DNAH17 (dynein axonemal heavy chain 17; also DNEL2, DNAHL1) is a beta-type outer dynein arm (ODA) heavy chain, the sperm-specific paralog of DNAH9 and DNAH11. It is a 4462-residue motor protein with an N-terminal tail that assembles with other ODA subunits, a ring of six AAA+ domains with the hydrolytic ATP site in AAA1, and a coiled-coil stalk with a microtubule-binding domain, and it generates force towards microtubule minus ends. DNAH17 is expressed in testicular germ cells from early spermatocytes to late spermatids and lies along the sperm flagellar axoneme (midpiece, principal piece and end piece). In human sperm the ODA heavy chains are DNAH17 (beta) and DNAH8 (gamma), whereas respiratory cilia use DNAH5, DNAH9 and DNAH11 and lack DNAH17. Loss of DNAH17 removes the outer arms from sperm, together with DNAH8, DNAI1 and the docking-complex proteins ODAD2 and ODAD4, but leaves the inner arms in place. Bi-allelic variants cause isolated male infertility with asthenozoospermia or asthenoteratozoospermia with multiple morphological abnormalities of the sperm flagella (MMAF; spermatogenic failure 39), without respiratory disease. Dnah17-/- mice show MMAF with disorganized axonemes and impaired flagellar assembly in spermatids; Dnah17 knockout rats are infertile, and an in-frame DNAH17 splice deletion in pigs causes MMAF. ICSI outcomes are variable and sometimes require oocyte activation. Candidate DNAH17 variants have also been reported in two families with left-right asymmetry disorders, which is not yet confirmed.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003777 microtubule motor activity | NAS PMID:9373155 Identification of dynein heavy chain genes expressed in huma... | ACCEPT | Summary: Microtubule motor activity, from the early testis survey of dynein heavy chain cDNAs. Reason: DNAH17 has a complete dynein motor (six AAA+ domains with an ATP-binding P-loop in AAA1, a stalk and microtubule-binding domain) and is the beta heavy chain of the sperm outer arm, whose heavy-chain ATPase activity drives flagellar beating. The more specific minus-end-directed microtubule motor activity is also annotated. Supporting Evidence: file:human/DNAH17/DNAH17-uniprot.txt Force generating protein component of the outer dynein arms 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:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro mapping from the dynein heavy chain AAA domain. Reason: Correct; UniProt annotates the AAA1 P-loop, but ATP binding is uninformative relative to the motor activity. Supporting Evidence: file:human/DNAH17/DNAH17-uniprot.txt FT BINDING 1847..1854 |
| GO:0005858 axonemal dynein complex | NAS PMID:9373155 Identification of dynein heavy chain genes expressed in huma... | ACCEPT | Summary: Axonemal dynein complex, from the early testis dynein survey. Reason: Correct general complex; DNAH17 is the beta heavy chain of the sperm outer dynein arm, which is also annotated. Supporting Evidence: PMID:31178125 Ξ³-type: DNAH5 and DNAH8 and Ξ²-type: DNAH9, DNAH11, and DNAH17 PMID:9373155 axonemal dyneins are essential for motility of cilia and flagella |
| GO:0005930 axoneme | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBD at node PTN000073047, seeded by beta-type axonemal heavy chains (DNAH9, DNAH11 and mouse orthologs) and by DNAH17 itself. Reason: Correct node placement for a beta ODA heavy chain. DNAH17 appears among the sources because it has its own experimental axoneme annotation, which is expected. 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, thus explaining the phenotype restricted to sperm cells. |
| GO:0005930 axoneme | IDA PMID:31178125 Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Oute... | ACCEPT | Summary: DNAH17 colocalizes with alpha-tubulin along the sperm axoneme of control men. Reason: Direct localization evidence. 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, thus explaining the phenotype restricted to sperm cells. |
| GO:0005930 axoneme | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of axoneme location. Reason: Agrees with the IDA evidence. 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, thus explaining the phenotype restricted to sperm cells. |
| GO:0007017 microtubule-based process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction of the very broad microtubule-based process. Reason: A broad process term, correct for a dynein motor but peripheral to the specific roles recorded under flagellated sperm motility and microtubule-based movement. 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 | ACCEPT | Summary: InterPro mapping from the dynein heavy chain family. Reason: Outer arm heavy chains drive microtubule sliding in the axoneme; accurate though general. 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:0008569 minus-end-directed microtubule motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBD at the root dynein heavy chain node PTN000743491, seeded by characterized cytoplasmic and axonemal dyneins. Reason: DNAH17 retains the AAA1 hydrolytic site, the stalk and the microtubule-binding domain, and there is no evidence of loss of motor function in this lineage. Minus-end-directed motor activity is the core molecular function. Supporting Evidence: file:human/DNAH17/DNAH17-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 (IPR004273). Reason: Same conclusion as the IBA. Supporting Evidence: file:human/DNAH17/DNAH17-uniprot.txt Produces force towards the minus ends of microtubules |
| GO:0030286 dynein complex | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBD for the generic dynein complex at root node PTN000743491. Reason: Correct but too general. DNAH17 is the beta heavy chain of the sperm outer dynein arm, which is better captured by outer dynein arm (already supported by IDA). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000743491 Β· PTN000743491 SUPPORTS TRANSFER Root-node dynein complex IBD transfers correctly; DNAH17 is in a dynein complex. Only the granularity is refined, to outer dynein arm. Proposed replacements: outer dynein arm Supporting Evidence: PMID:31178125 Ξ³-type: DNAH5 and DNAH8 and Ξ²-type: DNAH9, DNAH11, and DNAH17 PMID:39503742 DNAH8/DNAH17 and DNAI1, corresponding to the heavy and intermediate chains of ODAs |
| GO:0030286 dynein complex | IEA GO_REF:0000120 | MODIFY | Summary: Combined ARBA/InterPro inference of the generic dynein complex. Reason: As for the IBA: outer dynein arm is the specific complex. Proposed replacements: outer dynein arm Supporting Evidence: PMID:31178125 Ξ³-type: DNAH5 and DNAH8 and Ξ²-type: DNAH9, DNAH11, and DNAH17 |
| GO:0031514 motile cilium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to motile cilium (flagellum). Reason: Correct in that the sperm flagellum is a motile cilium, but DNAH17 is not detected in airway cilia; sperm flagellum is the informative term. Supporting Evidence: file:human/DNAH17/DNAH17-uniprot.txt Not detected in airway epithelial cells 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, thus explaining the phenotype restricted to sperm cells. |
| GO:0036126 sperm flagellum | IDA PMID:31178125 Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Oute... | ACCEPT | Summary: Immunostaining of DNAH17 along the flagella of control human sperm. Reason: Direct evidence; the sperm flagellum is where DNAH17 functions. 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, thus explaining the phenotype restricted to sperm cells. |
| GO:0036126 sperm flagellum | IDA PMID:39503742 DNAH3 deficiency causes flagellar inner dynein arm loss and ... | ACCEPT | Summary: DNAH17 immunostaining along the sperm flagella of controls and of DNAH3-mutant patients, used as an ODA marker. Reason: The DNAH3 paper stains DNAH17 in human and mouse sperm flagella as an outer arm marker; consistent with the other localization data. Supporting Evidence: PMID:39503742 DNAH8/DNAH17 and DNAI1, corresponding to the heavy and intermediate chains of ODAs |
| GO:0036157 outer dynein arm | IDA PMID:31178125 Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Oute... | ACCEPT | Summary: DNAH17 is identified as a component of the sperm ODA: patient sperm lose ODAs and DNAH8, and DNAH17 colocalizes with the axoneme in sperm but not in respiratory cilia. Reason: Core complex for DNAH17, supported by independent studies showing ODA loss in DNAH17-mutant sperm and co-depletion of ODA subunits. Supporting Evidence: PMID:31178125 By analyzing five male individuals who consulted for isolated infertility and displayed a loss of ODAs in their sperm cells but not in their respiratory cells, we identified bi-allelic mutations in DNAH17. PMID:41549443 revealed a lack of outer dynein arms (ODAs) in the middle, principal, and end pieces of the flagella |
| GO:0036158 outer dynein arm assembly | IDA PMID:31178125 Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Oute... | KEEP AS NON CORE | Summary: Loss of DNAH17 results in loss of ODAs (and of DNAH8) from sperm axonemes. Reason: DNAH17 contributes to outer arm assembly as an essential structural subunit: without it DNAH8, DNAI1, ODAD2 and ODAD4 fail to accumulate in sperm. This is participation as a component rather than as an assembly factor, so it is retained but not treated as core. Supporting Evidence: PMID:31178125 these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present PMID:40009974 DNAH17 deficiency impaired the assembly and docking of outer dynein arms, affected the acrosome reaction, and disrupted mitochondrial function. PMID:41549443 In addition to DNAH17, several proteins associated with ODA assembly, including ODAD4, ODAD2, DNAI1, and DNAH8, were among the top 10 downregulated proteins in DNAH17-mutant patients |
| GO:0045505 dynein intermediate chain binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBD at the root node PTN000743491, seeded by Dictyostelium cytoplasmic dynein. Reason: The outer arm heavy chain tail binds the ODA intermediate chains, and DNAI1 is co-depleted in DNAH17-mutant sperm, so the activity is plausible; there is no direct binding evidence for DNAH17 and binding is not the core motor function. Supporting Evidence: PMID:41549443 In addition to DNAH17, several proteins associated with ODA assembly, including ODAD4, ODAD2, DNAI1, and DNAH8, were among the top 10 downregulated proteins in DNAH17-mutant patients |
| GO:0045505 dynein intermediate chain binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro mapping (IPR026983). Reason: As for the IBA. Supporting Evidence: PMID:41549443 In addition to DNAH17, several proteins associated with ODA assembly, including ODAD4, ODAD2, DNAI1, and DNAH8, were among the top 10 downregulated proteins in DNAH17-mutant patients |
| GO:0051959 dynein light intermediate chain binding | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBD at the root dynein heavy chain node PTN000743491, seeded only by cytoplasmic dynein 1 heavy chains (DYNC1H1 Q14204, mouse Dync1h1, rat RGD:71042). Reason: Light intermediate chains are cytoplasmic dynein 1 subunits. The outer dynein arm has no light intermediate chain, and the axonemal DNALI1 is an inner arm subunit that remains present in DNAH17-deficient sperm. The root-node placement over-propagates a cytoplasmic-dynein-specific interaction to the ODA heavy chain lineage. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH ROLE CONFLATION Sources checked: PANTHER:PTN000743491 Β· PTN000743491 SUPPORTS SOURCE BUT NOT TARGET IBD at the root of the dynein heavy chain family, seeded only by cytoplasmic dynein 1 heavy chains, whose light intermediate chains are cytoplasmic-dynein-specific subunits. Outer arm heavy chains descend from this node but their complex has no light intermediate chain. Supporting Evidence: PMID:31178125 these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present file:human/DNAH17/DNAH17-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 mapping (IPR026983, dynein heavy chain family). Reason: Same argument as for the IBA. Supporting Evidence: PMID:31178125 these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present file:human/DNAH17/DNAH17-uniprot.txt Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains |
| GO:0060285 cilium-dependent cell motility | NAS PMID:9373155 Identification of dynein heavy chain genes expressed in huma... | MODIFY | Summary: Cilium-dependent cell motility, from the early testis dynein survey. Reason: The human study found DNAH17 along sperm axonemes but not the examined respiratory cilia, and affected men lost outer dynein arms in sperm while respiratory arms were preserved (PMID:31178125). Flagellated sperm motility therefore specifies the demonstrated sperm motor context more accurately than the broad cilium-dependent cell-motility term. DNAH17 participates as an outer-arm heavy-chain motor component, rather than being only a downstream marker of infertility. The Dnah17-null mouse phenotype independently supports the sperm-flagellar requirement (PMID:33070343); its disorganized flagella are not a direct measurement of purified motor kinetics. The original NAS source is retained, and the already-proposed GO:0030317 replacement provides the process coverage without a duplicate NEW row. Proposed replacements: flagellated sperm motility Supporting Evidence: PMID:31178125 By analyzing five male individuals who consulted for isolated infertility and displayed a loss of ODAs in their sperm cells but not in their respiratory cells, we identified bi-allelic mutations in DNAH17. PMID:33070343 Similar to those found in patients, Dnah17-/- mice also displayed MMAF phenotype along with completely disorganized axonemal structures. |
