Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol DKK3 contributors: mct/npt/pgu - updated : 10-05-2017
HGNC name dickkopf homolog 3 (Xenopus laevis)
HGNC id 2893
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