Affinage

DVL2

Segment polarity protein dishevelled homolog DVL-2 · UniProt O14641

Length
736 aa
Mass
78.9 kDa
Annotated
2026-06-09
65 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DVL2 is a cytoplasmic scaffold that transduces both canonical Wnt/β-catenin and non-canonical (PCP, Wnt/Ca²⁺) signals, functionally conserved from Drosophila dishevelled (PMID:8887313) and acting genetically upstream of GSK-3β to activate TCF-dependent transcription (PMID:10329628). In canonical signaling DVL2 co-localizes and co-immunoprecipitates with Axin and redirecting DVL2 redistributes Axin, establishing it as an Axin-recruiting hub that engages the β-catenin destruction complex (PMID:10329628). Pathway activation depends on CK1ε-mediated phosphorylation of DVL2 at S143 and T224, which is facilitated by the DDX3 subunit of CK1ε and by a Daple–CK1ε–DVL2 trimeric complex, with T224 phosphorylation required for full β-catenin transcriptional output (PMID:22609948, PMID:26892600, PMID:32888647); this phosphorylation is reversed by the phosphatase PP5, which acts at S143 and the 10B5 cluster and localizes with phospho-DVL2 to the basal body (PMID:29426949). At endogenous concentrations DVL2 forms Wnt-dependent supramolecular condensates at γ-tubulin/CEP164-positive centrosomal structures, driven by C-terminal LCR4 and CD2 regions whose aggregating residues and phenylalanine stickers are required for Wnt/β-catenin activation (PMID:35867833, PMID:39652469). Through its non-canonical outputs DVL2 activates Daam1/RhoA and binds Rab35 to drive Rac1-dependent breast cancer cell migration and actin/lamellipodial dynamics (PMID:22655072, PMID:23353182, PMID:15593083), and it nucleates a DVL2–Plk1–HEF1–Aurora-A axis downstream of Wnt5a–CK1ε to drive primary cilia disassembly (PMID:22609948). DVL2 abundance and pathway choice are set by a ubiquitin rheostat: WWP1 stabilizes DVL2 via K27-linked polyubiquitylation to favor PCP signaling while USP9X deubiquitylates it to favor canonical signaling, and multiple E3 ligases (RNF185, RNF123, NEDD4, Itch via K48-linked K343) target DVL2 for proteasomal degradation while GABARAPL1/p62 routes it to autophagic degradation (PMID:34139860, PMID:31340145, PMID:21691068, PMID:24727453, PMID:33205477, PMID:41793265, PMID:42168361). The DVL2 DEP domain binds phosphatidic acid in a pH-dependent manner (PMID:24606934), and a DACT1 missense variant that weakens DACT1–DVL2 binding associates with congenital kidney malformation (CAKUT), implicating the interaction in kidney development (PMID:36066768).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 Medium

    Established that the mammalian protein is a functional dishevelled ortholog, anchoring DVL2 in Wnt signal transduction rather than being a sequence homolog of unknown function.

    Evidence Genetic rescue of segmentation defects in dsh-null Drosophila embryos

    PMID:8887313

    Open questions at the time
    • Did not define which mammalian pathway branch (canonical vs PCP) is rescued
    • No molecular partners identified
  2. 1999 High

    Defined where DVL2 sits in the canonical cascade by showing it acts upstream of GSK-3β and physically associates with Axin, identifying DVL2 as an Axin-recruiting node of the destruction complex.

    Evidence Co-IP, CAAX-redirected co-localization, deletion mapping, and TCF-luciferase reporter assays

    PMID:10329628

    Open questions at the time
    • Mechanism by which Axin recruitment disrupts the destruction complex not resolved
    • No structural detail of the DVL2–Axin interface
  3. 2005 Medium

    Distinguished pathologic overexpression aggregates from functional puncta and tied endogenous DVL2 to actin-based migration, separating signaling-relevant condensates from artifacts.

    Evidence Live-cell time-lapse imaging with endosomal markers at graded expression; siRNA with actin/motility readouts in endothelial cells

    PMID:15593083 PMID:16263761

    Open questions at the time
    • Did not identify the molecular basis of physiological condensates
    • Cytoskeletal effectors downstream of DVL2 not defined here
  4. 2012 High

    Connected Wnt5a/CK1ε-driven DVL2 phosphorylation to specific non-canonical effectors, defining how DVL2 drives migration and cilia disassembly.

    Evidence Phospho-site mapping (S143/T224), Co-IP of DVL2–Plk1, cilia disassembly assays, and Daam1/RhoA GTPase/migration assays

    PMID:22609948 PMID:22655072

    Open questions at the time
    • How phosphorylation switches DVL2 between effector complexes unclear
    • Direct vs indirect DVL2–Plk1 binding not fully resolved
  5. 2013 Medium

    Extended the non-canonical effector map by placing Rab35 upstream of Rac1 in DVL2-driven migration and linking DVL2 to Dact1/Sestd1 PCP complexes through genetic synergy.

