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Q9NPG1

- FZD3_HUMAN

UniProt

Q9NPG1 - FZD3_HUMAN

Protein

Frizzled-3

Gene

FZD3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 1 (01 Oct 2000)
      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. G-protein coupled receptor activity Source: UniProtKB-KW
    2. PDZ domain binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. Wnt-activated receptor activity Source: BHF-UCL
    5. Wnt-protein binding Source: UniProtKB

    GO - Biological processi

    1. canonical Wnt signaling pathway Source: UniProtKB
    2. cell proliferation in midbrain Source: RefGenome
    3. commissural neuron axon guidance Source: RefGenome
    4. establishment of planar polarity Source: RefGenome
    5. facial nucleus development Source: RefGenome
    6. gonad development Source: RefGenome
    7. G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RefGenome
    8. hair follicle development Source: Ensembl
    9. inner ear morphogenesis Source: RefGenome
    10. neural tube closure Source: RefGenome
    11. neuron differentiation Source: UniProtKB
    12. neuron migration Source: Ensembl
    13. post-anal tail morphogenesis Source: Ensembl
    14. vasculature development 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_172638. Asymmetric localization of PCP proteins.
    REACT_172761. Ca2+ pathway.
    REACT_18372. Class B/2 (Secretin family receptors).
    SignaLinkiQ9NPG1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Frizzled-3
    Short name:
    Fz-3
    Short name:
    hFz3
    Gene namesi
    Name:FZD3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:4041. FZD3.

    Subcellular locationi

    GO - Cellular componenti

    1. apical part of cell Source: RefGenome
    2. apical plasma membrane Source: Ensembl
    3. axon Source: RefGenome
    4. cytoplasm Source: BHF-UCL
    5. dendrite Source: RefGenome
    6. integral component of membrane Source: UniProtKB-KW
    7. lateral plasma membrane Source: Ensembl
    8. neuronal cell body Source: RefGenome
    9. neuron projection membrane Source: RefGenome
    10. plasma membrane Source: BHF-UCL
    11. presynaptic active zone Source: RefGenome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28458.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 22221 PublicationAdd
    BLAST
    Chaini23 – 666644Frizzled-3PRO_0000012982Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi28 ↔ 89PROSITE-ProRule annotation
    Disulfide bondi36 ↔ 82PROSITE-ProRule annotation
    Glycosylationi42 – 421N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi73 ↔ 110PROSITE-ProRule annotation
    Disulfide bondi99 ↔ 133PROSITE-ProRule annotation
    Disulfide bondi103 ↔ 127PROSITE-ProRule annotation
    Glycosylationi265 – 2651N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi356 – 3561N-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

    MaxQBiQ9NPG1.
    PaxDbiQ9NPG1.
    PRIDEiQ9NPG1.

    PTM databases

    PhosphoSiteiQ9NPG1.

    Expressioni

    Tissue specificityi

    Widely expressed. Relatively high expression in the CNS, including regions of the limbic system, in kidney, pancreas, skeletal muscle, uterus and testis.

    Gene expression databases

    ArrayExpressiQ9NPG1.
    BgeeiQ9NPG1.
    CleanExiHS_FZD3.
    GenevestigatoriQ9NPG1.

    Organism-specific databases

    HPAiCAB024995.
    HPA042320.

    Interactioni

    Subunit structurei

    Interacts with VANGL2.By similarity

    Protein-protein interaction databases

    BioGridi113689. 1 interaction.
    IntActiQ9NPG1. 1 interaction.
    STRINGi9606.ENSP00000240093.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9NPG1.
    SMRiQ9NPG1. Positions 28-136, 182-507.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini23 – 205183ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini227 – 23711CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini259 – 28830ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini310 – 32819CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini350 – 37425ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini396 – 42025CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini442 – 47736ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini499 – 666168CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei206 – 22621Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei238 – 25821Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei289 – 30921Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei329 – 34921Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei375 – 39521Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei421 – 44121Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei478 – 49821Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini23 – 136114FZPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi502 – 5076Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity

    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

    eggNOGiNOG259824.
    HOGENOMiHOG000233237.
    HOVERGENiHBG006977.
    InParanoidiQ9NPG1.
    KOiK02329.
    OMAiMSWIVFY.
    OrthoDBiEOG7M3J01.
    PhylomeDBiQ9NPG1.
    TreeFamiTF317907.

