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Secreted frizzled-related protein 1 (FRP-1) (sFRP-1) (Secreted apoptosis-related protein 2) (SARP-2)

 SFRP1_HUMAN             Reviewed;         314 AA.
Q8N474; O00546; O14779;
15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
01-OCT-2002, sequence version 1.
25-OCT-2017, entry version 151.
RecName: Full=Secreted frizzled-related protein 1;
Short=FRP-1;
Short=sFRP-1;
AltName: Full=Secreted apoptosis-related protein 2;
Short=SARP-2;
Flags: Precursor;
Name=SFRP1; Synonyms=FRP, FRP1, SARP2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 39-78.
TISSUE=Embryonic lung fibroblast;
PubMed=9192640; DOI=10.1073/pnas.94.13.6770;
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.;
"Purification and molecular cloning of a secreted, Frizzled-related
antagonist of Wnt action.";
Proc. Natl. Acad. Sci. U.S.A. 94:6770-6775(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
TISSUE=Heart;
PubMed=9391078; DOI=10.1073/pnas.94.25.13636;
Melkonyan H.S., Chang W.C., Shapiro J.P., Mahadevappa M.,
Fitzpatrick P.A., Kiefer M.C., Tomei L.D., Umansky S.R.;
"SARPs: a family of secreted apoptosis-related proteins.";
Proc. Natl. Acad. Sci. U.S.A. 94:13636-13641(1997).
[3]
NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
PubMed=9724099;
DOI=10.1002/(SICI)1097-0215(19980925)78:1<95::AID-IJC15>3.0.CO;2-4;
Zhou Z., Wang J., Han X., Zhou J., Linder S.;
"Up-regulation of human secreted frizzled homolog in apoptosis and its
down-regulation in breast tumors.";
Int. J. Cancer 78:95-99(1998).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
PROTEIN SEQUENCE OF 32-314, DISULFIDE BONDS, MASS SPECTROMETRY,
GLYCOSYLATION AT ASN-173, AND MUTAGENESIS OF ASN-173 AND ASN-263.
PubMed=11741940; DOI=10.1074/jbc.M108533200;
Chong J.M., Ueren A., Rubin J.S., Speicher D.W.;
"Disulfide bond assignments of secreted Frizzled-related protein-1
provide insights about Frizzled homology and netrin modules.";
J. Biol. Chem. 277:5134-5144(2002).
[6]
INTERACTION WITH WNT1; WNT2 AND FRZD6.
PubMed=10347172; DOI=10.1074/jbc.274.23.16180;
Bafico A., Gazit A., Pramila T., Finch P.W., Yaniv A., Aaronson S.A.;
"Interaction of frizzled related protein (FRP) with Wnt ligands and
the frizzled receptor suggests alternative mechanisms for FRP
inhibition of Wnt signaling.";
J. Biol. Chem. 274:16180-16187(1999).
[7]
INDUCTION.
PubMed=11932307; DOI=10.1210/jcem.87.4.8375;
Fukuhara K., Kariya M., Kita M., Shime H., Kanamori T., Kosaka C.,
Orii A., Fujita J., Fujii S.;
"Secreted frizzled related protein 1 is overexpressed in uterine
leiomyomas, associated with a high estrogenic environment and
unrelated to proliferative activity.";
J. Clin. Endocrinol. Metab. 87:1729-1736(2002).
-!- 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. {ECO:0000250}.
-!- SUBUNIT: Interacts with WNT1, WNT2 and FRZD6. Interacts with WNT4,
WNT8 and MYOC (By similarity). {ECO:0000250}.
-!- INTERACTION:
O60353:FZD6; NbExp=3; IntAct=EBI-3940687, EBI-8754490;
-!- 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.
{ECO:0000269|PubMed:9391078}.
-!- 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. {ECO:0000269|PubMed:11932307,
ECO:0000269|PubMed:9724099}.
-!- DOMAIN: The FZ domain is involved in binding with Wnt ligands.
