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Q8N474 (SFRP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Secreted frizzled-related protein 1

Short name=FRP-1
Short name=sFRP-1
Alternative name(s):
Secreted apoptosis-related protein 2
Short name=SARP-2
Gene names
Name:SFRP1
Synonyms:FRP, FRP1, SARP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length314 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP1 decreases intracellular beta-catenin levels By similarity. Has antiproliferative effects on vascular cells, in vitro and in vivo, and can induce, in vivo, an angiogenic response. In vascular cell cycle, delays the G1 phase and entry into the S phase By similarity. In kidney development, inhibits tubule formation and bud growth in metanephroi By similarity. Inhibits WNT1/WNT4-mediated TCF-dependent transcription.

Subunit structure

Interacts with WNT1, WNT2 and FRZD6. Interacts with WNT4, WNT8 and MYOC By similarity. Ref.6

Subcellular location

Secreted. Note: Cell membrane or extracellular matrix-associated. Released by heparin-binding.

Tissue specificity

Widely expressed. Absent from lung, liver and peripheral blood leukocytes. Highest levels in heart and fetal kidney. Also expressed in testis, ovary, fetal brain and lung, leiomyomal cells, myometrial cells and vascular smooth muscle cells. Expressed in foreskin fibroblasts and in keratinocytes. Ref.2

Induction

Down-regulated in colorectal and breast tumors. Up-regulated in uterine leiomyomas under high estrogenic conditions. Expression, in leiomyomal cells, also increased both under hypoxic and serum deprivation conditions. Ref.3 Ref.7

Domain

The FZ domain is involved in binding with Wnt ligands By similarity.

Miscellaneous

May have therapeutic use in cardiac surgery.

Sequence similarities

Belongs to the secreted frizzled-related protein (sFRP) family.

Contains 1 FZ (frizzled) domain.

Contains 1 NTR domain.

Mass spectrometry

Molecular mass is 7266.4 Da from positions 169 - 210. Determined by MALDI. Isoform N-glycosylatedon Asn-173. Ref.5

Ontologies

Keywords
   Biological processDifferentiation
Wnt signaling pathway
   Cellular componentSecreted
   DomainSignal
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway involved in somitogenesis

Inferred from electronic annotation. Source: Ensembl

bone trabecula formation

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from direct assay PubMed 18787224. Source: BHF-UCL

cellular response to BMP stimulus

Inferred from expression pattern PubMed 16149051. Source: UniProtKB

cellular response to X-ray

Inferred from electronic annotation. Source: Ensembl

cellular response to estradiol stimulus

Inferred from expression pattern Ref.7. Source: UniProtKB

cellular response to estrogen stimulus

Inferred from direct assay PubMed 18941195. Source: UniProtKB

cellular response to fibroblast growth factor stimulus

Inferred from direct assay PubMed 17500071. Source: UniProtKB

cellular response to growth factor stimulus

Inferred from direct assay PubMed 17500071. Source: UniProtKB

cellular response to heparin

Inferred from direct assay PubMed 17500071. Source: UniProtKB

cellular response to hypoxia

Inferred from expression pattern Ref.7. Source: UniProtKB

cellular response to interleukin-1

Inferred from expression pattern PubMed 16149051. Source: UniProtKB

cellular response to prostaglandin E stimulus

Inferred from expression pattern PubMed 16149501. Source: UniProtKB

cellular response to starvation

Inferred from expression pattern Ref.7Ref.3. Source: UniProtKB

cellular response to transforming growth factor beta stimulus

Inferred from expression pattern PubMed 16149051. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from direct assay Ref.2. Source: UniProtKB

cellular response to vitamin D

Inferred from expression pattern PubMed 16149051. Source: UniProtKB

convergent extension involved in somitogenesis

Inferred from electronic annotation. Source: Ensembl

digestive tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral axis specification

