Q8N474 (SFRP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SFRP1
Synonyms:	FRP, FRP1, SARP2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	314 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 and WNT8 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-glycosylated on Asn-173. Ref.5

Ontologies

Keywords
Biological process	Differentiation Wnt signaling pathway
Cellular component	Secreted
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway involved in somitogenesis Inferred from electronic annotation. Source: Compara apoptotic DNA fragmentation Inferred from direct assay PubMed 14581477. Source: UniProtKB bone trabecula formation Inferred from electronic annotation. Source: Compara brain development Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor 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: Compara cellular response to estradiol stimulus Inferred from expression pattern Ref.7. Source: UniProtKB cellular response to fibroblast 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: Compara digestive tract morphogenesis Inferred from electronic annotation. Source: Compara dorsal/ventral axis specification Inferred from direct assay Ref.1. Source: UniProtKB embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome female gonad development Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara negative regulation of JUN kinase activity Inferred from electronic annotation. Source: Compara negative regulation of Wnt receptor 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 bone remodeling Inferred from mutant phenotype PubMed 19072540. Source: UniProtKB negative regulation of canonical Wnt receptor 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 cysteine-type endopeptidase activity Inferred from mutant phenotype PubMed 14581477. 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 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: Compara negative regulation of osteoblast proliferation Inferred from mutant phenotype PubMed 19072540. Source: UniProtKB negative regulation of osteoclast differentiation Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 10660608PubMed 19095296PubMed 19277043PubMed 20234818. Source: UniProtKB neural crest cell fate commitment Inferred from electronic annotation. Source: Compara neural tube closure Inferred from electronic annotation. Source: Compara osteoblast differentiation Inferred from expression pattern PubMed 16149051. Source: UniProtKB planar cell polarity pathway involved in neural tube closure Inferred from electronic annotation. Source: Compara positive regulation of Rac GTPase activity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of canonical Wnt receptor 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 epithelial cell proliferation Inferred from mutant phenotype PubMed 16288033. Source: UniProtKB 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 receptor 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-dependent 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: Compara 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: Compara 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 somatic stem cell maintenance Inferred from electronic annotation. Source: Compara stromal-epithelial cell signaling involved in prostate gland development Inferred from electronic annotation. Source: Compara ureteric bud development Inferred from electronic annotation. Source: Compara vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cell surface Inferred from direct assay Ref.1. Source: UniProtKB cytosol Inferred from direct assay PubMed 14581477. Source: UniProtKB extracellular space Inferred from direct assay PubMed 10980594PubMed 17500071Ref.1. 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_function	PDZ domain binding Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt-activated receptor activity Inferred from Biological aspect of Ancestor. Source: RefGenome cysteine-type endopeptidase activity Inferred from mutant phenotype PubMed 14581477. Source: UniProtKB drug binding Inferred from direct assay PubMed 19072540PubMed 19254787. Source: UniProtKB heparin binding Inferred from direct assay PubMed 10660608Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Ref.5
	Chain	32 – 314	283	Secreted frizzled-related protein 1		PRO_0000032538
Regions
	Domain	53 – 169	117	FZ
	Domain	186 – 306	121	NTR
Amino acid modifications
	Glycosylation	173	1	N-linked (GlcNAc...) Ref.5
	Disulfide bond	58 ↔ 121		Ref.5
	Disulfide bond	68 ↔ 114		Ref.5
	Disulfide bond	105 ↔ 140		Ref.5
	Disulfide bond	129 ↔ 166		Ref.5
	Disulfide bond	133 ↔ 157		Ref.5
	Disulfide bond	186 ↔ 256		Ref.5
	Disulfide bond	189 ↔ 258		Ref.5
	Disulfide bond	203 ↔ 306		Ref.5
Experimental info
	Mutagenesis	173	1	N → Q: Reduced molecular weight. Ref.5
	Mutagenesis	263	1	N → Q: No effect on molecular weight. Ref.5
	Sequence conflict	14	1	Missing Ref.1
	Sequence conflict	14	1	Missing Ref.3
	Sequence conflict	174	1	A → P in AAB70793. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8N474 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 29DD948706EB7143	FASTA	314	35,386
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00749245.
RefSeq	NP_003003.3. NM_003012.4.
UniGene	Hs.213424.
3D structure databases
ProteinModelPortal	Q8N474.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N474. 1 interaction.
STRING	9606.ENSP00000220772.
PTM databases
PhosphoSite	Q8N474.
Polymorphism databases
DMDM	61216811.
Proteomic databases
PaxDb	Q8N474.
PRIDE	Q8N474.
Protocols and materials databases
DNASU	6422.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000220772; ENSP00000220772; ENSG00000104332. ENST00000535263; ENSP00000442829; ENSG00000104332.
GeneID	6422.
KEGG	hsa:6422.
UCSC	uc003xnt.3. human.
Organism-specific databases
CTD	6422.
GeneCards	GC08M041119.
HGNC	HGNC:10776. SFRP1.
HPA	CAB008116.
MIM	604156. gene.
neXtProt	NX_Q8N474.
PharmGKB	PA35692.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG240950.
HOGENOM	HOG000231058.
HOVERGEN	HBG052928.
InParanoid	Q8N474.
KO	K02166.
OMA	KNCHAGT.
OrthoDB	EOG4868D5.
PhylomeDB	Q8N474.
Enzyme and pathway databases
SignaLink	Q8N474.
Gene expression databases
ArrayExpress	Q8N474.
Bgee	Q8N474.
CleanEx	HS_SFRP1.
Genevestigator	Q8N474.
GermOnline	ENSG00000104332. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR001134. Netrin_domain. IPR018933. Netrin_module_non-TIMP. IPR026559. SFRP1. IPR008993. TIMP-like_OB-fold. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF46. PTHR11309:SF46. 1 hit.
Pfam	PF01392. Fz. 1 hit. PF01759. NTR. 1 hit. [Graphical view]
SMART	SM00643. C345C. 1 hit. SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit. SSF50242. TIMP_like. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50189. NTR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8N474.
ChEMBL	CHEMBL5517.
GenomeRNAi	6422.
NextBio	24939.
SOURCE	Search...

Entry information

Entry name

SFRP1_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.