SFRP1 secreted frizzled related protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SFRP1provided by HGNC
Official Full Name: secreted frizzled related protein 1provided by HGNC
Primary source: HGNC:HGNC:10776
See related: Ensembl:ENSG00000104332 MIM:604156; Vega:OTTHUMG00000164074
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FRP; FRP1; FrzA; FRP-1; SARP2
Summary: This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. Members of this family act as soluble modulators of Wnt signaling; epigenetic silencing of SFRP genes leads to deregulated activation of the Wnt-pathway which is associated with cancer. This gene may also be involved in determining the polarity of photoreceptor cells in the retina. [provided by RefSeq, Sep 2009]
Expression: Broad expression in endometrium (RPKM 97.0), fat (RPKM 58.4) and 17 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 8p11.21

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	8	NC_000008.11 (41261957..41309471, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (41119476..41166990, complement)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

It has been found that miR-27a-3p modulated the Wnt/beta-catenin signaling pathway to promote epithelial-mesenchymal transition in oral squamous carcinoma stem cells by down-regulating SFRP1.
Title: MicroRNA-27a-3p Modulates the Wnt/β-Catenin Signaling Pathway to Promote Epithelial-Mesenchymal Transition in Oral Squamous Carcinoma Stem Cells by Targeting SFRP1.
sFRP1 overexpression in gastric cancer cells leads to increased cell proliferation and angiogenesis.
Title: Secreted frizzled-related protein 1 overexpression in gastric cancer: Relationship with radiological findings of dual-energy spectral CT and PET-CT.
Study determined that SFRP1 is downregulated during tumor formation probably by DNA methylation, and associates consistently with tumor suppressive functions.
Title: A pan-cancer analysis of secreted Frizzled-related proteins: re-examining their proposed tumour suppressive function.
co-transfection of sFRP1 siRNA with miR- 191 inhibitor sequence, it was found that the Wnt/beta-catenin signaling pathway was reactivated and the colony formation ability of RBE cells was restored.
Title: miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma.
WNT5b rs3803164, and SFRP1 rs3242 were significantly associated with lumbar spine BMD.
Title: A specific haplotype in potential miRNAs binding sites of secreted frizzled-related protein 1 (SFRP1) is associated with BMD variation in osteoporosis.
lost SFRP1 expression-induced Wnt/beta-catenin signaling due to the hypermethylation of the SFRP1 promoter could associate with keloid development
Title: Methylation of secreted frizzled-related protein 1 (SFRP1) promoter downregulates Wnt/β-catenin activity in keloids.
miR-1301-3p promoted the expansion of prostate cancer stem cells by inhibiting GSK3beta and SFRP1, and activating the Wnt pathway.
Title: miR-1301-3p promotes prostate cancer stem cell expansion by targeting SFRP1 and GSK3β.
Methylation level of the SFRP1 promoter region is increased in patients with RCC compared to normal controls and might be involved in the occurrence and development of RCC.
Title: SFRP1 Promoter Methylation and Renal Carcinoma Risk: A Systematic Review and Meta-Analysis.
Methylation of SFRP1, SFRP2, SDC2, and PRIMA1 promoter sequences was observed in 85.1%, 72.3%, 89.4%, and 80.9% of plasma samples from patients with Colorectal cancer and 89.2%, 83.8%, 81.1% and 70.3% from adenoma patients, respectively.
Title: Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples.
preliminary data show loss of SFRP1 protein expression caused by the SFRP1 promoter hypermethylation in a subset of high-grade serous ovarian carcinomas
Title: Methylation-associated silencing of SFRP1 gene in high-grade serous ovarian carcinomas.

