Affinage

DAAM1

Disheveled-associated activator of morphogenesis 1 · UniProt Q9Y4D1

Length
1078 aa
Mass
123.5 kDa
Annotated
2026-06-09
66 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DAAM1 is a diaphanous-related formin that serves as a core actin-nucleating scaffold in the non-canonical Wnt/planar cell polarity (PCP) pathway, coupling Wnt/Frizzled signaling to Rho-dependent cytoskeletal remodeling (PMID:11779461). It acts as a molecular bridge that physically links Dishevelled (Dvl) to RhoA, and Dvl-mediated relief of an intramolecular DAD–DID/GBD autoinhibitory interaction is the principal mode of DAAM1 activation, converting it into a Rho-activating effector (PMID:11779461, PMID:18162551). Once active, DAAM1 nucleates and bundles unbranched actin filaments through its FH2 domain, whose intrinsic assembly activity is gated by a 'locked' beta-strand conformation and by the length of the linker connecting the N-terminal region to the FH2 core (PMID:17482208, PMID:17986009). Productive filament assembly requires cooperating factors: Profilin1 engages the FH1 domain to drive Wnt-induced stress-fiber formation (PMID:17021034), Flightless-I enhances FH2 actin-assembly activity and aids Rho-dependent activation (PMID:20223827), and Fascin binds the FH2 domain to recruit and stabilize DAAM1 along filopodial and pseudopodial actin bundles (PMID:23850281, PMID:33458919). DAAM1 activity is further tuned post-translationally, requiring Src-mediated Tyr652 phosphorylation for homodimerization and actin polymerization—an event antagonized by the phosphatase-regulator PTPN3 (PMID:31406243). Through these activities DAAM1 organizes diverse actin-based structures and supports microtubule stabilization and MTOC/Golgi reorientation during directed migration and tip-cell polarization (PMID:20351293, PMID:20927366, PMID:26792835). Physiologically, DAAM1 is essential for vertebrate gastrulation and convergent extension (PMID:11779461), heart morphogenesis and sarcomere assembly downstream of Wnt5a (independently of RhoA in cardiomyocytes) (PMID:21177343, PMID:26526197), epithelial junction stability and E-cadherin-based adhesion (PMID:34233186), subapical actin organization in multiciliated cells via an Inturned/NPHP4 complex (PMID:26644512), and presynaptic and dendritic actin remodeling, with a neuronal FH2 microexon modulating DAAM1-dependent RHOA/ROCK signaling required for synaptic plasticity and memory (PMID:25897839, PMID:29972794, PMID:40328765). DAAM1 also drives cancer cell invasion and metastasis through WNT11-FZD7-DAAM1-RhoA-ROCK-Myosin II and integrin-coupled signaling, and additionally restrains integrin surface levels by binding and inhibiting the deubiquitinase USP10 independently of its actin functions (PMID:33082334, PMID:29752407, PMID:37562219).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 High

    Established DAAM1's founding role: how Wnt/Frizzled signals reach Rho was unknown, and DAAM1 was shown to physically bridge Dishevelled to RhoA, defining the molecular link of the non-canonical Wnt/PCP branch.

    Evidence Reciprocal Co-IP and dominant-negative/depletion experiments in human cells and Xenopus embryos with genetic epistasis

    PMID:11779461

    Open questions at the time
    • Did not resolve how Dvl binding activates DAAM1
    • No structural basis for the Dvl–DAAM1–RhoA bridge
  2. 2007 High

    Resolved the activation mechanism: Dvl binding to the DAD domain disrupts intramolecular autoinhibition, showing Dvl acts upstream to convert DAAM1 into an active Rho activator rather than Rho acting as the primary activator.

    Evidence Domain-deletion mutagenesis, Co-IP, and Xenopus convergent extension rescue assays

    PMID:18162551

    Open questions at the time
    • Quantitative kinetics of autoinhibition relief not measured
    • Interplay between Dvl and Rho/GTP in activation not fully resolved
  3. 2007 High

    Defined the structural basis of FH2 actin-assembly control: two crystal structures revealed a tethered/ring-shaped dimer with a 'locked' beta-strand conformation occluding the actin-binding surface, identifying an autoinhibited FH2 state whose disruption boosts assembly ~10-fold.

    Evidence X-ray crystallography (2.25 and 2.8 Å) with site-directed mutagenesis and in vitro actin assembly assays

    PMID:17482208 PMID:17986009

    Open questions at the time
    • How the locked conformation is released in cells unknown
    • No structure of full-length autoinhibited DAAM1
  4. 2006 Medium

    Identified the first cytoskeletal effectors: Profilin1 was shown to bind the FH1 domain and act downstream of DAAM1 for Wnt-induced stress fibers, and DAAM1 was found to bind GTP-RhoA/Cdc42 and collaborate with Src and CIP4 to remodel protrusions.

    Evidence Co-IP, immunofluorescence, Y2H, GTPase pull-downs, and siRNA knockdown with actin phenotype readouts

    PMID:16630611 PMID:17021034

    Open questions at the time
    • Direct vs indirect nature of some interactions not all resolved
    • Role of Cdc42/CIP4 axis in vivo not established
  5. 2007 Medium

    Showed DAAM1 has dynamic, stage-specific functions in vivo: during zebrafish convergent extension it first forms an EphB–Dvl2 complex routed into endocytic vesicles to modulate adhesion, then redistributes to actin to drive cell extension.

