Affinage

DACT1

Dapper homolog 1 · UniProt Q9NYF0

Length
836 aa
Mass
90.2 kDa
Annotated
2026-06-09
89 papers in source corpus 33 papers cited in narrative 33 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

DACT1 (Dapper/Dpr1/Frodo) is an intracellular scaffold protein that integrates and tunes Wnt signaling, acting through its physical association with Dishevelled to control both the canonical Wnt/β-catenin and non-canonical Wnt/PCP branches (PMID:11970895, PMID:16446366). It engages the DEP domain of Dishevelled and drives Dvl turnover, promoting pVHL-mediated ubiquitination and lysosomal/autophagic degradation of Dvl2, with knockdown stabilizing endogenous Dvl (PMID:16446366, PMID:25825496). Beyond degradation, DACT1 shuttles between cytoplasm and nucleus, where it disrupts β-catenin/LEF1 complexes and recruits HDAC1 to repress Wnt target transcription, and it can also restrict β-catenin's access to TCF without altering β-catenin stability (PMID:18936100, PMID:27122165). In the PCP pathway, DACT1 forms a complex with the transmembrane component Vangl2 and acts genetically upstream of it, controlling Dvl levels and localization and modulating Rho GTPase and JNK activity to govern convergent extension and cell polarity (PMID:19701191, PMID:20145239, PMID:40069199); mechanistically it induces Dvl oligomerization that switches Dvl from Vangl to Frizzled to initiate non-canonical signaling (PMID:40069199). DACT1 activity is set by post-translational control: PKA phosphorylation recruits 14-3-3β to attenuate Dvl degradation, while casein kinase 1 phosphorylation is antagonized by Cyclin G2 to keep DACT1 in an active Wnt-suppressing state (PMID:21262972, PMID:30547803, PMID:31978940). Upon TGF-β induction, DACT1 forms intrinsically-disordered-domain-dependent liquid-liquid phase-separated cytoplasmic condensates that sequester casein kinase 2 to repress Wnt signaling and drive cancer bone metastasis (PMID:33723425). DACT1 additionally promotes autophagy initiation by directly binding Beclin1 and Atg14L to enhance Vps34 lipid kinase activity (PMID:24980960). Human loss-of-function DACT1 missense variants in the DVL2-interaction region are associated with neural tube defects and CAKUT, linking its molecular activities to congenital disease (PMID:22610794, PMID:36066768).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    Established DACT1 as a direct Dishevelled-binding protein and defined its first function as a general Dishevelled antagonist that dampens both β-catenin and JNK outputs.

    Evidence Co-IP, reporter and JNK assays, Xenopus gain/loss-of-function

    PMID:11941372 PMID:11970895

    Open questions at the time
    • Whether antagonism vs. positive regulation is context-dependent was unresolved
    • No molecular basis for the opposing positive role in Frodo studies
  2. 2004 Medium

    Showed DACT1 links Dishevelled to TCF3 in a β-catenin-independent parallel pathway, expanding its mechanism beyond canonical Wnt.

    Evidence Co-IP and morpholino epistasis in Xenopus

    PMID:15329348

    Open questions at the time
    • Direct TCF3 binding domain not crystallized
    • Single-lab finding
  3. 2006 High

    Defined the degradation mechanism: DACT1 routes Dishevelled to lysosomal rather than proteasomal destruction via a DEP-domain/C-terminal interface, and identified parallel p120-catenin/Kaiso regulation.

    Evidence Domain-mapped Co-IP, lysosome/proteasome inhibitor and siRNA assays; Xenopus p120-catenin epistasis

    PMID:16446366 PMID:17084360

    Open questions at the time
    • E3 ligase mediating Dvl ubiquitination not yet identified
    • p120-catenin link is Medium-confidence single lab
  4. 2008 High

    Revealed a distinct nuclear mode of Wnt repression and a physiological role in adipogenesis, showing DACT1 acts at multiple subcellular sites.

    Evidence Fractionation, leptomycin B, Co-IP, reporter, zebrafish; adipogenesis differentiation with Sfrp1 rescue

    PMID:18936100 PMID:19073771

    Open questions at the time
    • Trigger coupling nuclear export to Wnt activation incompletely defined
    • Stoichiometry of β-catenin/LEF1 disruption unknown
  5. 2009 High

    Placed DACT1 genetically upstream of Vangl2 in the PCP pathway through reciprocal mouse rescue, defining its non-canonical role in cell polarity.

    Evidence Co-IP and reciprocal double-mutant genetic rescue in mice, immunofluorescence

    PMID:19701191

    Open questions at the time
    • How DACT1 lowers Vangl2 protein mechanistically not resolved here
  6. 2010 High

    Demonstrated DACT1 selectively governs PCP (Rho/JNK) by controlling Dvl level/localization while sparing canonical Wnt, and identified a postsynaptic role upstream of Rac in dendrite/spine development.

    Evidence Dact1 KO mice with pathway-specific assays; postsynaptic fractionation, mEPSC, GTPase assays, Rac1 rescue

    PMID:20145239 PMID:20335472

    Open questions at the time
    • Link between Dvl regulation and Rac activation at synapses not mechanistically bridged
  7. 2011 High

    Catalogued DACT family interactions (Vangl, Dvl, CK1δ/ε, leucine-zipper dimerization) and uncovered PKA/14-3-3β phosphoregulation that gates Dvl degradation, defining post-translational control.

