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O75084

- FZD7_HUMAN

UniProt

O75084 - FZD7_HUMAN

Protein

Frizzled-7

Gene

FZD7

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 2 (27 Sep 2004)
      Previous versions | rss
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    Functioni

    Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.

    GO - Molecular functioni

    1. frizzled binding Source: UniProtKB
    2. G-protein coupled receptor activity Source: UniProtKB-KW
    3. PDZ domain binding Source: UniProtKB
    4. protein binding Source: IntAct
    5. Wnt-activated receptor activity Source: RefGenome
    6. Wnt-protein binding Source: BHF-UCL

    GO - Biological processi

    1. axonogenesis Source: RefGenome
    2. brain development Source: RefGenome
    3. canonical Wnt signaling pathway Source: UniProtKB
    4. cellular response to retinoic acid Source: UniProtKB
    5. gonad development Source: RefGenome
    6. G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RefGenome
    7. mesenchymal to epithelial transition Source: BHF-UCL
    8. negative regulation of cell-substrate adhesion Source: BHF-UCL
    9. negative regulation of ectodermal cell fate specification Source: BHF-UCL
    10. neuron differentiation Source: UniProtKB
    11. non-canonical Wnt signaling pathway via JNK cascade Source: BHF-UCL
    12. positive regulation of epithelial cell proliferation involved in wound healing Source: BHF-UCL
    13. positive regulation of JNK cascade Source: BHF-UCL
    14. positive regulation of phosphorylation Source: BHF-UCL
    15. positive regulation of transcription, DNA-templated Source: BHF-UCL
    16. regulation of catenin import into nucleus Source: BHF-UCL
    17. regulation of transcription, DNA-templated Source: BHF-UCL
    18. skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration Source: Ensembl
    19. somatic stem cell division Source: Ensembl
    20. stem cell maintenance Source: BHF-UCL
    21. substrate adhesion-dependent cell spreading Source: Ensembl
    22. T cell differentiation in thymus Source: Ensembl
    23. vasculature development Source: RefGenome
    24. Wnt signaling pathway, calcium modulating pathway Source: RefGenome

    Keywords - Molecular functioni

    Developmental protein, G-protein coupled receptor, Receptor, Transducer

    Keywords - Biological processi

    Wnt signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_172581. PCP/CE pathway.
    REACT_18372. Class B/2 (Secretin family receptors).
    REACT_207044. TCF dependent signaling in response to WNT.
    SignaLinkiO75084.

    Protein family/group databases

    MEROPSiI93.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-7
    Short name:
    Fz-7
    Short name:
    hFz7
    Alternative name(s):
    FzE3
    Gene namesi
    Name:FZD7
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:4045. FZD7.

    Subcellular locationi

    Membrane By similarity; Multi-pass membrane protein By similarity. Cell membrane By similarity; Multi-pass membrane protein By similarity

    GO - Cellular componenti

    1. apical part of cell Source: RefGenome
    2. cytoplasm Source: RefGenome
    3. integral component of membrane Source: BHF-UCL
    4. neuron projection membrane Source: RefGenome
    5. plasma membrane Source: BHF-UCL

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28462.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3232Sequence AnalysisAdd
    BLAST
    Chaini33 – 574542Frizzled-7PRO_0000012996Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi49 ↔ 110PROSITE-ProRule annotation
    Disulfide bondi57 ↔ 103PROSITE-ProRule annotation
    Glycosylationi63 – 631N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi94 ↔ 131PROSITE-ProRule annotation
    Disulfide bondi120 ↔ 160PROSITE-ProRule annotation
    Disulfide bondi124 ↔ 148PROSITE-ProRule annotation
    Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO75084.
    PaxDbiO75084.
    PRIDEiO75084.

    PTM databases

    PhosphoSiteiO75084.

    Expressioni

    Tissue specificityi

    High expression in adult skeletal muscle and fetal kidney, followed by fetal lung, adult heart, brain, and placenta. Specifically expressed in squamous cell esophageal carcinomas.

    Gene expression databases

    BgeeiO75084.
    CleanExiHS_FZD7.
    GenevestigatoriO75084.

    Interactioni

    Subunit structurei

    Interacts with MAGI3 and DVL1 By similarity. Interacts with MYOC.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SDCBPO005604EBI-746917,EBI-727004
    WNT3P567033EBI-746917,EBI-3644922

    Protein-protein interaction databases

    BioGridi113920. 4 interactions.
    IntActiO75084. 6 interactions.
    MINTiMINT-1461434.
    STRINGi9606.ENSP00000286201.