Inferred from direct assay Ref.1. Source: UniProtKB

female gonad development

Inferred from electronic annotation. Source: Ensembl

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

hematopoietic progenitor cell differentiation

Inferred from direct assay PubMed 19778523. Source: UniProtKB

hematopoietic stem cell differentiation

Inferred from direct assay PubMed 19778523. Source: UniProtKB

male gonad development

Inferred from electronic annotation. Source: Ensembl

menstrual cycle phase

Inferred from expression pattern Ref.7. Source: UniProtKB

negative regulation of B cell differentiation

Inferred from mutant phenotype PubMed 18941195. Source: UniProtKB

negative regulation of BMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of JUN kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of Wnt signaling pathway

Inferred from direct assay PubMed 10660608PubMed 17500071PubMed 20208569Ref.1. Source: UniProtKB

negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification

Inferred from direct assay Ref.1. Source: UniProtKB

negative regulation of androgen receptor signaling pathway

Inferred from direct assay PubMed 19277043. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.7PubMed 14581477PubMed 16149051PubMed 16288033PubMed 19723665. Source: UniProtKB

negative regulation of bone remodeling

Inferred from mutant phenotype PubMed 19072540. Source: UniProtKB

negative regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 16149051PubMed 16288033PubMed 17443492PubMed 17471511PubMed 19095296PubMed 19277043PubMed 19569235Ref.2. Source: UniProtKB

negative regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation

Inferred from direct assay PubMed 17994217. Source: UniProtKB

negative regulation of cell growth

Inferred from direct assay PubMed 19569235PubMed 20208569. Source: UniProtKB

negative regulation of cell migration

Inferred from direct assay PubMed 10980594. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay PubMed 17443492PubMed 17994217PubMed 19277043PubMed 20208569. Source: UniProtKB

negative regulation of epithelial cell proliferation

Inferred from direct assay PubMed 19095296. Source: UniProtKB

negative regulation of epithelial to mesenchymal transition

Inferred from direct assay PubMed 19095296. Source: UniProtKB

negative regulation of fibroblast apoptotic process

Inferred from direct assay PubMed 14581477. Source: UniProtKB

negative regulation of fibroblast proliferation

Inferred from direct assay PubMed 19734317. Source: BHF-UCL

negative regulation of gene expression

Inferred from direct assay PubMed 10980594. Source: UniProtKB

negative regulation of insulin secretion

Inferred from direct assay PubMed 17994217. Source: UniProtKB

negative regulation of ossification

Inferred from direct assay PubMed 15677765. Source: UniProtKB

negative regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoblast proliferation

Inferred from mutant phenotype PubMed 19072540. Source: UniProtKB

negative regulation of osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 10980594. Source: UniProtKB

negative regulation of planar cell polarity pathway involved in axis elongation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 10660608PubMed 19095296PubMed 19277043PubMed 20234818. Source: UniProtKB

neural crest cell fate commitment

Inferred from electronic annotation. Source: Ensembl

neural tube closure

Inferred from electronic annotation. Source: Ensembl

osteoblast differentiation

Inferred from expression pattern PubMed 16149051. Source: UniProtKB

planar cell polarity pathway involved in neural tube closure

Inferred from electronic annotation. Source: Ensembl

positive regulation of Rac GTPase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of Wnt signaling pathway

Inferred from direct assay PubMed 10660608. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay PubMed 15677765Ref.2. Source: UniProtKB

positive regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 18941195. Source: UniProtKB

positive regulation of cell growth

Inferred from direct assay PubMed 10980594PubMed 16288033. Source: UniProtKB

positive regulation of cell proliferation

Inferred from direct assay PubMed 10980594. Source: UniProtKB

positive regulation of cell-matrix adhesion

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 16288033. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from direct assay Ref.2. Source: BHF-UCL

positive regulation of fat cell differentiation

Inferred from direct assay PubMed 15886250. Source: UniProtKB

positive regulation of fibroblast apoptotic process

Inferred from direct assay PubMed 14581477. Source: UniProtKB

positive regulation of focal adhesion assembly

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of non-canonical Wnt signaling pathway

Inferred from direct assay PubMed 19569235. Source: UniProtKB

positive regulation of smoothened signaling pathway

Inferred from mutant phenotype PubMed 17035233. Source: UniProtKB

positive regulation of stress fiber assembly

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 10660608PubMed 15886250PubMed 19569235. Source: UniProtKB

prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis

Inferred from electronic annotation. Source: Ensembl

proteolysis

Inferred from mutant phenotype PubMed 14581477. Source: GOC

regulation of angiogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of branching involved in prostate gland morphogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of cell cycle process