    Evidence Systematic Co-IP/domain mapping; phospho-site mutagenesis, PKA modulation, colony formation

    PMID:21262972 PMID:21718540

    Open questions at the time
    • Functional significance of dimerization not tested
    • 14-3-3β study single lab
  8. 2012 Medium

    Connected DACT1 molecular activity to human disease by showing NTD-patient missense variants lose Dvl2-degradation and JNK-inhibition function.

    Evidence Biochemical Dvl2 degradation and JNK phosphorylation assays of mutant constructs

    PMID:22610794

    Open questions at the time
    • No animal model of the specific variants
    • Causality vs. risk-association not fully established
  9. 2013 High

    Identified Sestd1 as a Dact1/Vangl2 partner that phenocopies Dact1 loss and links the complex to Rho activation, and established cooperation with Dvl1 at excitatory synapses; also revealed Wnt-independent NF-κB tumor suppression.

    Evidence Domain-mapped Co-IP, Sestd1 KO mouse, Vangl2 genetic rescue, Rho assay; conditional KO with viral rescue; gastric cancer NF-κB assays/xenograft

    PMID:23073659 PMID:23696638 PMID:23826333

    Open questions at the time
    • Mechanism linking Sestd1-Dact1 to Rho exchange factors unknown
    • NF-κB suppression mechanism is Medium-confidence single lab
  10. 2014 High

    Established a direct autophagy-promoting function via Beclin1/Atg14L/Vps34 and showed DACT1 is required for non-canonical Wnt5a-driven cardiomyocyte hypertrophy through the Vangl2/JNK axis.

    Evidence Co-IP, Vps34 kinase assay, autophagy puncta, conditional KO mouse; cardiomyocyte siRNA with JNK/Vangl2 readouts

    PMID:24879894 PMID:24980960

    Open questions at the time
    • How the autophagy and Wnt-scaffold functions are coordinated unclear
    • Cardiomyocyte study Medium-confidence single lab
  11. 2015 Medium

    Defined the molecular route of Dvl2 turnover (pVHL ubiquitination requiring Dvl2 aggregation, coupled to autophagy initiation) and identified MIZ1 as a regulator that disrupts the DACT1-Dvl2 interaction to enhance Wnt.

    Evidence Co-IP, ubiquitination and autophagy inhibitor assays; MIZ1 Co-IP and fractionation

    PMID:25558878 PMID:25825496

    Open questions at the time
    • Both single-lab studies
    • Direct vs. indirect role of DACT1 in pVHL recruitment not resolved
  12. 2018 Medium

    Extended the degradation model with March2 (E3 ligase whose Dsh interaction DACT1 stabilizes regionally) and Cyclin G2/CKI phosphoregulation keeping DACT1 active to suppress Wnt.

    Evidence Co-IP/ubiquitination in Xenopus; yeast two-hybrid, Co-IP, PLA, Ccng2 KO mice, CKI assays

    PMID:29549110 PMID:30547803

    Open questions at the time
    • Relationship between March2 and pVHL pathways unclear
    • Single-lab findings
  13. 2020 Medium

    Pinpointed CKI phosphorylation of DACT1 at Ser762 as the Cyclin G2-regulated switch controlling canonical Wnt suppression in disease tissue.

    Evidence Co-IP, phospho-site mapping, CKI inhibitor, Ccng2 KO mouse, fibrosis markers

    PMID:31978940

    Open questions at the time
    • Single lab
    • Kinase-DACT1 enzymology not reconstituted in vitro
  14. 2021 High

    Discovered that TGF-β-induced DACT1 forms IDR-dependent phase-separated condensates that sequester CK2 to repress Wnt and drive bone metastasis, providing a biophysical mechanism for Wnt suppression.

    Evidence Live imaging, LLPS assays, IDR deletion, condensate mass spectrometry, in vivo metastasis model; promoter mapping of TGF-β induction

    PMID:29136762 PMID:33723425

    Open questions at the time
    • How condensate formation is reversed/regulated not defined
    • Promoter study Low-confidence with no functional element follow-up
  15. 2022 Medium

    Established upstream regulation of DACT1 expression (FTO/m6A destabilization, CRNDE/p300/H3K27ac activation) and linked DACT1 DVL2-binding variants to CAKUT.

    Evidence MeRIP-seq/stability/RIP assays; ChIP and promoter reporter; exome sequencing, DVL2-binding Co-IP, CRISPR KO branching assay

    PMID:35121825 PMID:35802196 PMID:36066768

    Open questions at the time
    • Single-lab regulatory studies
    • CAKUT variant causality limited to cell-based assays
  16. 2025 High

    Resolved the non-canonical mechanism by showing DACT1 induces Dvl oligomerization that switches Dvl from Vangl to Frizzled signalosome clusters, and identified S1P2 receptor coupling to DACT1/Dvl/β-catenin in fibrosis.

    Evidence Xenopus CE assay, Co-IP, oligomerization-defective Dvl mutants, live imaging; S1P2 Co-IP, IF, bleomycin IPF model

    PMID:40069199 PMID:40222913

    Open questions at the time
    • Structural basis of the Dvl partner switch not solved
    • S1P2 link Medium-confidence single lab
  17. 2024 Medium

    Linked dact1/2 to convergent extension and craniofacial morphogenesis via regulation of the calpain capn8, identifying a calcium-dependent proteolysis output downstream of DACT.