    Evidence Co-IP, live imaging, dynamin dominant-negative inhibition, and subcellular fractionation in zebrafish

    PMID:17412835

    Open questions at the time
    • Molecular trigger for the localization switch unknown
    • Direct vs indirect EphB association not defined
  6. 2010 Medium

    Broadened DAAM1's output beyond actin: a constitutively active C-terminal construct inhibited endothelial proliferation/migration via microtubule stabilization, while DAAM1 localized to myosin IIB stress fibers via its N-terminus and was required for centrosome/Golgi reorientation in polarity.

    Evidence Constitutively active and N-terminal truncation constructs, pharmacological dissection, immunofluorescence, and wound-healing polarity assays

    PMID:20351293 PMID:20927366

    Open questions at the time
    • Mechanism by which DAAM1 stabilizes microtubules unknown
    • Link between MT and actin functions of DAAM1 unresolved
  7. 2010 Medium

    Identified Flightless-I as a cofactor that enhances DAAM1 FH2 actin-assembly activity and promotes GTP-Rho-mediated relief of autoinhibition, and is required for DAAM1-driven actin assembly in cells.

    Evidence Direct binding assays, in vitro actin assembly assays, and siRNA knockdown with actin readout

    PMID:20223827

    Open questions at the time
    • Stoichiometry and structural mode of Fli-I action unknown
    • Whether Fli-I acts on endogenous DAAM1 complexes in vivo untested
  8. 2011 High

    Demonstrated a non-redundant in vivo developmental requirement: Daam1-null mice show ventricular noncompaction and septal defects, with DAAM1 needed for cardiomyocyte F-actin assembly through a RhoA/Rac1/Cdc42-independent route.

    Evidence Gene-trap knockout mice, in vivo rescue, cardiomyocyte F-actin assays, and small-GTPase activity assays (negative for RhoA/Rac1/Cdc42)

    PMID:21177343

    Open questions at the time
    • Identity of the GTPase-independent effector pathway in heart unknown
    • Mechanistic basis of noncompaction not defined
  9. 2013 High

    Reconstituted a direct actin-bundling partnership: DAAM1 bundles actin along the entire filopodial shaft, and Fascin directly binds and recruits/stabilizes DAAM1 on actin bundles, establishing a cooperative mechanism for filopodia formation.

    Evidence Co-IP, in vitro pull-down with purified proteins, single-molecule TIRF microscopy, and siRNA knockdown with filopodia readout

    PMID:23850281

    Open questions at the time
    • Regulation of DAAM1–Fascin assembly by upstream signals unknown
  10. 2015 Medium

    Placed DAAM1 in tissue-specific actin-organizing complexes: it forms an Inturned/NPHP4 ternary complex organizing subapical actin for cilia polarization, and binds Piccolo to direct presynaptic F-actin polymerization at active zones.

    Evidence Co-IP and morpholino/loss-of-function knockdown with subapical and presynaptic F-actin readouts in Xenopus and neurons

    PMID:25897839 PMID:26644512

    Open questions at the time
    • How these adaptors target/activate DAAM1 mechanistically unclear
    • Direct vs indirect nature of Piccolo binding not fully defined
  11. 2015 High

    Refined the cardiac role: DAAM1 and DAAM2 are co-required for sarcomere assembly and myocardial maturation, acting in the Wnt5a pathway with reduced AKT (but unaffected RhoA) activity in double-KO hearts.

    Evidence Conditional and double knockout mice, genetic epistasis with Wnt5a, sarcomere structure and cardiac function analyses

    PMID:26526197

    Open questions at the time
    • Link between DAAM1 and AKT regulation not mechanistically defined
    • Redundancy boundaries between DAAM1 and DAAM2 incompletely mapped
  12. 2016 Medium

    Extended DAAM1's roles in polarity and localization control: it cooperates with Kif26b in the Dvl3 complex for tip-cell polarization via microtubule/MTOC repositioning, maintains lateral-membrane actin to preserve epithelial architecture (with WAVE complex), and its immobilized localization at actin nodes dictates the site of F-actin assembly.

    Evidence Co-IP, rescue experiments, siRNA knockdown, WAVE co-depletion epistasis, photoactivatable tracking, and rapamycin-inducible membrane targeting

    PMID:26792835 PMID:27760153 PMID:27807130

    Open questions at the time
    • What anchors/immobilizes DAAM1 at actin nodes unknown
    • How DAAM1 coordinates with the antagonistic WAVE pathway unresolved
  13. 2018 High

    Identified negative regulators and pathogen exploitation: MTSS1 binds the DAAM1 C-terminus and pauses its actin polymerization to control dendritic filopodial length, and the DAAM1 FH2 domain is directly hijacked by Borrelia BBA66 to drive coiling phagocytosis.

    Evidence Single-molecule speckle microscopy, Co-IP, MTSS1 conditional KO, plus Y2H/ELISA/pull-down/Co-IP and functional blocking for BBA66

    PMID:29746581 PMID:29972794

    Open questions at the time
    • How MTSS1 inhibition is relieved in vivo unknown
    • Host signaling triggered by BBA66–DAAM1 during phagocytosis undefined
  14. 2018 Medium

    Connected DAAM1 to integrin-driven invasion: type IV collagen activates an integrin αvβ3→DAAM1(DAD)→RhoA axis that drives invadopodia extension, stress-fiber assembly, and haptotaxis in breast cancer cells.

