DNAH5 (dynein axonemal heavy chain 5) is the gamma-type heavy chain of the outer dynein arm (ODA), the multi-subunit ATPase motor that attaches every 24 nm to the A-tubule of each outer doublet in motile cilia and powers ciliary beating by sliding adjacent doublets. It is a ~4,600-residue protein with an N-terminal tail that assembles with the ODA intermediate and light chains and a C-terminal motor head of six AAA+ modules and a microtubule-binding stalk; it moves toward microtubule minus ends. DNAH5 is present along the whole length of respiratory cilia, where it pairs with the beta heavy chain DNAH11 in proximal (type 1) ODAs and with DNAH9 in distal (type 2) ODAs, and it is also found in ependymal and embryonic nodal cilia. Human sperm flagella use DNAH8 instead. ODAs are preassembled in the cytoplasm with chaperones such as ZMYND10 before transport into the cilium, and DNAH5 is needed for the whole arm to form: without it the intermediate chain DNAI2 is not incorporated. Biallelic loss-of-function variants cause primary ciliary dyskinesia 3 (CILD3), the most common genetic cause of PCD with ODA defects. Respiratory cilia are immotile, mucociliary clearance fails, and about half of patients have situs inversus because nodal cilia do not beat. Dnah5 mutant mice reproduce PCD with situs inversus and develop hydrocephalus because ependymal flow is lost.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003341 cilium movement | IMP PMID:11062149 Homozygosity mapping of a gene locus for primary ciliary dys... | ACCEPT | Summary: Homozygosity mapping in a consanguineous PCD family with ciliary akinesia and absent outer dynein arms identified DNAH5 as the candidate gene. Reason: Cilium movement is the core process; ciliary akinesia is the phenotype of DNAH5 loss. Supporting Evidence: PMID:11062149 Direct examination of the respiratory cilia revealed ciliary akinesia. PMID:11062149 Electron microscopic examination of cilia showed absence of the outer dynein arms. |
| GO:0003341 cilium movement | IMP PMID:15750039 Mislocalization of DNAH5 and DNAH9 in respiratory cells from... | ACCEPT | Summary: Respiratory cilia lacking DNAH5 throughout the axoneme are immotile; distal loss leaves residual motility. Reason: Direct functional evidence linking DNAH5 to cilium beating. Supporting Evidence: PMID:15750039 Cilia with complete axonemal DNAH5 deficiency were immotile, whereas cilia with distal DNAH5 deficiency showed residual motility. |
| GO:0003341 cilium movement | IMP PMID:16627867 DNAH5 mutations are a common cause of primary ciliary dyskin... | ACCEPT | Summary: DNAH5 mutations in 30 PCD families; outer dynein arm defects in every patient examined. Reason: Large mutational series confirming that loss of DNAH5 abolishes ODA-driven ciliary beating. Supporting Evidence: PMID:16627867 Electron microscopic analyses in 22 patients with PCD with mutations invariably detected outer dynein arm ciliary defects. |
| GO:0003341 cilium movement | IMP PMID:23261302 Exome sequencing identifies mutations in CCDC114 as a cause ... | ACCEPT | Summary: Exome sequencing of PCD probands with ODA defects found DNAH5 mutations in some individuals (the paper's main subject is CCDC114). Reason: The abstract reports DNAH5 mutations in PCD patients with ciliary dysmotility; the curator had the full text. The annotation agrees with the rest of the DNAH5 literature. Supporting Evidence: PMID:23261302 In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD |
| GO:0003777 microtubule motor activity | IEA GO_REF:0000107 | TOO GENERAL | Summary: Ensembl Compara transfer from mouse Dnah5 of microtubule motor activity. Reason: DNAH5 is the gamma-type heavy chain of the outer dynein arm, the main force generator of ciliary beating, so microtubule motor activity is true. It is entailed by the more specific minus-end-directed microtubule motor activity, which this review accepts as the core activity. 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 file:human/DNAH5/DNAH5-uniprot.txt Force generating protein of respiratory cilia |
