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Q8N474

- SFRP1_HUMAN

UniProt

Q8N474 - SFRP1_HUMAN

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Protein

Secreted frizzled-related protein 1

Gene

SFRP1

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. cysteine-type endopeptidase activity Source: UniProtKB
  2. drug binding Source: UniProtKB
  3. frizzled binding Source: UniProtKB
  4. heparin binding Source: UniProtKB
  5. identical protein binding Source: BHF-UCL
  6. PDZ domain binding Source: RefGenome
  7. Wnt-activated receptor activity Source: RefGenome
  8. Wnt-protein binding Source: UniProtKB

GO - Biological processi

  1. bone trabecula formation Source: Ensembl
  2. brain development Source: RefGenome
  3. canonical Wnt signaling pathway Source: BHF-UCL
  4. cellular response to BMP stimulus Source: UniProtKB
  5. cellular response to estradiol stimulus Source: UniProtKB
  6. cellular response to estrogen stimulus Source: UniProtKB
  7. cellular response to fibroblast growth factor stimulus Source: UniProtKB
  8. cellular response to growth factor stimulus Source: UniProtKB
  9. cellular response to heparin Source: UniProtKB
  10. cellular response to hypoxia Source: UniProtKB
  11. cellular response to interleukin-1 Source: UniProtKB
  12. cellular response to prostaglandin E stimulus Source: UniProtKB
  13. cellular response to starvation Source: UniProtKB
  14. cellular response to transforming growth factor beta stimulus Source: UniProtKB
  15. cellular response to tumor necrosis factor Source: UniProtKB
  16. cellular response to vitamin D Source: UniProtKB
  17. cellular response to X-ray Source: Ensembl
  18. convergent extension involved in somitogenesis Source: Ensembl
  19. digestive tract morphogenesis Source: Ensembl
  20. dorsal/ventral axis specification Source: UniProtKB
  21. female gonad development Source: Ensembl
  22. gonad development Source: RefGenome
  23. hematopoietic progenitor cell differentiation Source: UniProtKB
  24. hematopoietic stem cell differentiation Source: UniProtKB
  25. male gonad development Source: Ensembl
  26. menstrual cycle phase Source: UniProtKB
  27. negative regulation of androgen receptor signaling pathway Source: UniProtKB
  28. negative regulation of apoptotic process Source: UniProtKB
  29. negative regulation of B cell differentiation Source: UniProtKB
  30. negative regulation of BMP signaling pathway Source: Ensembl
  31. negative regulation of bone remodeling Source: UniProtKB
  32. negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  33. negative regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation Source: UniProtKB
  34. negative regulation of cell growth Source: UniProtKB
  35. negative regulation of cell migration Source: UniProtKB
  36. negative regulation of cell proliferation Source: UniProtKB
  37. negative regulation of epithelial cell proliferation Source: UniProtKB
  38. negative regulation of epithelial to mesenchymal transition Source: UniProtKB
  39. negative regulation of fibroblast apoptotic process Source: UniProtKB
  40. negative regulation of fibroblast proliferation Source: BHF-UCL
  41. negative regulation of gene expression Source: UniProtKB
  42. negative regulation of insulin secretion Source: UniProtKB
  43. negative regulation of JUN kinase activity Source: Ensembl
  44. negative regulation of ossification Source: UniProtKB
  45. negative regulation of osteoblast differentiation Source: Ensembl
  46. negative regulation of osteoblast proliferation Source: UniProtKB
  47. negative regulation of osteoclast differentiation Source: Ensembl
  48. negative regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  49. negative regulation of planar cell polarity pathway involved in axis elongation Source: Ensembl
  50. negative regulation of transcription, DNA-templated Source: UniProtKB
  51. negative regulation of Wnt signaling pathway Source: UniProtKB
  52. negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification Source: UniProtKB
  53. neural crest cell fate commitment Source: Ensembl
  54. neural tube closure Source: Ensembl
  55. osteoblast differentiation Source: UniProtKB
  56. planar cell polarity pathway involved in neural tube closure Source: Ensembl
  57. positive regulation of apoptotic process Source: UniProtKB
  58. positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  59. positive regulation of cell growth Source: UniProtKB
  60. positive regulation of cell-matrix adhesion Source: BHF-UCL
  61. positive regulation of cell proliferation Source: UniProtKB
  62. positive regulation of epithelial cell proliferation Source: UniProtKB
  63. positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  64. positive regulation of fat cell differentiation Source: UniProtKB
  65. positive regulation of fibroblast apoptotic process Source: UniProtKB
  66. positive regulation of focal adhesion assembly Source: BHF-UCL
  67. positive regulation of non-canonical Wnt signaling pathway Source: UniProtKB
  68. positive regulation of Rac GTPase activity Source: BHF-UCL
  69. positive regulation of smoothened signaling pathway Source: UniProtKB
  70. positive regulation of stress fiber assembly Source: BHF-UCL
  71. positive regulation of transcription, DNA-templated Source: UniProtKB
  72. positive regulation of Wnt signaling pathway Source: UniProtKB
  73. prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis Source: Ensembl
  74. proteolysis Source: GOC
  75. regulation of angiogenesis Source: BHF-UCL
  76. regulation of branching involved in prostate gland morphogenesis Source: Ensembl
  77. regulation of cell cycle process Source: UniProtKB
  78. response to drug Source: UniProtKB
  79. response to organic cyclic compound Source: UniProtKB
  80. somatic stem cell maintenance Source: Ensembl
  81. stromal-epithelial cell signaling involved in prostate gland development Source: Ensembl
  82. ureteric bud development Source: Ensembl
  83. vasculature development Source: RefGenome
  84. 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_200643. 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: 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