    Evidence Co-IP, Rac1/Rho GTPase activity assays, migration assays, and double/triple KO mouse epistasis

    PMID:23353182 PMID:24505507

    Open questions at the time
    • Direct vs scaffolded nature of DVL2–Rab35 binding not resolved
    • How DVL2 partitions among competing PCP complexes unknown
  6. 2014 Medium

    Provided biophysical insight into DEP-domain membrane engagement and identified DVL2 as a proteasomal degradation target, beginning to define the lipid- and stability-control layers.

    Evidence NMR/MD/mutagenesis of DEP–phosphatidic acid binding; Co-IP and ubiquitination assays for RNF185

    PMID:24606934 PMID:24727453

    Open questions at the time
    • Functional consequence of DEP–PA binding for signaling not established
    • Ubiquitin linkage type used by RNF185 not characterized
  7. 2016 Medium

    Refined the CK1ε activation step by showing DDX3 acts as a CK1ε subunit facilitating DVL2 phosphorylation, linking it to tumor invasion.

    Evidence Phospho-DVL2 Western blot, CK1ε inhibitor, TCF reporter, invasion and xenograft assays

    PMID:26892600

    Open questions at the time
    • Whether DDX3 helicase activity is required not addressed
    • Direct DDX3–DVL2 contact not mapped
  8. 2018 Medium

    Identified PP5 as a DVL2 phosphatase counteracting CK1ε, establishing reversible phosphorylation at the basal body as a control point for ciliogenesis.

    Evidence In vitro dephosphorylation assay, Co-IP, phospho-specific siRNA analysis, basal-body localization

    PMID:29426949

    Open questions at the time
    • Relative contributions of PP5 vs PP2A in vivo not quantified
    • How phosphatase recruitment is timed to cilia dynamics unknown
  9. 2019 High

    Defined a WWP1–USP9X ubiquitin rheostat as the molecular switch specifying canonical versus PCP output from DVL2, explaining how one scaffold routes distinct signals.

    Evidence Deubiquitylase assays, Co-IP, ubiquitin-mutant analysis, pathway reporters, localization

    PMID:31340145

    Open questions at the time
    • How ubiquitin status mechanically alters DVL2 conformation/partner choice unclear
    • Upstream signals controlling WWP1 vs USP9X balance not defined
  10. 2020 Medium

    Resolved how Daple licenses CK1ε phosphorylation of DVL2 at T224 and added RNF123/CCNG2 as a degradation arm controlling PCP-JNK output.

    Evidence Co-IP with Daple ΔGCV mutants, phospho-specific WB, reporter assays; RNF123 ubiquitination and migration assays

    PMID:32888647 PMID:33205477

    Open questions at the time
    • Stoichiometry of the Daple–CK1ε–DVL2 trimer unknown
    • Whether RNF123 and WWP1 compete on shared lysines untested
  11. 2022 High

    Demonstrated that endogenous DVL2 forms Wnt-dependent condensates at centrosomal structures, reframing DVL2 puncta as physiological signaling organelles rather than aggregates.

    Evidence CRISPR mEos3.2 knock-in, PALM/DNA-PAINT superresolution, centrosomal co-localization, Wnt reporters

    PMID:35867833

    Open questions at the time
    • Functional role of centrosomal localization for β-catenin output not fully defined
    • Relationship between condensate and destruction-complex assembly unresolved
  12. 2024 High

    Identified the C-terminal LCR4 and CD2 regions as the sequence determinants of endogenous DVL2 oligomerization/condensation required for pathway activation, mechanistically linking material properties to signaling.

    Evidence Ultracentrifugation at endogenous levels, deletion/fusion constructs, sticker point mutagenesis, Wnt reporter

    PMID:39652469

    Open questions at the time
    • How DIX-mediated polymerization integrates with LCR4/CD2 condensation not resolved
    • Regulation of these regions by phosphorylation/ubiquitination untested
  13. 2025 Medium

    Expanded the degradation network and stability modulators of DVL2 across disease contexts, including K48/K343 Itch ubiquitylation, PRICKLE3–USP9X stabilization, and lncRNA-mediated stabilization.

