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Q6FHJ7

- SFRP4_HUMAN

UniProt

Q6FHJ7 - SFRP4_HUMAN

Protein

Secreted frizzled-related protein 4

Gene

SFRP4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 104 (01 Oct 2014)
      Sequence version 2 (15 Mar 2005)
      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. SFRP4 may act as a regulator of adult uterine morphology and function. Increases apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling By similarity. Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake.By similarity

    GO - Molecular functioni

    1. PDZ domain binding Source: RefGenome
    2. Wnt-activated receptor activity Source: RefGenome
    3. Wnt-protein binding Source: RefGenome

    GO - Biological processi

    1. brain development Source: RefGenome
    2. cell differentiation Source: UniProtKB-KW
    3. decidualization Source: RefGenome
    4. epithelium development Source: RefGenome
    5. gonad development Source: RefGenome
    6. mammary gland involution Source: RefGenome
    7. menstrual cycle phase Source: BHF-UCL
    8. negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
    9. negative regulation of cell proliferation Source: BHF-UCL
    10. negative regulation of JNK cascade Source: RefGenome
    11. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    12. negative regulation of sodium-dependent phosphate transport Source: BHF-UCL
    13. phosphate ion homeostasis Source: BHF-UCL
    14. positive regulation of apoptotic process Source: BHF-UCL
    15. positive regulation of canonical Wnt signaling pathway Source: MGI
    16. positive regulation of epidermal cell differentiation Source: BHF-UCL
    17. positive regulation of gene expression Source: BHF-UCL
    18. positive regulation of keratinocyte apoptotic process Source: BHF-UCL
    19. positive regulation of receptor internalization Source: BHF-UCL
    20. response to hormone Source: BHF-UCL
    21. vasculature development Source: RefGenome
    22. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Differentiation, Wnt signaling pathway

    Protein family/group databases

    MEROPSiI93.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Secreted frizzled-related protein 4
    Short name:
    sFRP-4
    Alternative name(s):
    Frizzled protein, human endometrium
    Short name:
    FrpHE
    Gene namesi
    Name:SFRP4
    Synonyms:FRPHE
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:10778. SFRP4.

    Subcellular locationi

    Secreted 1 Publication
    Note: Cytoplasmic in ovarian tumor cells.

    GO - Cellular componenti

    1. cell surface Source: BHF-UCL
    2. cytoplasm Source: UniProtKB
    3. extracellular space Source: BHF-UCL
    4. nucleus Source: BHF-UCL

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA35694.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 346328Secreted frizzled-related protein 4PRO_0000032550Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi24 ↔ 85By similarity
    Disulfide bondi32 ↔ 78By similarity
    Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi68 – 681N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi69 ↔ 108By similarity
    Disulfide bondi97 ↔ 136By similarity
    Disulfide bondi101 ↔ 125By similarity
    Glycosylationi116 – 1161N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi194 – 1941N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi240 – 2401N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ6FHJ7.
    PRIDEiQ6FHJ7.

    PTM databases

    PhosphoSiteiQ6FHJ7.

    Expressioni

    Tissue specificityi

    Expressed in mesenchymal cells. Highly expressed in the stroma of proliferative endometrium. Expressed in cardiomyocytes. Shows moderate to strong expression in ovarian tumors with expression increasing as the tumor stage increases. In ovarian tumors, expression levels are inversely correlated with expression of CTNNB1 (at protein level).2 Publications

    Inductioni

    Increased levels in failing myocardium. Up-regulated in several tumor types including ostomalacia-associated tumors and endometrial and breast carcinomas.

    Gene expression databases

    ArrayExpressiQ6FHJ7.
    BgeeiQ6FHJ7.
    CleanExiHS_SFRP4.
    GenevestigatoriQ6FHJ7.

    Organism-specific databases

    HPAiHPA009712.