    Evidence Zebrafish compound mutants, scRNAseq, capn8 overexpression phenocopy

    PMID:39570288

    Open questions at the time
    • How dact1/2 regulate capn8 mRNA mechanistically unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DACT1's many activities — Dvl degradation, nuclear repression, PCP scaffolding, condensate formation, and autophagy — are spatially and temporally partitioned within a single cell remains unresolved.
  • No integrated model coordinating cytoplasmic, nuclear, and condensate pools
  • No structure of full-length DACT1 or its complexes
  • Endogenous stoichiometry with Dvl/Vangl2 not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-9612973 Autophagy 2
Partners
ATG14BECN1CCNG2CSNK1DDVL2SESTD1VANGL2YWHAB
Complex memberships
Beclin1-Vps34-Atg14L autophagy initiation complexDACT1 phase-separated cytoplasmic condensateDACT1-Vangl2-Sestd1 PCP complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 DACT1 (Dapper) was isolated as a Dishevelled-interacting protein; it colocalizes with Dishevelled intracellularly and forms a complex with Axin, GSK-3, CKI, and β-catenin. Overexpression increases Axin and GSK-3 in this complex, decreasing soluble β-catenin and reducing β-catenin-responsive gene activation. DACT1 also inhibits Dishevelled-mediated activation of JNK, demonstrating it acts as a general Dishevelled antagonist. Co-immunoprecipitation, reporter assays, Xenopus overexpression/depletion, colocalization Developmental cell High 11970895
2002 Frodo (DACT1 ortholog in Xenopus) binds Dishevelled and synergizes with XDsh in secondary axis induction; dominant-negative Frodo and antisense depletion inhibit axial development in response to XDsh and XWnt8 and suppress TCF-reporter activation, establishing Frodo as an essential positive regulator of Wnt signaling in certain developmental contexts. Xenopus overexpression, dominant-negative constructs, antisense oligonucleotide depletion, TCF reporter assay, Co-IP Nature cell biology High 11941372
2004 The conserved N-terminal domain of Frodo (DACT1) associates with TCF3, while the C-terminus binds Dishevelled. Frodo and Dapper are required cell-autonomously for neural tissue formation and organizer gene expression in a β-catenin-independent manner, linking Dsh and TCF to regulate Wnt target genes in a parallel pathway. Co-IP (TCF3 binding), morpholino knockdown, in vivo reporter assays, epistasis analysis in Xenopus Development (Cambridge, England) Medium 15329348
2006 Human DACT1 (Dpr1) inhibits Wnt signaling by promoting lysosomal (not proteasomal) degradation of Dishevelled. The interaction interface is formed between the DEP domain of Dvl and the central/C-terminal regions of Dpr1. The C-terminal 225 amino acids act as a dominant negative. Knockdown of Dpr1 upregulates endogenous Dvl2 protein. Co-IP with domain mapping, lysosome/proteasome inhibitor assays, siRNA knockdown, Western blot The Journal of biological chemistry High 16446366
2006 Frodo (DACT1 ortholog) binds p120-catenin and mediates Wnt-induced stabilization of p120-catenin, which in turn promotes nuclear sequestration of the transcriptional repressor Kaiso. Dsh and Frodo act as upstream regulators of the p120-catenin/Kaiso signaling pathway. Co-IP, Xenopus embryo assays, dominant-negative constructs, reporter assays Developmental cell Medium 17084360
2008 Dpr1 is a nucleocytoplasmic shuttling protein. Endogenous Dpr1 localizes throughout the cell; Wnt1 induces its nuclear export. Leptomycin B causes nuclear accumulation. Nuclear Dpr1 antagonizes Wnt signaling by interacting with β-catenin and LEF1, disrupting their complex, and associating with HDAC1 to enhance the LEF1-HDAC1 repressive interaction. NLS and NES sequences were identified within Dpr1. Subcellular fractionation, leptomycin B treatment, Co-IP, reporter assays, zebrafish embryo assays, domain mapping The Journal of biological chemistry High 18936100
2008 Dact1 regulates adipogenesis by coordinating the Wnt/β-catenin signaling network. Dact1 knockdown impairs adipogenesis through activation of Wnt/β-catenin signaling; this is reversed by secreted Frizzled-related protein 1 (Sfrp1). Dact1 overexpression promotes adipogenesis and confers resistance to Wnt ligand-induced anti-adipogenesis through increased Sfrp expression and reduced Wnt expression. siRNA knockdown, overexpression, adipogenesis differentiation assays, Wnt reporter assays, in vivo mouse models Diabetes Medium 19073771
2009 Dact1 forms a protein complex with Vangl2 (a PCP transmembrane component). In Dact1 mutant mice, Vangl2 is increased at the primitive streak, associated with abnormal E-cadherin distribution and altered PCP biochemistry. Heterozygous Vangl2 mutation rescues recessive Dact1 phenotypes, and loss of Dact1 rescues semidominant Vangl2 phenotypes, establishing Dact1 as an upstream regulator of Vangl2 in the PCP pathway. Co-immunoprecipitation, genetic epistasis (double mutant rescue), immunofluorescence, Western blot in mouse knockout Nature genetics High 19701191
2010 Dact1 loss in mice causes deregulation of PCP signaling (altered Rho GTPase and JNK activity) with the canonical Wnt/β-catenin pathway largely unaffected. Dvl protein levels and cellular distribution are altered in the primitive streak of Dact1 knockout embryos, with increased Dvl2 accumulating in cortical cell regions, indicating Dact1 controls PCP by regulating Dvl protein level and localization. Dact1 knockout mice, PCP reporter assays, Rho/JNK activity assays, immunofluorescence, Western blot The Journal of biological chemistry High 20145239