    Evidence IP, GST pull-down, shRNA knockdown, dominant-negative constructs, RhoA activity and haptotaxis assays

    PMID:29752407

    Open questions at the time
    • Indirect nature of integrin–DAD association not molecularly resolved
    • In vivo relevance to tumor invasion not tested here
  15. 2019 High

    Defined a phosphorylation switch and additional pathway nodes: Src-mediated Tyr652 phosphorylation (opposed by PTPN3) is required for DAAM1 homodimerization and actin polymerization driving cancer migration, while a Daam1/WGEF/Rho branch supports Xenopus pronephric tubulogenesis.

    Evidence Co-IP/pull-down, Src kinase and phosphosite mutagenesis, in vitro actin assays, migration/invasion assays, plus morpholino epistasis in Xenopus/zebrafish

    PMID:21804089 PMID:31406243

    Open questions at the time
    • Upstream signals controlling Tyr652 phosphorylation in normal tissue unknown
    • How phosphorylation couples to autoinhibition release unresolved
  16. 2020 Medium

    Revealed a non-formin signaling role and pathway-selectivity function: WNT11-FZD7-DAAM1 drives amoeboid invasion/metastasis via RhoA-ROCK-Myosin II, and Daam1/2 bind the Wnt inhibitor RNF43 to restrain canonical Wnt by promoting Frizzled degradation.

    Evidence Knockdown/dominant-negative with RhoA/Myosin II assays and in vivo metastasis models; Daam1/2 double-KO organoids/mice with RNF43 Co-IP and Wnt reporters

    PMID:33082334 PMID:38000028

    Open questions at the time
    • Mechanism by which DAAM1/2 promotes RNF43-dependent Fzd turnover unknown
    • How DAAM1 partitions between canonical and non-canonical Wnt outputs unclear
  17. 2021 Medium

    Added partners and adhesion functions: YWHAZ (14-3-3ζ) forms a complex with DAAM1 required for microfilament remodeling and RhoA activation in cancer migration, while FH2-dependent DAAM1 activity organizes junctional F-actin and E-cadherin localization for epithelial adhesion.

    Evidence Co-IP, immunofluorescence, siRNA/overexpression with RhoA assays, miR-613 luciferase reporters, and live imaging with FH2 mutant rescue in nephron/MDCK cells

    PMID:34233186 PMID:34453038

    Open questions at the time
    • Functional consequence of 14-3-3ζ binding on DAAM1 conformation unknown
    • How FH2 activity directs E-cadherin localization mechanistically undefined
  18. 2023 Medium

    Uncovered an actin-independent regulatory function: the DAAM1 FH2 domain binds and inhibits the deubiquitinase USP10, preventing αv-integrin deubiquitination and limiting integrin surface accumulation, thereby restraining myofibroblast differentiation.

    Evidence Y2H, PLA, Co-IP, in vitro DUB activity assays with the FH2 domain, siRNA knockdown, and integrin ubiquitination assays

    PMID:37562219

    Open questions at the time
    • Structural basis for FH2-mediated DUB inhibition unknown
    • Whether this function is regulated by Wnt/PCP signaling untested
  19. 2024 Medium

    Identified RIL (and FNBP1) as new Wnt-responsive partners binding the C-terminal actin-nucleating region of Daam1, with double knockdown producing synergistic Xenopus gastrulation defects, reinforcing DAAM1's scaffolding role in non-canonical Wnt signaling.

    Evidence Co-IP, immunofluorescence, gain/loss-of-function in Xenopus, and genetic epistasis (double-knockdown synergy)

    PMID:38968989

    Open questions at the time
    • Molecular function of RIL/FNBP1 on DAAM1 activity unknown
    • Mammalian relevance of these interactions untested
  20. 2025 High

    Defined isoform-level tuning of DAAM1 in the brain: a conserved neuronal microexon extending the FH2 linker alters actin polymerization, and its deletion impairs neuritogenesis, synaptic plasticity, and memory through elevated RHOA/ROCK signaling rescuable by ROCK inhibition.

    Evidence CRISPR microexon deletion in mice, in vitro actin assays, LTP electrophysiology, spine/calcium imaging, behavioral tests, and pharmacological ROCK rescue