| 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 DNAH5 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/DNAH5/DNAH5-uniprot.txt Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function. |
| GO:0005737 cytoplasm | IDA PMID:29916806 ZMYND10 functions in a chaperone relay during axonemal dynei... | KEEP AS NON CORE | Summary: DNAH5 is detected in the cytoplasm of differentiating multiciliated cells, where outer dynein arms are preassembled with chaperones (ZMYND10, FKBP8, HSP90) before transport into cilia. Reason: Accurate: cytoplasmic DNAH5 is the preassembly pool. The functional location is the axoneme. Supporting Evidence: PMID:29916806 In control immature human nasal brush epithelial cells, we detected PLA signals consistent with DNAI2 and DNAH5 existing in both cytoplasmic and axonemal complexes (Figure 4A). |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of cytoplasm localization from mouse Dnah5. Reason: Correct for the preassembly pool, but not where the protein acts. Supporting Evidence: PMID:23849778 which are preassembled in the cytoplasm prior to transport to the ciliary axonemal compartment |
| GO:0005858 axonemal dynein complex | IEA GO_REF:0000107 | TOO GENERAL | Summary: Ensembl Compara transfer of axonemal dynein complex. Reason: Correct, but entailed by the more specific outer dynein arm term, which this review accepts (by IDA, IMP, IBA and IEA). 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:0005930 axoneme | IDA PMID:15750039 Mislocalization of DNAH5 and DNAH9 in respiratory cells from... | ACCEPT | Summary: Immunofluorescence shows DNAH5 along the respiratory ciliary axoneme. Reason: Direct localization of an outer dynein arm heavy chain to the axoneme; DNAH5 is a standard diagnostic marker of ODAs. Supporting Evidence: PMID:15750039 In normal ciliated airway epithelium, DNAH5 and DNAH9 show a specific regional distribution along the ciliary axoneme, indicating the existence of at least two distinct ODA types. |
| GO:0005930 axoneme | IDA PMID:16492982 Axonemal localization of the dynein component DNAH5 is not a... | ACCEPT | Summary: Immunofluorescence shows DNAH5 along the respiratory ciliary axoneme. Reason: Direct localization of an outer dynein arm heavy chain to the axoneme; DNAH5 is a standard diagnostic marker of ODAs. Supporting Evidence: PMID:16492982 High-resolution immunofluorescence studies of respiratory epithelial cells with SCD identified in vitro and in vivo normal axonemal DNAH5 localization. |
| GO:0005930 axoneme | IDA PMID:18950741 DNAI2 mutations cause primary ciliary dyskinesia with defect... | ACCEPT | Summary: Immunofluorescence shows DNAH5 along the respiratory ciliary axoneme. Reason: Direct localization of an outer dynein arm heavy chain to the axoneme; DNAH5 is a standard diagnostic marker of ODAs. Supporting Evidence: PMID:18950741 Respiratory cilia contain at least two distinct ODA types: type 1, DNAH9 negative and DNAH5 positive (proximal ciliary axoneme); and type 2, DNAH9 and DNAH5 positive (distal ciliary axoneme). |
| GO:0005930 axoneme | IDA PMID:23849778 ARMC4 mutations cause primary ciliary dyskinesia with random... | ACCEPT | Summary: DNAH5 staining used as an ODA marker in respiratory cilia of ARMC4 patients and controls. Reason: The abstract does not name DNAH5, but the curator read the full text; axonemal DNAH5 in control cilia is reproduced in many other papers, so the annotation is accepted. Supporting Evidence: PMID:23849778 We demonstrate that ARMC4 is an axonemal protein that is necessary for proper targeting and anchoring of ODAs. |
| GO:0005930 axoneme | IDA PMID:24203976 Combined exome and whole-genome sequencing identifies mutati... | ACCEPT | Summary: Immunofluorescence shows DNAH5 along the respiratory ciliary axoneme. Reason: Direct localization of an outer dynein arm heavy chain to the axoneme; DNAH5 is a standard diagnostic marker of ODAs. Supporting Evidence: PMID:24203976 In healthy individuals, both ARMC4 and DNAH5 are localised along the length of the axoneme of respiratory epithelial cells. |