    Family and domain databases

    Gene3Di1.10.2000.10. 1 hit.
    InterProiIPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026553. FZD3_vertebrates.
    IPR017981. GPCR_2-like.
    [Graphical view]
    PANTHERiPTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF22. PTHR11309:SF22. 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]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Long (identifier: Q9NPG1-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAMTWIVFSL WPLTVFMGHI GGHSLFSCEP ITLRMCQDLP YNTTFMPNLL    50
    NHYDQQTAAL AMEPFHPMVN LDCSRDFRPF LCALYAPICM EYGRVTLPCR 100
    RLCQRAYSEC SKLMEMFGVP WPEDMECSRF PDCDEPYPRL VDLNLAGEPT 150
    EGAPVAVQRD YGFWCPRELK IDPDLGYSFL HVRDCSPPCP NMYFRREELS 200
    FARYFIGLIS IICLSATLFT FLTFLIDVTR FRYPERPIIF YAVCYMMVSL 250
    IFFIGFLLED RVACNASIPA QYKASTVTQG SHNKACTMLF MILYFFTMAG 300
    SVWWVILTIT WFLAAVPKWG SEAIEKKALL FHASAWGIPG TLTIILLAMN 350
    KIEGDNISGV CFVGLYDVDA LRYFVLAPLC LYVVVGVSLL LAGIISLNRV 400
    RIEIPLEKEN QDKLVKFMIR IGVFSILYLV PLLVVIGCYF YEQAYRGIWE 450
    TTWIQERCRE YHIPCPYQVT QMSRPDLILF LMKYLMALIV GIPSVFWVGS 500
    KKTCFEWASF FHGRRKKEIV NESRQVLQEP DFAQSLLRDP NTPIIRKSRG 550
    TSTQGTSTHA SSTQLAMVDD QRSKAGSIHS KVSSYHGSLH RSRDGRYTPC 600
    SYRGMEERLP HGSMSRLTDH SRHSSSHRLN EQSRHSSIRD LSNNPMTHIT 650
    HGTSMNRVIE EDGTSA 666
    Length:666
    Mass (Da):76,263
    Last modified:October 1, 2000 - v1
    Checksum:i46D7C46E21160215
    GO
    Isoform Short (identifier: Q9NPG1-2)

    Also known as: FZD3deltaC

    Sequence is not available
    Length:
    Mass (Da):

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti127 – 1271C → R in BAF84169. (PubMed:14702039)Curated
    Sequence conflicti402 – 4021I → V in BAF84169. (PubMed:14702039)Curated
    Sequence conflicti664 – 6641T → A in BAF84169. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti4 – 41T → S.1 Publication
    Corresponds to variant rs140115204 [ dbSNP | Ensembl ].
    VAR_066960
    Natural varianti199 – 1991L → M.1 Publication
    VAR_066961
    Natural varianti545 – 5451I → V.1 Publication
    VAR_066962

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB039723 mRNA. Translation: BAA94968.1.
    AJ272427 mRNA. Translation: CAB89114.1.
    AY005130 mRNA. Translation: AAF89088.1.
    AK291480 mRNA. Translation: BAF84169.1.
    CCDSiCCDS6069.1. [Q9NPG1-1]
    PIRiJC7312.
    RefSeqiNP_059108.1. NM_017412.3. [Q9NPG1-1]
    NP_665873.1. NM_145866.1. [Q9NPG1-1]
    UniGeneiHs.40735.
    Hs.734277.

    Genome annotation databases

    EnsembliENST00000240093; ENSP00000240093; ENSG00000104290. [Q9NPG1-1]
    ENST00000537916; ENSP00000437489; ENSG00000104290. [Q9NPG1-1]
    GeneIDi7976.
    KEGGihsa:7976.
    UCSCiuc003xgx.3. human. [Q9NPG1-1]

    Polymorphism databases

    DMDMi17433071.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB039723 mRNA. Translation: BAA94968.1 .
    AJ272427 mRNA. Translation: CAB89114.1 .
    AY005130 mRNA. Translation: AAF89088.1 .
    AK291480 mRNA. Translation: BAF84169.1 .
    CCDSi CCDS6069.1. [Q9NPG1-1 ]
    PIRi JC7312.
    RefSeqi NP_059108.1. NM_017412.3. [Q9NPG1-1 ]
    NP_665873.1. NM_145866.1. [Q9NPG1-1 ]
    UniGenei Hs.40735.
    Hs.734277.