    PMID:40328765

    Open questions at the time
    • How the microexon biophysically alters FH2 actin output not fully resolved
    • Tissue/cell-type breadth of microexon-regulated functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DAAM1's multiple regulatory inputs—Dvl-mediated autoinhibition relief, Tyr652 phosphorylation, cofactor binding (Fli-I, Fascin, 14-3-3ζ, MTSS1), and the neuronal microexon—are integrated to select among its actin, microtubule, and non-formin (USP10) outputs in a given cell type remains unresolved.
  • No unified structural model of full-length regulated DAAM1
  • Quantitative hierarchy of activating and inhibitory inputs unknown
  • Determinants of actin- vs microtubule- vs DUB-directed function undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 7 GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 5 GO:0005856 cytoskeleton 4 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-1643685 Disease 3
Partners
DVLFSCN1MTSS1PFN1RHOASRCUSP10YWHAZ
Complex memberships
Dvl3–DAAM1–Kif26b PCP complexDvl–DAAM1–RhoA complexInturned–NPHP4–DAAM1 ternary complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 DAAM1 binds directly to both Dishevelled (Dvl) and RhoA, acting as a molecular bridge that mediates Wnt/Frizzled-induced Dvl-Rho complex formation and Rho activation downstream of Frizzled receptor signaling. Inhibition or depletion of Daam1 prevents Wnt/Fz activation of Rho and blocks Xenopus gastrulation without affecting beta-catenin signaling, placing Daam1 specifically in the non-canonical Wnt/PCP branch. Co-immunoprecipitation, dominant-negative/depletion experiments in human cells and Xenopus embryos, genetic epistasis Cell High 11779461
2007 DAAM1 activation is mediated primarily by Dishevelled (Dvl) binding rather than by Rho. Dvl binds to the DAD (diaphanous autoregulatory domain) of DAAM1, disrupting the intramolecular GBD/DID–DAD autoinhibitory interaction. Removal of the DAD or DAD mutations convert DAAM1 into an active protein capable of inducing Rho activation. Thus, Dvl acts upstream of Daam1, which in turn activates RhoA. Domain-deletion mutagenesis, co-immunoprecipitation, Xenopus convergent extension rescue assays Proceedings of the National Academy of Sciences of the United States of America High 18162551
2007 Crystal structure of the DAAM1 FH2 domain at 2.25 Å resolution reveals a tethered-dimer architecture similar to yeast Bni1 but with a novel 'locked' conformation in which two beta-strands formed by linker ends occlude the actin-binding surfaces. Mutations disrupting this beta-strand lock increase actin assembly activity ~10-fold, indicating this occluded conformation represents an autoinhibited state of the FH2 domain. X-ray crystallography (SAD phasing, 2.25 Å), site-directed mutagenesis, in vitro actin assembly assay Journal of molecular biology High 17482208
2007 Crystal structure of human DAAM1 FH2 domain at 2.8 Å shows a head-to-tail ring-shaped dimer. Actin assembly assays with DAAM1 mutants demonstrate that the length of the linker connecting the N-terminal domain to the core FH2 region is critical for actin assembly activity. X-ray crystallography, in vitro actin assembly assays with FH2 mutants Genes to cells : devoted to molecular & cellular mechanisms High 17986009
2006 Profilin1 interacts with the FH1 domain of DAAM1 and co-localizes with DAAM1 on actin stress fibers in response to Wnt signaling. Depletion of Profilin1 inhibits stress fiber formation induced by non-canonical Wnt signaling in mammalian cells, placing Profilin1 as a downstream effector of DAAM1 for cytoskeletal changes. Co-immunoprecipitation, immunofluorescence, siRNA knockdown with actin phenotype readout in mammalian cells and Xenopus Development (Cambridge, England) High 17021034
2006 DAAM1 binds RhoA and Cdc42 in a GTP-dependent manner and interacts with the SH3 domain of CIP4 (Cdc42 effector). DAAM1 also interacts and collaborates with non-receptor tyrosine kinase Src to induce branched protrusion formation. Ectopic DAAM1 expression induces cell rounding, branched protrusions, and reduction of stress fibers. Yeast two-hybrid, co-immunoprecipitation, GTPase pull-down assays, cell morphology overexpression experiments Experimental cell research Medium 16630611
2007 In zebrafish notochord, DAAM1 dynamically changes subcellular localization during convergent extension: early it forms a complex with EphB receptors and Dishevelled 2 that is incorporated into dynamin-dependent endocytic vesicles, removing EphB from the cell surface to switch cell adhesiveness; later, DAAM1 co-localizes with the actin cytoskeleton to drive cell extension. Co-immunoprecipitation, live imaging, dynamin dominant-negative inhibition, subcellular fractionation in zebrafish Proceedings of the National Academy of Sciences of the United States of America Medium 17412835
2010 Constitutively active C-terminal DAAM1 inhibits endothelial cell proliferation and migration by inducing microtubule (MT) stabilization, not solely actin polymerization. MT stabilization alone was sufficient to reproduce the inhibitory effect; actin polymerization inhibition alone (jasplakinolide) was not. This places DAAM1 as a regulator of MT stability in endothelial cells downstream of Wnt/PCP signaling. Expression of constitutively active DAAM1 construct, pharmacological dissection (jasplakinolide, MT stabilizers), endothelial cell proliferation/migration/network formation assays in vitro and in vivo Proceedings of the National Academy of Sciences of the United States of America Medium 20351293
2010 DAAM1 localizes to acto-myosin stress fibers, specifically co-localizing with myosin IIB-containing ventral actin stress fibers. The N-terminal region of DAAM1 (residues 1–440) is responsible for this targeting and interacts with myosin IIB fibers independently of F-actin or RhoA binding. DAAM1 depletion blocks centrosome/Golgi reorientation during wound healing, revealing a role in cell polarity establishment. Specific antibody immunofluorescence, N-terminal truncation constructs, wound-healing polarity assays, DAAM1-stable overexpression lines in U2OS cells PloS one Medium 20927366