2010 Dact1 localizes to postsynaptic fractions in forebrain neurons. Dact1 knockout neurons have simpler dendritic arbors, fewer spines, reduced excitatory synapses and miniature EPSCs (inhibitory synapses unaffected). Loss of Dact1 decreases activated Rac. Recombinant Dact1 or constitutively active Rac1 (but not Rho or Cdc42) rescues dendrite and spine phenotypes, placing Dact1 upstream of Rac in a pathway for dendritic development. Subcellular fractionation, KO mouse neurons, electrophysiology (mEPSC), GTPase activity assays, rescue with constitutively active Rac1 The Journal of neuroscience High 20335472
2011 All three Dact paralogs form complexes with Vangl, Dvl, and CK1δ/ε proteins across species. Dact proteins dimerize and heterodimerize through their conserved N-terminal leucine-zipper domains. Weaker, paralog-specific interactions were detected with catenin superfamily members including p120-catenin. Interactions with GSK3, LEF/TCF, HDAC1, and TGFβ receptors were paralog-specific, weak, or condition-sensitive. Systematic co-immunoprecipitation in HEK293 cells, domain deletion mapping BMC biochemistry Medium 21718540
2011 14-3-3β interacts with human Dpr1, and this interaction is dependent on PKA-mediated phosphorylation of Dpr1 at Ser-237 and Ser-827. 14-3-3β binding attenuates Dpr1's ability to promote Dvl degradation, thereby enhancing Wnt signaling. PKA-mediated Dpr1 phosphorylation correlates with growth and tumor formation of colon cancer cells. Co-IP, phosphorylation site mutagenesis, PKA inhibitor/activator assays, Western blot for Dvl levels, colony formation assay The Journal of biological chemistry High 21262972
2012 DACT1 missense mutations N356K and R45W (identified in human NTD patients) show loss-of-function or reduced activity in inducing Dvl2 degradation and inhibiting JNK phosphorylation, linking specific DACT1 molecular activities to human neural tube defect risk. Biochemical assays of DVL2 degradation, JNK phosphorylation assay with mutant constructs Human mutation Medium 22610794
2013 Sestd1 is a novel binding partner of both Vangl2 and Dact1, with the Sestd1-Dact1 interface formed by the C-terminal region of Sestd1 and the N-terminal region of Dact1. Loss of Sestd1 precisely phenocopies loss of Dact1, and both show reciprocal genetic rescue interactions with Vangl2 mutation. Dact1 and Sestd1 interaction can induce Rho GTPase activation in cell-based assays. Co-immunoprecipitation with domain mapping, Sestd1 knockout mouse with phenotypic analysis, genetic epistasis with Vangl2, Rho GTPase activation assay The Journal of biological chemistry High 23696638
2013 Dact1 is required cell-autonomously for excitatory synapse formation on cortical interneuron dendrites. Synapse numbers in Dact1-deficient interneurons are rescued by virally-mediated re-expression of Dact1, expression of the binding partner Dishevelled-1, and partially by DISC1, establishing Dact1 functions in cooperation with Dvl1 at postsynaptic sites. Conditional KO (Dlx-I12b enhancer-Cre), viral rescue, synapse counting, immunostaining PloS one Medium 23826333
2013 Dapper1 promotes tumor suppression in gastric cancer by inhibiting NF-κB activation and its downstream factors (Bcl-2, Bcl-X, IL-8, TNF-α), in addition to its known Wnt antagonism, establishing a Wnt-independent tumor suppressor mechanism. Stable transfection, colony formation, apoptosis assay, NF-κB reporter assay, cytokine protein measurement, xenograft model Molecular medicine (Cambridge, Mass.) Medium 23073659
2014 Dpr1 directly interacts with Beclin1 and Atg14L, enhances the Beclin1-Vps34 interaction, and increases Vps34 lipid kinase activity, promoting autophagosome formation. Dpr1 ablation in the CNS results in motor coordination defects and accumulation of p62 and ubiquitinated proteins. Co-IP, Vps34 kinase activity assay, LC3/Atg14L/DFCP1 puncta formation assay, conditional KO mouse phenotype, Western blot for LC3 lipidation and p62 Cell research High 24980960
2014 Dpr1 is essential for Wnt5a-induced cardiomyocyte hypertrophy via the non-canonical Wnt/PCP pathway. Dpr1 depletion inhibits JNK phosphorylation downstream of non-canonical Wnt and causes increased Vangl2 protein levels with Vangl2 enrichment in perinuclear vesicles, indicating Dpr1 regulates the Vangl2/JNK axis. siRNA knockdown in cardiomyocytes, JNK phosphorylation assay, cell surface area measurement, Western blot for Vangl2, immunofluorescence FEBS letters Medium 24879894
2015 Dpr1 promotes pVHL-mediated ubiquitination of Dvl2 and its subsequent autophagic degradation. Dpr1 knockdown decreases Dvl2-pVHL interaction and Dvl2 ubiquitination. The autophagic degradation of Dvl2 by Dpr1 requires Dvl2 aggregation. Protein aggregates (Dvl2, p62, Htt103Q) stimulate autophagy initiation (Beclin1-Vps34 interaction, Atg14L puncta) in a Dpr1-dependent manner. Co-IP, ubiquitination assay, autophagy inhibitor assays, Atg14L/Beclin1 interaction Co-IP, siRNA knockdown The Journal of biological chemistry Medium 25825496
2015 MIZ1 interacts with Dpr1 and attenuates Dpr1's ability to induce Dvl2 degradation. Upon Wnt3a stimulation or Dpr1/Dvl2 overexpression, MIZ1 translocates from nucleus to cytoplasm, disrupting the Dpr1-Dvl2 interaction, thereby enhancing Wnt signaling. Co-IP, subcellular fractionation, Western blot for Dvl2 levels, cell proliferation assay The Biochemical journal Medium 25558878
2016 Dact1 and Dact2 are required for neural crest cell delamination (EMT) in Xenopus and chick. They inhibit Wnt/β-catenin signaling upstream of TCF transcriptional activity, and regulate subcellular distribution of β-catenin (preventing TCF co-activation) without affecting β-catenin stability. Morpholino knockdown in Xenopus and chick, in vivo Wnt reporter assays, β-catenin subcellular localization analysis, rescue experiments Development (Cambridge, England) Medium 27122165
