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Q61091

- FZD8_MOUSE

UniProt

Q61091 - FZD8_MOUSE

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Protein

Frizzled-8

Gene

Fzd8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes (By similarity). The beta-catenin canonical signaling pathway 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. Coreceptor along with RYK of Wnt proteins, such as WNT1.By similarity4 Publications

GO - Molecular functioni

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

GO - Biological processi

  1. angiogenesis Source: MGI
  2. axonogenesis Source: RefGenome
  3. brain development Source: RefGenome
  4. canonical Wnt signaling pathway Source: MGI
  5. gonad development Source: RefGenome
  6. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  7. positive regulation of JUN kinase activity Source: MGI
  8. positive regulation of protein phosphorylation Source: MGI
  9. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  10. regulation of transcription from RNA polymerase II promoter Source: RefGenome
  11. T cell differentiation in thymus Source: MGI
  12. vasculature development Source: RefGenome
  13. Wnt signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_214043. PCP/CE pathway.

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-8
Short name:
Fz-8
Short name:
mFz8
Gene namesi
Name:Fzd8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 18

Organism-specific databases

MGIiMGI:108460. Fzd8.

Subcellular locationi

GO - Cellular componenti

  1. cell projection Source: RefGenome
  2. cytoplasm Source: RefGenome
  3. Golgi apparatus Source: UniProtKB-KW
  4. integral component of membrane Source: UniProtKB-KW
  5. plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi685 – 6851V → A: Reduces interaction with GOPC. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 685658Frizzled-8PRO_0000013001Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 961 PublicationPROSITE-ProRule annotation
Disulfide bondi43 ↔ 891 PublicationPROSITE-ProRule annotation
Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi80 ↔ 1181 PublicationPROSITE-ProRule annotation
Disulfide bondi107 ↔ 1481 PublicationPROSITE-ProRule annotation
Disulfide bondi111 ↔ 1351 PublicationPROSITE-ProRule annotation
Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence Analysis
Glycosylationi473 – 4731N-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

PRIDEiQ61091.

PTM databases

PhosphoSiteiQ61091.

Expressioni

Tissue specificityi

Expressed in chondrocytes.

Gene expression databases

BgeeiQ61091.
CleanExiMM_FZD8.
GenevestigatoriQ61091.

Interactioni

Subunit structurei

Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly with LRP5 or LRP6; the interaction is promoted by Wnt-binding and signaling and inhibited by DKK1 (By similarity). Interacts (via the PDZ-binding motif) with GPOC (via its PDZ domain). Interacts with RSPO1 and RSPO3.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GopcQ8BH603EBI-6171689,EBI-296357
LRP6O755814EBI-6171689,EBI-910915From a different organism.

Protein-protein interaction databases

BioGridi199781. 4 interactions.
DIPiDIP-41258N.
IntActiQ61091. 4 interactions.
MINTiMINT-1782989.
STRINGi10090.ENSMUSP00000039660.

Structurei

Secondary structure

1
685
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi41 – 433
Beta strandi49 – 513
Helixi62 – 698
Helixi70 – 723
Helixi73 – 786
Helixi84 – 929
Helixi108 – 12417
Helixi131 – 1333
Helixi135 – 1373
Beta strandi144 – 1463

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IJYX-ray1.35A/B28-155[»]
4F0AX-ray3.25A28-150[»]
ProteinModelPortaliQ61091.
SMRiQ61091. Positions 35-150, 230-612.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61091.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 272245ExtracellularSequence AnalysisAdd
BLAST
Topological domaini294 – 30916CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini331 – 39464ExtracellularSequence AnalysisAdd
BLAST
Topological domaini416 – 43722CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini459 – 48123ExtracellularSequence AnalysisAdd
BLAST
Topological domaini503 – 53028CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini552 – 58231ExtracellularSequence AnalysisAdd
BLAST
Topological domaini604 – 68582CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei273 – 29321Helical; Name=1Sequence AnalysisAdd
BLAST
Transmembranei310 – 33021Helical; Name=2Sequence AnalysisAdd
BLAST
Transmembranei395 – 41521Helical; Name=3Sequence AnalysisAdd
BLAST
Transmembranei438 – 45821Helical; Name=4Sequence AnalysisAdd
BLAST
Transmembranei482 – 50221Helical; Name=5Sequence AnalysisAdd
BLAST
Transmembranei531 – 55121Helical; Name=6Sequence AnalysisAdd
BLAST
Transmembranei583 – 60321Helical; Name=7Sequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 151122FZPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni71 – 788Palmitate-binding groove
Regioni95 – 1006Wnt-binding
Regioni147 – 1526Wnt-binding

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi606 – 6116Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
Motifi683 – 6853PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi168 – 1736Poly-Pro
Compositional biasi353 – 3619Poly-Ala
Compositional biasi640 – 65415Poly-GlyAdd
BLAST

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.

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ61091.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG7M3J01.
TreeFamiTF317907.