2010 Flightless-I (Fli-I), a gelsolin family protein, binds directly to DAAM1 and mDia1, enhances their intrinsic actin assembly activity in vitro, and promotes GTP-Rho-mediated relief of DAAM1 autoinhibition. Fli-I is required for DAAM1-induced actin assembly in living cells. Direct binding assays, in vitro actin assembly assay, siRNA knockdown with actin assembly readout The Journal of biological chemistry Medium 20223827
2011 Daam1-deficient mice exhibit ventricular noncompaction, double outlet right ventricles, and septal defects with embryonic/neonatal lethality. Daam1 is required for filamentous actin assembly and organization in cardiomyocytes. Importantly, Daam1-mediated cytoskeletal regulation in the heart does not operate through RhoA, Rac1, or Cdc42. Gene-trap knockout mice, in vivo genetic rescue, F-actin assembly/organization assays in cardiomyocytes, small GTPase activity assays (negative results for RhoA/Rac1/Cdc42) Development (Cambridge, England) High 21177343
2013 DAAM1 is a potent actin-bundling protein that localizes along the entire filopodial shaft (not only tips). Fascin co-immunoprecipitates with DAAM1 from cell extracts; purified fascin directly binds DAAM1; and single-molecule TIRF imaging shows fascin recruits DAAM1 to and stabilizes DAAM1 on actin bundles in vitro. Silencing fascin causes loss of DAAM1 from filopodial shafts. Together, DAAM1 and fascin directly collaborate in actin bundling required for filopodial formation. Co-immunoprecipitation, in vitro pull-down with purified proteins, single-molecule TIRF microscopy, siRNA knockdown with filopodia morphology readout Current biology : CB High 23850281
2015 Inturned acts as an adaptor protein forming a ternary complex with NPHP4 and DAAM1 in multiciliated cells of Xenopus epidermis. Knockdown of daam1 (but not formin-2) disrupts the subapical actin web required for proper cilia polarization and directional fluid flow, placing DAAM1 downstream of Inturned/NPHP4 in organizing the subapical actin network. Co-immunoprecipitation, morpholino knockdown in Xenopus multiciliated cells, immunofluorescence of subapical actin and basal bodies The Journal of cell biology Medium 26644512
2015 Piccolo directly binds Daam1 at presynaptic active zones. Daam1 activation promotes Piccolo binding and spatially directs F-actin polymerization at the active zone. Daam1 loss-of-function impairs presynaptic F-actin assembly in neurons, similar to loss of Piccolo or Profilin. Co-immunoprecipitation, protein-protein interaction assays, Daam1 overexpression/knockdown with presynaptic F-actin readout in neurons PloS one Medium 25897839
2015 DAAM1 and DAAM2 are co-required for sarcomere assembly and myocardial maturation. Myocardial-specific Daam1 CKO mice have noncompaction cardiomyopathy and disordered cardiomyocyte polarity; Daam1/Daam2 double KO (DKO) mice show severely disrupted sarcomere structure and reduced cardiac function. Genetic interaction with Wnt5a (Daam1 CKO in Wnt5a-null background worsens phenotype) confirms DAAM1 acts in the Wnt5a pathway. RhoA was unaffected in DKO hearts, but AKT activity was reduced. Conditional knockout mice (floxed allele), Daam1/2 double KO, genetic epistasis with Wnt5a null, sarcomere structure analysis, cardiac function measurements Developmental biology High 26526197
2016 DAAM1 accumulates at lateral membrane contacts (LCs) of epithelial junctions and regulates the actin filaments there. DAAM1 depletion disperses actin filaments at LCs, enhances LC membrane motility (dependent on the WAVE complex and its downstream targets), and causes invasion of neighboring cell layers, disrupting polarized epithelial architecture. siRNA knockdown, immunofluorescence, live-cell imaging of membrane motility, WAVE complex component co-depletion epistasis The Journal of cell biology Medium 27807130
2016 Kif26b (a kinesin) is recruited into the Dvl3/DAAM1 complex. Kif26b and DAAM1 cooperatively regulate endothelial cell tip-cell polarization and directed migration via microtubule stabilization and MTOC/Golgi repositioning. Ectopic Kif26b expression rescues the polarization defect caused by DAAM1 depletion, indicating Kif26b acts downstream of or in parallel to DAAM1 in the Dvl3/DAAM1 PCP complex. Co-immunoprecipitation, siRNA knockdown, 3D angiogenesis assay, MTOC/Golgi localization analysis, rescue experiment Molecular biology of the cell Medium 26792835
2016 DAAM1 localizes at cytoplasmic actin nodes and is immobilized there (demonstrated by photoactivatable tracking). Forced membrane targeting of DAAM1 via rapamycin-dependent linkage enhances F-actin assembly at the plasma membrane relative to cytoplasm, demonstrating that DAAM1's localization determines the site of actin network assembly during cytoskeletal recovery. Photoactivatable GFP tracking, rapamycin-inducible membrane targeting, Latrunculin A washout actin recovery assay, live-cell imaging PloS one Medium 27760153
2018 MTSS1 (inverse-BAR protein) binds to DAAM1 at its C-terminus and pauses DAAM1-mediated F-actin polymerization, as shown by single-molecule speckle microscopy. DAAM1 localizes to the tips of Purkinje cell dendritic filopodia and its overactivation causes excessive contact-induced retraction, phenocopying MTSS1 knockout. MTSS1 thus functions as a formin inhibitor of DAAM1 to control dendritic filopodial length and final neuronal morphology. Single-molecule speckle microscopy of F-actin polymerization, Co-IP, conditional knockout mice (MTSS1), overactivation constructs with dendritic morphology readout Cell reports High 29972794
2018 Integrin αvβ3 associates (indirectly) with the C-terminal DAD domain of DAAM1 in breast cancer cells. Type IV collagen activates integrin αvβ3→DAAM1→RhoA signaling to promote invadopodia extension and cell haptotaxis. DAAM1 knockdown or dominant-negative N-DAAM1 abrogates collagen-induced RhoA activity, stress fiber assembly, invadopodia extension, and haptotaxis. Immunoprecipitation, GST pull-down, shRNA knockdown, dominant-negative constructs, RhoA activity assay, Boyden chamber haptotaxis assay The Journal of biological chemistry Medium 29752407