Submit: New GeneRIF Correction See all GeneRIFs (153)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of secreted frizzled-related protein 1 (SFRP1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 has the ability to induce expression of FRP-1 on peripheral blood mononuclear cells (PBMC)	PubMed
Envelope surface glycoprotein gp160, precursor	env	Antibodies raised against the human fusion regulatory protein 1 (FRP-1; CD98) molecule suppress cell fusion mediated by HIV-1 gp160	PubMed
	env	Co-cultivation of PBMC with HIV-1 gp160-expressing HeLa cells results in the increased expression of FRP-1 on T cells	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation, organism-specific biosystem (from WikiPathways)
BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation, organism-specific biosystemThis pathway is based on figure 6 from Li et al. BMP2 is activated by cAMP which promotes WNT4 expression in Human Primary Endometrial Stromal Cells (HPESCs) through SMAD1/5/8. WNT4 then induces FOXO...
Endoderm Differentiation, organism-specific biosystem (from WikiPathways)
Endoderm Differentiation, organism-specific biosystemModel depicting endoderm specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell lin...
Negative regulation of TCF-dependent signaling by WNT ligand antagonists, organism-specific biosystem (from REACTOME)
Negative regulation of TCF-dependent signaling by WNT ligand antagonists, organism-specific biosystemSeveral unrelated families of secreted proteins antagonize WNT signaling. Secreted frizzled-related proteins (sFRPs) have a cysteine rich domain (CRD) that is also found in FZD and ROR receptors, wh...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by Wnt, organism-specific biosystem (from REACTOME)
Signaling by Wnt, organism-specific biosystemWNT signaling pathways control a wide range of developmental and adult process in metozoans including cell proliferation, cell fate decisions, cell polarity and stem cell maintenance (reviewed in Sai...
TCF dependent signaling in response to WNT, organism-specific biosystem (from REACTOME)
TCF dependent signaling in response to WNT, organism-specific biosystem19 WNT ligands and 10 FZD receptors have been identified in human cells; interactions amongst these ligands and receptors vary in a developmental and tissue-specific manner and lead to activation of ...
Validated targets of C-MYC transcriptional repression, organism-specific biosystem (from Pathway Interaction Database)
Validated targets of C-MYC transcriptional repression, organism-specific biosystem
Validated targets of C-MYC transcriptional repression
Wnt signaling pathway, organism-specific biosystem (from KEGG)
Wnt signaling pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
Wnt signaling pathway, conserved biosystem (from KEGG)
Wnt signaling pathway, conserved biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-105250 (e-PCR)
- UniSTS:169252