| GO:0005930 axoneme | IDA PMID:26387594 Loss-of-Function GAS8 Mutations Cause Primary Ciliary Dyskin... | ACCEPT | Summary: Immunofluorescence shows DNAH5 along the respiratory ciliary axoneme. Reason: Direct localization of an outer dynein arm heavy chain to the axoneme; DNAH5 is a standard diagnostic marker of ODAs. Supporting Evidence: PMID:26387594 The absence of the N-DRC protein GAS8 from the whole ciliary axoneme as well as the normal axonemal localization of the ODA protein DNAH5 are shown in Figure 1 |
| GO:0005930 axoneme | IDA PMID:26909801 DNAH11 Localization in the Proximal Region of Respiratory Ci... | ACCEPT | Summary: DNAH5 used as an ODA marker alongside DNAH11 in respiratory cilia. Reason: The abstract reports that ODA localization of DNAH11 is retained in cilia lacking ODAs and uses DNAH5 as the ODA marker in the full text; axonemal DNAH5 is well established. Supporting Evidence: PMID:26909801 DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). |
| GO:0005930 axoneme | IDA PMID:29916806 ZMYND10 functions in a chaperone relay during axonemal dynei... | ACCEPT | Summary: Proximity ligation detects DNAH5 with DNAI2 in both cytoplasmic and axonemal complexes. Reason: Direct localization of DNAH5 in the axoneme. Supporting Evidence: PMID:29916806 In control immature human nasal brush epithelial cells, we detected PLA signals consistent with DNAI2 and DNAH5 existing in both cytoplasmic and axonemal complexes (Figure 4A). |
| GO:0005930 axoneme | IDA PMID:31178125 Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Oute... | ACCEPT | Summary: DNAH5 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 localization. Reason: Agrees with the many IDA annotations. Supporting Evidence: PMID:18950741 Respiratory cilia contain at least two distinct ODA types: type 1, DNAH9 negative and DNAH5 positive (proximal ciliary axoneme); and type 2, DNAH9 and DNAH5 positive (distal ciliary axoneme). |
| 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:11788826 Mutations in DNAH5 cause primary ciliary dyskinesia and rand... | ACCEPT | Summary: Loss-of-function DNAH5 mutations identified in PCD patients with randomized left-right asymmetry. Reason: DNAH5-containing ODAs power the nodal cilia whose leftward flow breaks left-right symmetry; about half of DNAH5 patients have situs inversus. The acts_upstream_of_or_within qualifier is appropriate because DNAH5 acts through cilium motility. Supporting Evidence: PMID:11788826 Sequence analysis in individuals with PCD with randomization of LR asymmetry identified mutations resulting in non-functional DNAH5 proteins. |
| GO:0007368 determination of left/right symmetry | IMP PMID:17515466 Congenital heart disease and other heterotaxic defects in a ... | ACCEPT | Summary: In a cohort of 337 PCD patients, situs abnormalities and heterotaxy were associated with mutations in ODA genes including DNAH5. Reason: Supports the laterality role of DNAH5 through nodal cilia motility. Supporting Evidence: PMID:17515466 Seven of 12 patients with heterotaxy who were genotyped had mutations in DNAI1 or DNAH5. |
| GO:0007368 determination of left/right symmetry | IMP PMID:22499950 High prevalence of respiratory ciliary dysfunction in congen... | ACCEPT | Summary: Heterotaxy patients with congenital heart disease and ciliary dysfunction were screened for PCD gene mutations. Reason: The abstract names DNAI1 and DNAH11 mutations, not DNAH5; the curator presumably found DNAH5 variants in the full text, which is not cached. The laterality role of DNAH5 is independently well supported (PMID:11788826, PMID:17515466, mouse Dnah5 mutant), so the annotation is accepted. Supporting Evidence: PMID:22499950 Heterotaxy patients with CD were enriched for mutations in PCD genes. |
| 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: DNAH5 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/DNAH5/DNAH5-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: DNAH5 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/DNAH5/DNAH5-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 | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to the generic dynein complex. Reason: Correct but too general. DNAH5 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:15750039 Mislocalization of DNAH5 and DNAH9 in respiratory cells from... | MARK AS OVER ANNOTATED | Summary: The paper assessed sperm tail function in a DNAH5 patient, but found normal ODA heavy chain distribution in sperm. Reason: The cached abstract argues against a direct role: sperm of a DNAH5-mutant patient kept normal ODA heavy chains, and DNAH5 is not detected along the human sperm axoneme, where DNAH8 is the gamma heavy chain. Any sperm motility defect in DNAH5 patients is therefore not explained by loss of DNAH5 from the flagellum. Supporting Evidence: PMID:15750039 In contrast to respiratory cilia, sperm tails from a patient with DNAH5 mutations had normal ODA heavy chain distribution, suggesting different modes of ODA generation in these cell types. 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:0030317 flagellated sperm motility | IMP PMID:18492703 Mutations in dynein genes in patients affected by isolated n... | MARK AS OVER ANNOTATED | Summary: Heterozygous, maternally inherited dynein variants (one each in DNAI1, DNAH5, DNAH11) were associated with isolated asthenozoospermia in 7 of 90 men. Reason: Weak genetic evidence: single heterozygous variants, no axonemal defect, and no functional test. DNAH5 protein is not detected in the human sperm axoneme, so a direct 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:18492703 No ultrastructural axonemal anomaly was detected in sperm. 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: DNAH5 is present in respiratory motile cilia. Reason: Correct; the more specific 9+2 motile cilium and axoneme annotations also exist. 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:0036157 outer dynein arm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT places outer dynein arm membership at node PTN002472868, the outer-arm gamma heavy chain clade (human DNAH5 and mouse Dnah8 as experimental sources). Reason: Core cellular component. DNAH5 is the gamma heavy chain of both proximal and distal ODA types in respiratory cilia. 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. PMID:18950741 Respiratory cilia contain at least two distinct ODA types: type 1, DNAH9 negative and DNAH5 positive (proximal ciliary axoneme); and type 2, DNAH9 and DNAH5 positive (distal ciliary axoneme). |
| GO:0036157 outer dynein arm | IDA PMID:16627867 DNAH5 mutations are a common cause of primary ciliary dyskin... | ACCEPT | Summary: Mutant DNAH5 is lost from the axoneme and ODAs are absent by electron microscopy. Reason: Core cellular component. Supporting Evidence: PMID:16627867 Mutant DNAH5 was absent throughout the ciliary axoneme in seven patients and remained detectable in the proximal ciliary axoneme in one patient carrying compound heterozygous splicing mutations at the 3'-end (IVS75-2A>T, IVS76+5G>A). |
| GO:0036157 outer dynein arm | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of outer dynein arm from mouse Dnah5. Reason: Correct; agrees with the experimental annotations. 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:0036157 outer dynein arm | IMP PMID:11062149 Homozygosity mapping of a gene locus for primary ciliary dys... | ACCEPT | Summary: The DNAH5-linked PCD family lacks outer dynein arms. Reason: Absence of ODAs on loss of a heavy chain is consistent with DNAH5 being a structural component of the arm. Supporting Evidence: PMID:11062149 Electron microscopic examination of cilia showed absence of the outer dynein arms. |
| GO:0036157 outer dynein arm | IMP PMID:11788826 Mutations in DNAH5 cause primary ciliary dyskinesia and rand... | ACCEPT | Summary: DNAH5 is the human orthologue of the Chlamydomonas outer-arm gamma heavy chain and loss-of-function mutations cause PCD. Reason: Core component; supported by orthology and phenotype. Supporting Evidence: PMID:11788826 which encodes a protein highly similar to the Chlamydomonas gamma-dynein heavy chain |