2018 DAAM1 FH2 domain directly binds the Borrelia burgdorferi surface lipoprotein BBA66, as demonstrated by yeast two-hybrid, ELISA, pull-down, and co-immunoprecipitation with recombinant proteins. This interaction mediates coiling phagocytosis of B. burgdorferi by human neuroglial cells; BBA66-deficient mutant strains show strongly reduced coiling. Yeast two-hybrid, recombinant protein pull-down, co-immunoprecipitation, ELISA, confocal colocalization, anti-Daam1 antibody blocking PloS one Medium 29746581
2019 PTPN3 (a FERM/PDZ-domain phosphatase) inhibits Src activity and thereby prevents Src-mediated phosphorylation of DAAM1 at Tyr652. Tyr652 phosphorylation of DAAM1 is required for DAAM1 homodimer formation and actin polymerization. A phosphodeficient DAAM1 mutant (Y652F) inhibits F-actin assembly and suppresses lung cancer cell migration and invasion. Protein interaction assays (Co-IP/pulldown), Src kinase assay, phosphorylation site mutagenesis, in vitro actin polymerization assay, cancer cell migration/invasion assays Oncogene High 31406243
2019 In the developing Xenopus nephron, DAAM1 functions in pronephric tubulogenesis through a Daam1/WGEF (ArhGEF19)/Rho signaling branch of the Wnt/PCP pathway. Knockdown of Daam1 reduces late pronephric epithelial markers; inhibiting multiple nodes of the Daam1 pathway reduces tubulogenesis without affecting early patterning. Morpholino knockdown in Xenopus and zebrafish, epistasis experiments along the pathway, marker gene expression analysis Journal of the American Society of Nephrology : JASN Medium 21804089
2020 WNT11-FZD7-DAAM1 signaling activates Rho-ROCK1/2-Myosin II to drive amoeboid invasion, tumour-initiating potential, and metastasis in melanoma cells. Mechanistically, WNT11 signals through the Frizzled-7 receptor to DAAM1, which then activates the RhoA-ROCK1/2-Myosin II axis. siRNA/shRNA knockdown, dominant-negative constructs, RhoA/Myosin II activity assays, in vivo metastasis models, pathway epistasis Nature communications Medium 33082334
2020 Daam1/2 double knockout in intestinal cells stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Frizzled (Fzd) receptor. Daam1/2 interact with the Wnt inhibitor RNF43. Loss of Daam1/2 thus impairs noncanonical Wnt/PCP signaling and disrupts Paneth cell differentiation, demonstrating that DAAM1 asymmetrically regulates canonical vs. noncanonical Wnt branches. Daam1/2 double knockout organoids/mice, Co-immunoprecipitation of Daam1/2 with RNF43, single-cell RNA sequencing, Wnt reporter assays Science advances Medium 38000028
2021 YWHAZ (14-3-3ζ) directly interacts with and co-localizes with DAAM1 in breast cancer cells. This YWHAZ-DAAM1 complex is required for DAAM1-mediated microfilament remodeling and RhoA activation. MiR-613 directly targets both YWHAZ and DAAM1, and blocking the YWHAZ-DAAM1 complex inhibits cell migration. Co-immunoprecipitation, immunofluorescence co-localization, siRNA/overexpression experiments, RhoA activity assay, luciferase reporter for miR-613 targeting Cell death discovery Medium 34453038
2021 Daam1 localizes to newly formed cell contacts in the developing nephron, and its depletion decreases junctional F-actin microfilament localization and slows F-actin turnover. The FH2 domain of DAAM1 mediates efficient localization of junctional E-cadherin. Daam1 depletion impairs organized movement of renal cells, demonstrating that Daam1 formin activity is required for E-cadherin-based intercellular adhesion and epithelial organization. Live imaging in Xenopus nephron and MDCK cells, siRNA knockdown, FH2 domain mutant rescue, junctional F-actin and E-cadherin localization assays Cell reports Medium 34233186
2021 Daam1 interacts with Fascin via its formin homology (FH) domains, specifically the FH2 domain, in breast cancer cells. Co-knockdown of Daam1 or Fascin prevents their co-localization on actin filaments and impairs pseudopodia formation and cell migration, confirming that Daam1-Fascin interaction through FH2 is required for actin filament assembly and cell motility. Co-immunoprecipitation, domain-mapping pulldown (FH1, FH2, DAD constructs), immunofluorescence co-localization, siRNA knockdown with migration assay Cell proliferation Medium 33458919
2023 DAAM1 FH2 domain binds to and inhibits the deubiquitinase (DUB) activity of USP10 independently of DAAM1's actin-polymerizing functions. This interaction prevents USP10 from deubiquitinating αv-integrins, thereby suppressing integrin cell surface accumulation. Loss of DAAM1 increases αv-, β1-, β5-integrin levels, recycling, and fibronectin deposition, promoting myofibroblast differentiation. Yeast two-hybrid, proximity ligation assay (PLA), co-immunoprecipitation, DUB activity assay with DAAM1 FH2 domain, siRNA knockdown, integrin ubiquitination assays European journal of cell biology Medium 37562219
2024 RIL (Reversion Induced LIM domain protein) is a new binding partner of Daam1, interacting with the C-terminal actin-nucleating portion of Daam1 in a Wnt-responsive manner. RIL co-localizes with Daam1 at the plasma membrane on actin fibers. Loss of both RIL and Daam1 synergizes to produce severe Xenopus gastrulation defects, indicating they function in the same non-canonical Wnt signaling pathway. RIL also synergizes with another Daam1-interacting protein FNBP1. Co-immunoprecipitation, immunofluorescence, gain/loss-of-function in Xenopus, genetic epistasis (double knockdown synergy) Developmental biology Medium 38968989
2025 A conserved neuronal microexon within the DAAM1 FH2 domain (extending the FH2 linker region) alters actin polymerization. Genomic deletion of this microexon in mice causes neuritogenesis defects, increased calcium influx, fewer immature dendritic spines, impaired long-term potentiation, and memory deficits. These phenotypes are associated with increased RHOA/ROCK signaling and are partially rescued by ROCK inhibitor treatment, placing the microexon as a modulator of DAAM1-dependent RHOA/ROCK signaling in neurons. Genomic microexon deletion (CRISPR), in vitro actin polymerization assay, LTP electrophysiology, dendritic spine analysis, calcium imaging, behavioral memory tests, pharmacological ROCK inhibitor rescue Nature communications High 40328765