    Evidence Site-specific ubiquitination assays, KO mice, tripartite Co-IP, lncRNA RIP and rescue assays

    PMID:40973792 PMID:41135528 PMID:42168361

    Open questions at the time
    • How competing ligases/deubiquitinases are coordinated on DVL2 in a single context unknown
    • Lysine usage overlap among Itch, WWP1, RNF123 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DVL2's phosphorylation code, ubiquitin rheostat, condensate material state, and conformational autoinhibition are integrated in real time to select between canonical and non-canonical outputs remains unresolved.
  • No unified model linking DEP-PA binding, LCR4/CD2 condensation, and ubiquitin status
  • Autoinhibition and partner-specific conformational changes characterized mainly in preprints

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0008289 lipid binding 1
Localization
GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005929 cilium 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2
Partners
AXIN1CSNK1EDAAM1DACT1PLK1RAB35USP9XWWP1
Complex memberships
DVL2 Wnt-dependent centrosomal condensateDVL2–Plk1 complexDaple–CK1ε–DVL2 complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 DVL2 co-localizes and co-immunoprecipitates with Axin; Axin residues 603–810 contain DVL2-association determinants. DVL2 activates TCF-dependent transcription upstream of GSK-3β, and this activation is blocked by co-expression of Axin or GSK-3β. Redirecting DVL2 localization via a CAAX motif also redistributes Axin, confirming close physical association. Co-immunoprecipitation, co-localization with CAAX-motif redirected protein, TCF-luciferase reporter assay, deletion analysis The EMBO journal High 10329628
1996 DVL2 is a mammalian homolog of Drosophila dishevelled that can partially rescue segmentation defects in dsh-null fly embryos, demonstrating functional conservation of its role in transducing the Wingless/Wnt signal. Genetic rescue assay in dsh-null Drosophila embryos; sequence analysis Mechanisms of development Medium 8887313
2012 DVL2 is phosphorylated at S143 and T224 by CK1ε downstream of Wnt5a signaling. Phosphorylated DVL2 directly interacts with Plk1, forming a DVL2–Plk1 complex that stabilizes HEF1 and activates Aurora-A kinase to drive primary cilia disassembly. Phosphorylation mapping, co-immunoprecipitation, RNAi knockdown, cilia disassembly assay, kinase inhibitor studies The EMBO journal High 22609948
2012 Wnt5a activates DVL2, which in turn activates Daam1 and RhoA to promote stress fiber formation and breast cancer cell migration. Dominant-negative DVL2 mutants or DVL2 siRNA abolish Wnt5a-induced Daam1/RhoA activation and migration. siRNA knockdown, dominant-negative overexpression, RhoA activity assay (pulldown), stress fiber staining, Matrigel migration assay PloS one Medium 22655072
2013 DVL2 physically binds Rab35 (shown by co-immunoprecipitation and immunofluorescence), and this DVL2–Rab35 interaction is required upstream of Rac1 activation for Wnt5a-driven breast cancer cell migration. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, Rac1 activity assay, cell migration assay Cellular signalling Medium 23353182
2005 DVL2 cytoplasmic puncta are protein aggregates formed at high expression levels and are not required for canonical Wnt signaling. They do not co-localize with early or late endocytic markers, and time-lapse analysis shows short-range random movement without originating from the plasma membrane. Live-cell time-lapse imaging, endosomal marker co-localization, signaling reporter assay at graded expression levels Journal of cell science Medium 16263761
2021 WWP1 E3 ubiquitin ligase directly interacts with DVL2 and stabilizes it via K27-linked polyubiquitination, thereby activating the DVL2/CaMKII/HDAC4/MEF2C pathway and driving cardiac hypertrophy. WWP1 knockout prevents TAC-induced hypertrophy. Co-immunoprecipitation, mass spectrometry, ubiquitination assay (K27-linkage specific), pulse-chase assay, reporter gene assay, AAV9-shRNA in vivo model, echocardiography Circulation High 34139860
2019 USP9X deubiquitylates DVL2; USP9X-mediated deubiquitylation promotes canonical Wnt activation, whereas increased DVL2 ubiquitylation (by WWP1) is associated with DVL2 localization to actin-rich projections and activation of the PCP pathway. Thus a WWP1–USP9X ubiquitin rheostat on DVL2 specifies canonical vs. PCP pathway output. Deubiquitylase assay, Co-IP, ubiquitin mutant analysis, pathway reporter assay, fluorescence localization Cell reports High 31340145