    Interactioni

    Protein-protein interaction databases

    IntActiQ6FHJ7. 2 interactions.
    STRINGi9606.ENSP00000410715.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6FHJ7.
    SMRiQ6FHJ7. Positions 22-144.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini19 – 139121FZPROSITE-ProRule annotationAdd
    BLAST
    Domaini178 – 307130NTRPROSITE-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

    eggNOGiNOG304384.
    HOVERGENiHBG070536.
    InParanoidiQ6FHJ7.
    KOiK02185.
    OMAiNITRMPN.
    OrthoDBiEOG79PJPC.
    PhylomeDBiQ6FHJ7.

    Family and domain databases

    Gene3Di1.10.2000.10. 1 hit.
    InterProiIPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR001134. Netrin_domain.
    IPR018933. Netrin_module_non-TIMP.
    IPR026560. SFRP4.
    IPR008993. TIMP-like_OB-fold.
    [Graphical view]
    PANTHERiPTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF7. PTHR11309:SF7. 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.

    Q6FHJ7-1 [UniParc]FASTAAdd to Basket

    « Hide

    MFLSILVALC LWLHLALGVR GAPCEAVRIP MCRHMPWNIT RMPNHLHHST    50
    QENAILAIEQ YEELVDVNCS AVLRFFLCAM YAPICTLEFL HDPIKPCKSV 100
    CQRARDDCEP LMKMYNHSWP ESLACDELPV YDRGVCISPE AIVTDLPEDV 150
    KWIDITPDMM VQERPLDVDC KRLSPDRCKC KKVKPTLATY LSKNYSYVIH 200
    AKIKAVQRSG CNEVTTVVDV KEIFKSSSPI PRTQVPLITN SSCQCPHILP 250
    HQDVLIMCYE WRSRMMLLEN CLVEKWRDQL SKRSIQWEER LQEQRRTVQD 300
    KKKTAGRTSR SNPPKPKGKP PAPKPASPKK NIKTRSAQKR TNPKRV 346
    Length:346
    Mass (Da):39,827
    Last modified:March 15, 2005 - v2
    Checksum:i75D04089E446CE80
    GO

    Sequence cautioni

    The sequence BAG63683.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti19 – 191V → M in CAG46532. 1 PublicationCurated
    Sequence conflicti77 – 771L → F in AAC04617. (PubMed:10211996)Curated
    Sequence conflicti141 – 1411A → V in CAG46555. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti320 – 3201P → T.4 Publications
    Corresponds to variant rs1802073 [ dbSNP | Ensembl ].
    VAR_051964
    Natural varianti340 – 3401R → K.2 Publications
    Corresponds to variant rs1802074 [ dbSNP | Ensembl ].
    VAR_051965

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF026692 mRNA. Translation: AAC04617.1.
    DQ420628 mRNA. Translation: ABD83351.1.
    AK302357 mRNA. Translation: BAG63683.1. Different initiation.
    CR541731 mRNA. Translation: CAG46532.1.
    CR541755 mRNA. Translation: CAG46555.1.
    BT019679 mRNA. Translation: AAV38485.1.
    CH236951 Genomic DNA. Translation: EAL23981.1.
    BC047684 mRNA. Translation: AAH47684.1.
    BC058911 mRNA. Translation: AAH58911.1.
    CCDSiCCDS5453.1.
    RefSeqiNP_003005.2. NM_003014.3.
    UniGeneiHs.658169.

    Genome annotation databases

    EnsembliENST00000436072; ENSP00000410715; ENSG00000106483.
    GeneIDi6424.
    KEGGihsa:6424.
    UCSCiuc003tfo.4. human.

    Polymorphism databases

    DMDMi61216780.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF026692 mRNA. Translation: AAC04617.1 .
    DQ420628 mRNA. Translation: ABD83351.1 .
    AK302357 mRNA. Translation: BAG63683.1 . Different initiation.
    CR541731 mRNA. Translation: CAG46532.1 .
    CR541755 mRNA. Translation: CAG46555.1 .
    BT019679 mRNA. Translation: AAV38485.1 .
    CH236951 Genomic DNA. Translation: EAL23981.1 .
    BC047684 mRNA. Translation: AAH47684.1 .
    BC058911 mRNA. Translation: AAH58911.1 .
    CCDSi CCDS5453.1.
    RefSeqi NP_003005.2. NM_003014.3.
    UniGenei Hs.658169.

