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FLASH GENE
Symbol DKK2 contributors: mct/pgu - updated : 05-01-2017
HGNC name dickkopf homolog 2 (Xenopus laevis)
HGNC id 2892
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
  • key role of MSX1 in driving tooth development through the bud-to-cap transition is to control the expression of DKK2
    • 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