Inferred from mutant phenotype Ref.3. Source: UniProtKB

response to drug

Inferred from direct assay PubMed 19072540PubMed 19254787. Source: UniProtKB

response to organic cyclic compound

Inferred from direct assay PubMed 20208569. Source: UniProtKB

somatic stem cell maintenance

Inferred from electronic annotation. Source: Ensembl

stromal-epithelial cell signaling involved in prostate gland development

Inferred from electronic annotation. Source: Ensembl

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcell surface

Inferred from direct assay Ref.1. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 14581477. Source: UniProtKB

extracellular matrix

Inferred from direct assay Ref.6. Source: BHF-UCL

extracellular space

Inferred from direct assay PubMed 10980594PubMed 17500071Ref.1. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708PubMed 23376485. Source: UniProt

intracellular

Inferred from direct assay PubMed 17500071. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

proteinaceous extracellular matrix

Inferred from direct assay Ref.1. Source: BHF-UCL

   Molecular_functionPDZ domain binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-activated receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-protein binding

Inferred from physical interaction PubMed 10660608PubMed 19072540. Source: UniProtKB

cysteine-type endopeptidase activity

Inferred from mutant phenotype PubMed 14581477. Source: UniProtKB

drug binding

Inferred from direct assay PubMed 19072540PubMed 19254787. Source: UniProtKB

frizzled binding

Inferred from physical interaction PubMed 1927703PubMed 19277043. Source: UniProtKB

heparin binding

Inferred from direct assay PubMed 10660608Ref.5. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.6. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.6. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FZD6O603533EBI-3940687,EBI-8754490

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Ref.5
Chain32 – 314283Secreted frizzled-related protein 1
PRO_0000032538

Regions

Domain53 – 169117FZ
Domain186 – 306121NTR

Amino acid modifications

Glycosylation1731N-linked (GlcNAc...) Ref.5
Disulfide bond58 ↔ 121 Ref.5
Disulfide bond68 ↔ 114 Ref.5
Disulfide bond105 ↔ 140 Ref.5
Disulfide bond129 ↔ 166 Ref.5
Disulfide bond133 ↔ 157 Ref.5
Disulfide bond186 ↔ 256 Ref.5
Disulfide bond189 ↔ 258 Ref.5
Disulfide bond203 ↔ 306 Ref.5

Experimental info

Mutagenesis1731N → Q: Reduced molecular weight. Ref.5
Mutagenesis2631N → Q: No effect on molecular weight. Ref.5
Sequence conflict141Missing Ref.1
Sequence conflict141Missing Ref.3
Sequence conflict1741A → P in AAB70793. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q8N474 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 29DD948706EB7143

FASTA31435,386
        10         20         30         40         50         60 
MGIGRSEGGR RGAALGVLLA LGAALLAVGS ASEYDYVSFQ SDIGPYQSGR FYTKPPQCVD 

        70         80         90        100        110        120 
IPADLRLCHN VGYKKMVLPN LLEHETMAEV KQQASSWVPL LNKNCHAGTQ VFLCSLFAPV 

       130        140        150        160        170        180 
CLDRPIYPCR WLCEAVRDSC EPVMQFFGFY WPEMLKCDKF PEGDVCIAMT PPNATEASKP 

       190        200        210        220        230        240 
QGTTVCPPCD NELKSEAIIE HLCASEFALR MKIKEVKKEN GDKKIVPKKK KPLKLGPIKK 

       250        260        270        280        290        300 
KDLKKLVLYL KNGADCPCHQ LDNLSHHFLI MGRKVKSQYL LTAIHKWDKK NKEFKNFMKK 