    3D structure databases

    ProteinModelPortali Q6FHJ7.
    SMRi Q6FHJ7. Positions 22-144.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q6FHJ7. 2 interactions.
    STRINGi 9606.ENSP00000410715.

    Protein family/group databases

    MEROPSi I93.001.

    PTM databases

    PhosphoSitei Q6FHJ7.

    Polymorphism databases

    DMDMi 61216780.

    Proteomic databases

    PaxDbi Q6FHJ7.
    PRIDEi Q6FHJ7.

    Protocols and materials databases

    DNASUi 6424.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000436072 ; ENSP00000410715 ; ENSG00000106483 .
    GeneIDi 6424.
    KEGGi hsa:6424.
    UCSCi uc003tfo.4. human.

    Organism-specific databases

    CTDi 6424.
    GeneCardsi GC07M037912.
    H-InvDB HIX0033524.
    HGNCi HGNC:10778. SFRP4.
    HPAi HPA009712.
    MIMi 606570. gene.
    neXtProti NX_Q6FHJ7.
    PharmGKBi PA35694.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG304384.
    HOVERGENi HBG070536.
    InParanoidi Q6FHJ7.
    KOi K02185.
    OMAi NITRMPN.
    OrthoDBi EOG79PJPC.
    PhylomeDBi Q6FHJ7.

    Miscellaneous databases

    GeneWikii SFRP4.
    GenomeRNAii 6424.
    NextBioi 24947.
    PROi Q6FHJ7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q6FHJ7.
    Bgeei Q6FHJ7.
    CleanExi HS_SFRP4.
    Genevestigatori Q6FHJ7.

    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.
    IPR026560. SFRP4.
    IPR008993. TIMP-like_OB-fold.
    [Graphical view ]
    PANTHERi PTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF7. PTHR11309:SF7. 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. "Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy."
      Abu-Jawdeh G.M., Comella N., Brown L.F., Tognazzi K., Kocher O.
      Lab. Invest. 79:439-447(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Endometrium.
    2. "Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent."
      Berndt T., Craig T.A., Bowe A.E., Vassiliadis J., Reczek D., Finnegan R., Jan De Beur S.M., Schiavi S.C., Kumar R.
      J. Clin. Invest. 112:785-794(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], POSSIBLE FUNCTION AS A PHOSPHATURIC AGENT.
      Tissue: Mesenchymal tumor.
    3. "Open reading frame of the human secreted frizzled related protein 4."
      Drake J.M., Zeps N., Dharmarajan A.
      Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-320.
      Tissue: Ovary.
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS THR-320 AND LYS-340.
      Tissue: Testis.
    5. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    6. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    7. "Human chromosome 7: DNA sequence and biology."
      Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
      , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
      Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-320.
    8. "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], VARIANTS THR-320 AND LYS-340.
      Tissue: Brain.
    9. "Expression of secreted frizzled related proteins 3 and 4 in human ventricular myocardium correlates with apoptosis related gene expression."
      Schumann H., Holtz J., Zerkowski H.R., Hatzfeld M.
      Cardiovasc. Res. 45:720-728(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    10. "Expression of secreted frizzled-related protein 4 (SFRP4) in primary serous ovarian tumours."
      Drake J., Shearwood A.M., White J., Friis R., Zeps N., Charles A., Dharmarajan A.
      Eur. J. Gynaecol. Oncol. 30:133-141(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiSFRP4_HUMAN
    AccessioniPrimary (citable) accession number: Q6FHJ7
    Secondary accession number(s): B4DYC1
    , O14877, Q05BG7, Q1ZYW2, Q4G124, Q6FHM0, Q6PD64
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 15, 2005
    Last sequence update: March 15, 2005
    Last modified: October 1, 2014
    This is version 104 of the entry and version 2 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3