Affinage

ODAD3

Outer dynein arm-docking complex subunit 3 · UniProt A5D8V7

Length
595 aa
Mass
69.1 kDa
Annotated
2026-06-10
12 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ODAD3 (CCDC151) is a conserved axonemal coiled-coil protein that mediates the assembly and ciliary docking of outer dynein arms (ODAs), the motor complexes that power motile ciliary and flagellar beating (PMID:25192045, PMID:24088566). In respiratory cilia, ODAD3 physically associates with the ODA docking complex through interaction with CCDC114, and its loss abolishes axonemal assembly of the ODA component DNAH5 together with the ODA-DC-associated proteins CCDC114 and ARMC4, abrogating ODA deployment (PMID:25192045). ODAD3 acts within a shared distal-ODA deployment pathway with LRRC56, which it binds directly; loss of LRRC56 strips ODAD3 from the distal axoneme, and disease-associated variants in either gene disrupt their reciprocal localization and interaction (PMID:41229303). The protein is required broadly for motile cilia function across tissues: its loss in mice causes communicating hydrocephalus linked to ependymal expression, laterality defects, and male infertility, while germ-cell-restricted activity during spermatogenesis underlies asthenoteratozoospermia with multiple morphological abnormalities of the sperm flagella (MMAF) in a dose-dependent manner (PMID:31383820, PMID:38920681). Loss-of-function mutations cause primary ciliary dyskinesia (PMID:25192045).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2013 Medium

    Establishing that ODAD3 is functionally required for motile cilia answered whether this coiled-coil protein contributes to dynein arm assembly in vivo and connected it to planar cell polarity signaling.

    Evidence Morpholino knockdown in zebrafish with cilia phenotyping and genetic interaction with prickle1, plus mammalian cell knockdown

    PMID:24067530

    Open questions at the time
    • Morpholino phenotypes not confirmed with stable mutants
    • Molecular basis of the prickle1 genetic interaction unresolved
    • No direct biochemical demonstration of dynein arm binding
  2. 2013 High

    Biochemical characterization of the Chlamydomonas ortholog ODA10 defined how the protein behaves relative to the canonical docking complex, showing it binds axonemes independently of ODA dynein and depends on ODA5 for stability.

    Evidence Positional cloning, HA-tagged cDNA rescue, detergent/salt extraction, sucrose gradient sedimentation, and axoneme rebinding assay in Chlamydomonas

    PMID:24088566

    Open questions at the time
    • Relationship of ODA10 behavior to the vertebrate ODA-DC not fully reconciled
    • ODA5 has no clearly defined vertebrate counterpart in the timeline
    • Stoichiometry and binding site on the axoneme not resolved
  3. 2014 High

    Identifying ODAD3 as an ODA-DC-related protein that physically binds CCDC114 explained the molecular cause of a human ciliopathy by showing its loss prevents axonemal assembly of ODA and ODA-DC components.

    Evidence Co-immunoprecipitation, immunofluorescence, zebrafish and mouse mutant models, and human genetic analysis across three families

    PMID:25192045

    Open questions at the time
    • Structural basis of the CCDC151–CCDC114 interaction unknown
    • Order of assembly within the docking complex not established
    • Whether interaction with DNAH5/ARMC4 is direct or indirect not determined
  4. 2019 High

    A targeted mouse knockout established the in vivo organismal consequences of ODAD3 loss, linking ependymal expression to communicating hydrocephalus and defining laterality and fertility defects.

    Evidence Targeted gene deletion in mice with microCT imaging, β-galactosidase reporter expression, and histology

    PMID:31383820

    Open questions at the time
    • Cellular mechanism linking ependymal cilia loss to communicating hydrocephalus not detailed
    • Does not separate developmental from adult requirements
  5. 2024 High

    Conditional deletion clarified the germ-cell-autonomous, developmentally timed role of ODAD3 in spermatogenesis, defining MMAF and a gene dosage effect on fertility.

    Evidence Conditional gene deletion in adult male mice with expression timing, seminiferous tubule analysis, and sperm motility/morphology assessment

    PMID:38920681

    Open questions at the time
    • Molecular step in flagellar assembly that fails not pinpointed
    • Mechanism of the spermiogenesis/spermiation arrest unresolved
  6. 2025 High

    Demonstrating a direct ODAD3–LRRC56 interaction placed both proteins in a shared pathway controlling distal deployment of ODA and ODA-DC and connected disease variants to disrupted localization.

    Evidence In vivo AP-MS, targeted knockdown, in vivo imaging, and disease-variant functional analysis in Xenopus laevis

    PMID:41229303

    Open questions at the time
    • Whether LRRC56 binds ODAD3 directly or via the docking complex not fully separated
    • Mechanism establishing proximal-versus-distal axonemal patterning unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural architecture of the vertebrate ODA-DC and the precise assembly hierarchy by which ODAD3 recruits CCDC114, ARMC4, and DNAH5 onto the axoneme remain undefined.
  • No structural model of the ODAD3-containing docking complex
  • Assembly order and direct-versus-indirect partner relationships unresolved
  • Mechanism of distal axonemal targeting not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005929 cilium 3 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-1643685 Disease 1
Partners
CCDC114LRRC56
Complex memberships
outer dynein arm docking complex (ODA-DC)

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CCDC151 (ODAD3) encodes an axonemal coiled-coil protein required for assembly of outer dynein arms (ODAs) and ODA docking complex (ODA-DC) components onto ciliary microtubules. Loss-of-function mutations abolish CCDC151 assembly into respiratory cilia and cause failure of axonemal assembly of the ODA component DNAH5 and ODA-DC-associated components CCDC114 and ARMC4. Co-immunoprecipitation demonstrated that CCDC151 physically interacts with CCDC114, identifying it as an ODA-DC-related protein. Immunofluorescence microscopy, co-immunoprecipitation, zebrafish and mouse mutant models, human genetic analysis American journal of human genetics High 25192045
2013 CCDC151 (ODAD3) is required for dynein arm assembly in IFT-dependent motile cilia. In zebrafish, morpholino depletion of Ccdc151 impairs motile cilia function in Kupffer's vesicle and pronephros by disrupting dynein arm assembly. Additionally, ccdc151 interacts genetically with prickle1 in controlling cell division orientation in the pronephros, and knockdown in mammalian cells affects primary cilium length. Morpholino knockdown in zebrafish, immunofluorescence, genetic interaction (epistasis with prickle1), mammalian cell knockdown Human molecular genetics Medium 24067530
2013 In Chlamydomonas, ODA10 (ortholog of ODAD3/CCDC151) encodes a conserved coiled-coil axonemal protein that is present in both cytoplasm and flagella, remains axonemal after detergent treatment, and is extracted with 0.6 M NaCl. ODA10p sediments near the top of sucrose gradients (not with 23S ODA proteins), and both ODA dynein and ODA10p can bind independently to oda10-mutant axonemes. ODA10p is absent from oda5 flagella and cytoplasm, indicating that ODA5p is required for ODA10p stability in vivo. These results indicate ODA10p does not function as part of a traditional docking complex. Positional cloning, HA-tagged cDNA rescue, detergent extraction, salt extraction, sucrose gradient sedimentation, axoneme rebinding assay Molecular biology of the cell High 24088566
2019 Loss of Ccdc151 (Odad3) in mice via targeted gene deletion leads to perinatal lethality, congenital hydrocephalus, defects in left-right body asymmetry, and male infertility. Beta-galactosidase reporter expression confirmed Ccdc151 expression in ependymal cells lining the ventricular brain system, linking loss of function to hydrocephalus. The hydrocephalus is communicating in nature (aqueduct of Sylvius remains continuous). Ccdc151 deletion in adult animals results in abnormal sperm counts and defective sperm motility. Targeted gene deletion in mice, microCT imaging, β-galactosidase reporter expression, histological analysis Disease models & mechanisms High 31383820
2024 Conditional deletion of Odad3 in adult male mice leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF). Odad3 expression begins during the first wave of spermatogenesis at the meiotic stage and is restricted to germ cells in the adult testes. Odad3-deficient mice display defects in spermatogenesis with accumulation at spermiogenesis and spermiation phases. Heterozygous knockout males show reduced sperm count, motility, abnormal morphology, and shorter fertile lifespan, indicating a gene dosage effect. Conditional gene deletion in mice, expression analysis (timing during spermatogenesis), seminiferous tubule analysis, sperm motility and morphology assessment Cells High 38920681
2025 ODAD3 physically interacts with LRRC56 as part of the ODA docking complex in vertebrate multiciliated cells. In vivo affinity purification mass spectrometry in Xenopus laevis showed that Lrrc56 binds ODA docking complex components including Odad3. Loss of lrrc56 by knockdown caused distal loss of Odad3 from the axoneme, and disease-associated variants in both LRRC56 and ODAD3 disrupted their localization and interaction, placing both in a shared functional pathway for distal ODA and ODA-DC deployment. In vivo affinity purification mass spectrometry (AP-MS), targeted knockdown in Xenopus laevis, in vivo imaging, disease-variant functional analysis Disease models & mechanisms High 41229303

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation. American journal of human genetics 133 25192045
2013 The coiled-coil domain containing protein CCDC151 is required for the function of IFT-dependent motile cilia in animals. Human molecular genetics 43 24067530
2014 Nonsense mutation in coiled-coil domain containing 151 gene (CCDC151) causes primary ciliary dyskinesia. Human mutation 33 25224326
2013 Chlamydomonas ODA10 is a conserved axonemal protein that plays a unique role in outer dynein arm assembly. Molecular biology of the cell 26 24088566
2019 Functional loss of Ccdc151 leads to hydrocephalus in a mouse model of primary ciliary dyskinesia. Disease models & mechanisms 23 31383820
2018 Whole-exome sequencing identifies a novel CCDC151 mutation, c.325G>T (p.E109X), in a patient with primary ciliary dyskinesia and situs inversus. Journal of human genetics 17 30504913
2020 Identification of a frame shift mutation in the CCDC151 gene in a Han-Chinese family with Kartagener syndrome. Bioscience reports 12 32490514
2021 Case Report: Identification of a Novel ODAD3 Variant in a Patient With Primary Ciliary Dyskinesia. Frontiers in genetics 6 33719352
2024 The Odad3 Gene Is Necessary for Spermatozoa Development and Male Fertility in Mice. Cells 3 38920681
2019 Correction: Whole-exome sequencing identifies a novel CCDC151 mutation, c.325GT (p.E109X), in a patient with primary ciliary dyskinesia and situs inversus. Journal of human genetics 2 31178588
2025 Physical and functional interaction of Lrrc56 and Odad3 controls deployment of axonemal dyneins in vertebrate multiciliated cells. bioRxiv : the preprint server for biology 0 40631331
2025 Physical and functional interaction of the ciliopathy proteins Lrrc56 and Odad3 control deployment of axonemal dyneins in vertebrate multiciliated cells. Disease models & mechanisms 0 41229303

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