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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Nervous brain         Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

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
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed diabete type 2   may be a potential therapeutic target for treating type 2 diabetes cardiovascular atheroma cardiac may be a viable therapeutic target in the treatment of ischemic vascular diseases

ANIMAL & CELL MODELS