| GO:0036157 outer dynein arm | IMP PMID:22499950 High prevalence of respiratory ciliary dysfunction in congen... | ACCEPT | Summary: Annotation from the heterotaxy/ciliary dysfunction cohort study. Reason: The abstract does not mention DNAH5; the curator had the full text. DNAH5 membership of the outer dynein arm is beyond doubt, so the annotation is accepted. 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:0036158 outer dynein arm assembly | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT annotation of outer dynein arm assembly at the gamma heavy chain node PTN002472868. Reason: As the gamma heavy chain, DNAH5 is required for the whole ODA to assemble: without it the intermediate chain DNAI2 is not incorporated in either ODA type. This is participation as a structural subunit, not just a downstream requirement. Supporting Evidence: PMID:18950741 demonstrating in a complementary manner that DNAH5 is also essential for the axonemal assembly of the ODA protein DNAI2 within ODA types 1 and 2. |
| GO:0036158 outer dynein arm assembly | IMP PMID:11062149 Homozygosity mapping of a gene locus for primary ciliary dys... | ACCEPT | Summary: Absent ODAs in the DNAH5-linked PCD family. Reason: DNAH5 loss prevents ODA assembly. Supporting Evidence: PMID:11062149 Electron microscopic examination of cilia showed absence of the outer dynein arms. |
| GO:0036158 outer dynein arm assembly | IMP PMID:11788826 Mutations in DNAH5 cause primary ciliary dyskinesia and rand... | ACCEPT | Summary: Non-functional DNAH5 alleles in PCD patients with ODA defects. Reason: Consistent with DNAH5 being required to build the arm. Supporting Evidence: PMID:11788826 Sequence analysis in individuals with PCD with randomization of LR asymmetry identified mutations resulting in non-functional DNAH5 proteins. |
| GO:0036158 outer dynein arm assembly | IMP PMID:15750039 Mislocalization of DNAH5 and DNAH9 in respiratory cells from... | ACCEPT | Summary: Mutant DNAH5 is absent from the axoneme and accumulates at microtubule-organizing centres. Reason: Shows the arm fails to reach and assemble on the axoneme without functional DNAH5. Supporting Evidence: PMID:15750039 DNAH5 was completely or only distally absent from the respiratory ciliary axoneme in patients with PCD with DNAH5- (n = 3) or DNAI1- (n = 1) mutations, respectively, and instead accumulated at the microtubule-organizing centers. |
| GO:0036158 outer dynein arm assembly | IMP PMID:16627867 DNAH5 mutations are a common cause of primary ciliary dyskin... | ACCEPT | Summary: Mutant DNAH5 mislocalizes and ODAs are missing in all patients examined. Reason: Supports DNAH5 being required for ODA assembly. Supporting Evidence: PMID:16627867 High-resolution immunofluorescence imaging of respiratory epithelial cells from eight patients with DNAH5 mutations showed mislocalization of mutant DNAH5 and accumulation at the microtubule organizing centers. |
| GO:0036158 outer dynein arm assembly | IMP PMID:18950741 DNAI2 mutations cause primary ciliary dyskinesia with defect... | ACCEPT | Summary: In DNAH5-mutant cilia the ODA intermediate chain DNAI2 is absent from the axoneme. Reason: Direct evidence that DNAH5 is needed to assemble the other ODA subunits into the axoneme. Supporting Evidence: PMID:18950741 demonstrating in a complementary manner that DNAH5 is also essential for the axonemal assembly of the ODA protein DNAI2 within ODA types 1 and 2. |
| GO:0036158 outer dynein arm assembly | IMP PMID:22499950 High prevalence of respiratory ciliary dysfunction in congen... | ACCEPT | Summary: Annotation from the heterotaxy cohort study. Reason: DNAH5 is not named in the abstract and the full text is not cached; the function is well established from other papers, so the curator's annotation is accepted. Supporting Evidence: PMID:18950741 demonstrating in a complementary manner that DNAH5 is also essential for the axonemal assembly of the ODA protein DNAI2 within ODA types 1 and 2. |
| GO:0036158 outer dynein arm assembly | IMP PMID:23261302 Exome sequencing identifies mutations in CCDC114 as a cause ... | ACCEPT | Summary: DNAH5 mutations found by exome sequencing in PCD probands with ODA defects. Reason: Consistent with the role of DNAH5 in ODA assembly. Supporting Evidence: PMID:23261302 To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. |