    Structurei

    3D structure databases

    ProteinModelPortaliO75084.
    SMRiO75084. Positions 49-155, 204-565.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini33 – 256224ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini278 – 28811CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini310 – 33627ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini358 – 37922CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini401 – 42323ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini445 – 47026CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini492 – 52837ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini550 – 57425CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei257 – 27721Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei289 – 30921Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei337 – 35721Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei380 – 40021Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei424 – 44421Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei471 – 49121Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei529 – 54921Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini44 – 163120FZPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi552 – 5576Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
    Motifi572 – 5743PDZ-binding

    Domaini

    Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.By similarity
    The FZ domain is involved in binding with Wnt ligands.By similarity

    Sequence similaritiesi

    Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG257258.
    HOGENOMiHOG000233237.
    HOVERGENiHBG006977.
    InParanoidiO75084.
    KOiK02432.
    OMAiCVERFSE.
    OrthoDBiEOG7M3J01.
    PhylomeDBiO75084.
    TreeFamiTF317907.

    Family and domain databases

    Gene3Di1.10.2000.10. 1 hit.
    InterProiIPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026552. FZD7.
    IPR017981. GPCR_2-like.
    [Graphical view]
    PANTHERiPTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF31. PTHR11309:SF31. 1 hit.
    PfamiPF01534. Frizzled. 1 hit.
    PF01392. Fz. 1 hit.
    [Graphical view]
    PRINTSiPR00489. FRIZZLED.
    SMARTiSM00063. FRI. 1 hit.
    [Graphical view]
    SUPFAMiSSF63501. SSF63501. 1 hit.
    PROSITEiPS50038. FZ. 1 hit.
    PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    O75084-1 [UniParc]FASTAAdd to Basket

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    MRDPGAAAPL SSLGLCALVL ALLGALSAGA GAQPYHGEKG ISVPDHGFCQ    50
    PISIPLCTDI AYNQTILPNL LGHTNQEDAG LEVHQFYPLV KVQCSPELRF 100
    FLCSMYAPVC TVLDQAIPPC RSLCERARQG CEALMNKFGF QWPERLRCEN 150
    FPVHGAGEIC VGQNTSDGSG GPGGGPTAYP TAPYLPDLPF TALPPGASDG 200
    RGRPAFPFSC PRQLKVPPYL GYRFLGERDC GAPCEPGRAN GLMYFKEEER 250
    RFARLWVGVW SVLCCASTLF TVLTYLVDMR RFSYPERPII FLSGCYFMVA 300
    VAHVAGFLLE DRAVCVERFS DDGYRTVAQG TKKEGCTILF MVLYFFGMAS 350
    SIWWVILSLT WFLAAGMKWG HEAIEANSQY FHLAAWAVPA VKTITILAMG 400
    QVDGDLLSGV CYVGLSSVDA LRGFVLAPLF VYLFIGTSFL LAGFVSLFRI 450
    RTIMKHDGTK TEKLEKLMVR IGVFSVLYTV PATIVLACYF YEQAFREHWE 500
    RTWLLQTCKS YAVPCPPGHF PPMSPDFTVF MIKYLMTMIV GITTGFWIWS 550
    GKTLQSWRRF YHRLSHSSKG ETAV 574
    Length:574
    Mass (Da):63,620
    Last modified:September 27, 2004 - v2
    Checksum:i801934246B426DF5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti8 – 81A → V in BAA32424. (PubMed:9707618)Curated
    Sequence conflicti15 – 151L → F in BAA32424. (PubMed:9707618)Curated
    Sequence conflicti201 – 2011R → K in BAA32424. (PubMed:9707618)Curated
    Sequence conflicti308 – 3081L → F in BAA32424. (PubMed:9707618)Curated
    Sequence conflicti408 – 4081S → N in BAA32424. (PubMed:9707618)Curated
    Sequence conflicti415 – 4151L → F in BAA32424. (PubMed:9707618)Curated
    Sequence conflicti433 – 4331L → F in BAA32424. (PubMed:9707618)Curated
    Sequence conflicti447 – 4471L → F in BAA32424. (PubMed:9707618)Curated
    Sequence conflicti534 – 5341Y → C in BAA32424. (PubMed:9707618)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti24 – 241G → D.
    Corresponds to variant rs35111363 [ dbSNP | Ensembl ].
    VAR_049292
    Natural varianti24 – 241G → S.1 Publication
    VAR_033024
    Natural varianti196 – 1961G → E.
    Corresponds to variant rs34908164 [ dbSNP | Ensembl ].
    VAR_033941
    Natural varianti487 – 4871A → V.
    Corresponds to variant rs35600847 [ dbSNP | Ensembl ].
    VAR_033942

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB010881 mRNA. Translation: BAA32424.1.
    AB017365 mRNA. Translation: BAA34668.1.
    AC069148 Genomic DNA. Translation: AAX93250.1.
    CH471063 Genomic DNA. Translation: EAW70298.1.
    BC015915 mRNA. Translation: AAH15915.1.
    CCDSiCCDS2351.1.
    PIRiJE0339.
    RefSeqiNP_003498.1. NM_003507.1.
    UniGeneiHs.173859.