2018 March2, a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by ubiquitin-mediated lysosomal degradation of Dishevelled. Dapper1 (Dpr1) stabilizes the interaction between March2 and Dsh specifically in the dorso-animal region of Xenopus embryos, enabling regional specificity of Dsh degradation for vertebrate head formation. Co-IP, ubiquitination assay, dominant-negative/morpholino constructs in Xenopus, regional expression analysis Development (Cambridge, England) Medium 29549110
2018 Cyclin G2 interacts with Dapper1 (Dpr1), and this interaction impacts CKI-mediated phosphorylation of Dpr1 — cyclin G2 binding decreases Dpr1 phosphorylation by CKI, keeping Dpr1 in an active (unphosphorylated) state that suppresses Wnt/β-catenin signaling. This mechanism underlies cyclin G2-mediated inhibition of gastric cancer cell growth and migration. Yeast two-hybrid screening, Co-IP, Duolink PLA, TOPFlash reporter, Ccng2 knockout mice, CKI phosphorylation assay Journal of experimental & clinical cancer research : CR Medium 30547803
2019 miR-125b-5p targets DACT1 (validated by luciferase assay), and DACT1 negatively regulates pancreatic β-cell function by promoting JNK signaling; miR-125b-5p improves β-cell function through inhibiting the JNK pathway via DACT1 suppression in T2DM mouse models. Luciferase reporter (miR-125b-5p → DACT1), siRNA knockdown, miRNA mimic/inhibitor transfection, JNK pathway readout Life sciences Low 30684546
2020 Cyclin G2 interaction with Dapper1 decreases phosphorylation of Dpr1 at Ser762 by casein kinase 1 (CKI), thereby suppressing canonical Wnt signaling and protecting against tubulointerstitial fibrosis in diabetic nephropathy. Co-IP, phosphorylation site identification, CKI inhibitor assay, Ccng2 KO mouse, fibrosis markers Journal of cellular and molecular medicine Medium 31978940
2021 TGF-β induces DACT1 expression, and DACT1 forms cytoplasmic protein condensates via liquid-liquid phase separation (LLPS) that do not co-localize with known organelles. These condensates require intrinsically disordered domains. Mass spectrometry of isolated condensates revealed sequestration of casein kinase 2 (a Wnt pathway activator), thereby repressing Wnt signaling. DACT1 condensates are maintained in vivo and are critical for breast and prostate cancer bone metastasis. Live-cell imaging, phase separation assay (LLPS), intrinsically disordered domain deletion, mass spectrometry of condensate proteome, in vivo xenograft bone metastasis model Nature cell biology High 33723425
2021 TGF-β increases DACT1 expression in intestinal epithelial cells; the minimal DACT1 promoter is located in the region -500bp to +1bp with a potential regulatory element near -335bp. Wnt signaling has no effect on DACT1 expression. Promoter deletion analysis, site-directed mutagenesis, luciferase reporter assay Biomedicine & pharmacotherapy Low 29136762
2022 FTO (m6A demethylase) reduces the mRNA stability of DACT1 via m6A demethylation, decreasing DACT1 expression and activating Wnt signaling in osteosarcoma. The m6A reader IGF2BP1 participates in stabilizing DACT1 mRNA. MeRIP-seq, RNA-seq, mRNA stability assay, RIP assay, IGF2BP1 knockdown, luciferase reporter Oncogene Medium 35121825
2022 lncRNA CRNDE promotes DACT1 expression by recruiting p300 histone acetyltransferase to enrich H3K27ac at the DACT1 promoter, thereby upregulating DACT1 transcription and inhibiting Wnt/β-catenin pathway activation. ChIP assay for H3K27ac, Co-IP for CRNDE-p300 interaction, DACT1 promoter reporter, in vivo OA model Cellular and molecular life sciences : CMLS Medium 35802196
2022 Heterozygous DACT1 missense variants located in the DVL2 interaction region cause CAKUT. Biochemical characterization revealed reduced binding of mutant DACT1 to DVL2. In CRISPR/Cas9-induced Dact1-/- murine inner medullary collecting duct cells, tubule formation was impaired in a branching morphogenesis assay. Whole-exome sequencing, Co-IP with DVL2 binding quantification, CRISPR/Cas9 KO, branching morphogenesis assay Human genetics Medium 36066768
2025 Dact1 induces Dishevelled oligomerization, which causes Dvl to dissociate from Vangl but remain associated with Frizzled as signalosome-like clusters, co-aggregating with Fz upon non-canonical Wnt induction. Dact1 antagonizes Vangl and synergizes with wild-type Dvl but not oligomerization-defective Dvl mutants, indicating that Dact1 promotes the Dvl binding-partner switch from Vangl to Fz to initiate non-canonical Wnt signaling during convergent extension. Xenopus CE assay, Co-IP with Vangl/Fz/Dvl, Dvl oligomerization-defective mutants, live imaging of protein clusters, non-canonical Wnt induction assay Nature communications High 40069199
2025 Activated S1P2 receptor binds to Dapper1 (Dpr1), decreasing Dvl degradation and causing β-catenin accumulation. The S1P2-Dpr1 binding also leads to S1P2 receptor nuclear translocation, where it activates CREB1 to promote EMT in pulmonary fibrosis. Co-immunoprecipitation (S1P2-Dpr1), immunofluorescence for nuclear translocation, Western blot for β-catenin, bleomycin IPF mouse model British journal of pharmacology Medium 40222913
2024 Dact1 and Dact2 contribute to convergent extension and craniofacial morphogenesis in zebrafish; compound dact1/2 mutants phenocopy wnt11f2 mutants. dact1/2 regulate the mRNA expression of the calpain capn8, and capn8 overexpression phenocopies dact1/2 craniofacial dysmorphology, establishing a novel role for dact1/2 in regulating calcium-dependent proteolysis during embryogenesis. Zebrafish compound mutant generation, single-cell RNAseq, comparative whole-transcriptome analysis, overexpression of capn8 eLife Medium 39570288