       310 
MKNHECPTFQ SVFK 

« Hide

References

« Hide 'large scale' references
[1]"Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action."
Finch P.W., He X., Kelley M.J., Uren A., Schaudies R.P., Popescu N.C., Rudikoff S., Aaronson S.A., Varmus H.E., Rubin J.S.
Proc. Natl. Acad. Sci. U.S.A. 94:6770-6775(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 39-78.
Tissue: Embryonic lung fibroblast.
[2]"SARPs: a family of secreted apoptosis-related proteins."
Melkonyan H.S., Chang W.C., Shapiro J.P., Mahadevappa M., Fitzpatrick P.A., Kiefer M.C., Tomei L.D., Umansky S.R.
Proc. Natl. Acad. Sci. U.S.A. 94:13636-13641(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Heart.
[3]"Up-regulation of human secreted frizzled homolog in apoptosis and its down-regulation in breast tumors."
Zhou Z., Wang J., Han X., Zhou J., Linder S.
Int. J. Cancer 78:95-99(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Disulfide bond assignments of secreted Frizzled-related protein-1 provide insights about Frizzled homology and netrin modules."
Chong J.M., Ueren A., Rubin J.S., Speicher D.W.
J. Biol. Chem. 277:5134-5144(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-314, DISULFIDE BONDS, MASS SPECTROMETRY, GLYCOSYLATION AT ASN-173, MUTAGENESIS OF ASN-173 AND ASN-263.
[6]"Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling."
Bafico A., Gazit A., Pramila T., Finch P.W., Yaniv A., Aaronson S.A.
J. Biol. Chem. 274:16180-16187(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WNT1; WNT2 AND FRZD6.
[7]"Secreted frizzled related protein 1 is overexpressed in uterine leiomyomas, associated with a high estrogenic environment and unrelated to proliferative activity."
Fukuhara K., Kariya M., Kita M., Shime H., Kanamori T., Kosaka C., Orii A., Fujita J., Fujii S.
J. Clin. Endocrinol. Metab. 87:1729-1736(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF001900 mRNA. Translation: AAB61576.1.
AF017987 mRNA. Translation: AAB70793.1.
AF056087 mRNA. Translation: AAC12877.1.
BC036503 mRNA. Translation: AAH36503.1.
CCDSCCDS34886.1.
RefSeqNP_003003.3. NM_003012.4.
UniGeneHs.213424.

3D structure databases

ProteinModelPortalQ8N474.
SMRQ8N474. Positions 67-162.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112320. 7 interactions.
IntActQ8N474. 3 interactions.
STRING9606.ENSP00000220772.

Chemistry

BindingDBQ8N474.
ChEMBLCHEMBL5517.

Protein family/group databases

MEROPSI93.001.

PTM databases

PhosphoSiteQ8N474.

Polymorphism databases

DMDM61216811.

Proteomic databases

MaxQBQ8N474.
PaxDbQ8N474.
PRIDEQ8N474.

Protocols and materials databases

DNASU6422.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000220772; ENSP00000220772; ENSG00000104332.
GeneID6422.
KEGGhsa:6422.
UCSCuc003xnt.3. human.

Organism-specific databases

CTD6422.
GeneCardsGC08M041119.
HGNCHGNC:10776. SFRP1.
HPACAB008116.
MIM604156. gene.
neXtProtNX_Q8N474.
PharmGKBPA35692.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG240950.
HOGENOMHOG000231058.
HOVERGENHBG052928.
InParanoidQ8N474.
KOK02166.
OMADDVCIAM.
OrthoDBEOG789CBZ.
PhylomeDBQ8N474.
TreeFamTF350133.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ8N474.

Gene expression databases

ArrayExpressQ8N474.
BgeeQ8N474.
CleanExHS_SFRP1.
GenevestigatorQ8N474.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026559. SFRP1.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF46. PTHR11309:SF46. 1 hit.
PfamPF01392. Fz. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTSM00643. C345C. 1 hit.
SM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF50242. SSF50242. 1 hit.
SSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSecreted_frizzled-related_protein_1.
GenomeRNAi6422.
NextBio24939.
PROQ8N474.
SOURCESearch...

Entry information

Entry nameSFRP1_HUMAN
AccessionPrimary (citable) accession number: Q8N474
Secondary accession number(s): O00546, O14779
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 1, 2002
Last modified: July 9, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM