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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

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       highly Homo sapiens Digestive mouth         Homo sapiens Endocrine pancreas       highly Homo sapiens Adult Nervous brain       highly   spinal cord         Reproductive male system testis       Mus musculus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial absorptive excretory digestive epithelium (mucosa)     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens Adult Lymphoid/Immune macrophage Homo sapiens Reproductive Sertoli 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer reproductive testis adenovirus vector DKK3 may lead to developing less insulting and non-genotoxic therapeutic measures against testicular cancer cardiovascular cardiomyopathy   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