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation. Developmental cell 227 11970895
2003 Identification and characterization of human DAPPER1 and DAPPER2 genes in silico. International journal of oncology 141 12632086
2006 Dapper 1 antagonizes Wnt signaling by promoting dishevelled degradation. The Journal of biological chemistry 134 16446366
2021 TGF-β-induced DACT1 biomolecular condensates repress Wnt signalling to promote bone metastasis. Nature cell biology 99 33723425
2002 Frodo interacts with Dishevelled to transduce Wnt signals. Nature cell biology 94 11941372
2008 Dact1, a nutritionally regulated preadipocyte gene, controls adipogenesis by coordinating the Wnt/beta-catenin signaling network. Diabetes 85 19073771
2006 Frodo links Dishevelled to the p120-catenin/Kaiso pathway: distinct catenin subfamilies promote Wnt signals. Developmental cell 84 17084360
2013 DACT1, an antagonist to Wnt/β-catenin signaling, suppresses tumor cell growth and is frequently silenced in breast cancer. Breast cancer research : BCR 82 23497530
2005 HDPR1, a novel inhibitor of the WNT/beta-catenin signaling, is frequently downregulated in hepatocellular carcinoma: involvement of methylation-mediated gene silencing. Oncogene 73 15580286
2009 Posterior malformations in Dact1 mutant mice arise through misregulated Vangl2 at the primitive streak. Nature genetics 70 19701191
2014 Dapper1 promotes autophagy by enhancing the Beclin1-Vps34-Atg14L complex formation. Cell research 63 24980960
2004 The involvement of Frodo in TCF-dependent signaling and neural tissue development. Development (Cambridge, England) 60 15329348
2010 Loss of Dact1 disrupts planar cell polarity signaling by altering dishevelled activity and leads to posterior malformation in mice. The Journal of biological chemistry 55 20145239
2008 Dapper1 is a nucleocytoplasmic shuttling protein that negatively modulates Wnt signaling in the nucleus. The Journal of biological chemistry 55 18936100
2022 M6A demethylase FTO-mediated downregulation of DACT1 mRNA stability promotes Wnt signaling to facilitate osteosarcoma progression. Oncogene 54 35121825
1990 CRYStallize: a crystallographic symmetry display and handling subpackage in TOM/FRODO. Journal of molecular graphics 48 2282356
2019 MicroRNA-125b-5p improves pancreatic β-cell function through inhibiting JNK signaling pathway by targeting DACT1 in mice with type 2 diabetes mellitus. Life sciences 42 30684546
2018 Cyclin G2 suppresses Wnt/β-catenin signaling and inhibits gastric cancer cell growth and migration through Dapper1. Journal of experimental & clinical cancer research : CR 41 30547803
2017 MiR-324-3p promotes tumor growth through targeting DACT1 and activation of Wnt/β-catenin pathway in hepatocellular carcinoma. Oncotarget 41 29029464
2018 miR-124 promotes proliferation and neural differentiation of neural stem cells through targeting DACT1 and activating Wnt/β-catenin pathways. Molecular and cellular biochemistry 39 29786763
2012 Oncogenic function of DACT1 in colon cancer through the regulation of β-catenin. PloS one 38 22470507
2016 Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2. Development (Cambridge, England) 37 27122165
2004 Two Frodo/Dapper homologs are expressed in the developing brain and mesoderm of zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 36 15188426
2015 The Wnt Signaling Antagonist Dapper1 Accelerates Dishevelled2 Degradation via Promoting Its Ubiquitination and Aggregate-induced Autophagy. The Journal of biological chemistry 34 25825496
2019 Evaluating reproducibility of AI algorithms in digital pathology with DAPPER. PLoS computational biology 33 30917113
2012 Identification of novel rare mutations of DACT1 in human neural tube defects. Human mutation 33 22610794
2010 Dact1 is a postsynaptic protein required for dendrite, spine, and excitatory synapse development in the mouse forebrain. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 20335472
2011 All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl, Dvl, and serine/threonine kinases. BMC biochemistry 31 21718540
2006 Dact1 presomitic mesoderm expression oscillates in phase with Axin2 in the somitogenesis clock of mice. Developmental dynamics : an official publication of the American Association of Anatomists 31 17013874
2017 DACT1 Overexpression in type I ovarian cancer inhibits malignant expansion and cis-platinum resistance by modulating canonical Wnt signalling and autophagy. Scientific reports 29 28839145
2012 Dapper homolog 1 is a novel tumor suppressor in gastric cancer through inhibiting the nuclear factor-κB signaling pathway. Molecular medicine (Cambridge, Mass.) 29 23073659
2014 Dapper-1 is essential for Wnt5a induced cardiomyocyte hypertrophy by regulating the Wnt/PCP pathway. FEBS letters 27 24879894