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell 675 11779461
2007 Mechanism of activation of the Formin protein Daam1. Proceedings of the National Academy of Sciences of the United States of America 142 18162551
2012 Dvl2-dependent activation of Daam1 and RhoA regulates Wnt5a-induced breast cancer cell migration. PloS one 102 22655072
2013 The formin Daam1 and fascin directly collaborate to promote filopodia formation. Current biology : CB 101 23850281
2011 Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart morphogenesis. Development (Cambridge, England) 98 21177343
2006 The diaphanous-related formin DAAM1 collaborates with the Rho GTPases RhoA and Cdc42, CIP4 and Src in regulating cell morphogenesis and actin dynamics. Experimental cell research 92 16630611
2006 Profilin is an effector for Daam1 in non-canonical Wnt signaling and is required for vertebrate gastrulation. Development (Cambridge, England) 84 17021034
2007 Structure of the FH2 domain of Daam1: implications for formin regulation of actin assembly. Journal of molecular biology 79 17482208
2020 WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion. Nature communications 73 33082334
2018 miR-613 inhibits cell migration and invasion by downregulating Daam1 in triple-negative breast cancer. Cellular signalling 71 29339084
2007 Daam1 regulates the endocytosis of EphB during the convergent extension of the zebrafish notochord. Proceedings of the National Academy of Sciences of the United States of America 55 17412835
2010 Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 54 20351293
2017 Involvement of testicular DAAM1 expression in zinc protection against cadmium-induced male rat reproductive toxicity. Journal of cellular physiology 50 28332181
2015 The polarity protein Inturned links NPHP4 to Daam1 to control the subapical actin network in multiciliated cells. The Journal of cell biology 49 26644512
2010 DAAM1 is a formin required for centrosome re-orientation during cell migration. PloS one 47 20927366
2015 DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly. Developmental biology 46 26526197
2018 MTSS1 Regulation of Actin-Nucleating Formin DAAM1 in Dendritic Filopodia Determines Final Dendritic Configuration of Purkinje Cells. Cell reports 40 29972794
2011 Pronephric tubulogenesis requires Daam1-mediated planar cell polarity signaling. Journal of the American Society of Nephrology : JASN 40 21804089
2018 Integrin αvβ3-associated DAAM1 is essential for collagen-induced invadopodia extension and cell haptotaxis in breast cancer cells. The Journal of biological chemistry 38 29752407
2007 Crystal structure of human DAAM1 formin homology 2 domain. Genes to cells : devoted to molecular & cellular mechanisms 38 17986009
2017 Daam1 activates RhoA to regulate Wnt5a‑induced glioblastoma cell invasion. Oncology reports 36 29207169
2010 Flightless-I (Fli-I) regulates the actin assembly activity of diaphanous-related formins (DRFs) Daam1 and mDia1 in cooperation with active Rho GTPase. The Journal of biological chemistry 36 20223827
2021 Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis. Genes 34 34208970
2021 YWHAZ interacts with DAAM1 to promote cell migration in breast cancer. Cell death discovery 34 34453038
2016 Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity-signaling pathway. Molecular biology of the cell 33 26792835
2015 Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1. PloS one 31 25897839
2014 Daam1 is a regulator of filopodia formation and phagocytic uptake of Borrelia burgdorferi by primary human macrophages. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 24696301
2004 Identification of chick and mouse Daam1 and Daam2 genes and their expression patterns in the central nervous system. Brain research. Developmental brain research 29 15464228
2020 D-Aspartate Upregulates DAAM1 Protein Levels in the Rat Testis and Induces Its Localization in Spermatogonia Nucleus. Biomolecules 28 32353957
2019 A DAAM1 3'-UTR SNP mutation regulates breast cancer metastasis through affecting miR-208a-5p-DAAM1-RhoA axis. Cancer cell international 28 30911286
2019 DAAM1-mediated migration and invasion of ovarian cancer cells are suppressed by miR-208a-5p. Pathology, research and practice 28 31104928
2016 First Evidence of DAAM1 Localization During the Post-Natal Development of Rat Testis and in Mammalian Sperm. Journal of cellular physiology 27 26831620
2023 The simultaneous administration of microplastics and cadmium alters rat testicular activity and changes the expression of PTMA, DAAM1 and PREP. Frontiers in cell and developmental biology 25 36968197
2019 PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization. Oncogene 25 31406243