2011 GABARAPL1 interacts with DVL2 (via p62 adaptor) and mediates its degradation through the autophagy pathway, thereby suppressing Wnt/β-catenin signaling. Blocking autophagy with 3-MA prevents DVL2 degradation. Yeast two-hybrid screening, co-immunoprecipitation, autophagy inhibitor (3-MA) rescue, luciferase reporter assay Cellular physiology and biochemistry Medium 21691068
2014 The DVL2 DEP domain binds phosphatidic acid (PA) through its basic helix 3 and a contiguous loop in a pH-dependent manner. PA binding induces conformational changes in helix 2 and β-strand 4. Interaction is pH-dependent, resembling deprotonation of PA. NMR spectroscopy, molecular-dynamics simulations, site-directed mutagenesis, biophysical binding assays Biophysical journal High 24606934
2014 RNF185 E3 ubiquitin ligase interacts with DVL2, promotes its ubiquitination and proteasomal degradation, thereby inhibiting canonical Wnt/β-catenin signaling and negatively regulating osteogenic differentiation of MC3T3-E1 cells. Co-immunoprecipitation, ubiquitination assay, Western blot for protein levels, luciferase reporter assay, ALP activity assay Biochemical and biophysical research communications Medium 24727453
2018 PP5 (PPP5C) is a phosphatase of DVL2 that directly interacts with and dephosphorylates DVL2, including at S143 and the 10B5 cluster. PP5 knockdown elevates DVL2 phosphorylation at basal levels and upon Wnt stimulation. PP5 is distinct from PP2A in which DVL2 phosphorylation sites it regulates. PP5 localizes to the basal body of primary cilia where S143-phosphorylated DVL2 also resides. Co-immunoprecipitation, in vitro phosphatase assay, siRNA knockdown with phospho-specific antibodies, immunofluorescence localization, ciliogenesis assay Scientific reports Medium 29426949
2016 DDX3, a subunit of CK1ε, facilitates CK1ε-mediated phosphorylation of DVL2, which promotes β-catenin/TCF activation and tumor invasion in colorectal cancer. Pharmacological inhibition of CK1ε suppresses DVL2 phosphorylation and invasion. Western blotting for pDVL2, CK1ε inhibitor (PF4800567) treatment, TCF reporter assay, invasion assay, xenograft model Scientific reports Medium 26892600
2005 DVL2 is present in post-developmental endothelial cells as a phosphoprotein, localized in both F-actin-free and F-actin-associated cytoplasmic pools. siRNA-mediated silencing of DVL2 causes aberrant membrane activity, failure to extend lamellipodia, and actin filament disorganization, indicating DVL2 regulates cell migration via actin cytoskeleton. siRNA knockdown, immunolabeling, Western blotting, time-lapse cell motility assay Journal of cellular physiology Medium 15593083
2011 Stau1 RNA-binding protein binds the 3′ UTR of Dvl2 mRNA and stabilizes it in undifferentiated myoblasts. Stau1 knockdown shortens Dvl2 mRNA half-life; during myogenic differentiation, Stau1 dissociates from Dvl2 3′ UTR, reducing Dvl2 mRNA levels. Forced Dvl2 expression inhibits myogenic differentiation. RNA immunoprecipitation, mRNA stability assay, Western blot, qRT-PCR, overexpression in C2C12 differentiation assay Biochemical and biophysical research communications Medium 22166206
2022 Endogenous DVL2 (tagged with mEos3.2 at its genomic locus) forms Wnt-dependent supramolecular condensates (~1 per cell at physiological levels) that localize to γ-tubulin- and CEP164-positive centrosomal structures in a cell cycle-dependent manner. Single-molecule PALM/DNA-PAINT demonstrates repetitive internal organization of these condensates. CRISPR genome-engineered endogenous mEos3.2-DVL2, live-cell superresolution imaging (PALM), DNA-PAINT, immunofluorescence co-localization, Wnt pathway reporter assays Proceedings of the National Academy of Sciences of the United States of America High 35867833
2020 The Daple–CK1ε–DVL2 trimeric complex is required for CK1ε-mediated phosphorylation of DVL2 at T224. Daple lacking its C-terminal DVL-binding motif (ΔGCV) retains CK1ε binding but cannot induce DVL2 phosphorylation. T224 phosphorylation is required for full β-catenin transcriptional activity. Wnt3a stimulation increases Daple membrane localization and Daple–DVL2 association. Co-immunoprecipitation, dominant-negative Daple mutants, phospho-specific Western blot, TCF/LEF luciferase reporter assay, siRNA knockdown Biochemical and biophysical research communications Medium 32888647
2013 Sestd1 forms complexes with DVL2 independently of both Dact1 and Vangl2. DVL2 enhances Dact1/Sestd1-mediated Rho family GTPase activation in cell-based assays consistent with PCP pathway function. Genetic synergy: Dvl2 KO is recessive alone but causes dominant embryonic lethality in Sestd1 or Dact1 KO backgrounds. Co-immunoprecipitation, Rho GTPase activation assay, genetic epistasis in double/triple KO mice Communicative & integrative biology Medium 24505507