SHGC-79057 (e-PCR)
- UniSTS:95880

SFRP1_1897 (e-PCR)
- UniSTS:280993

G19941 (e-PCR)
- UniSTS:36269

A002C42 (e-PCR)
- UniSTS:36270

G43220 (e-PCR)
- UniSTS:94897

RH12508 (e-PCR)
- UniSTS:49333

Homology

Homologs of the SFRP1 gene: The SFRP1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 209 organisms have orthologs with human gene SFRP1
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
Wnt-protein binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Wnt-protein binding	IDA Inferred from Direct Assay more info	PubMed
Wnt-protein binding	IPI Inferred from Physical Interaction more info	PubMed
Wnt-protein binding	NAS Non-traceable Author Statement more info	PubMed
cysteine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
drug binding	IDA Inferred from Direct Assay more info	PubMed
frizzled binding	IPI Inferred from Physical Interaction more info	PubMed
heparin binding	IDA Inferred from Direct Assay more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
Wnt signaling pathway involved in somitogenesis	IEA Inferred from Electronic Annotation more info
bone trabecula formation	IEA Inferred from Electronic Annotation more info
canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
cellular response to BMP stimulus	IEP Inferred from Expression Pattern more info	PubMed
cellular response to X-ray	IEA Inferred from Electronic Annotation more info
cellular response to estradiol stimulus	IEP Inferred from Expression Pattern more info	PubMed
cellular response to estrogen stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to fibroblast growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to heparin	IDA Inferred from Direct Assay more info	PubMed
cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
cellular response to interleukin-1	IEP Inferred from Expression Pattern more info	PubMed
cellular response to prostaglandin E stimulus	IEP Inferred from Expression Pattern more info	PubMed
cellular response to starvation	IEP Inferred from Expression Pattern more info	PubMed
cellular response to transforming growth factor beta stimulus	IEP Inferred from Expression Pattern more info	PubMed
cellular response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed
cellular response to vitamin D	IEP Inferred from Expression Pattern more info	PubMed
convergent extension involved in somitogenesis	IEA Inferred from Electronic Annotation more info
digestive tract morphogenesis	IEA Inferred from Electronic Annotation more info
dopaminergic neuron differentiation	IEA Inferred from Electronic Annotation more info
dorsal/ventral axis specification	IDA Inferred from Direct Assay more info	PubMed
female gonad development	IEA Inferred from Electronic Annotation more info
hematopoietic progenitor cell differentiation	IDA Inferred from Direct Assay more info	PubMed
hematopoietic stem cell differentiation	IDA Inferred from Direct Assay more info	PubMed
male gonad development	IEA Inferred from Electronic Annotation more info
negative regulation of B cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of JUN kinase activity	IEA Inferred from Electronic Annotation more info
negative regulation of Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of Wnt signaling pathway	NAS Non-traceable Author Statement more info	PubMed
negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification	IDA Inferred from Direct Assay more info	PubMed
negative regulation of androgen receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of bone remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of epithelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of epithelial to mesenchymal transition	IDA Inferred from Direct Assay more info	PubMed
negative regulation of fibroblast apoptotic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of fibroblast proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
negative regulation of insulin secretion	IDA Inferred from Direct Assay more info	PubMed
negative regulation of ossification	IDA Inferred from Direct Assay more info	PubMed
negative regulation of ossification	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of osteoblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of osteoclast differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of planar cell polarity pathway involved in axis elongation	IEA Inferred from Electronic Annotation more info
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
neural crest cell fate commitment	IEA Inferred from Electronic Annotation more info
non-canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
osteoblast differentiation	IEP Inferred from Expression Pattern more info	PubMed
planar cell polarity pathway involved in neural tube closure	IEA Inferred from Electronic Annotation more info
positive regulation of GTPase activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell-matrix adhesion	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	IDA Inferred from Direct Assay more info	PubMed
positive regulation of fat cell differentiation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of fibroblast apoptotic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of focal adhesion assembly	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of non-canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of stress fiber assembly	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	IEA Inferred from Electronic Annotation more info
proteolysis	IEA Inferred from Electronic Annotation more info
regulation of angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
regulation of branching involved in prostate gland morphogenesis	IEA Inferred from Electronic Annotation more info
regulation of cell cycle process	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of midbrain dopaminergic neuron differentiation	IEA Inferred from Electronic Annotation more info
regulation of neuron projection development	IEA Inferred from Electronic Annotation more info
response to drug	IDA Inferred from Direct Assay more info	PubMed
response to organic cyclic compound	IDA Inferred from Direct Assay more info	PubMed
somatic stem cell population maintenance	IEA Inferred from Electronic Annotation more info
stromal-epithelial cell signaling involved in prostate gland development	IEA Inferred from Electronic Annotation more info
ureteric bud development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell surface	IDA Inferred from Direct Assay more info	PubMed
collagen-containing extracellular matrix	HDA more info	PubMed
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
collagen-containing extracellular matrix	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
extracellular exosome	HDA more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	HDA more info	PubMed
extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extracellular space	IDA Inferred from Direct Assay more info	PubMed
intracellular	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: secreted frizzled-related protein 1

Names: SARP-2; frizzled-related protein; sFRP-1; secreted apoptosis-related protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_003012.4 → NP_003003.3 secreted frizzled-related protein 1 precursor

See identical proteins and their annotated locations for NP_003003.3

Status: REVIEWED

Source sequence(s)

BC036503, BQ002015, CB956696, CN271890, DA571541

Consensus CDS

CCDS34886.1

UniProtKB/Swiss-Prot

Q8N474

Related

ENSP00000220772.3, OTTHUMP00000225802, ENST00000220772.7, OTTHUMT00000377132

Conserved Domains (2) summary

cd07443
Location:52 → 175

CRD_SFRP1; Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt activity

cd03580
Location:183 → 306

NTR_Sfrp1_like; NTR domain, Secreted frizzled-related protein (Sfrp) 1-like subfamily; composed of proteins similar to human Sfrp1, Sfrp2 and Sfrp5. Sfrps are soluble proteins containing an NTR domain C-terminal to a cysteine-rich Frizzled domain. They show diverse ...