2022 LncRNA CRNDE hinders the progression of osteoarthritis by epigenetic regulation of DACT1. Cellular and molecular life sciences : CMLS 23 35802196
2005 Frodo proteins: modulators of Wnt signaling in vertebrate development. Differentiation; research in biological diversity 23 16219036
2012 Involvement of the WNT and FGF signaling pathways in non-isolated anorectal malformations: sequencing analysis of WNT3A, WNT5A, WNT11, DACT1, FGF10, FGFR2 and the T gene. International journal of molecular medicine 22 22961180
2013 Dapper-1 induces myocardial remodeling through activation of canonical Wnt signaling in cardiomyocytes. Hypertension (Dallas, Tex. : 1979) 21 23509077
2017 Heterozygous Pathogenic Variant in DACT1 Causes an Autosomal-Dominant Syndrome with Features Overlapping Townes-Brocks Syndrome. Human mutation 20 28054444
2013 Dapper antagonist of catenin-1 cooperates with Dishevelled-1 during postsynaptic development in mouse forebrain GABAergic interneurons. PloS one 18 23826333
2018 Head formation requires Dishevelled degradation that is mediated by March2 in concert with Dapper1. Development (Cambridge, England) 17 29549110
2013 SEC14 and spectrin domains 1 (Sestd1) and Dapper antagonist of catenin 1 (Dact1) scaffold proteins cooperatively regulate the Van Gogh-like 2 (Vangl2) four-pass transmembrane protein and planar cell polarity (PCP) pathway during embryonic development in mice. The Journal of biological chemistry 17 23696638
2011 Protein kinase A-mediated 14-3-3 association impedes human Dapper1 to promote dishevelled degradation. The Journal of biological chemistry 17 21262972
2015 Expression and epigenetic regulation of DACT1 and DACT2 in oral squamous cell carcinoma. Cancer biomarkers : section A of Disease markers 16 25524937
1990 Molecular conformational space analysis using computer graphics: going beyond FRODO. Journal of molecular graphics 16 2282358
2020 A newly identified lncRNA H1FX-AS1 targets DACT1 to inhibit cervical cancer via sponging miR-324-3p. Cancer cell international 15 32760225
2017 Dapper1 attenuates hepatic gluconeogenesis and lipogenesis by activating PI3K/Akt signaling. Molecular and cellular endocrinology 14 28237722
2011 Cytoplasmic HDPR1 is involved in regional lymph node metastasis and tumor development via beta-catenin accumulation in esophageal squamous cell carcinoma. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 14 21525190
2020 Cyclin G2 regulates canonical Wnt signalling via interaction with Dapper1 to attenuate tubulointerstitial fibrosis in diabetic nephropathy. Journal of cellular and molecular medicine 13 31978940
2010 Dact1-3 mRNAs exhibit distinct expression domains during tooth development. Gene expression patterns : GEP 13 20170752
2019 Effects of DACT1 methylation status on invasion and metastasis of nasopharyngeal carcinoma. Biological research 12 31182157
2005 Identification and characterization of rat Dact1 and Dact2 genes in silico. International journal of molecular medicine 12 15870912
2006 Vertebrate homologues of Frodo are dynamically expressed during embryonic development in tissues undergoing extensive morphogenetic movements. Developmental dynamics : an official publication of the American Association of Anatomists 11 16278878
2023 Safety, Immunologic, and Clinical Activity of Durvalumab in Combination with Olaparib or Cediranib in Advanced Leiomyosarcoma: Results of the DAPPER Clinical Trial. Clinical cancer research : an official journal of the American Association for Cancer Research 10 37566240
2019 DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43. Brazilian journal of cardiovascular surgery 10 31545578
2017 DACT1 overexpression inhibits proliferation, enhances apoptosis, and increases daunorubicin chemosensitivity in KG-1α cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 29037126
2015 Myc-interacting zinc-finger protein 1 positively regulates Wnt signalling by protecting Dishevelled from Dapper1-mediated degradation. The Biochemical journal 10 25558878
2013 SEC14 and Spectrin Domains 1 (Sestd1), Dishevelled 2 (Dvl2) and Dapper Antagonist of Catenin-1 (Dact1) co-regulate the Wnt/Planar Cell Polarity (PCP) pathway during mammalian development. Communicative & integrative biology 10 24505507
2009 Chicken dapper genes are versatile markers for mesodermal tissues, embryonic muscle stem cells, neural crest cells, and neurogenic placodes. Developmental dynamics : an official publication of the American Association of Anatomists 9 19347952
2005 Regulation of the early expression patterns of the zebrafish Dishevelled-interacting proteins Dapper1 and Dapper2. Developmental dynamics : an official publication of the American Association of Anatomists 9 15765513
2022 In vitro evaluation of the pogostone effects on the expression of PTEN and DACT1 tumor suppressor genes, cell cycle, and apoptosis in ovarian cancer cell line. Research in pharmaceutical sciences 8 35280836