{ECO:0000250}.
-!- MASS SPECTROMETRY: Mass=7266.4; Method=MALDI; Range=169-210;
Note=Isoform N-glycosylated on Asn-173.;
Evidence={ECO:0000269|PubMed:11741940};
-!- MISCELLANEOUS: May have therapeutic use in cardiac surgery.
-!- SIMILARITY: Belongs to the secreted frizzled-related protein
(sFRP) family. {ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; AF001900; AAB61576.1; -; mRNA.
EMBL; AF017987; AAB70793.1; -; mRNA.
EMBL; AF056087; AAC12877.1; -; mRNA.
EMBL; BC036503; AAH36503.1; -; mRNA.
CCDS; CCDS34886.1; -.
RefSeq; NP_003003.3; NM_003012.4.
UniGene; Hs.213424; -.
ProteinModelPortal; Q8N474; -.
SMR; Q8N474; -.
BioGrid; 112320; 8.
IntAct; Q8N474; 5.
STRING; 9606.ENSP00000220772; -.
BindingDB; Q8N474; -.
ChEMBL; CHEMBL5517; -.
MEROPS; I93.002; -.
iPTMnet; Q8N474; -.
PhosphoSitePlus; Q8N474; -.
BioMuta; SFRP1; -.
DMDM; 61216811; -.
EPD; Q8N474; -.
MaxQB; Q8N474; -.
PaxDb; Q8N474; -.
PeptideAtlas; Q8N474; -.
PRIDE; Q8N474; -.
DNASU; 6422; -.
Ensembl; ENST00000220772; ENSP00000220772; ENSG00000104332.
GeneID; 6422; -.
KEGG; hsa:6422; -.
UCSC; uc003xnt.4; human.
CTD; 6422; -.
DisGeNET; 6422; -.
EuPathDB; HostDB:ENSG00000104332.11; -.
GeneCards; SFRP1; -.
HGNC; HGNC:10776; SFRP1.
HPA; CAB008116; -.
HPA; HPA064870; -.
MIM; 604156; gene.
neXtProt; NX_Q8N474; -.
OpenTargets; ENSG00000104332; -.
PharmGKB; PA35692; -.
eggNOG; KOG3577; Eukaryota.
eggNOG; ENOG410XRC8; LUCA.
GeneTree; ENSGT00890000139384; -.
HOGENOM; HOG000231058; -.
HOVERGEN; HBG052928; -.
InParanoid; Q8N474; -.
KO; K02166; -.
OMA; DDVCIAM; -.
OrthoDB; EOG091G0F7I; -.
PhylomeDB; Q8N474; -.
TreeFam; TF350133; -.
Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
SignaLink; Q8N474; -.
SIGNOR; Q8N474; -.
ChiTaRS; SFRP1; human.
GeneWiki; Secreted_frizzled-related_protein_1; -.
GenomeRNAi; 6422; -.
PRO; PR:Q8N474; -.
Proteomes; UP000005640; Chromosome 8.
Bgee; ENSG00000104332; -.
CleanEx; HS_SFRP1; -.
ExpressionAtlas; Q8N474; baseline and differential.
Genevisible; Q8N474; HS.
GO; GO:0009986; C:cell surface; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
GO; GO:0031012; C:extracellular matrix; IDA:BHF-UCL.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
GO; GO:0005622; C:intracellular; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
GO; GO:0005578; C:proteinaceous extracellular matrix; IDA:BHF-UCL.
GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
GO; GO:0008144; F:drug binding; IDA:UniProtKB.
GO; GO:0005109; F:frizzled binding; IPI:UniProtKB.
GO; GO:0004930; F:G-protein coupled receptor activity; IBA:GO_Central.
GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
GO; GO:0042813; F:Wnt-activated receptor activity; IBA:GO_Central.
GO; GO:0017147; F:Wnt-protein binding; IDA:MGI.
