Affinage

DNAAF10

Dynein axonemal assembly factor 10 · UniProt Q96MX6

Length
357 aa
Mass
39.7 kDa
Annotated
2026-06-09
36 papers in source corpus 9 papers cited in narrative 9 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

DNAAF10 (Monad/WDR92) is a conserved cytoplasmic WD40-repeat protein that functions as a dynein arm assembly factor required for the cytoplasmic preassembly of axonemal motors that power motile cilia (PMID:30428028, PMID:31116681). In Chlamydomonas, loss of WDR92 produces aflagellate or short-flagella cells whose axonemes lack inner and outer dynein arms (PMID:30428028, PMID:31116681), and the protein is specifically required for the cytoplasmic stability of axonemal dynein heavy chains while sparing IFT dynein heavy chain, placing its action upstream of ciliary transport at the level of dynein heavy-chain folding and stability (PMID:31116681). WDR92 carries out this role as part of an HSP90 co-chaperone system: immunoprecipitation identified inner dynein arm heavy chains together with the R2TP-like complex (RuvBL1, RPAP3, MOT48) and additional DNAAFs (ODA7, DYX1C) as binding partners (PMID:30428028), and its dosage genetically interacts with and stabilizes DNAAF4/PF23 (PMID:38498551). Consistent with this assembly role, planarian WDR92 knockdown yields cilia with reduced beat frequency, partial loss of dynein arms, and axonemal architectural defects (PMID:26912790). Independently of ciliary assembly, DNAAF10 was characterized as a modulator of TNF-alpha/cycloheximide-induced caspase-3 activation and apoptosis acting together with its physical partners RPAP3 and PIH1D1 (PMID:16487927, PMID:18538670, PMID:21078300), and as an exosome-bound protein that binds the amphiregulin mRNA 3'-UTR to promote its decay and thereby suppress breast cancer cell invasion (PMID:23844004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2006 Medium

    Established the first functional readout for an uncharacterized WD40 protein by showing it modulates death signaling, before any ciliary or chaperone role was known.

    Evidence Overexpression in HEK293 cells with TNF-alpha/cycloheximide-induced caspase-3 and apoptosis assays

    PMID:16487927

    Open questions at the time
    • Single overexpression assay in one cell line without loss-of-function confirmation
    • No mechanism linking the protein to caspase activation defined
    • No endogenous role established
  2. 2008 Medium

    Identified the first physical partner, RPAP3, and placed Monad and RPAP3 in a shared apoptosis-modulatory pathway.

    Evidence Affinity purification/MS for interaction plus RPAP3 overexpression and RNAi with apoptosis/caspase-3 assays in HEK293 and HeLa

    PMID:18538670

    Open questions at the time
    • Did not place the interaction in the context of a defined chaperone complex
    • Mechanism by which the RPAP3 association affects caspase-3 unresolved
  3. 2010 Medium

    Connected Monad to the R2TP complex by demonstrating interaction with PIH1D1, broadening the protein's partner network beyond RPAP3.

    Evidence Reciprocal Co-IP and siRNA knockdown with doxorubicin-induced apoptosis/caspase-3 assays in HEK293 and U2OS

    PMID:21078300

    Open questions at the time
    • Did not link R2TP membership to a substrate or assembly function
    • Apoptosis modulation mechanism still phenomenological
  4. 2013 Medium

    Revealed a distinct post-transcriptional function: directing amphiregulin mRNA decay through the RNA exosome to restrain tumor cell invasion.

    Evidence Co-IP with exosome and with amphiregulin 3'-UTR, knockdown invasion assay with neutralizing-antibody rescue in MDA-MB-231 cells

    PMID:23844004

    Open questions at the time
    • Relationship between this RNA-decay role and the chaperone/ciliary roles unknown
    • Direct RNA binding versus exosome-mediated bridging not resolved
    • Single cell-line context
  5. 2016 Medium

    Provided the first in vivo evidence that WDR92 is required to build motile ciliary axonemes, linking it to dynein arm integrity at the ultrastructural level.

    Evidence RNAi knockdown in planaria with locomotion assay and TEM of ciliary ultrastructure

    PMID:26912790

    Open questions at the time
    • Molecular substrate within the axoneme not identified
    • Cytoplasmic versus axonemal site of action not distinguished
  6. 2019 High

    Defined WDR92 as a cytoplasmic dynein arm assembly factor acting within an R2TP-like chaperone network alongside dynein heavy chains and other DNAAFs.