2020 CCNG2 promotes polyubiquitination-mediated degradation of DVL2 via the E3 ligase RNF123. RNF123 interacts with DVL2; CCNG2 upregulates RNF123, leading to DVL2 destabilization, suppression of Wnt/PCP-JNK signaling, and impaired trophoblast migration and invasion. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown (RNF123), Western blot, JNK activity assay, migration/invasion assay FASEB journal Medium 33205477
2021 DVL2 interacts with the C-terminus of TNFR1 and mediates TNFR1 endocytosis, thereby inhibiting NF-κB signaling. IL-13 upregulates DVL2 expression via STAT6. This mechanism coordinates NF-κB and Wnt signaling in colitis-associated colorectal cancer. Co-immunoprecipitation, endocytosis assay, STAT6 inhibitor, siRNA knockdown, NF-κB reporter assay Cancer science Medium 34807493
2024 DVL2 oligomers form at endogenous protein concentrations via two distinct regions in its C-terminus: LCR4 (low-complexity region 4) mediates pre-oligomerization via aggregating residues, while adjacent CD2 promotes condensate formation via phenylalanine stickers. Point mutations inactivating these sites impair Wnt/β-catenin pathway activation by DVL2. Biochemical ultracentrifugation assay at endogenous levels, deletion/fusion constructs, point mutagenesis, condensate microscopy, Wnt reporter assay eLife High 39652469
2022 METTL16 methyltransferase suppresses DVL2 protein levels via m6A modification of DVL2 mRNA, inhibiting its translation and thereby suppressing Wnt/β-catenin signaling in pancreatic ductal adenocarcinoma. m6A sequencing/mapping, METTL16 overexpression/knockdown, Western blot for DVL2, Wnt reporter assay, in vitro and in vivo metastasis assays Journal of Cancer Medium 37859814
2020 Low disturbed fluid shear stress (1 dyne/cm²) promotes primary cilia assembly via DVL2 in endothelial cells. DVL2 co-immunoprecipitates with Bbs8 and γ-tubulin. DVL2 overexpression increases ciliated cell percentages under shear; DVL2 silencing decreases them and reduces Bbs8 and γ-tubulin expression, indicating DVL2 facilitates basal body apical docking through Bbs8 and γ-tubulin. Microfluidic chamber, co-immunoprecipitation, siRNA knockdown, overexpression, immunofluorescence Histochemistry and cell biology Medium 32776193
2019 TM4SF1 interacts with DVL2 and strengthens the DVL2–Axin interaction, thereby promoting β-catenin/TCF signaling in hepatocellular carcinoma. TM4SF1 downregulation increases β-catenin ubiquitination. Co-immunoprecipitation, ubiquitination assay, TCF reporter assay, siRNA knockdown Journal of cellular and molecular medicine Medium 31876386
2022 DACT1 missense variants located in its DVL2 interaction region show reduced binding to DVL2 in biochemical characterization and associate with CAKUT in humans, establishing the DVL2–DACT1 protein–protein interaction as functionally required for normal kidney development. Whole-exome sequencing, biochemical binding assay (reduced DVL2 binding of mutant DACT1), CRISPR/Cas9 Dact1 KO in murine collecting duct cells (branching morphogenesis assay) Human genetics Medium 36066768
2015 APPL1 endocytic adaptor physically interacts with DVL2 and synergizes with it to potentiate AP-1 (c-Jun)-driven transcription in non-canonical Wnt signaling, specifically increasing MMP1 expression in a JNK-dependent manner. This function requires endosomal recruitment of APPL1. Co-immunoprecipitation, AP-1/TCF reporter assay, JNK inhibitor, endosomal localization assay, MMP1 expression measurement FEBS letters Medium 25622892
2023 Wnt5a–Ror1 signaling at the cell surface requires Rif (a Rho-family GTPase) to activate DVL2 phosphorylation. Rif interacts with Ror1 and is required for 3D matrix-induced polarized filopodia in lung adenocarcinoma cells. Co-immunoprecipitation, Western blot for pDVL2, siRNA knockdown of Rif and Ror1, 3D Matrigel culture, in vivo tumor assay The Journal of biological chemistry Medium 37703992
2023 HCMV viral protein pUL8 interacts with DVL2 and β-catenin via a PDZ-binding domain; loss of pUL8 interaction with the β-catenin–DVL2 complex restricts viral reactivation in CD34+ hematopoietic progenitor cells. Co-immunoprecipitation, PDZ-binding domain mutant analysis, viral reactivation assay in CD34+ HPCs Journal of virology Medium 37772824
2025 LINC01612 lncRNA interacts with DVL2 protein and enhances DVL2 stability by reducing its ubiquitination, thereby maintaining WNT signaling required for human definitive endoderm differentiation. DVL2 overexpression rescues endoderm differentiation defects caused by LINC01612 loss. shRNA knockdown, Co-IP of LINC01612 with DVL2, ubiquitination assay, WNT reporter assay, CRISPR promoter deletion, rescue by DVL2 overexpression Stem cell reports Medium 41135528
