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Protein

Secreted frizzled-related protein 1

Gene

SFRP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • drug binding Source: UniProtKB
  • frizzled binding Source: UniProtKB
  • heparin binding Source: UniProtKB
  • identical protein binding Source: BHF-UCL
  • Wnt-protein binding Source: UniProtKB

GO - Biological processi

  • bone trabecula formation Source: Ensembl
  • canonical Wnt signaling pathway Source: BHF-UCL
  • cellular response to BMP stimulus Source: UniProtKB
  • cellular response to estradiol stimulus Source: UniProtKB
  • cellular response to estrogen stimulus Source: UniProtKB
  • cellular response to fibroblast growth factor stimulus Source: UniProtKB
  • cellular response to growth factor stimulus Source: UniProtKB
  • cellular response to heparin Source: UniProtKB
  • cellular response to hypoxia Source: UniProtKB
  • cellular response to interleukin-1 Source: UniProtKB
  • cellular response to prostaglandin E stimulus Source: UniProtKB
  • cellular response to starvation Source: UniProtKB
  • cellular response to transforming growth factor beta stimulus Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • cellular response to vitamin D Source: UniProtKB
  • cellular response to X-ray Source: Ensembl
  • convergent extension involved in somitogenesis Source: Ensembl
  • digestive tract morphogenesis Source: Ensembl
  • dorsal/ventral axis specification Source: UniProtKB
  • female gonad development Source: Ensembl
  • hematopoietic progenitor cell differentiation Source: UniProtKB
  • hematopoietic stem cell differentiation Source: UniProtKB
  • male gonad development Source: Ensembl
  • menstrual cycle phase Source: UniProtKB
  • negative regulation of androgen receptor signaling pathway Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of B cell differentiation Source: UniProtKB
  • negative regulation of BMP signaling pathway Source: Ensembl
  • negative regulation of bone remodeling Source: UniProtKB
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation Source: UniProtKB
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell migration Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of epithelial cell proliferation Source: UniProtKB
  • negative regulation of epithelial to mesenchymal transition Source: UniProtKB
  • negative regulation of fibroblast apoptotic process Source: UniProtKB
  • negative regulation of fibroblast proliferation Source: BHF-UCL
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of insulin secretion Source: UniProtKB
  • negative regulation of JUN kinase activity Source: Ensembl
  • negative regulation of ossification Source: UniProtKB
  • negative regulation of osteoblast differentiation Source: Ensembl
  • negative regulation of osteoblast proliferation Source: UniProtKB
  • negative regulation of osteoclast differentiation Source: Ensembl
  • negative regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  • negative regulation of planar cell polarity pathway involved in axis elongation Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification Source: UniProtKB
  • neural crest cell fate commitment Source: Ensembl
  • non-canonical Wnt signaling pathway Source: GO_Central
  • osteoblast differentiation Source: UniProtKB
  • planar cell polarity pathway involved in neural tube closure Source: Ensembl
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  • positive regulation of cell growth Source: UniProtKB
  • positive regulation of cell-matrix adhesion Source: BHF-UCL
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of epithelial cell proliferation Source: UniProtKB
  • positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  • positive regulation of fat cell differentiation Source: UniProtKB
  • positive regulation of fibroblast apoptotic process Source: UniProtKB
  • positive regulation of focal adhesion assembly Source: BHF-UCL
  • positive regulation of GTPase activity Source: BHF-UCL
  • positive regulation of non-canonical Wnt signaling pathway Source: UniProtKB
  • positive regulation of smoothened signaling pathway Source: UniProtKB
  • positive regulation of stress fiber assembly Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of Wnt signaling pathway Source: UniProtKB
  • prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis Source: Ensembl
  • proteolysis Source: GOC
  • regulation of angiogenesis Source: BHF-UCL
  • regulation of branching involved in prostate gland morphogenesis Source: Ensembl
  • regulation of cell cycle process Source: UniProtKB
  • response to drug Source: UniProtKB
  • response to organic cyclic compound Source: UniProtKB
  • somatic stem cell maintenance Source: Ensembl
  • stromal-epithelial cell signaling involved in prostate gland development Source: Ensembl
  • ureteric bud development Source: Ensembl
  • Wnt signaling pathway involved in somitogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_264383. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
SignaLinkiQ8N474.

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:SFRP1
Synonyms:FRP, FRP1, SARP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:10776. SFRP1.

Subcellular locationi

  • Secreted

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

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: BHF-UCL
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • intracellular Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • proteinaceous extracellular matrix Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi173 – 1731N → Q: Reduced molecular weight. 1 Publication
Mutagenesisi263 – 2631N → Q: No effect on molecular weight. 1 Publication

Organism-specific databases

PharmGKBiPA35692.

Polymorphism and mutation databases

BioMutaiSFRP1.
DMDMi61216811.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 31311 PublicationAdd
BLAST
Chaini32 – 314283Secreted frizzled-related protein 1PRO_0000032538Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi58 ↔ 1211 Publication
Disulfide bondi68 ↔ 1141 Publication
Disulfide bondi105 ↔ 1401 Publication
Disulfide bondi129 ↔ 1661 Publication
Disulfide bondi133 ↔ 1571 Publication
Glycosylationi173 – 1731N-linked (GlcNAc...)1 Publication
Disulfide bondi186 ↔ 2561 Publication
Disulfide bondi189 ↔ 2581 Publication
Disulfide bondi203 ↔ 3061 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ8N474.
PaxDbiQ8N474.
PRIDEiQ8N474.

PTM databases

PhosphoSiteiQ8N474.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

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.2 Publications

Gene expression databases

BgeeiQ8N474.
CleanExiHS_SFRP1.
ExpressionAtlasiQ8N474. baseline and differential.
GenevisibleiQ8N474. HS.