GO; GO:0060346; P:bone trabecula formation; IEA:Ensembl.
GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL.
GO; GO:0071773; P:cellular response to BMP stimulus; IEP:UniProtKB.
GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:UniProtKB.
GO; GO:0071391; P:cellular response to estrogen stimulus; IDA:UniProtKB.
GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IDA:UniProtKB.
GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:UniProtKB.
GO; GO:0071504; P:cellular response to heparin; IDA:UniProtKB.
GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
GO; GO:0071347; P:cellular response to interleukin-1; IEP:UniProtKB.
GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEP:UniProtKB.
GO; GO:0009267; P:cellular response to starvation; IEP:UniProtKB.
GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:UniProtKB.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
GO; GO:0071305; P:cellular response to vitamin D; IEP:UniProtKB.
GO; GO:0071481; P:cellular response to X-ray; IEA:Ensembl.
GO; GO:0090246; P:convergent extension involved in somitogenesis; IEA:Ensembl.
GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl.
GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl.
GO; GO:0009950; P:dorsal/ventral axis specification; IDA:UniProtKB.
GO; GO:0008585; P:female gonad development; IEA:Ensembl.
GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IDA:UniProtKB.
GO; GO:0060218; P:hematopoietic stem cell differentiation; IDA:UniProtKB.
GO; GO:0008584; P:male gonad development; IEA:Ensembl.
GO; GO:0022601; P:menstrual cycle phase; IEP:UniProtKB.
GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IDA:UniProtKB.
GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
GO; GO:0045578; P:negative regulation of B cell differentiation; IMP:UniProtKB.
GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl.
GO; GO:0046851; P:negative regulation of bone remodeling; IMP:UniProtKB.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
GO; GO:2000080; P:negative regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation; IDA:UniProtKB.
GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB.
GO; GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB.
GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:UniProtKB.
GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IDA:UniProtKB.
GO; GO:0048147; P:negative regulation of fibroblast proliferation; IDA:BHF-UCL.
GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB.
GO; GO:0046676; P:negative regulation of insulin secretion; IDA:UniProtKB.
GO; GO:0043508; P:negative regulation of JUN kinase activity; IEA:Ensembl.
GO; GO:0030279; P:negative regulation of ossification; IDA:UniProtKB.
GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
GO; GO:0033689; P:negative regulation of osteoblast proliferation; IMP:UniProtKB.
GO; GO:0045671; P:negative regulation of osteoclast differentiation; IEA:Ensembl.
GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
GO; GO:2000041; P:negative regulation of planar cell polarity pathway involved in axis elongation; IEA:Ensembl.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
GO; GO:2000054; P:negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification; IDA:UniProtKB.
GO; GO:0014034; P:neural crest cell fate commitment; IEA:Ensembl.
GO; GO:0001649; P:osteoblast differentiation; IEP:UniProtKB.
GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; IEA:Ensembl.
GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISS:BHF-UCL.
GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:UniProtKB.
GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; IDA:BHF-UCL.
GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:UniProtKB.
GO; GO:2000271; P:positive regulation of fibroblast apoptotic process; IDA:UniProtKB.
GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISS:BHF-UCL.
GO; GO:0043547; P:positive regulation of GTPase activity; ISS:BHF-UCL.
GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; IDA:UniProtKB.
GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:UniProtKB.
GO; GO:0051496; P:positive regulation of stress fiber assembly; ISS:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IDA:UniProtKB.
GO; GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; IEA:Ensembl.
GO; GO:0045765; P:regulation of angiogenesis; ISS:BHF-UCL.
GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IEA:Ensembl.
GO; GO:0010564; P:regulation of cell cycle process; IMP:UniProtKB.
GO; GO:1904956; P:regulation of midbrain dopaminergic neuron differentiation; IEA:Ensembl.
GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl.
GO; GO:0042493; P:response to drug; IDA:UniProtKB.
GO; GO:0014070; P:response to organic cyclic compound; IDA:UniProtKB.
GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
GO; GO:0044345; P:stromal-epithelial cell signaling involved in prostate gland development; IEA:Ensembl.
GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
GO; GO:0090244; P:Wnt signaling pathway involved in somitogenesis; IEA:Ensembl.
Gene3D; 1.10.2000.10; -; 1.
InterPro; IPR015526; Frizzled/SFRP.
InterPro; IPR020067; Frizzled_dom.
InterPro; IPR036790; Frizzled_dom_sf.
InterPro; IPR001134; Netrin_domain.
InterPro; IPR018933; Netrin_module_non-TIMP.
InterPro; IPR026559; SFRP1.
InterPro; IPR008993; TIMP-like_OB-fold.
PANTHER; PTHR11309; PTHR11309; 1.
PANTHER; PTHR11309:SF87; PTHR11309:SF87; 1.
Pfam; PF01392; Fz; 1.
Pfam; PF01759; NTR; 1.
SMART; SM00643; C345C; 1.
SMART; SM00063; FRI; 1.
SUPFAM; SSF50242; SSF50242; 1.
SUPFAM; SSF63501; SSF63501; 1.
PROSITE; PS50038; FZ; 1.
PROSITE; PS50189; NTR; 1.
1: Evidence at protein level;
Complete proteome; Developmental protein; Differentiation;
Direct protein sequencing; Disulfide bond; Glycoprotein;
Reference proteome; Secreted; Signal; Wnt signaling pathway.
SIGNAL 1 31 {ECO:0000269|PubMed:11741940}.
CHAIN 32 314 Secreted frizzled-related protein 1.
/FTId=PRO_0000032538.
DOMAIN 53 169 FZ. {ECO:0000255|PROSITE-
ProRule:PRU00090}.
DOMAIN 186 306 NTR. {ECO:0000255|PROSITE-
ProRule:PRU00295}.
CARBOHYD 173 173 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:11741940}.
DISULFID 58 121 {ECO:0000269|PubMed:11741940}.
DISULFID 68 114 {ECO:0000269|PubMed:11741940}.
DISULFID 105 140 {ECO:0000269|PubMed:11741940}.
DISULFID 129 166 {ECO:0000269|PubMed:11741940}.
DISULFID 133 157 {ECO:0000269|PubMed:11741940}.
DISULFID 186 256 {ECO:0000269|PubMed:11741940}.
DISULFID 189 258 {ECO:0000269|PubMed:11741940}.
DISULFID 203 306 {ECO:0000269|PubMed:11741940}.
MUTAGEN 173 173 N->Q: Reduced molecular weight.
{ECO:0000269|PubMed:11741940}.
MUTAGEN 263 263 N->Q: No effect on molecular weight.
{ECO:0000269|PubMed:11741940}.
CONFLICT 14 14 Missing (in Ref. 1 and 3). {ECO:0000305}.
CONFLICT 174 174 A -> P (in Ref. 2; AAB70793).
{ECO:0000305}.
SEQUENCE 314 AA; 35386 MW; 29DD948706EB7143 CRC64;
MGIGRSEGGR RGAALGVLLA LGAALLAVGS ASEYDYVSFQ SDIGPYQSGR FYTKPPQCVD
IPADLRLCHN VGYKKMVLPN LLEHETMAEV KQQASSWVPL LNKNCHAGTQ VFLCSLFAPV
CLDRPIYPCR WLCEAVRDSC EPVMQFFGFY WPEMLKCDKF PEGDVCIAMT PPNATEASKP
QGTTVCPPCD NELKSEAIIE HLCASEFALR MKIKEVKKEN GDKKIVPKKK KPLKLGPIKK
KDLKKLVLYL KNGADCPCHQ LDNLSHHFLI MGRKVKSQYL LTAIHKWDKK NKEFKNFMKK
MKNHECPTFQ SVFK


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Genprice Inc, Invoices and accounting
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