2021 Dact1 is expressed during chicken and mouse skeletal myogenesis and modulated in human muscle diseases. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 8 34252542
2021 Histone Deacetylation Regulated by KDM1A to Suppress DACT1 in Proliferation and Migration of Cervical Cancer. Analytical cellular pathology (Amsterdam) 8 34350095
2016 Association analysis of DACT1 genetic variants and gastric cancer risk in a Chinese Han population: a case-control study. OncoTargets and therapy 8 27729806
2022 Methylation analysis of APC, AXIN2, DACT1, RASSF1A and MGMT gene promoters in non-small cell lung cancer. Pathology, research and practice 7 35489124
2022 Heterozygous variants in the DVL2 interaction region of DACT1 cause CAKUT and features of Townes-Brocks syndrome 2. Human genetics 7 36066768
2017 Dact1, a Wnt-Pathway Inhibitor, Mediates Human Mesangial Cell TGF-β1-Induced Apoptosis. Journal of cellular physiology 7 27714812
2016 Dapper homolog 1 alpha suppresses metastasis ability of gastric cancer through inhibiting planar cell polarity pathway. Oncotarget 7 27833078
2012 Relationships among MTHFR a1298c gene polymorphisms and methylation status of Dact1 gene in transitional cell carcinomas. Asian Pacific journal of cancer prevention : APJCP 7 23244112
2020 Rapid semen identification from mixed body fluids using methylation-sensitive high-resolution melting analysis of the DACT1 gene. Legal medicine (Tokyo, Japan) 6 33189063
2021 FRugally Optimized DNA Octomer (FRODO) qPCR Measurement of HIV and SIV in Human and Nonhuman Primate Samples. Current protocols 5 33861500
2014 DACT1 is involved in human placenta development by promoting Wnt signaling. Archives of gynecology and obstetrics 5 25424899
2013 Dapper Antagonist of Catenin-1 (Dact1) contributes to dendrite arborization in forebrain cortical interneurons. Communicative & integrative biology 5 24567777
2024 Genetic requirement of dact1/2 to regulate noncanonical Wnt signaling and calpain 8 during embryonic convergent extension and craniofacial morphogenesis. eLife 4 39570288
2020 Dact-4 is a Xenopus laevis Spemann organizer gene related to the Dapper/Frodo antagonist of β-catenin family of proteins. Gene expression patterns : GEP 4 33186756
2016 Genetic analysis of DACT1 in 100 Chinese Han women with Müllerian duct anomalies. Reproductive biomedicine online 4 26856455
2011 The role of aberrant promoter hypermethylation of DACT1 in bladder urothelial carcinoma. Journal of biomedical research 4 23554767
2025 Inhibition of sphingosine-1-phosphate receptor-2 attenuates idiopathic pulmonary fibrosis by preventing its binding to dapper1 in bronchial epithelial cells. British journal of pharmacology 3 40222913
2023 Different expression of DACT1, DACT2, and CYCLIN D1 genes in human colorectal cancer tissues and its association with clinicopathological characteristics. Nucleosides, nucleotides & nucleic acids 3 37610179
2018 Expression of DACT1 in children with asthma and its regulation mechanism. Experimental and therapeutic medicine 3 29456669
2015 DAPPER: a data-mining resource for protein-protein interactions. BioData mining 3 26405458
2014 Expression analysis of Dact1 in mice using a LacZ reporter. Gene expression patterns : GEP 3 24681206
2025 Dact1 induces Dishevelled oligomerization to facilitate binding partner switch and signalosome formation during convergent extension. Nature communications 2 40069199
2025 FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1. Open life sciences 2 40356725
2017 TGF-β signaling regulates DACT1 expression in intestinal epithelial cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2 29136762
2010 [Mechanism of As(2)O(3) on hdpr1 gene demethylation in Jurkat cell line]. Zhongguo shi yan xue ye xue za zhi 2 21176356
2013 Impacts of single nucleotide polymorphisms and haplotypes in the bovine Dapper1 gene on body weight. Genetics and molecular research : GMR 1 23661450
2026 DACT1 as a Potential Therapeutic Target in Gastric Cancer: Insights from Integrative Bioinformatics and Experimental Analysis. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 0 41662679
2025 Extracellular vesicle miR-425-5p promotes visceral fat reduction via DACT1 suppression in SGLT2i-treated diabetes. Frontiers in endocrinology 0 41446634
2025 DACT1 inhibits cuproptosis and promotes cell malignancy via activation of PI3K/AKT signaling in laryngeal squamous cell carcinoma. European journal of medical research 0 41469752
2024 Genetic requirement of dact1/2 to regulate noncanonical Wnt signaling and calpain 8 during embryonic convergent extension and craniofacial morphogenesis. bioRxiv : the preprint server for biology 0 37986847

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