Organism-specific databases

HPAiCAB008116.

Interactioni

Subunit structurei

Interacts with WNT1, WNT2 and FRZD6. Interacts with WNT4, WNT8 and MYOC (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
FZD6O603533EBI-3940687,EBI-8754490

Protein-protein interaction databases

BioGridi112320. 7 interactions.
IntActiQ8N474. 3 interactions.
STRINGi9606.ENSP00000220772.

Structurei

3D structure databases

ProteinModelPortaliQ8N474.
SMRiQ8N474. Positions 67-162.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini53 – 169117FZPROSITE-ProRule annotationAdd
BLAST
Domaini186 – 306121NTRPROSITE-ProRule annotationAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation
Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG240950.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000231058.
HOVERGENiHBG052928.
InParanoidiQ8N474.
KOiK02166.
OMAiCDNEMKS.
OrthoDBiEOG789CBZ.
PhylomeDBiQ8N474.
TreeFamiTF350133.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026559. SFRP1.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF46. PTHR11309:SF46. 1 hit.
PfamiPF01392. Fz. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTiSM00643. C345C. 1 hit.
SM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
SSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8N474-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGIGRSEGGR RGAALGVLLA LGAALLAVGS ASEYDYVSFQ SDIGPYQSGR
60 70 80 90 100
FYTKPPQCVD IPADLRLCHN VGYKKMVLPN LLEHETMAEV KQQASSWVPL
110 120 130 140 150
LNKNCHAGTQ VFLCSLFAPV CLDRPIYPCR WLCEAVRDSC EPVMQFFGFY
160 170 180 190 200
WPEMLKCDKF PEGDVCIAMT PPNATEASKP QGTTVCPPCD NELKSEAIIE
210 220 230 240 250
HLCASEFALR MKIKEVKKEN GDKKIVPKKK KPLKLGPIKK KDLKKLVLYL
260 270 280 290 300
KNGADCPCHQ LDNLSHHFLI MGRKVKSQYL LTAIHKWDKK NKEFKNFMKK
310
MKNHECPTFQ SVFK
Length:314
Mass (Da):35,386
Last modified:October 1, 2002 - v1
Checksum:i29DD948706EB7143
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti14 – 141Missing (PubMed:9192640).Curated
Sequence conflicti14 – 141Missing (PubMed:9724099).Curated
Sequence conflicti174 – 1741A → P in AAB70793 (PubMed:9391078).Curated

Mass spectrometryi

Molecular mass is 7266.4 Da from positions 169 - 210. Determined by MALDI. Isoform N-glycosylated on Asn-173.1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF001900 mRNA. Translation: AAB61576.1.
AF017987 mRNA. Translation: AAB70793.1.
AF056087 mRNA. Translation: AAC12877.1.
BC036503 mRNA. Translation: AAH36503.1.
CCDSiCCDS34886.1.
RefSeqiNP_003003.3. NM_003012.4.
UniGeneiHs.213424.

Genome annotation databases

EnsembliENST00000220772; ENSP00000220772; ENSG00000104332.
GeneIDi6422.
KEGGihsa:6422.
UCSCiuc003xnt.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF001900 mRNA. Translation: AAB61576.1.
AF017987 mRNA. Translation: AAB70793.1.
AF056087 mRNA. Translation: AAC12877.1.
BC036503 mRNA. Translation: AAH36503.1.
CCDSiCCDS34886.1.
RefSeqiNP_003003.3. NM_003012.4.
UniGeneiHs.213424.

3D structure databases

ProteinModelPortaliQ8N474.
SMRiQ8N474. Positions 67-162.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112320. 7 interactions.
IntActiQ8N474. 3 interactions.
STRINGi9606.ENSP00000220772.

Chemistry

BindingDBiQ8N474.
ChEMBLiCHEMBL5517.

Protein family/group databases

MEROPSiI93.001.

PTM databases

PhosphoSiteiQ8N474.

Polymorphism and mutation databases

BioMutaiSFRP1.
DMDMi61216811.

Proteomic databases

MaxQBiQ8N474.
PaxDbiQ8N474.
PRIDEiQ8N474.

Protocols and materials databases

DNASUi6422.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220772; ENSP00000220772; ENSG00000104332.
GeneIDi6422.
KEGGihsa:6422.
UCSCiuc003xnt.3. human.

Organism-specific databases

CTDi6422.
GeneCardsiGC08M041119.
HGNCiHGNC:10776. SFRP1.
HPAiCAB008116.
MIMi604156. gene.
neXtProtiNX_Q8N474.
PharmGKBiPA35692.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG240950.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000231058.
HOVERGENiHBG052928.
InParanoidiQ8N474.
KOiK02166.
OMAiCDNEMKS.
OrthoDBiEOG789CBZ.
PhylomeDBiQ8N474.
TreeFamiTF350133.

Enzyme and pathway databases

ReactomeiREACT_264383. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
SignaLinkiQ8N474.

Miscellaneous databases

ChiTaRSiSFRP1. human.
GeneWikiiSecreted_frizzled-related_protein_1.
GenomeRNAii6422.
NextBioi24939.
PROiQ8N474.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N474.
CleanExiHS_SFRP1.
ExpressionAtlasiQ8N474. baseline and differential.
GenevisibleiQ8N474. HS.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026559. SFRP1.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF46. PTHR11309:SF46. 1 hit.
PfamiPF01392. Fz. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTiSM00643. C345C. 1 hit.
SM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
SSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiSFRP1_HUMAN
AccessioniPrimary (citable) accession number: Q8N474
Secondary accession number(s): O00546, O14779
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 1, 2002
Last modified: June 24, 2015
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

May have therapeutic use in cardiac surgery.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.