| 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/DNAH5/DNAH5-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/DNAH5/DNAH5-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/DNAH5/DNAH5-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/DNAH5/DNAH5-uniprot.txt Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains |
| GO:0060271 cilium assembly | IMP PMID:16492982 Axonemal localization of the dynein component DNAH5 is not a... | MODIFY | Summary: In this study DNAH5 localization was compared between primary and secondary (IL-13-induced) ciliary dyskinesia. Reason: DNAH5-deficient cells still grow cilia: the defect is the absence of outer dynein arms from otherwise formed axonemes. Cilium assembly is therefore too broad; the specific process DNAH5 is needed for is outer dynein arm assembly. Proposed replacements: outer dynein arm assembly Supporting Evidence: PMID:16492982 We have recently shown that in respiratory epithelial cells from PCD patients with outer dynein arm defects the dynein protein DNAH5 is mislocalized and either completely or partially absent from the ciliary axoneme. |
| 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 DNAH5 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 Dnah5. Reason: Motile 9+0 nodal cilia carry ODAs and drive the leftward flow that sets left-right asymmetry; situs inversus in half of DNAH5 patients and in Dnah5-mutant mice reflects their dysfunction. Supporting Evidence: PMID:11912187 reproduces most of the classical features of PCD, including recurrent respiratory infections, situs inversus and ciliary immotility |
| 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 DNAH5 in the axonemes of 9+2 respiratory cilia. Supporting Evidence: PMID:18950741 Respiratory cilia contain at least two distinct ODA types: type 1, DNAH9 negative and DNAH5 positive (proximal ciliary axoneme); and type 2, DNAH9 and DNAH5 positive (distal ciliary axoneme). |
| GO:0097729 9+2 motile cilium | IDA PMID:26909801 DNAH11 Localization in the Proximal Region of Respiratory Ci... | ACCEPT | Summary: DNAH5 detected in human respiratory (9+2) cilia. Reason: Correct. Supporting Evidence: PMID:26909801 DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). |
| 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:18950741 Respiratory cilia contain at least two distinct ODA types: type 1, DNAH9 negative and DNAH5 positive (proximal ciliary axoneme); and type 2, DNAH9 and DNAH5 positive (distal ciliary axoneme). |
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Download this section (compressed HTML)Q: Why do DNAH5-mutant patients sometimes report reduced male fertility when DNAH5 is not detected in the human sperm axoneme (DNAH8 is the sperm gamma chain)? Is there a minor sperm pool of DNAH5, or are fertility effects secondary (e.g. efferent duct cilia)?
Q: Do human DNAH5 patients have ependymal flow defects comparable to the hydrocephalus of Dnah5 mutant mice, and should cerebrospinal fluid circulation be annotated to the human gene?
Q: PANTHER (UniProt cross-reference) classifies DNAH5 in PTHR46532:SF13, a subfamily named after cytoplasmic dynein 1 heavy chain, whereas its PAINT IBAs come from the outer-arm gamma heavy chain node PTN002472868. Is the current PANTHER subfamily assignment of DNAH5 correct?
Q: Is the IBA for dynein light intermediate chain binding (node PTN000743491) placed too deep, given that only cytoplasmic dynein complexes contain light intermediate chains?
Experiment: Cryo-ET of DNAH5-deficient human airway cilia (or Dnah5 knockout mouse trachea) to define which ODA subunits are retained and whether DNAH9/DNAH11 can dock without the gamma chain.
Type: cryo-electron tomography
Experiment: Immunostaining of human and mouse ependymal cilia and efferent duct cilia for DNAH5, with high-speed videomicroscopy in DNAH5 patient-derived ependymal or brain organoid models, to test a conserved ependymal role.
Type: immunofluorescence and videomicroscopy
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