2024 In macrophages, DVL2 promotes nuclear YAP–HSF1 interaction, which activates HSF1 target gene eEF2, thereby inhibiting NOD1/caspase-1/GSDMD pyroptosis and NF-κB signaling. Myeloid-specific Dvl2 KO reduces YAP–HSF1 colocalization, enhances NOD1-driven pyroptosis, and worsens ischemia/reperfusion liver injury. Myeloid-specific KO mouse model, co-immunoprecipitation (YAP–HSF1), caspase-1/GSDMD activation assays, adoptive macrophage transfer, hepatocyte co-culture assay Redox biology Medium 39644526
2026 AJUBA acts as a co-activator of C/EBPβ to enhance NEDD4 transcription; NEDD4 then promotes ubiquitin-mediated degradation of DVL2, preventing Ca²⁺/CaMKII/HDAC4 pathway activation and protecting against cardiac hypertrophy. AJUBA KO worsens cardiac hypertrophy and dysfunction. AJUBA KO mouse, reporter assay for C/EBPβ/NEDD4 transcription, co-immunoprecipitation, ubiquitination assay, echocardiography Cell biology international Medium 41793265
2026 E3 ubiquitin ligase Itch promotes K48-linked ubiquitination of DVL2 at lysine 343, leading to its proteasomal degradation and suppression of GSK-3β/β-catenin signaling, thereby alleviating kidney fibrosis. Itch KO mice show exacerbated fibrosis and increased DVL2 levels. Co-immunoprecipitation, site-specific ubiquitination assay (K343 mutation), Itch KO mice, Western blot, fibrosis markers Cell death and differentiation Medium 42168361
2025 PRICKLE3 interacts with USP9X and DVL2 in a tripartite complex; PRICKLE3–USP9X interaction inhibits DVL2 ubiquitination, stabilizing DVL2 and activating canonical WNT signaling. PRICKLE3–DVL2 interaction also enhances β-catenin phosphorylation at S675 to promote its nuclear translocation. Co-immunoprecipitation, ubiquitination assay, Western blot, PRICKLE3 KO/OE in NSCLC cells, in vivo tumor model Oncogene Medium 40973792
2022 Cancer-associated SF3B1 mutation causes aberrant 3′ splice site selection in DVL2 pre-mRNA using an alternative branchpoint sequence (BPS) with higher affinity for U2 snRNA than the canonical BPS. The aberrant splicing does not require the canonical 3′ splice site or polypyrimidine tract; BPS position and U2 snRNA affinity together determine BPS selection. Minigene splicing assay, BPS swapping mutagenesis, U2 snRNA affinity analysis, SF3B1 mutant cell lines Biochemical and biophysical research communications Medium 33561744
2025 Profilin2 directly interacts with DVL2 in vitro via the extreme C-terminus of DVL2 (beyond the polyproline motif), without engaging the PDZ or DEP domains. DVL2 adopts an autoinhibited conformation through intramolecular binding of its extreme C-terminus to its PDZ domain, yet profilin2 retains binding in this autoinhibited state. Co-localization (fluorescence), in vitro pulldown assay, deletion/domain mapping, autoinhibition assay bioRxivpreprint Low bio_10.1101_2025.10.09.681388
2025 The C-terminus of DVL2 interacts with the centrosomal protein Kizuna (Kiz); Kiz induces an open DVL2 conformation enabling recruitment of PKCδ to stabilize the apical microtubule meshwork. This DVL2–Kiz–PKCδ axis is required for primary cilia formation (primary cilia in the eye, multicilia in MCE, and mono-motile cilia in the GRP) in Xenopus. Co-immunoprecipitation (DVL2–Kiz), conformational assay, in vivo Xenopus loss-of-function, ciliogenesis readout bioRxivpreprint Low bio_10.1101_2025.11.12.688108
2025 Daple and its paralog Girdin-L bear unique extended C-terminal PDZ-binding motifs that bind the DVL2 PDZ domain with exceptionally high affinity. Deletion of these motifs or DVL2's PDZ domain results in elongated primary cilia unresponsive to Wnt5a-stimulated disassembly, establishing this DVL2 PDZ–Daple/Girdin-L interaction as the molecular basis for Wnt5a-driven cilia disassembly. Proximity labeling, structural/biophysical analysis, deletion mutants, Wnt5a cilia disassembly assay in HEK293T cells bioRxivpreprint Low bio_10.1101_2025.09.26.678488
2025 CK1δ/ε inhibition blocks DVL2 condensate formation, as shown by image-based screening with CK1δ/ε kinase inhibitors; genetic epistasis with APC, Axin1, and MCC loss-of-function alleles modulates this effect on Wnt signaling, placing CK1δ/ε-mediated DVL2 phosphorylation upstream of condensate dynamics in the Wnt pathway. Image-based high-throughput screen, CK1δ/ε inhibitors, endogenous DVL2-mEos3.2, phosphoproteomics, genetic epistasis (APC/Axin1/MCC KO) bioRxivpreprint Low bio_10.1101_2025.01.11.632522

