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FLASH GENE

Symbol

SFRP2

contributors: mct/pgu - updated : 16-09-2016

HGNC name	secreted frizzled-related protein 2
HGNC id	10777

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a frizzled-like cysteine-rich domain
	a conserved hydrophilic carboxyterminal domain

HOMOLOGY

interspecies	homolog to Drosophila frizzled polarity
	homolog to murine Sfrp 2

Homologene

FAMILY

secreted frizzled-related protein (sFRP) family

CATEGORY

secretory , signaling

SUBCELLULAR LOCALIZATION	extracellular
	intracellular

basic FUNCTION	likely involved in WNT binding
	WNT-frizzled proteins signaling pathways
	may regulate hematopoietic stem cells
	involved in embryonic development as well as pathological conditions including bone and myocardial disorders and cancer
	having role as an enhancer of Wnt/beta-catenin signaling, a result with biological impact for both normal development and diverse pathologies such as tumorigenesis
	augments canonical Wnt3a/beta-catenin signaling at the level of its cell surface receptor
	potential enhancer of canonical Wnt signaling and therefore has a possible role as a paracrine/autocrine positive modulator of this key cellular signal transduction pathway
	SFRP1, SFRP2 can either promote or suppress Wnt/CTNNB1 signaling, depending on cellular context, concentration and most likely the expression pattern of Fzd receptors
	SFRP1, SFRP2 play a role in lens development, at least in part, by regulating aspects of WNT/CTNNB1 signaling in lens epithelial cells
	is a key profibrotic cytokine in the heart
	SFRP2 enhanced osteo-/dentinogenic differentiation via Osterix, a key transcription factor in stem cells derived from apical papillae (SCAPs)

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	regulating the intracellular level of beta catenin
	SFRP1, SFRP2 inhibits the ADAM10 metalloprotease, which might have important implications in pathological events, including cancer and Alzheimer disease
	HR repressed the expression of Wnt inhibitors, including SOSTDC1, DKKL1, SFRP1, and SFRP2
	SREBPF1 regulated transcriptional activation of the SFRP2 gene in chondrogenic cells
	FRP2 may promote cardiac fibrocalcification through coordinate activation of tolloid-like metalloproteinases and ALPL
	silencing KDM2A, a histone demethylase and BCL6 co-repressor, derepressed SFRP2 transcription by increasing histone H3K4 and H3K36 methylation at the SFRP2 promoter

cell & other

REGULATION

repressed by

DKK1 that negates all SFRP2 effects on Wnt3a signaling

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in retinitis pigmentosa tumoral       loss of function in colorectal cancer tumoral     --over   repressed Wnt target genes and induced changes in the expression of numerous genes related to proliferation, growth and apoptosis in gastric cancer cells tumoral     --low   silencing leads to oncogenic activation of the Wnt pathway and contributes to cervical cancer progression through the epithelial mesenchymal transition program tumoral     --low   by hypermethylation in primary hepatocellular carcinoma constitutional       loss of function of SFRP1 and SFRP2, two postulated Wnt antagonists, perturbs retinal neurogenesis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	methylated SFRP2 and TMEFF2 detected in 94.2 p100, and 71.2 p100 of colorecal cancer (CRC), and methylation testing of fecal DNA may be a simple and promising non-invasive screening method for CRC and precancerous lesions
Therapy target

ANIMAL & CELL MODELS