Sfrp1 secreted frizzled-related protein 1 [ Rattus norvegicus (Norway rat) ]

Gene ID: 84402, updated on 13-Apr-2024

Summary

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Official Symbol: Sfrp1provided by RGD
Official Full Name: secreted frizzled-related protein 1provided by RGD
Primary source: RGD:621074
See related: Ensembl:ENSRNOG00000017783 AllianceGenome:RGD:621074
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: sFRP-1
Summary: Predicted to enable several functions, including Wnt-protein binding activity; frizzled binding activity; and heparin binding activity. Involved in several processes, including cellular response to prostaglandin E stimulus; negative regulation of osteoclast differentiation; and osteoblast differentiation. Predicted to be located in cell surface; collagen-containing extracellular matrix; and cytosol. Predicted to be active in extracellular space. Orthologous to human SFRP1 (secreted frizzled related protein 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Kidney (RPKM 136.3), Spleen (RPKM 109.3) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

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See Sfrp1 in Genome Data Viewer

Location:: 16q12.5

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	16	NC_086034.1 (75278325..75316736, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	16	NC_051351.1 (68575763..68614180, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	16	NC_005115.4 (73372007..73410777, complement)

Chromosome 16 - NC_086034.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sfrp1 as a Pivotal Paracrine Factor in the Trained Pericardial Stem Cells that Foster Reparative Activity.
Title: Sfrp1 as a Pivotal Paracrine Factor in the Trained Pericardial Stem Cells that Foster Reparative Activity.
Secreted frizzled-related protein 3 alleviated cardiac remodeling induced by angiotensin II via inhibiting oxidative stress and apoptosis in mice.
Title: Secreted frizzled-related protein 3 alleviated cardiac remodeling induced by angiotensin II via inhibiting oxidative stress and apoptosis in mice.
Secreted Frizzled-Related Protein 1 Promotes Odontoblastic Differentiation and Reparative Dentin Formation in Dental Pulp Cells.
Title: Secreted Frizzled-Related Protein 1 Promotes Odontoblastic Differentiation and Reparative Dentin Formation in Dental Pulp Cells.
sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway.
Title: sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway.
MiR-30a-3p promotes ovariectomy-induced osteoporosis in rats via targeting SFRP1.
Title: MiR-30a-3p promotes ovariectomy-induced osteoporosis in rats via targeting SFRP1.
MiR-542-3p play an important role in bone formation via inhibiting SFRP1 expression.
Title: miR-542-3p prevents ovariectomy-induced osteoporosis in rats via targeting SFRP1.
Sfrp1 directly protected cardiomyoblasts from hypoxia and reoxygenation-induced reperfusion injury and apoptosis through inhibition of the Wnt signaling pathway and plays cardioprotective role on ischemic damage.
Title: Secreted frizzled related protein 1 protects H9C2 cells from hypoxia/re-oxygenation injury by blocking the Wnt signaling pathway.
Sfrp1 gene protects cardiomyocytes from H2O2-induced oxidative stress through restraining the Wnt/Frizzled pathway.
Title: FrzA gene protects cardiomyocytes from H2O2-induced oxidative stress through restraining the Wnt/Frizzled pathway.
study indicates that increased expression of both SFRP1 and SFRP3 may contribute to the pathogenesis of IUGR placental dysfunction, whereas the loss of these proteins may be involved in the development of human trophoblastic tumors.
Title: Immunohistochemical expression of SFRP1 and SFRP3 proteins in normal and malignant reproductive tissues of rats and humans.
CSF-1 and EMAP-II may contribute to the reduced SFRP-1 expression seen on day 3, while TNF-alpha may contribute to the reduced SFRP-1 expression at day 9 in dental follicle.
Title: Regulation of SFRP-1 expression in the rat dental follicle.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH141243 (e-PCR)
- UniSTS:223239

