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FLASH GENE
Symbol DACT1 contributors: mct/pgu - updated : 10-05-2022
HGNC name dishevelled binding antagonist of beta catenin 1
HGNC id 17748
Corresponding disease
TBS2 Townes-Brocks syndrome 2
Location 14q23.1      Physical location : 59.104.756 - 59.115.036
Synonym name
  • hepatocellular carcinoma novel gene 3 protein
  • heptacellular carcinoma novel gene 3
  • dapper, antagonist of beta-catenin, homolog 1 (Xenopus laevis)
  • Synonym symbol(s) DAPPER1, THYEX3, HDPR1, DAPPER, FRODO, DPR1
    DNA
    TYPE fragile site
    STRUCTURE 14.26 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure a CpG island located at the promoter region
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 3766 - 799 - 2003 12632086
    4 - 3877 - 836 - 2003 12632086
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   highly
    Endocrineparathyroid   highly
    Lymphoid/Immunethymus    
    Nervousbrain     Homo sapiens
     nerve   highly Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text
  • placenta, fetal brain, fetal eye
  • in the presomitic mesoderm and somites during segmentation, in the limb bud mesenchyme and other mesoderm-derived tissues, and in the central nervous system (CNS)
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a coiled-coil motif
  • a PDZ binding motif
  • one crib domain
  • one WH1 domain
  • two WH2 domains
  • a classical nuclear localization signal (NLS)
  • a nuclear export signal (NES)
  • conjugated PhosphoP
    mono polymer complex
    HOMOLOGY
    interspecies ortholog to murine Dact1
    ortholog to xenopus Xl.7602
    Homologene
    FAMILY
  • dapper family
  • Dact family of scaffold proteins
  • Trio family of GTPase regulatory proteins
  • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text shuttles between the cytoplasm and the nucleus
    basic FUNCTION
  • acting as an inhibitor of Dsh-mediated signaling pathways during development
  • may stabililize the beta-catenin degradation complex by binding to DSH
  • required for normal vertebrate development
  • negatively modulates the basal activity of Wnt/CTNNB signaling in the nucleus by keeping LEF1 in the repressive state and controls Wnt/CTNNB signaling in both the cytoplasm and the nucleus
  • preadipocyte gene involved in the regulation of human adipogenesis
  • regulates adipogenesis through coordinated effects on gene expression that selectively alter intracellular and paracrine/autocrine components of the Wnt/beta-catenin signaling pathway
  • contributes to morphogenesis at the primitive streak by regulating VANGL2 upstream of cell adhesion and the PCP pathway
  • DACT1 and DACT3 may contribute to early tooth formation by modulation of Wnt signaling pathways in the mesenchyme, including preodontoblasts
  • can negatively modulate Wnt signaling by promoting DVL degradation in the cytoplasm and disrupting the CTNNB1·LEF1 complex in the nucleus
  • during neuronal differentiation, plays a critical role in a molecular pathway promoting Rac activity underlying the elaboration of dendrites and the establishment of spines and excitatory synapses
  • cytoplasmic regulator of intracellular signaling, inhibiting Wnt signaling
  • cytoplasmic protein expression was associated with tumor malignant progression via beta-catenin accumulation
  • conserved role for DACT proteins in kinase-regulated biochemistry involving VANGLl and DVL
  • principal role for all DACT family members is in the Planar Cell Polarity pathway (PCP)
  • DACT1 is an important positive regulator in colon cancer
  • SESTD1, DVL2 and DACT1 co-regulate the Wnt/Planar Cell Polarity (PCP) pathway during mammalian development
  • developmental requirement for DACT1 during dendrite arborization, in hippocampal pyramidal neurons, is also present in cortical interneurons
  • plays a positive role in autophagy, and promotes the basal and starvation-induced autophagy
  • might play an important role in human placenta development via promoting Wnt signaling 9)
  • functions in embryonic development and tumorigenesis
  • DACT1 is critical to breast and prostate cancer bone metastasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    transcriptional activation of target genes of the WNT signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to DSH
  • interacting protein of DVL1, and a central mediator in Wnt signaling
  • binds Dishevelled, catenins, and other signaling proteins
  • YWHAB interacts with DACT1 (YWHAB binding attenuates the ability of hDpr1 to promote Dishevelled (Dvl) degradation, thus enhancing Wnt signaling)
  • SESTD1-DACT1 interaction can induce Rho GTPase activation
  • SESTD1 cooperates with DACT1 in VANGL2 regulation and in the planar cell polarity (PCP) pathway during mammalian embryonic development
  • DACT1 enhances the ATG14-BECN1-PIK3C3 complex formation and PIK3C3 kinase activity
  • DACT1 increases autophagosome formation as indicated by elevated puncta formation of MAP1LC3A, ATG14 and ZFYVE1 (Double FYVE-containing protein 1)
  • TGFB1 inhibits WNT signaling to enhance the function of DACT1 inhibiting Wnt signaling
  • CCNG2 regulates canonical Wnt signalling via interaction with DACT1 to attenuate tubulointerstitial fibrosis in diabetic nephropathy
  • KDM1A was found to negatively regulate DACT1 through histone deacetylation
  • cell & other
    REGULATION
    induced by TGFB1, and forms protein condensates in the cytoplasm to repress Wnt signalling
    ASSOCIATED DISORDERS
    corresponding disease(s) TBS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in hepatoma cell lines, associated with methylation of promoter CpG island
    tumoral   LOH    
    in hepatocellular carcinoma
    tumoral     --low  
    in hepatocellular carcinoma
    tumoral     --low  
    by hypermethylated CpG sites of DACT1 promoter significantly associated with the poorer survival in gastric cancer (GC).
    Susceptibility
    Variant & Polymorphism
    Candidate gene a potent cancer-associated gene
    Marker
  • its cytoplasmic expression may serve as a potential predictive factor for lymph node metastasis and tumor development in esophageal squamous cell carcinoma
  • Therapy target
    ANIMAL & CELL MODELS