2016 Formin DAAM1 Organizes Actin Filaments in the Cytoplasmic Nodal Actin Network. PloS one 25 27760153
2016 DAAM1 stabilizes epithelial junctions by restraining WAVE complex-dependent lateral membrane motility. The Journal of cell biology 22 27807130
2020 LINC01006 facilitates cell proliferation, migration and invasion in prostate cancer through targeting miR-34a-5p to up-regulate DAAM1. Cancer cell international 21 33088221
2018 First evidence of DAAM1 localization in mouse seminal vesicles and its possible involvement during regulated exocytosis. Comptes rendus biologies 21 29571963
2020 DAAM1 and PREP are involved in human spermatogenesis. Reproduction, fertility, and development 20 31972124
2021 Formin homology domains of Daam1 bind to Fascin and collaboratively promote pseudopodia formation and cell migration in breast cancer. Cell proliferation 19 33458919
2008 Localization of the Diaphanous-related formin Daam1 to neuronal dendrites. Neuroscience letters 18 18832009
2017 Daam1 regulates fascin for actin assembly in mouse oocyte meiosis. Cell cycle (Georgetown, Tex.) 17 28682694
2012 Deletion of a single-copy DAAM1 gene in congenital heart defect: a case report. BMC medical genetics 17 22857009
2019 Wnt5a/ROR1 activates DAAM1 and promotes the migration in osteosarcoma cells. Oncology reports 16 31894282
2020 Placental defects lead to embryonic lethality in mice lacking the Formin and PCP proteins Daam1 and Daam2. PloS one 14 32353019
2021 SNHG15 facilitated malignant behaviors of oral squamous cell carcinoma through targeting miR-188-5p/DAAM1. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 12 33742497
2018 Regulation of neural crest development by the formin family protein Daam1. Genesis (New York, N.Y. : 2000) 12 29673042
2018 Human neuroglial cells internalize Borrelia burgdorferi by coiling phagocytosis mediated by Daam1. PloS one 12 29746581
2023 Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2. Science advances 11 38000028
2021 The Wnt/PCP formin Daam1 drives cell-cell adhesion during nephron development. Cell reports 11 34233186
2019 Divergent roles of the Wnt/PCP Formin Daam1 in renal ciliogenesis. PloS one 11 31469868
2023 The novel role of etoposide in inhibiting the migration and proliferation of small cell lung cancer and breast cancer via targeting Daam1. Biochemical pharmacology 9 36858182
2021 Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins, DAAM1 and PREP, in Human Testicular Disorders. International journal of molecular sciences 7 34360857
2021 Daam1 Overexpression Promotes Gastric Cancer Progression and Regulates ERK and AKT Signaling Pathways. OncoTargets and therapy 6 34475767
2017 Implication of overexpression of dishevelled-associated activator of morphogenesis 1 (Daam-1) for the pathogenesis of human Idiopathic Pulmonary Arterial Hypertension (IPAH). Diagnostic pathology 6 28288669
2025 A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation. Nature communications 5 40328765
2023 Characterization of Expression and Function of the Formins FHOD1, INF2, and DAAM1 in HER2-Positive Breast Cancer. Journal of breast cancer 3 37985384
2024 Reversion induced LIM domain protein (RIL) is a Daam1-interacting protein and regulator of the actin cytoskeleton during non-canonical Wnt signaling. Developmental biology 2 38968989
2023 FOXD3 confers chemo-sensitivity in ovarian cancer through a miR-335/DAAM1/myosin II axis-dependent mechanism. Journal of ovarian research 2 36627652
2023 The formin DAAM1 regulates the deubiquitinase activity of USP10 and integrin homeostasis. European journal of cell biology 2 37562219
2022 MicroRNA-137 Inhibits Esophageal Squamous Cell Carcinoma by Downregulating DAAM1. Protein and peptide letters 2 35986526
2025 ARC Expands the DAAM1 Microexon-Mediated Actin-RHOA/ROCK Interplay. Cytoskeleton (Hoboken, N.J.) 1 40488380
2025 Polycystin-1 Mutant Alters Mechanotransduction in Response to Collagen and Extracellular Matrix Stiffness via Daam1-Dependent Microfilament Remodeling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40789101
2026 Flexibility-driven design of etoposide derivatives targeting Daam1: a thermodynamics-guided strategy against breast cancer metastasis. Journal of computer-aided molecular design 0 42213223
2025 Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer. Cancer cell international 0 39881344
2025 The Complicity of DAAM1, PTMA, RSPH6A, and Steroidogenic Genes in the Fertility of Male Rats Exposed to Cadmium During Gestation and Lactation: Attenuation by PREOG. Reproductive sciences (Thousand Oaks, Calif.) 0 40629240

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