uninformative; part of the motor activity. |
| GO:0005930 axoneme | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to axoneme. Reason: DNAH10 is localized along the sperm flagellar axoneme and in respiratory cilia. Supporting Evidence: PMID:34237282 Immunostaining analysis indicated that DNAH10 localized to the entire sperm flagellum of control spermatozoa. |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro mapping to microtubule-based movement. Reason: True, but entailed by cilium movement involved in cell motility (GO:0060294), which this review ACCEPTs, and by flagellated sperm motility (GO:0030317), proposed here as NEW; both are descendants of microtubule-based movement. |
| GO:0008569 minus-end-directed microtubule motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference at the deep dynein heavy chain node PTN000743491. Reason: Minus-end-directed motor activity is ancestral to the dynein heavy chain family; DNAH10 keeps the complete motor domain, and truncating variants that remove the motor domain cause disease. Supporting Evidence: file:human/DNAH10/DNAH10-uniprot.txt towards the minus ends of microtubules. |
| GO:0008569 minus-end-directed microtubule motor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to minus-end-directed motor activity. Reason: Consistent with the IBA and the intact motor domain. |
| GO:0030286 dynein complex | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT inference of dynein complex membership. Reason: True, but entailed by inner dynein arm (GO:0036156), which this review proposes as a NEW annotation (DNAH10 is a heavy chain of the I1/f inner arm); inner dynein arm is a descendant of dynein complex. |
| GO:0030286 dynein complex | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro mapping to dynein complex. Reason: True, but entailed by inner dynein arm (GO:0036156), proposed in this review as a NEW annotation; inner dynein arm is a descendant of dynein complex. |
| GO:0036126 sperm flagellum | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of sperm flagellum location. Reason: DNAH10 is detected along the entire sperm flagellum. Supporting Evidence: PMID:34237282 Immunostaining analysis indicated that DNAH10 localized to the entire sperm flagellum of control spermatozoa. |
| GO:0045505 dynein intermediate chain binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference at PTN000743491 of dynein intermediate chain binding. Reason: The ACCEPT rests on DNAH10's membership of the I1/f inner arm, whose subunits include the intermediate chains DNAI3, DNAI4 and DNAI7, together with the conserved intermediate-chain-binding stem of dynein heavy chains. Direct contact between DNAH10 and a specific intermediate chain has not been demonstrated: the mouse data show only that Dnah10 co-purifies with Dynein-f subunits and needs the IC138 ortholog Wdr78 for its ciliary localization. Supporting Evidence: PMID:40898283 The IDAf complex comprises intermediate chains (DNAI3, DNAI4, DNAI7), light chains (DYNLRB1, DYNRB2, DYNLL1), and heavy chains (DNAH2, DNAH10, DNAH12). PMID:30060180 Our results also provide the first experimental evidence that validates Dnah10 and Dnah2 as HCs and Wdr78, Wdr63, and Casc1 as ICs of vertebrate Dynein-f PMID:30060180 depletion of Wdr78 by RNAi in mEPCs selectively disrupted ciliary localizations of other Dynein-f subunits, such as the HCs (Dnah10 and Dnah2) and the ICs (Wdr63 and Casc1) |
| GO:0045505 dynein intermediate chain binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro DHC domain mapping to dynein intermediate chain binding. Reason: Rests on DNAH10's membership of the I1/f arm, which contains the intermediate chains DNAI3, DNAI4 and DNAI7, rather than on a demonstrated contact with a specific intermediate chain. Supporting Evidence: PMID:40898283 The IDAf complex comprises intermediate chains (DNAI3, DNAI4, DNAI7), light chains (DYNLRB1, DYNRB2, DYNLL1), and heavy chains (DNAH2, DNAH10, DNAH12). |
| GO:0051959 dynein light intermediate chain binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT inference at the deep node PTN000743491, seeded by cytoplasmic dynein-1 heavy chains (human DYNC1H1, mouse, rat). Reason: Light intermediate chain binding is a property of cytoplasmic dynein-1 and of DNALI1-containing single-headed IDAs. DNAH10 belongs to the two-headed I1/f arm, whose described composition has no light intermediate chain, and DNAH10 localizes normally in DNALI1-deficient sperm, whereas the DNALI1-associated heavy chains DNAH1 and DNAH7 are lost. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000743491 SUPPORTS SOURCE BUT NOT TARGET Deep dynein heavy chain node spanning cytoplasmic and axonemal lineages; the light intermediate chain binding descends from it to all axonemal heavy chains, including the I1/f lineage, which has no light intermediate chain subunit. UniProtKB:Q14204 SUPPORTS SOURCE BUT NOT TARGET DYNC1H1 binds the dynein-1 light intermediate chains; valid for cytoplasmic dynein-1 only. Supporting Evidence: PMID:36792588 Being a component of subspecies I1Ξ±, DNAH10 was not affected by the loss of DNALI1 PMID:36792588 Conversely, DNAH1, DNAH7, and DNAH10 were not required for the flagellar distribution of DNALI1. |
| GO:0051959 dynein light intermediate chain binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro DHC domain mapping to light intermediate chain binding. Reason: Family-wide mapping; DNAH10 localizes independently of DNALI1 and its arm is not known to contain a light intermediate chain. Supporting Evidence: PMID:36792588 Being a component of subspecies I1Ξ±, DNAH10 was not affected by the loss of DNALI1 |