RH135173 (e-PCR)
- UniSTS:218450

Sfrp1 (e-PCR), detects polymorphism
- UniSTS:507219

RH135431 (e-PCR)
- UniSTS:218708

RH141094 (e-PCR)
- UniSTS:223092

Sfrp1 (e-PCR), detects polymorphism
- UniSTS:527536

RH137493 (e-PCR)
- UniSTS:219581

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables Wnt-protein binding	IEA Inferred from Electronic Annotation more info
enables Wnt-protein binding	ISO Inferred from Sequence Orthology more info
enables cysteine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info
enables cysteine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables frizzled binding	IEA Inferred from Electronic Annotation more info
enables frizzled binding	ISO Inferred from Sequence Orthology more info
enables heparin binding	IEA Inferred from Electronic Annotation more info
enables heparin binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in BMP signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of BMP signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in Wnt signaling pathway involved in somitogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within Wnt signaling pathway involved in somitogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within Wnt signaling pathway, planar cell polarity pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within anterior/posterior pattern specification	ISO Inferred from Sequence Orthology more info
involved_in bone trabecula formation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within bone trabecula formation	ISO Inferred from Sequence Orthology more info
involved_in canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in cellular response to BMP stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to X-ray	IEA Inferred from Electronic Annotation more info
involved_in cellular response to X-ray	ISO Inferred from Sequence Orthology more info
involved_in cellular response to estradiol stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to estradiol stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to estrogen stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to estrogen stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to fibroblast growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to fibroblast growth factor stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to growth factor stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to heparin	IEA Inferred from Electronic Annotation more info
involved_in cellular response to heparin	ISO Inferred from Sequence Orthology more info
involved_in cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hypoxia	ISO Inferred from Sequence Orthology more info
involved_in cellular response to interleukin-1	IEA Inferred from Electronic Annotation more info
involved_in cellular response to interleukin-1	ISO Inferred from Sequence Orthology more info
involved_in cellular response to prostaglandin E stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to prostaglandin E stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to prostaglandin E stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to starvation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to transforming growth factor beta stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to transforming growth factor beta stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
involved_in cellular response to tumor necrosis factor	ISO Inferred from Sequence Orthology more info
involved_in cellular response to vitamin D	IEA Inferred from Electronic Annotation more info
involved_in cellular response to vitamin D	ISO Inferred from Sequence Orthology more info
involved_in convergent extension involved in somitogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within convergent extension involved in somitogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within development of primary male sexual characteristics	ISO Inferred from Sequence Orthology more info
involved_in digestive tract morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within digestive tract morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in dopaminergic neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in dopaminergic neuron differentiation	ISO Inferred from Sequence Orthology more info
involved_in dorsal/ventral axis specification	IEA Inferred from Electronic Annotation more info
involved_in dorsal/ventral axis specification	ISO Inferred from Sequence Orthology more info
involved_in extrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of extrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in female gonad development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within female gonad development	ISO Inferred from Sequence Orthology more info
involved_in hematopoietic progenitor cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in hematopoietic stem cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in hematopoietic stem cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within hemopoiesis	ISO Inferred from Sequence Orthology more info
involved_in male gonad development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within male gonad development	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of B cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of B cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of BMP signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of Wnt signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of androgen receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of androgen receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of bone remodeling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of bone remodeling	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell growth	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell migration	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell migration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of epithelial to mesenchymal transition	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of epithelial to mesenchymal transition	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of fibroblast apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of fibroblast apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of fibroblast proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of insulin secretion	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ossification	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of ossification	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ossification	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of osteoblast differentiation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of osteoblast proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of osteoblast proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of osteoblast proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of osteoclast differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of osteoclast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of osteoclast differentiation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of planar cell polarity pathway involved in axis elongation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of planar cell polarity pathway involved in axis elongation	ISO Inferred from Sequence Orthology more info
involved_in neural crest cell fate commitment	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neural crest cell fate commitment	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neural tube closure	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neural tube development	ISO Inferred from Sequence Orthology more info
involved_in osteoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in osteoblast differentiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in osteoblast differentiation	ISO Inferred from Sequence Orthology more info
involved_in osteoclast differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of osteoclast differentiation	ISO Inferred from Sequence Orthology more info
involved_in planar cell polarity pathway involved in axis elongation	IEA Inferred from Electronic Annotation more info
acts_upstream_of planar cell polarity pathway involved in axis elongation	ISO Inferred from Sequence Orthology more info
involved_in planar cell polarity pathway involved in neural tube closure	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within planar cell polarity pathway involved in neural tube closure	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell growth	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of extrinsic apoptotic signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of fat cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of fat cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of fat cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of fibroblast apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of fibroblast apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of non-canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of non-canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of smoothened signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in regulation of branching involved in prostate gland morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of branching involved in prostate gland morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in regulation of cell cycle process	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell cycle process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of establishment of planar polarity	ISO Inferred from Sequence Orthology more info
involved_in regulation of midbrain dopaminergic neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in regulation of midbrain dopaminergic neuron differentiation	ISO Inferred from Sequence Orthology more info
involved_in regulation of neuron projection development	IEA Inferred from Electronic Annotation more info
involved_in regulation of neuron projection development	ISO Inferred from Sequence Orthology more info
involved_in regulation of ossification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to organic cyclic compound	ISO Inferred from Sequence Orthology more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	ISO Inferred from Sequence Orthology more info
involved_in somatic stem cell population maintenance	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within somatic stem cell population maintenance	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within somitogenesis	ISO Inferred from Sequence Orthology more info
involved_in somitogenesis	ISO Inferred from Sequence Orthology more info
involved_in stromal-epithelial cell signaling involved in prostate gland development	IEA Inferred from Electronic Annotation more info
involved_in stromal-epithelial cell signaling involved in prostate gland development	ISO Inferred from Sequence Orthology more info
involved_in ureteric bud development	IEA Inferred from Electronic Annotation more info
involved_in ureteric bud development	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in collagen-containing extracellular matrix	IEA Inferred from Electronic Annotation more info
located_in collagen-containing extracellular matrix	ISO Inferred from Sequence Orthology more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: secreted frizzled-related protein 1

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_001276712.2 → NP_001263641.2 secreted frizzled-related protein 1 precursor

Status: VALIDATED

Source sequence(s)

JAXUCZ010000016

UniProtKB/TrEMBL

A6IW39, F1LLX7

Related

ENSRNOP00000024128.5, ENSRNOT00000024128.7

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 ...