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Interaction of axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription. The EMBO journal 208 10329628
2012 Identification of a novel Wnt5a-CK1ɛ-Dvl2-Plk1-mediated primary cilia disassembly pathway. The EMBO journal 140 22609948
2012 Dvl2-dependent activation of Daam1 and RhoA regulates Wnt5a-induced breast cancer cell migration. PloS one 102 22655072
1996 Conservation of dishevelled structure and function between flies and mice: isolation and characterization of Dvl2. Mechanisms of development 93 8887313
2021 Targeting E3 Ubiquitin Ligase WWP1 Prevents Cardiac Hypertrophy Through Destabilizing DVL2 via Inhibition of K27-Linked Ubiquitination. Circulation 80 34139860
2018 TRIM14 promotes chemoresistance in gliomas by activating Wnt/β-catenin signaling via stabilizing Dvl2. Oncogene 65 29867201
2005 Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta. Journal of cell science 65 16263761
2011 MiR-221 expression affects invasion potential of human prostate carcinoma cell lines by targeting DVL2. Medical oncology (Northwood, London, England) 60 21487968
2010 Dvl2 promotes intestinal length and neoplasia in the ApcMin mouse model for colorectal cancer. Cancer research 53 20663899
2013 Rab35 is required for Wnt5a/Dvl2-induced Rac1 activation and cell migration in MCF-7 breast cancer cells. Cellular signalling 50 23353182
2011 GABARAPL1 negatively regulates Wnt/β-catenin signaling by mediating Dvl2 degradation through the autophagy pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 48 21691068
2019 USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification. Cell reports 46 31340145
2016 DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis. Scientific reports 45 26892600
2021 ASPM promotes hepatocellular carcinoma progression by activating Wnt/β-catenin signaling through antagonizing autophagy-mediated Dvl2 degradation. FEBS open bio 35 34428354
2022 Exosomal circ_0091741 promotes gastric cancer cell autophagy and chemoresistance via the miR-330-3p/TRIM14/Dvl2/Wnt/β-catenin axis. Human cell 34 36323918
2022 CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling. Journal of translational medicine 31 35509083
2019 Loss of lncRNA-SNHG7 Promotes the Suppression of Hepatic Stellate Cell Activation via miR-378a-3p and DVL2. Molecular therapy. Nucleic acids 30 31272073
2018 HMGA2 enhances 5-fluorouracil chemoresistance in colorectal cancer via the Dvl2/Wnt pathway. Oncotarget 30 29515783
2020 FOXM1/DVL2/Snail axis drives metastasis and chemoresistance of colorectal cancer. Aging 25 33291076
2017 RAP1B, a DVL2 binding protein, activates Wnt/beta-catenin signaling in esophageal squamous cell carcinoma. Gene 24 28119087
2012 Association of DVL2 and AXIN2 gene polymorphisms with cleft lip with or without cleft palate in a Polish population. Birth defects research. Part A, Clinical and molecular teratology 23 22887353
2019 TM4SF1, a binding protein of DVL2 in hepatocellular carcinoma, positively regulates beta-catenin/TCF signalling. Journal of cellular and molecular medicine 22 31876386
2014 High expression of IGFBP7 in fibroblasts induced by colorectal cancer cells is co-regulated by TGF-β and Wnt signaling in a Smad2/3-Dvl2/3-dependent manner. PloS one 21 24427302
2014 Biophysical and molecular-dynamics studies of phosphatidic acid binding by the Dvl-2 DEP domain. Biophysical journal 21 24606934
2022 Superresolution microscopy localizes endogenous Dvl2 to Wnt signaling-responsive biomolecular condensates. Proceedings of the National Academy of Sciences of the United States of America 20 35867833
2021 Canine DVL2 variant contributes to brachycephalic phenotype and caudal vertebral anomalies. Human genetics 20 33599851
2014 The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Biochemical and biophysical research communications 19 24727453
2018 Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation. Journal of cellular and molecular medicine 18 30468298
2021 Dvl2 facilitates the coordination of NF-κB and Wnt signaling to promote colitis-associated colorectal progression. Cancer science 17 34807493
2021 Vesicle transporter GOLT1B mediates the cell membrane localization of DVL2 and PD-L2 and promotes colorectal cancer metastasis. Cancer cell international 16 34059062
2019 MiR-495 targeting dvl-2 represses the inflammatory response of ankylosing spondylitis. American journal of translational research 16 31217850
2011 Stau1 regulates Dvl2 expression during myoblast differentiation. Biochemical and biophysical research communications 16 22166206
2018 Study of microRNAs targeted Dvl2 on the osteoblasts differentiation of rat BMSCs in hyperlipidemia environment. Journal of cellular physiology 14 29226968