    Genome annotation databases

    EnsembliENST00000286201; ENSP00000286201; ENSG00000155760.
    GeneIDi8324.
    KEGGihsa:8324.
    UCSCiuc002uyw.1. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB010881 mRNA. Translation: BAA32424.1 .
    AB017365 mRNA. Translation: BAA34668.1 .
    AC069148 Genomic DNA. Translation: AAX93250.1 .
    CH471063 Genomic DNA. Translation: EAW70298.1 .
    BC015915 mRNA. Translation: AAH15915.1 .
    CCDSi CCDS2351.1.
    PIRi JE0339.
    RefSeqi NP_003498.1. NM_003507.1.
    UniGenei Hs.173859.

    3D structure databases

    ProteinModelPortali O75084.
    SMRi O75084. Positions 49-155, 204-565.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113920. 4 interactions.
    IntActi O75084. 6 interactions.
    MINTi MINT-1461434.
    STRINGi 9606.ENSP00000286201.

    Protein family/group databases

    MEROPSi I93.001.
    GPCRDBi Search...

    PTM databases

    PhosphoSitei O75084.

    Proteomic databases

    MaxQBi O75084.
    PaxDbi O75084.
    PRIDEi O75084.

    Protocols and materials databases

    DNASUi 8324.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000286201 ; ENSP00000286201 ; ENSG00000155760 .
    GeneIDi 8324.
    KEGGi hsa:8324.
    UCSCi uc002uyw.1. human.

    Organism-specific databases

    CTDi 8324.
    GeneCardsi GC02P202863.
    HGNCi HGNC:4045. FZD7.
    MIMi 603410. gene.
    neXtProti NX_O75084.
    PharmGKBi PA28462.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG257258.
    HOGENOMi HOG000233237.
    HOVERGENi HBG006977.
    InParanoidi O75084.
    KOi K02432.
    OMAi CVERFSE.
    OrthoDBi EOG7M3J01.
    PhylomeDBi O75084.
    TreeFami TF317907.

    Enzyme and pathway databases

    Reactomei REACT_172581. PCP/CE pathway.
    REACT_18372. Class B/2 (Secretin family receptors).
    REACT_207044. TCF dependent signaling in response to WNT.
    SignaLinki O75084.

    Miscellaneous databases

    ChiTaRSi FZD7. human.
    GeneWikii FZD7.
    GenomeRNAii 8324.
    NextBioi 31171.
    PROi O75084.
    SOURCEi Search...

    Gene expression databases

    Bgeei O75084.
    CleanExi HS_FZD7.
    Genevestigatori O75084.

    Family and domain databases

    Gene3Di 1.10.2000.10. 1 hit.
    InterProi IPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026552. FZD7.
    IPR017981. GPCR_2-like.
    [Graphical view ]
    PANTHERi PTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF31. PTHR11309:SF31. 1 hit.
    Pfami PF01534. Frizzled. 1 hit.
    PF01392. Fz. 1 hit.
    [Graphical view ]
    PRINTSi PR00489. FRIZZLED.
    SMARTi SM00063. FRI. 1 hit.
    [Graphical view ]
    SUPFAMi SSF63501. SSF63501. 1 hit.
    PROSITEi PS50038. FZ. 1 hit.
    PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals."
      Tanaka S., Akiyoshi T., Mori M., Wands J.R., Sugimachi K.
      Proc. Natl. Acad. Sci. U.S.A. 95:10164-10169(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], COUPLING TO BETA-CATENIN PATHWAY.
      Tissue: Esophageal carcinoma.
    2. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7."
      Sagara N., Toda G., Hirai M., Terada M., Katoh M.
      Biochem. Biophys. Res. Commun. 252:117-122(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal lung.
    5. "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: Lung.
    6. Cited for: INTERACTION WITH MYOC.
    7. "Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas."
      Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., Boerresen-Dale A.-L.
      Breast Cancer Res. 9:R5-R5(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT SER-24.

    Entry informationi

    Entry nameiFZD7_HUMAN
    AccessioniPrimary (citable) accession number: O75084
    Secondary accession number(s): O94816, Q53S59, Q96B74
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: September 27, 2004
    Last modified: October 1, 2014
    This is version 132 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. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3