| GO:0060294 cilium movement involved in cell motility | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference for cilium movement involved in cell motility from the axonemal dynein clade. Reason: DNAH10 sits in the axonemal clade that inherited this function, and human, mouse and zebrafish loss-of-function data show it is needed for normal motile ciliary beating. Supporting Evidence: PMID:40898283 In summary, disruption of DNAH10 would render the IDAf complex instability, altering the beating frequency and direction of motile cilia. PMID:34915022 Using a stably segregating dnah10 mutant zebrafish, we showed that the ependymal monocilia lining the hindbrain and spinal canal displayed reduced beat frequency |
| GO:0097228 sperm principal piece | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunostaining of DNAH10 in the sperm principal piece. Reason: Antibody-based HPA localization to a subregion; DNAH10 is found along the entire flagellum. |
| GO:0097729 9+2 motile cilium | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of activity in 9+2 motile cilia. Reason: DNAH10 is lost from patient respiratory cilia, whose axonemes become disordered, and Dnah10 mutant mice develop PCD. Supporting Evidence: PMID:37314648 Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia |
| GO:0036156 inner dynein arm | ISO PMID:30060180 Vertebrate Dynein-f depends on Wdr78 for axonemal localizati... | NEW | Summary: DNAH10 is a heavy chain of the two-headed inner dynein arm f (I1), together with DNAH2 and the intermediate chains DNAI3, DNAI4 and DNAI7. Unlike DNAH1 and DNAH2, it has no inner dynein arm annotation, only the generic dynein complex. Reason: Coded ISO from the mouse ortholog Dnah10 (MGI:1860299). The primary experimental basis is PMID:30060180, in which Wdr78 pull-downs from mouse ependymal cells recovered Dnah10 with the other Dynein-f subunits and Wdr78 depletion removed Dnah10 from the cilium, which the authors present as the first experimental validation of Dnah10 as a Dynein-f heavy chain. PMID:40898283 is corroborating but not a direct assay of arm membership: its subunit list comes from re-used published cryo-EM structures, and its own assay was co-immunoprecipitation of Dnah10 with CCDC73, CFAP57 and DYNLL1 in mouse lung, so it is not used as the evidence code source here. Loss of inner dynein arms in patient sperm and DNALI1-independent localization as an I1-alpha component are consistent with the assignment. The paralogous inner-arm heavy chains DNAH1 and DNAH2 already carry this term. Supporting Evidence: PMID:30060180 Mass spectrometric analysis identified multiple subunits of Dynein-f (Dnah2, Dnah10, Tctex1, and Wdr63) PMID:40898283 The IDAf complex comprises intermediate chains (DNAI3, DNAI4, DNAI7), light chains (DYNLRB1, DYNRB2, DYNLL1), and heavy chains (DNAH2, DNAH10, DNAH12). PMID:30060180 Our results also provide the first experimental evidence that validates Dnah10 and Dnah2 as HCs and Wdr78, Wdr63, and Casc1 as ICs of vertebrate Dynein-f PMID:36792588 Being a component of subspecies I1Ξ±, DNAH10 was not affected by the loss of DNALI1 |
| GO:0030317 flagellated sperm motility | IMP PMID:34237282 Bi-allelic mutations of DNAH10 cause primary male infertilit... | NEW | Summary: Biallelic DNAH10 variants in five men cause asthenoteratozoospermia with MMAF and loss of inner dynein arms, and Dnah10 knockout and knock-in mice reproduce the phenotype. Reason: DNAH10 lacks any sperm motility annotation despite replicated human (several cohorts) and mouse loss-of-function evidence. As a motor heavy chain within the flagellar axoneme it does part of the work of flagellar beating. The paralogous inner-arm heavy chains DNAH1 and DNAH2 carry the same term. Supporting Evidence: PMID:34237282 Morphological and ultrastructural analyses of the spermatozoa obtained from men harboring bi-allelic DNAH10 variants revealed striking flagellar defects with the absence of inner dynein arms (IDAs). PMID:34237282 Furthermore, the phenotypes were recapitulated in mouse models lacking Dnah10 or expressing a disease-associated variant, confirming the involvement of DNAH10 in human MMAF. PMID:34657236 ultrastructural analysis by transmission electron microscopy showed significant inner dynein arm (IDA) deficiency in sperm flagella |
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Download this section (compressed HTML)Q: Why do some DNAH10 families present only with MMAF and others with full PCD (including situs inversus)? Does this track with allele type (truncating versus missense) or with modifiers?
Q: A structure-based listing places DNAH12 in the IDAf complex with DNAH2 and DNAH10 (PMID:40898283). Is DNAH12 a genuine I1/f subunit, or a neighbouring single-headed arm component near radial spoke 1?
Q: Is the reported bridging of the UCHL3-PACRG complex during manchette transport (PMID:41058558) a direct function of DNAH10, or a consequence of defective flagellar assembly?
Q: Is the reported primary-cilium and Hedgehog phenotype in Dnah10-deficient skeletal cells (PMID:42086325) reproducible, and is DNAH10 present in primary cilia at all?
Experiment: Cryo-ET of the 96-nm repeat in Dnah10 knockout mouse sperm and tracheal cilia to test whether the whole I1/f arm (including DNAH2 and DNAI3/DNAI4) is lost, and whether the tether/tether-head complex is affected.
Type: cryo-electron tomography
Experiment: Immunolocalization of DNAH10 in primary cilia of chondrocytes and osteoblasts, with a knockout control, to test the proposed primary-cilium role.
Type: immunofluorescence microscopy
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