  1. cell surface Source: UniProtKB
  2. cytosol Source: UniProtKB
  3. extracellular matrix Source: BHF-UCL
  4. extracellular space Source: UniProtKB
  5. extracellular vesicular exosome Source: UniProt
  6. intracellular Source: UniProtKB
  7. plasma membrane Source: UniProtKB
  8. 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.

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.
GenevestigatoriQ8N474.

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.
OMAiDDVCIAM.
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.

Polymorphism databases

DMDMi61216811.

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 .
CCDSi CCDS34886.1.
RefSeqi NP_003003.3. NM_003012.4.
UniGenei Hs.213424.

3D structure databases

ProteinModelPortali Q8N474.
SMRi Q8N474. Positions 67-162.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112320. 7 interactions.
IntActi Q8N474. 3 interactions.
STRINGi 9606.ENSP00000220772.

Chemistry

BindingDBi Q8N474.
ChEMBLi CHEMBL5517.

Protein family/group databases

MEROPSi I93.001.

PTM databases

PhosphoSitei Q8N474.

Polymorphism databases

DMDMi 61216811.

Proteomic databases

MaxQBi Q8N474.
PaxDbi Q8N474.
PRIDEi Q8N474.

Protocols and materials databases

DNASUi 6422.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000220772 ; ENSP00000220772 ; ENSG00000104332 .
GeneIDi 6422.
KEGGi hsa:6422.
UCSCi uc003xnt.3. human.

Organism-specific databases

CTDi 6422.
GeneCardsi GC08M041119.
HGNCi HGNC:10776. SFRP1.
HPAi CAB008116.
MIMi 604156. gene.
neXtProti NX_Q8N474.
PharmGKBi PA35692.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG240950.
GeneTreei ENSGT00760000118864.
HOGENOMi HOG000231058.
HOVERGENi HBG052928.
InParanoidi Q8N474.
KOi K02166.
OMAi DDVCIAM.
OrthoDBi EOG789CBZ.
PhylomeDBi Q8N474.
TreeFami TF350133.

Enzyme and pathway databases

Reactomei REACT_200643. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
SignaLinki Q8N474.

Miscellaneous databases

ChiTaRSi SFRP1. human.
GeneWikii Secreted_frizzled-related_protein_1.
GenomeRNAii 6422.
NextBioi 24939.
PROi Q8N474.
SOURCEi Search...

Gene expression databases

Bgeei Q8N474.
CleanExi HS_SFRP1.
ExpressionAtlasi Q8N474. baseline and differential.
Genevestigatori Q8N474.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026559. SFRP1.
IPR008993. TIMP-like_OB-fold.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF46. PTHR11309:SF46. 1 hit.
Pfami PF01392. Fz. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view ]
SMARTi SM00643. C345C. 1 hit.
SM00063. FRI. 1 hit.
[Graphical view ]
SUPFAMi SSF50242. SSF50242. 1 hit.
SSF63501. SSF63501. 1 hit.
PROSITEi PS50038. FZ. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: November 26, 2014
This is version 121 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