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FLASH GENE
Symbol DKK2 contributors: mct/pgu - updated : 05-01-2015
HGNC name dickkopf homolog 2 (Xenopus laevis)
HGNC id 2892
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Nervousbrain    
Respiratorylung    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo, fetal
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal peptide
  • two clusters of ten cysteine residues separated by a linker region, and the second Cys-rich domains of DKK1 and DKK2 played a more important role in the inhibition of canonical Wnt signaling
  • a potential C terminal N glycosylation site, and binding of the C-terminal cysteine-rich domain to the Wnt coreceptor, LRP5/6 is implicated in Wnt antagonism
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to murine Dkk2
    Homologene
    FAMILY
  • dickkopf family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    text secreted form undergoing proteolytic process
    basic FUNCTION
  • inhibitor of WNT signaling, mediating interactions between epithelial and mesenchymal cells
  • key regulator of the corneal versus epidermal fate of the ocular surface epithelium
  • having a role in late stages of osteoblast differentiation into mineralized matrices, partially mediated by its Wnt signaling antagonistic activity
  • essential integration node between retinoic acid and canonical Wnt signaling during eye development
  • might play important roles through inhibition of canonical Wnt signaling in the periimplantation uterus
  • Wnt antagonist, silenced in some cancers
  • inhibits renal cancer progression through apoptotic and cell cycle pathways
  • distinct functions of DKK1 and DKK2 in controlling angiogenesis
  • may regulate glucose metabolism by regulating hepatic glucose output, probably through increasing hepatic glycogen concentrations
  • is a key player in Ewing sarcoma invasion and osteolysis and also in the differential phenotype of Ewing sarcoma cells
  • BMP4 signaling suppresses tooth developmental inhibitors in the tooth mesenchyme, including DKK2 and OSR2, and synergizes with MSX1 to activate mesenchymal odontogenic potential for tooth morphogenesis and sequential tooth formation
  • DKK1, DKK2, DKK3, DKK4 are known to modulate Wnt/CTNNB1 signaling, which is activated during bone formation
  • DKK1 and DKK2 have differential roles in normalization and functionality of tumor blood vessels, in addition to angiogenesis
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    Wnt beta catenin signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • WNT proteins
  • LRP6, through the second cluster of cysteine residues (C terminus) and inducing removal of LRP6 from the plasma membrane, interaction inhibited by the N terminus of DKK1
  • interact with LRP5 and LRP6 to modulate canonical Wnt signaling during development, and are known to be expressed in the developing heart
  • cell & other
    REGULATION
    Other regulated during the osteogenic differentiation, probably by WNT(WNT7B)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    epigenetically silenced by methylation in higher grades and stages of renal cell carcinoma (RCC)
    constitutional     --low  
    in osteoporosis
    tumoral     --over  
    in Ewing sarcoma compared with corresponding normal tissues
    constitutional       loss of function
    resulted in osteopenia because of its role in osteoblast terminal differentiation
    Susceptibility to alcohol dependence
    Variant & Polymorphism SNP
  • rs427983, rs419558, rs399087 associated to alcohol dependence
  • rs17037102 may be the causal SNP associated with alcohol-related harm in alcoholic subjects
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    may be a potential therapeutic target for treating type 2 diabetes
    cardiovascularatheromacardiac
    may be a viable therapeutic target in the treatment of ischemic vascular diseases
    ANIMAL & CELL MODELS