Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

SFRP1

contributors: mct/shn/pgu - updated : 12-12-2018

HGNC name	secreted frizzled-related protein 1
HGNC id	10776

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	8p11.21      Physical location : 41.119.475 - 41.166.990
Synonym name	secreted apoptosis-related protein 2
	frizzled-related protein 1
Synonym symbol(s)	SARP2, FZDS1, FRP, FRP-1,sFRP-1, FrzA

DNA

TYPE	functioning gene
STRUCTURE	47.50 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	SFRP1 promoter was hypermethylated in keloid tissues, compared with that in normal skin tissues

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D8S532 - D8S1118 - SFRP1 - D8S268 - D8S1115 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003012 3 - 4465 NP_003003 36 314 - 1997 9192640

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 vessel       predominantly Homo sapiens Digestive intestine large intestine colon   highly   intestine small intestine     highly Lymphoid/Immune spleen       moderately Reproductive female system placenta     moderately   female system ovary     highly   male system testis     highly   male system prostate     highly Urinary kidney       highly Visual eye lens       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Homo sapiens Adult

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens Visual lens fibers Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

Text	Brain and kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a frizzled-like cysteine-rich domain (CRD)
	a region between AAs 73-86 within the second loop of the CRD necessary for the optimal Wnt inhibitory function
	a conserved hydrophilic carboxy-terminal domain

HOMOLOGY

interspecies	homolog to Drosophila frizzled polarity
	homolog to Sfrp1, Mus musculus
	ortholog to Sfrp1, Rattus norvegicus
	ortholog to SFRP1, Pan troglodytes
	ortholog to sfrp1a, Danio rerio

Homologene

FAMILY

secreted frizzled-related protein (sFRP) family

CATEGORY

tumor suppressor , signaling

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane

basic FUNCTION	may be involved in retina cell differentiation
	having ability to guide growth cone movement via the frizzled 2 receptor
	suppressed hepatoma cells growth through WNT canonical signaling pathway
	WNT signalling antagonist, playing a role in the development of multiple solid tumour types
	regulating hematopoietic stem cells
	transcriptional repression target of the t(8;21) fusion protein
	SFRP1 functions as a secreted mediator of senescence through inhibition of Wnt signaling and activation of the retinoblastoma (RB1) pathway
	is an extracellular component of stress-induced senescence signaling that responds to potentially carcinogenic stresses such as DNA damage and oxidative insult and induces cellular senescence in an autocrine and paracrine fashion, which may lead to non-cell-autonomous tumor suppression
	putative tumor suppressor gene that is frequently down-regulated in multiple carcinomas, is a crucial regulatory protein for spermiation
	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
	expression of SFRP1 is a critical factor required for maintaining appropriate cellular signaling in response to the onset of obesity
	SFRP1 and FRZB act as WNT signaling pathway antagonists and play an important role in embryonic development and carcinogenesis
	role of SFRP1 in age-related cardiac deterioration and fibrosis
	loss of SFRP1 likely contributes to tumor progression by altering the expression of a critical transcription factor in both the epithelium and the immune system
	WNT7A and SFRP1 play likely opposite roles to ensure proper neural progenitors (NP) progeny in the developing cortex
	multifunctional regulator of BMP, WNT and NOTCH1 signaling strongly expressed during early telencephalic development
	by controlling WNT and NOTCH1 signaling in opposite directions, SFRP1 promotes hippocampal patterning and balances medio-lateral and antero-posterior cortex expansion

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	wingless-type MMTV integration site family member 1,WNT1 and wingless-type MMTV integration site family member 2, WNT2
	wingless-type MMTV integration site family member 4,WNT4
	Frizzled-2, Fz2
	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
	DNA damage enhances SFRP1 secretion by a TP53-dependent mechanism
	regulates spermatid adhesion in the testis via dephosphorylation of focal adhesion kinase and the nectin-3 adhesion protein complex
	downregulation of CBX5 can decrease H3K9me3 enrichment and DNA methylation rate of SFRP1 promoter, resulting in restoring the expression of SFRP1

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in breast carcinoma (expression was inversely correlated with tumor stage but not with tumor grade or lymph node status tumoral       loss of function by hypermethylation in colorectal cancer and in ovarian cancers tumoral       loss of function by hypermethylation in non-small-cell lung cancer (NSCLC) tumoral       loss of function by promoter hypermethylation, predominant mechanism of SFRP1 gene silencing in breast cancer and is associated with unfavourable prognosis tumoral     --low   in transitional cell carcinomas of the bladder 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   markedly reduced in both the breast cancer cell lines and primary tumour specimens relative to normal primary mammary epithelial cells even when SFRP1 is amplified tumoral     --low   by hypermethylation in primary hepatocellular carcinoma tumoral     --low   methylation-associated silencing of SFRP1 frequently occurs in renal cell carcinoma and plays a pivotal role in early carcinogenesis tumoral     --low   by promoter methylation frequently found in renal cell carcinoma constitutional       loss of function of SFRP1 and SFRP2, two postulated Wnt antagonists, perturbs retinal neurogenesis constitutional     --low   by hypermethylation in keloid tissues, compared with that in normal skin tissues tumoral     --low   decreased markedly in patients with acute myeloid leukemia (AML) compared to controls constitutional     --low   of SFRP1 may contribute to the pathogenesis of IUGR placental dysfunction, whereas the loss of the protein may be involved in the development of human trophoblastic tumors

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous dermatology   might be a therapeutic target for keloid treatment

ANIMAL & CELL MODELS

	in postnatal Sfrp1-/- animals the anterior hippocampus is reduced and the neocortex is shorter in the antero-posterior and medio-lateral axis but is thicker
	loss of Sfrp1 exacerbates weight gain, glucose homeostasis and inflammation in mice in response to diet induced obesity