| GO:0060294 cilium movement involved in cell motility | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBD at root node PTN000743491, seeded by many axonemal heavy chains. Reason: The positive PAINT movement assertion is retained, with a more specific human sperm context. DNAH17 localizes along sperm axonemes but was not detected in the examined respiratory cilia; affected men lost sperm outer dynein arms while respiratory arms were preserved (PMID:31178125). The heavy-chain motor participates in flagellar beating, and the Dnah17-null mouse phenotype independently supports the sperm requirement without measuring purified motor kinetics (PMID:33070343). GO:0030317 flagellated sperm motility is an is_a child of GO:0060294 and therefore refines this supported movement claim. It is the same replacement already supplied on the imported GO:0060285 cilium-dependent cell motility row, not a separate NEW annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: flagellated sperm motility 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:0097225 sperm midpiece | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence of the sperm midpiece. Reason: Consistent with ODA loss from the middle piece of DNAH17-mutant sperm, which implies DNAH17-containing arms there. Supporting Evidence: PMID:41549443 revealed a lack of outer dynein arms (ODAs) in the middle, principal, and end pieces of the flagella |
| GO:0097228 sperm principal piece | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence of the sperm principal piece. Reason: Consistent with ODA loss along the principal piece of DNAH17-mutant sperm. Supporting Evidence: PMID:41549443 revealed a lack of outer dynein arms (ODAs) in the middle, principal, and end pieces of the flagella |
| GO:0097229 sperm end piece | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence of the sperm end piece. Reason: Consistent with ODA loss in the end piece of DNAH17-mutant sperm. Supporting Evidence: PMID:41549443 revealed a lack of outer dynein arms (ODAs) in the middle, principal, and end pieces of the flagella |
| GO:0097229 sperm end piece | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of sperm end piece. Reason: Agrees with the HPA IDA annotation. Supporting Evidence: PMID:41549443 revealed a lack of outer dynein arms (ODAs) in the middle, principal, and end pieces of the flagella |
| GO:0097729 9+2 motile cilium | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBD at root node PTN000743491 for 9+2 motile cilium. Reason: Formally correct because the sperm flagellum is a 9+2 motile cilium, but DNAH17 is absent from airway multiciliated cells, so the node-level location is broader than the gene's actual distribution. Sperm flagellum is the informative location. Supporting Evidence: file:human/DNAH17/DNAH17-uniprot.txt Not detected in airway epithelial cells 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, thus explaining the phenotype restricted to sperm cells. |
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Download this section (compressed HTML)Q: Is DNAH17 truly absent from all multiciliated epithelia (airway, ependyma, oviduct) and from the embryonic node, and can the reported laterality-disorder variants be explained by a nodal role?
Q: Why do some DNAH17 genotypes give isolated asthenozoospermia with ODA loss but normal flagellar shape, while others give full MMAF with axonemal disorganization; does the protein have a structural role in flagellar assembly beyond the ODA?
Q: Is the association of DNAH17 deficiency with fertilization failure after ICSI a direct consequence of DNAH17 loss (e.g. via reduced PLCZ1) or an independent defect?
Experiment: Cryo-electron tomography of Dnah17-/- and Dnah8-/- mouse sperm axonemes, and of patient sperm with missense alleles, to locate the beta and gamma heavy chains in the sperm ODA and to test their interdependence.
Type: cryo-electron tomography
Experiment: Examine Dnah17-/- mouse embryos for nodal cilia motility and situs defects, to test the candidate left-right asymmetry association.
Type: mouse genetics and live imaging of nodal cilia
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