Family and domain databases

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

Q61091-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MEWGYLLEVT SLLAALAVLQ RSSGAAAASA KELACQEITV PLCKGIGYNY
60 70 80 90 100
TYMPNQFNHD TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY
110 120 130 140 150
KKPLPPCRSV CERAKAGCAP LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD
160 170 180 190 200
YNRTDLTTAA PSPPRRLPPP PPPGEQPPSG SGHSRPPGAR PPHRGGSSRG
210 220 230 240 250
SGDAAAAPPS RGGKARPPGG GAAPCEPGCQ CRAPMVSVSS ERHPLYNRVK
260 270 280 290 300
TGQIANCALP CHNPFFSQDE RAFTVFWIGL WSVLCFVSTF ATVSTFLIDM
310 320 330 340 350
ERFKYPERPI IFLSACYLFV SVGYLVRLVA GHEKVACSGG APGAGGAGGA
360 370 380 390 400
GGAAAAGAGA AGAGASSPGA RGEYEELGAV EQHVRYETTG PALCTVVFLL
410 420 430 440 450
VYFFGMASSI WWVILSLTWF LAAGMKWGNE AIAGYSQYFH LAAWLVPSVK
460 470 480 490 500
SIAVLALSSV DGDPVAGICY VGNQSLDNLR GFVLAPLVIY LFIGTMFLLA
510 520 530 540 550
GFVSLFRIRS VIKQQGGPTK THKLEKLMIR LGLFTVLYTV PAAVVVACLF
560 570 580 590 600
YEQHNRPRWE ATHNCPCLRD LQPDQARRPD YAVFMLKYFM CLVVGITSGV
610 620 630 640 650
WVWSGKTLES WRALCTRCCW ASKGAAVGAG AGGSGPGGSG PGPGGGGGHG
660 670 680
GGGGSLYSDV STGLTWRSGT ASSVSYPKQM PLSQV
Length:685
Mass (Da):73,045
Last modified:July 27, 2011 - v2
Checksum:i9DB95F068BC45CD8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti347 – 3471A → R in AAC52433. (PubMed:8626800)Curated
Sequence conflicti363 – 3631A → R in AAC52433. (PubMed:8626800)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U43321 Genomic DNA. Translation: AAC52433.1.
CH466592 Genomic DNA. Translation: EDL23012.1.
BC132543 mRNA. Translation: AAI32544.1.
BC138062 mRNA. Translation: AAI38063.1.
CCDSiCCDS29048.1.
RefSeqiNP_032084.2. NM_008058.2.
UniGeneiMm.184289.

Genome annotation databases

EnsembliENSMUST00000041080; ENSMUSP00000039660; ENSMUSG00000036904.
GeneIDi14370.
KEGGimmu:14370.
UCSCiuc008eag.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U43321 Genomic DNA. Translation: AAC52433.1 .
CH466592 Genomic DNA. Translation: EDL23012.1 .
BC132543 mRNA. Translation: AAI32544.1 .
BC138062 mRNA. Translation: AAI38063.1 .
CCDSi CCDS29048.1.
RefSeqi NP_032084.2. NM_008058.2.
UniGenei Mm.184289.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1IJY X-ray 1.35 A/B 28-155 [» ]
4F0A X-ray 3.25 A 28-150 [» ]
ProteinModelPortali Q61091.
SMRi Q61091. Positions 35-150, 230-612.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 199781. 4 interactions.
DIPi DIP-41258N.
IntActi Q61091. 4 interactions.
MINTi MINT-1782989.
STRINGi 10090.ENSMUSP00000039660.

Protein family/group databases

MEROPSi I93.001.
GPCRDBi Search...

PTM databases

PhosphoSitei Q61091.

Proteomic databases

PRIDEi Q61091.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000041080 ; ENSMUSP00000039660 ; ENSMUSG00000036904 .
GeneIDi 14370.
KEGGi mmu:14370.
UCSCi uc008eag.2. mouse.

Organism-specific databases

CTDi 8325.
MGIi MGI:108460. Fzd8.

Phylogenomic databases

eggNOGi NOG257258.
GeneTreei ENSGT00760000118864.
HOGENOMi HOG000233236.
HOVERGENi HBG006977.
InParanoidi Q61091.
KOi K02375.
OMAi HEKVACN.
OrthoDBi EOG7M3J01.
TreeFami TF317907.

Enzyme and pathway databases

Reactomei REACT_214043. PCP/CE pathway.

Miscellaneous databases

EvolutionaryTracei Q61091.
NextBioi 285853.
PROi Q61091.
SOURCEi Search...

Gene expression databases

Bgeei Q61091.
CleanExi MM_FZD8.
Genevestigatori Q61091.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 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

« Hide 'large scale' publications
  1. "A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled."
    Wang Y., Macke J.P., Abella B.S., Andreasson K., Worley P., Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J.
    J. Biol. Chem. 271:4468-4476(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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.
  4. "Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner."
    Sheldahl L.C., Park M., Malbon C.C., Moon R.T.
    Curr. Biol. 9:695-698(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BETA-CATENIN SIGNALING.
  5. "Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein."
    Hsieh J.C., Rattner A., Smallwood P.M., Nathans J.
    Proc. Natl. Acad. Sci. U.S.A. 96:3546-3551(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  6. "Identification of a PDZ domain containing Golgi protein, GOPC, as an interaction partner of frizzled."
    Yao R., Maeda T., Takada S., Noda T.
    Biochem. Biophys. Res. Commun. 286:771-778(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GOPC, SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-685.
  7. "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth."
    Lu W., Yamamoto V., Ortega B., Baltimore D.
    Cell 119:97-108(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression."
    Nam J.-S., Turcotte T.J., Smith P.F., Choi S., Yoon J.K.
    J. Biol. Chem. 281:13247-13257(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RSPO1 AND RSPO3, FUNCTION.
  9. "Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains."
    Dann C.E., Hsieh J.-C., Rattner A., Sharma D., Nathans J., Leahy D.J.
    Nature 412:86-90(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 28-155, DISULFIDE BONDS.
  10. "Structural basis of Wnt recognition by Frizzled."
    Janda C.Y., Waghray D., Levin A.M., Thomas C., Garcia K.C.
    Science 337:59-64(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 28-150 IN COMPLEX WITH XENOPUS WNT8.

Entry informationi

Entry nameiFZD8_MOUSE
AccessioniPrimary (citable) accession number: Q61091
Secondary accession number(s): A2RTK9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3