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Protein

Secreted frizzled-related protein 1

Gene

SFRP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

May have therapeutic use in cardiac surgery.

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • drug binding Source: UniProtKB
  • frizzled binding Source: UniProtKB
  • G-protein coupled receptor activity Source: GO_Central
  • heparin binding Source: UniProtKB
  • identical protein binding Source: BHF-UCL
  • Wnt-activated receptor activity Source: GO_Central
  • Wnt-protein binding Source: MGI

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
  • dopaminergic neuron differentiation 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
  • 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
  • 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
  • regulation of angiogenesis Source: BHF-UCL
  • regulation of branching involved in prostate gland morphogenesis Source: Ensembl
  • regulation of cell cycle process Source: UniProtKB
  • regulation of midbrain dopaminergic neuron differentiation Source: Ensembl
  • regulation of neuron projection development Source: Ensembl
  • response to drug Source: UniProtKB
  • response to organic cyclic compound Source: UniProtKB
  • somatic stem cell population 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

Keywordsi

Molecular functionDevelopmental protein
Biological processDifferentiation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-3772470 Negative regulation of TCF-dependent signaling by WNT ligand antagonists
SignaLinkiQ8N474
SIGNORiQ8N474

Protein family/group databases

MEROPSiI93.002

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
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104332.11
HGNCiHGNC:10776 SFRP1
MIMi604156 gene
neXtProtiNX_Q8N474

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi173N → Q: Reduced molecular weight. 1 Publication1
Mutagenesisi263N → Q: No effect on molecular weight. 1 Publication1

Organism-specific databases

DisGeNETi6422
OpenTargetsiENSG00000104332
PharmGKBiPA35692

Chemistry databases

ChEMBLiCHEMBL5517

Polymorphism and mutation databases

BioMutaiSFRP1
DMDMi61216811

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 311 PublicationAdd BLAST31
ChainiPRO_000003253832 – 314Secreted frizzled-related protein 1Add BLAST283

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi58 ↔ 1211 Publication
Disulfide bondi68 ↔ 1141 Publication
Disulfide bondi105 ↔ 1401 Publication
Disulfide bondi129 ↔ 1661 Publication
Disulfide bondi133 ↔ 1571 Publication
Glycosylationi173N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi186 ↔ 2561 Publication
Disulfide bondi189 ↔ 2581 Publication
Disulfide bondi203 ↔ 3061 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ8N474
MaxQBiQ8N474
PaxDbiQ8N474
PeptideAtlasiQ8N474
PRIDEiQ8N474
ProteomicsDBi71892

PTM databases

iPTMnetiQ8N474
PhosphoSitePlusiQ8N474

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

BgeeiENSG00000104332
CleanExiHS_SFRP1
ExpressionAtlasiQ8N474 baseline and differential
GenevisibleiQ8N474 HS

Organism-specific databases

HPAiCAB008116
HPA064870

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

GO - Molecular functioni

  • frizzled binding Source: UniProtKB
  • identical protein binding Source: BHF-UCL
  • Wnt-protein binding Source: MGI

Protein-protein interaction databases

BioGridi112320, 8 interactors
IntActiQ8N474, 6 interactors
MINTiQ8N474
STRINGi9606.ENSP00000220772

Chemistry databases

BindingDBiQ8N474

Structurei

3D structure databases

ProteinModelPortaliQ8N474
SMRiQ8N474
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 169FZPROSITE-ProRule annotationAdd BLAST117
Domaini186 – 306NTRPROSITE-ProRule annotationAdd BLAST121

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOGENOMiHOG000231058
HOVERGENiHBG052928
InParanoidiQ8N474
KOiK02166
OMAiDDVCIAM
OrthoDBiEOG091G0F7I
PhylomeDBiQ8N474
TreeFamiTF350133

Family and domain databases

Gene3Di1.10.2000.10, 1 hit
InterProiView protein in InterPro
IPR015526 Frizzled/SFRP
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR001134 Netrin_domain
IPR018933 Netrin_module_non-TIMP
IPR026559 SFRP1
IPR008993 TIMP-like_OB-fold
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF87 PTHR11309:SF87, 1 hit
PfamiView protein in Pfam
PF01392 Fz, 1 hit
PF01759 NTR, 1 hit
SMARTiView protein in SMART
SM00643 C345C, 1 hit
SM00063 FRI, 1 hit
SUPFAMiSSF50242 SSF50242, 1 hit
SSF63501 SSF63501, 1 hit
PROSITEiView protein in PROSITE
PS50038 FZ, 1 hit
PS50189 NTR, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti14Missing (PubMed:9192640).Curated1
Sequence conflicti14Missing (PubMed:9724099).Curated1
Sequence conflicti174A → P in AAB70793 (PubMed:9391078).Curated1

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.4 human

Similar proteinsi

Entry informationi

Entry nameiSFRP1_HUMAN
AccessioniPrimary (citable) accession number: Q8N474
Secondary accession number(s): O00546, O14779
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 1, 2002
Last modified: July 18, 2018
This is version 155 of the entry and version 1 of the sequence. See 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

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

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