    Evidence Insertional mutagenesis with axonemal EM phenotype, IP-MS and Co-IP of R2TP-like components in Chlamydomonas

    PMID:30428028

    Open questions at the time
    • Direct enzymatic/chaperone activity on heavy chains not reconstituted
    • Order of substrate hand-off among DNAAFs unresolved
  7. 2019 High

    Pinpointed WDR92's role to the cytoplasmic stability of axonemal dynein heavy chains, acting upstream of ciliary transport and sparing IFT dynein.

    Evidence Chlamydomonas mutant gel-filtration fractionation with immunoblotting, EM, and double-mutant epistasis

    PMID:31116681

    Open questions at the time
    • Biochemical mechanism of heavy-chain folding/stabilization not reconstituted in vitro
    • Selectivity for axonemal over IFT dynein heavy chain mechanistically unexplained
  8. 2024 Medium

    Showed that WDR92 dosage cooperates with another DNAAF (PF23/DNAAF4) and influences its stability, indicating combinatorial control of ciliary assembly capacity.

    Evidence Chlamydomonas diploid second-site non-complementation under cycloheximide sensitization with PF23 immunoblotting

    PMID:38498551

    Open questions at the time
    • Direct physical basis for WDR92-dependent PF23 stabilization not shown
    • Whether the interaction is direct or via shared substrate unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How WDR92/DNAAF10 mechanistically reconciles its cytoplasmic dynein-assembly role with its reported apoptosis-modulatory and mRNA-decay functions, and whether a direct chaperone activity on dynein heavy chains can be reconstituted, remains unresolved.
  • No reconstituted biochemical assay of WDR92 chaperone activity
  • No structural model of WDR92 within the PAQosome/R2TP assembly
  • No human disease linkage established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 2 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-392499 Metabolism of proteins 1
Partners
DNAAF4DYX1C1MOT48PIH1D1RPAP3RUVBL1
Complex memberships
PAQosome/R2TP-prefoldin-like complex

