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Q8N474

- SFRP1_HUMAN

UniProt

Q8N474 - SFRP1_HUMAN

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
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Oct 2002)
      Previous versions | rss
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    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. protein binding Source: IntAct
    8. Wnt-activated receptor activity Source: RefGenome
    9. 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

    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

    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

    ArrayExpressiQ8N474.
    BgeeiQ8N474.
    CleanExiHS_SFRP1.
    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.
    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

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    MGIGRSEGGR RGAALGVLLA LGAALLAVGS ASEYDYVSFQ SDIGPYQSGR    50
    FYTKPPQCVD IPADLRLCHN VGYKKMVLPN LLEHETMAEV KQQASSWVPL 100
    LNKNCHAGTQ VFLCSLFAPV CLDRPIYPCR WLCEAVRDSC EPVMQFFGFY 150
    WPEMLKCDKF PEGDVCIAMT PPNATEASKP QGTTVCPPCD NELKSEAIIE 200
    HLCASEFALR MKIKEVKKEN GDKKIVPKKK KPLKLGPIKK KDLKKLVLYL 250
    KNGADCPCHQ LDNLSHHFLI MGRKVKSQYL LTAIHKWDKK NKEFKNFMKK 300
    MKNHECPTFQ SVFK 314
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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.
    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

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

    Gene expression databases

    ArrayExpressi Q8N474.
    Bgeei Q8N474.
    CleanExi HS_SFRP1.
    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

    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: October 1, 2014
    This is version 119 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