    3D structure databases

    ProteinModelPortali Q9NPG1.
    SMRi Q9NPG1. Positions 28-136, 182-507.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113689. 1 interaction.
    IntActi Q9NPG1. 1 interaction.
    STRINGi 9606.ENSP00000240093.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q9NPG1.

    Polymorphism databases

    DMDMi 17433071.

    Proteomic databases

    MaxQBi Q9NPG1.
    PaxDbi Q9NPG1.
    PRIDEi Q9NPG1.

    Protocols and materials databases

    DNASUi 7976.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000240093 ; ENSP00000240093 ; ENSG00000104290 . [Q9NPG1-1 ]
    ENST00000537916 ; ENSP00000437489 ; ENSG00000104290 . [Q9NPG1-1 ]
    GeneIDi 7976.
    KEGGi hsa:7976.
    UCSCi uc003xgx.3. human. [Q9NPG1-1 ]

    Organism-specific databases

    CTDi 7976.
    GeneCardsi GC08P028351.
    HGNCi HGNC:4041. FZD3.
    HPAi CAB024995.
    HPA042320.
    MIMi 606143. gene.
    neXtProti NX_Q9NPG1.
    PharmGKBi PA28458.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG259824.
    HOGENOMi HOG000233237.
    HOVERGENi HBG006977.
    InParanoidi Q9NPG1.
    KOi K02329.
    OMAi MSWIVFY.
    OrthoDBi EOG7M3J01.
    PhylomeDBi Q9NPG1.
    TreeFami TF317907.

    Enzyme and pathway databases

    Reactomei REACT_172581. PCP/CE pathway.
    REACT_172638. Asymmetric localization of PCP proteins.
    REACT_172761. Ca2+ pathway.
    REACT_18372. Class B/2 (Secretin family receptors).
    SignaLinki Q9NPG1.

    Miscellaneous databases

    ChiTaRSi FZD3. human.
    GeneWikii FZD3.
    GenomeRNAii 7976.
    NextBioi 30495.
    PROi Q9NPG1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9NPG1.
    Bgeei Q9NPG1.
    CleanExi HS_FZD3.
    Genevestigatori Q9NPG1.

    Family and domain databases

    Gene3Di 1.10.2000.10. 1 hit.
    InterProi IPR000539. Frizzled.
    IPR015526. Frizzled/SFRP.
    IPR020067. Frizzled_dom.
    IPR026553. FZD3_vertebrates.
    IPR017981. GPCR_2-like.
    [Graphical view ]
    PANTHERi PTHR11309. PTHR11309. 1 hit.
    PTHR11309:SF22. PTHR11309:SF22. 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. "Molecular cloning and genomic structure of human frizzled-3 at chromosome 8p21."
      Kirikoshi H., Koike J., Sagara N., Saitoh T., Tokuhara M., Tanaka K., Sekihara H., Hirai M., Katoh M.
      Biochem. Biophys. Res. Commun. 271:8-14(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal brain.
    2. "Identification, gene structure and expression of human frizzled-3 (FZD3)."
      Sala C.F., Formenti E., Terstappen G.C., Caricasole A.
      Biochem. Biophys. Res. Commun. 273:27-34(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal brain.
    3. "Characterization of mouse frizzled-3 expression in hair follicle development and identification of the human homolog in keratinocytes."
      Hung B.S., Wang X.-Q., Cam G.R., Rothnagel J.A.
      J. Invest. Dermatol. 116:940-946(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Keratinocyte.
    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].
      Tissue: Brain.
    5. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
      Zhang Z., Henzel W.J.
      Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 23-37.
    6. Cited for: VARIANTS SER-4; MET-199 AND VAL-545.

    Entry informationi

    Entry nameiFZD3_HUMAN
    AccessioniPrimary (citable) accession number: Q9NPG1
    Secondary accession number(s): A8K615
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 5, 2001
    Last sequence update: October 1, 2000
    Last modified: October 1, 2014
    This is version 125 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

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 8
      Human chromosome 8: 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