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Monad (WDR92/DNAAF10) is a novel WD40 repeat protein containing only two WD40 repeats; overexpression in HEK293 cells potentiated apoptosis and caspase-3 activation induced by TNF-alpha and cycloheximide, establishing a pro-apoptotic modulatory role. Overexpression in HEK293 cells, caspase-3 activation assay, apoptosis assay Biochemical and biophysical research communications Medium 16487927
2008 Monad (WDR92/DNAAF10) physically interacts with RPAP3 (RNA polymerase II-associated protein 3); RPAP3 overexpression potentiated caspase-3 activation and apoptosis induced by TNF-alpha/cycloheximide, and RPAP3 knockdown significantly reduced this apoptosis, placing Monad and RPAP3 in the same apoptosis-modulatory pathway. Affinity purification and mass spectrometry to identify RPAP3 as Monad-binding protein; RPAP3 overexpression and RNAi knockdown with apoptosis/caspase-3 assays in HEK293 and HeLa cells FEBS letters Medium 18538670
2010 PIH1D1, a subunit of the R2TP complex, physically interacts with both RPAP3 and Monad (WDR92/DNAAF10) in HEK293 and U2OS cells; knockdown of PIH1D1 enhanced apoptosis and caspase-3 activation induced by doxorubicin, placing Monad within the R2TP complex as a modulator of apoptosis. Co-immunoprecipitation; siRNA knockdown with apoptosis and caspase-3 activation assays Biochemical and biophysical research communications Medium 21078300
2013 Monad (WDR92/DNAAF10) is an exosome-bound protein that inhibits breast cancer cell invasion by specifically interacting with both the 3'-UTR of amphiregulin mRNA (an EGFR ligand) and the RNA-degrading exosome complex, thereby enhancing amphiregulin mRNA decay; knockdown of Monad increased invasion, which was rescued by anti-amphiregulin neutralizing antibody. Co-immunoprecipitation of Monad with exosome and with 3'-UTR of amphiregulin mRNA; Monad knockdown invasion assay; neutralizing antibody rescue experiment in MDA-MB-231 cells PloS one Medium 23844004
2016 WDR92 (DNAAF10) is a cytoplasmic protein required for the correct architectural assembly of motile cilia; RNAi knockdown in planarian Schmidtea mediterranea reduced organismal movement and caused cilia with reduced beat frequency, partial loss of dynein arms, incomplete B-tubule closure, and central pair defects, establishing WDR92 as part of a cytoplasmic chaperone system required to fold key components of motile ciliary axonemes. RNAi knockdown in planaria; behavioral assay (locomotion); transmission electron microscopy of ciliary ultrastructure; RT-PCR confirmation of knockdown Molecular biology of the cell Medium 26912790
2018 WDR92 (DNAAF10) is a component of the PAQosome, a large multisubunit chaperone complex comprising the R2TP complex, the URI1 prefoldin-like complex, RPB5, and WDR92 itself; WDR92 is thus structurally embedded within this chaperone assembly involved in macromolecular complex assembly and stabilization. Biochemical characterization and complex composition analysis described in review/overview based on prior purification data Advances in experimental medicine and biology Low 30484152
2019 WDR92 (DNAAF10) is a cytoplasmic DNAAF (dynein arm assembly factor) in Chlamydomonas; loss of WDR92 via insertional mutagenesis caused aflagellate cells or cells with stumpy/short flagella and loss of axonemal dynein arms; immunoprecipitation of WDR92 followed by mass spectrometry identified inner dynein arm heavy chains and multiple DNAAFs (RuvBL1, RPAP3, MOT48, ODA7, DYX1C) as binding partners; WDR92 physically interacted with the R2TP-like complex (MOT48-RuvBL1/2-RPAP3) and linked other DNAAFs, indicating WDR92 functions in dynein preassembly in association with the HSP90 co-chaperone R2TP-like complex. DNA insertional mutagenesis; electron microscopy of axonemal ultrastructure; immunoprecipitation followed by mass spectrometry; co-immunoprecipitation of R2TP-like complex components Journal of molecular cell biology High 30428028
2019 WDR92 (DNAAF10) is specifically required for the cytoplasmic stability of axonemal dynein heavy chains but not IFT dynein heavy chain; a Chlamydomonas wdr92-1 mutant missing the last four WD repeats builds only ~0.7-μm cilia lacking both inner and outer dynein arms; gel filtration of cytoplasmic extracts showed that wdr92-1 extracts almost completely lacked all three outer arm heavy chains while IFT dynein heavy chain was present normally; a wdr92-1 tpg1-2 double mutant built ~7-μm immotile cilia completely lacking dynein arms, indicating WDR92 acts upstream of ciliary transport on cytoplasmic dynein heavy chain folding/stability. Chlamydomonas mutant characterization; electron microscopy; gel filtration fractionation of cytoplasmic extracts followed by immunoblotting; double mutant epistasis analysis Molecular biology of the cell High 31116681
2024 Genetic dosage of WDR92 (DNAAF10) interacts with DNAAF4/PF23 in Chlamydomonas diploids; double heterozygosity for wdr92 and pf23 showed second-site non-complementation (SSNC) in a protein-synthesis-inhibited sensitized assay, assembling shorter cilia than wild-type; immunoblots showed PF23 protein levels were reduced by half in pf23/wdr92 heterozygotes, indicating that WDR92 dosage influences PF23 stability and that multiple DNAAF gene dosage cooperates to determine ciliary assembly capacity. Chlamydomonas diploid second-site non-complementation screen; cilia length measurement under cycloheximide-sensitized conditions; immunoblotting for PF23 protein levels PLoS genetics Medium 38498551

