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FLASH GENE
Symbol DKK3 contributors: mct/npt/pgu - updated : 10-05-2017
HGNC name dickkopf homolog 3 (Xenopus laevis)
HGNC id 2893
Location 11p15.3      Physical location : 11.984.544 - 12.030.917
Synonym name
  • RIG-like 7.1
  • RIG-like 5-6
  • inhibitor of WNT signaling dickkopf 3
  • regulated in glioma
  • reduced expression in immortalized cells
    • Synonym symbol(s) REIC, Dickkopf-3, RIG
    DNA
    TYPE functioning gene
    STRUCTURE 46.37 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text all transcripts encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2769 38.3 350 - 1999 10570958
    8 - 2755 38.3 350 - 1999 10570958
    7 - 2587 38.3 350 - 1999 10570958
    - - 2788 - 364 - 1999 10570958
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Digestivemouth     Homo sapiens
    Endocrinepancreas   highly Homo sapiensAdult
    Nervousbrain   highly
     spinal cord    
    Reproductivemale systemtestis    Mus musculus
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa)   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiensAdult
    Lymphoid/Immunemacrophage Homo sapiens
    ReproductiveSertoli cell Mus musculus
    cell lineage
    cell lines
    fluid/secretion secreted
    at STAGE
    physiological period embryo, pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal peptide
  • two clusters of ten cysteine residues
  • a short linker
  • a potential C terminal N glycosylation site
    • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to murine Dkk3
    Homologene
    FAMILY
  • dickkopf family
    • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • localized around the ER of human fibroblasts
    • basic FUNCTION
  • inhibitor of WNT signaling
  • mediating interactions between epithelial and mesenchymal cells
  • playing a role in melanoma tumor progression
  • inhibitor of the Wnt/beta-catenin pathway
  • immune modulator with a crucial role for CD8 T-cell tolerance
  • role for DKK3 in down-regulating CD8 T-cell reactivity
  • is a component of the genetic circuitry regulating aldosterone biosynthesis in the adrenal cortex
  • DKK3 mediated regulation of spermatogenesis via WNT4/CTNNB1 modulation
  • DKK1, DKK2, DKK3, DKK4 are known to modulate Wnt/CTNNB1 signaling, which is activated during bone formation
  • is a novel modulator interfering with B cell fate as well as the maintenance program of B cells, leading to changes in B cell immune responses
  • induces stem cell differentiation into smooth muscle lineage via ATF6 signalling
  • DKK3 promotes cell survival during oxidative stress by suppressing the expression of the superoxide-producing enzyme XDH
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS development
    text
  • embryogenesis
  • morphogenesis
    • PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • WNT proteins
  • LRP6 through the second cluster of cysteine residues
  • interacting with CTNNB1 (DKK3 is a negative regulator of beta-catenin and its downregulation contribute to an activation of the beta-catenin signaling pathway)
  • DYNLT1 is a novel interaction partner of DKK3 (interaction and functions occur around the ER)
  • DKK3 acts as a cardioprotective regulator of pathological cardiac hypertrophy and that this function largely occurs via the regulation of MAP3K5/MAPK14 signalling
  • PPM1D controls DKK3-dependent inhibition of neuronal differentiation during aging, suggesting that regulating PPM1D levels could prevent certain aspects of functional decline of the aging brain
  • SGTA is a novel interacting partner of DKK3
  • DKK3 protein interferes with SGTA dimerization, promotes dynein-dependent AR transport and then upregulates AR signaling
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in non small cell lung carcinoma (with poor differentiation), in cervical cancer (promoter was methylated in cervical cancer)
    tumoral     --low  
    in kidney, urinary bladder, liver, prostate, pancreas cancers
    tumoral     --low  
    resulting in impairment of glandular structure and uncontrolled prostate epithelial cell (PrEC) proliferation, both of which are crucial for prostate cancer progression
    tumoral     --over  
    induces cancer cell apoptosis through endoplasmic reticulum (ER) stress
    tumoral     --low  
    in all of the seminoma and non-seminomatous germ cell tumor tissues
    tumoral     --over  
    strongly expressed in ganglioneuroma but only weakly in neuroblastoma
    tumoral     --low  
    by promoter methylation in breast cancer, and proves as a novel prognostic marker potentially useful in the clinical management of this disease
    tumoral     --over  
    in hepatoblastomas and hepatocellular carcinomas
    tumoral     --low  
    in the hyperproliferative epidermis including skin cancers and non-cancerous proliferative disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene for prostate cancer (variant comprising the N-terminal 78 amino acid region most strongly induced ER stress and apoptosis in prostate cancer cells)
    Marker
  • could be a potential tumor marker for the early detection of Oral squamous cell carcinoma (OSCC)
    • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivetestis
    adenovirus vector DKK3 may lead to developing less insulting and non-genotoxic therapeutic measures against testicular cancer
    cardiovascularcardiomyopathy 
    could serve as a therapeutic target for the treatment of cardiomyopathy and heart failure
    cancer  
    upregulation DKK3 protein expression could be a promising option for cancer therapy
    ANIMAL & CELL MODELS