2018 PP5 (PPP5C) is a phosphatase of Dvl2. Scientific reports 14 29426949
2020 Cyclin G2 upregulation impairs migration, invasion, and network formation through RNF123/Dvl2/JNK signaling in the trophoblast cell line HTR8/SVneo, a possible role in preeclampsia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13 33205477
2020 The Daple-CK1ε complex regulates Dvl2 phosphorylation and canonical Wnt signaling. Biochemical and biophysical research communications 12 32888647
2005 Dvl2 silencing in postdevelopmental cells results in aberrant cell membrane activity and actin disorganization. Journal of cellular physiology 11 15593083
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
2024 Macrophage Dvl2 deficiency promotes NOD1-Driven pyroptosis and exacerbates inflammatory liver injury. Redox biology 9 39644526
2023 Suppression of Wnt/β-catenin Signaling in PDAC via METTL16-mediated N6-methyladenosine Modification of DVL2. Journal of Cancer 9 37859814
2020 TBX1 and Basal Cell Carcinoma: Expression and Interactions with Gli2 and Dvl2 Signaling. International journal of molecular sciences 9 31963474
2019 Genetic Polymorphisms in APC, DVL2, and AXIN1 Are Associated with Susceptibility, Advanced TNM Stage or Tumor Location in Colorectal Cancer. The Tohoku journal of experimental medicine 9 31723073
2017 The Fungal Metabolite Brefeldin A Inhibits Dvl2-Plk1-Dependent Primary Cilium Disassembly. Molecules and cells 9 28614913
2021 MiR-29c-3p reduces bone loss in rats with diabetic osteoporosis via targeted regulation of Dvl2 expression. European review for medical and pharmacological sciences 8 33577018
2020 PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin. OncoTargets and therapy 8 33116587
2023 HCMV UL8 interaction with β-catenin and DVL2 regulates viral reactivation in CD34+ hematopoietic progenitor cells. Journal of virology 7 37772824
2022 Heterozygous variants in the DVL2 interaction region of DACT1 cause CAKUT and features of Townes-Brocks syndrome 2. Human genetics 7 36066768
2020 Low fluid shear stress promoted ciliogenesis via Dvl2 in hUVECs. Histochemistry and cell biology 7 32776193
2016 The expression of SFRP1, SFRP3, DVL1, and DVL2 proteins in testicular germ cell tumors. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 7 27599467
2023 Aquaporin 9 is involved in CRC metastasis through DVL2-dependent Wnt/β-catenin signaling activation. Gastroenterology report 6 37360194
2023 Rho family small GTPase Rif regulates Wnt5a-Ror1-Dvl2 signaling and promotes lung adenocarcinoma progression. The Journal of biological chemistry 5 37703992
2022 DACT3 has a tumor-inhibiting role in acute myeloid leukemia via the suppression of Wnt/β-catenin signaling by DVL2. Journal of biochemical and molecular toxicology 5 35187752
2021 Characterization of the aberrant splicing of DVL2 induced by cancer-associated SF3B1 mutation. Biochemical and biophysical research communications 5 33561744
2021 Aberrant expression of SFRP1, SFRP3, DVL2 and DVL3 Wnt signaling pathway components in diffuse gastric carcinoma. Oncology letters 5 34691249
2015 APPL1 endocytic adaptor as a fine tuner of Dvl2-induced transcription. FEBS letters 5 25622892
2024 ZNF460-mediated upregulation of APCDD1L-DT promotes cholangiocarcinoma development by inhibiting the ubiquitin-mediated degradation of DVL2. Cancer gene therapy 3 39210030
2024 Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling. eLife 3 39652469
2025 PRICKLE3-USP9X interaction-mediated DVL2 deubiquitination promotes the progression of non-small cell lung cancer via canonical WNT pathway. Oncogene 1 40973792
2023 Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 genes enhance gastric cancer development in the presence of Helicobacter pylori. Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology 1 36720664
2026 AJUBA Attenuates Pathological Cardiac Hypertrophy by Enhancing NEDD4-Mediated Ubiquitination and Degradation of DVL2. Cell biology international 0 41793265
2026 Association of the Disheveled 2 (DVL2) Gene c.2044delC Variant with Increased Risk of Canine Cleft Palate. Animal genetics 0 42037250
2026 The E3 ubiquitin ligase Itch plays an essential role in kidney fibrosis by inhibiting Dvl2/GSK3β/β-catenin signaling pathway. Cell death and differentiation 0 42168361
2025 The LINC01612-DVL2-WNT axis promotes human endoderm differentiation. Stem cell reports 0 41135528
2025 CPZ promotes the proliferation of gastric cancer by activating the Wnt pathway through binding with DVL2. Discover oncology 0 41217683
2020 Erratum: Loss of lncRNA-SNHG7 Promotes the Suppression of Hepatic Stellate Cell Activation via miR-378a-3p and DVL2. Molecular therapy. Nucleic acids 0 33376628

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