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Finding composite regulatory patterns in DNA sequences. Bioinformatics (Oxford, England) 108 12169566
2016 Selection signature analysis reveals genes associated with tail type in Chinese indigenous sheep. Animal genetics 78 27807880
1991 Ultrastructure of human retinal cell transplants with long survival times in rats. Experimental eye research 62 1936181
1988 Growth and synapse formation among major classes of adult salamander retinal neurons in vitro. Neuron 53 3272187
2006 Monad, a WD40 repeat protein, promotes apoptosis induced by TNF-alpha. Biochemical and biophysical research communications 47 16487927
2020 Genomic Scan for Selection Signature Reveals Fat Deposition in Chinese Indigenous Sheep with Extreme Tail Types. Animals : an open access journal from MDPI 45 32365604
1987 Development of the rhesus monkey retina: II. A three-dimensional analysis of the sequences of synaptic combinations in the inner plexiform layer. The Journal of comparative neurology 42 3624556
1990 Early differentiation of ganglion, amacrine, bipolar, and Muller cells in the developing fovea of human retina. The Journal of comparative neurology 37 2298931
2020 LRRTM4: A Novel Regulator of Presynaptic Inhibition and Ribbon Synapse Arrangements of Retinal Bipolar Cells. Neuron 33 31974009
2008 Molecular cloning of novel Monad binding protein containing tetratricopeptide repeat domains. FEBS letters 33 18538670
2018 Genetic variants in fat- and short-tailed sheep from high-throughput RNA-sequencing data. Animal genetics 30 30069889
2019 Chlamydomonas WDR92 in association with R2TP-like complex and multiple DNAAFs to regulate ciliary dynein preassembly. Journal of molecular cell biology 27 30428028
2013 PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription. FEBS letters 25 24036451
2010 PIH1D1, a subunit of R2TP complex, inhibits doxorubicin-induced apoptosis. Biochemical and biophysical research communications 23 21078300
2009 RPAP3 interacts with Reptin to regulate UV-induced phosphorylation of H2AX and DNA damage. Journal of cellular biochemistry 23 19180575
1980 Kinetic and cooperative mechanisms of ligand binding to hemoglobin. The Journal of biological chemistry 23 7372673
2019 WDR92 is required for axonemal dynein heavy chain stability in cytoplasm. Molecular biology of the cell 21 31116681
2016 A prefoldin-associated WD-repeat protein (WDR92) is required for the correct architectural assembly of motile cilia. Molecular biology of the cell 18 26912790
2012 Axonal synapses utilize multiple synaptic ribbons in the mammalian retina. PloS one 16 23284975
2018 The Multiple Functions of the PAQosome: An R2TP- and URI1 Prefoldin-Based Chaperone Complex. Advances in experimental medicine and biology 15 30484152
2004 A sensitive enzymatic assay for the determination of sucrose in serum and urine. Clinica chimica acta; international journal of clinical chemistry 11 15115695
2013 Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA. PloS one 10 23844004
1990 Cytological analysis of tetraploid hybrids between sweet potato and diploid Ipomoea trifida (H. B. K.) Don. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 9 24221067
2022 Integrative analysis prioritizes the relevant genes and risk factors for chronic venous disease. Journal of vascular surgery. Venous and lymphatic disorders 8 35218958
2019 Genome Wide Analysis Approach Suggests Chromosome 2 Locus to be Associated with Thiazide and Thiazide Like-Diuretics Blood Pressure Response. Scientific reports 8 31754133
2021 Cytological and morphology characteristics of natural microsporogenesis within Camellia oleifera. Physiology and molecular biology of plants : an international journal of functional plant biology 6 34092947
2014 Discovery of a dicer-independent, cell-type dependent alternate targeting sequence generator: implications in gene silencing & pooled RNAi screens. PloS one 6 24987961
2023 Characterization of Systemic and Culprit-Coronary Artery miR-483-5p Expression in Chronic CAD and Acute Myocardial Infarction Male Patients. International journal of molecular sciences 4 37239897
2020 Transcriptomic and Proteomic Analysis of Clear Cell Foci (CCF) in the Human Non-Cirrhotic Liver Identifies Several Differentially Expressed Genes and Proteins with Functions in Cancer Cell Biology and Glycogen Metabolism. Molecules (Basel, Switzerland) 3 32927708
2024 Gene dosage of independent dynein arm motor preassembly factors influences cilia assembly in Chlamydomonas reinhardtii. PLoS genetics 2 38498551
2007 Efficient composite pattern finding from monad patterns. International journal of bioinformatics research and applications 2 18048174
2016 Programs as Polypeptides. Artificial life 1 27824500
2026 Autopoiesis as viability-localized self-production in a topos. Bio Systems 0 42107485
2025 Unitary Entities Are the True "Atoms". Entropy (Basel, Switzerland) 0 41294962
2024 The synchronic, diachronic cell as the holism of consciousness. Progress in biophysics and molecular biology 0 38408617
2020 Cytogenetic and pollen identification of genus Gagnepainia (Zingiberaceae) in Thailand. Comparative cytogenetics 0 31988702

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