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Q61091 (FZD8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-8

Short name=Fz-8
Short name=mFz8
Gene names
Name:Fzd8
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length685 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.5 Ref.7 Ref.8

Subunit structure

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. Ref.6 Ref.8

Subcellular location

Membrane; Multi-pass membrane protein. Golgi apparatus. Cell membrane; Multi-pass membrane protein. Note: Colocalizes with GOPC at the Golgi apparatus. Ref.5 Ref.6

Tissue specificity

Expressed in chondrocytes.

Domain

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.

Post-translational modification

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

Sequence similarities

Belongs to the G-protein coupled receptor Fz/Smo family.

Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell membrane
Golgi apparatus
Membrane
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell differentiation in thymus

Inferred from mutant phenotype PubMed 11265645. Source: MGI

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from direct assay Ref.8. Source: MGI

embryo development

Inferred from Biological aspect of Ancestor. Source: RefGenome

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17360443. Source: MGI

positive regulation of JUN kinase activity

Inferred from direct assay PubMed 15195140. Source: MGI

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 15143170. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17360443. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell projection

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 15035989. Source: BHF-UCL

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from physical interaction Ref.6. Source: BHF-UCL

Wnt-activated receptor activity

Inferred from physical interaction Ref.7. Source: MGI

Wnt-protein binding

Inferred from physical interaction Ref.7. Source: MGI

receptor binding

Inferred from physical interaction PubMed 11029007. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GopcQ8BH603EBI-6171689,EBI-296357
LRP6O755814EBI-6171689,EBI-910915From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 685658Frizzled-8
PRO_0000013001

Regions

Topological domain28 – 272245Extracellular Potential
Transmembrane273 – 29321Helical; Name=1; Potential
Topological domain294 – 30916Cytoplasmic Potential
Transmembrane310 – 33021Helical; Name=2; Potential
Topological domain331 – 39464Extracellular Potential
Transmembrane395 – 41521Helical; Name=3; Potential
Topological domain416 – 43722Cytoplasmic Potential
Transmembrane438 – 45821Helical; Name=4; Potential
Topological domain459 – 48123Extracellular Potential
Transmembrane482 – 50221Helical; Name=5; Potential
Topological domain503 – 53028Cytoplasmic Potential
Transmembrane531 – 55121Helical; Name=6; Potential
Topological domain552 – 58231Extracellular Potential
Transmembrane583 – 60321Helical; Name=7; Potential
Topological domain604 – 68582Cytoplasmic Potential
Domain30 – 151122FZ
Region71 – 788Palmitate-binding groove
Region95 – 1006Wnt-binding
Region147 – 1526Wnt-binding
Motif606 – 6116Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif683 – 6853PDZ-binding
Compositional bias168 – 1736Poly-Pro
Compositional bias353 – 3619Poly-Ala
Compositional bias640 – 65415Poly-Gly

Amino acid modifications

Glycosylation491N-linked (GlcNAc...) Potential
Glycosylation1521N-linked (GlcNAc...) Potential
Glycosylation4731N-linked (GlcNAc...) Potential
Disulfide bond35 ↔ 96 Ref.9
Disulfide bond43 ↔ 89 Ref.9
Disulfide bond80 ↔ 118 Ref.9
Disulfide bond107 ↔ 148 Ref.9
Disulfide bond111 ↔ 135 Ref.9

Experimental info

Mutagenesis6851V → A: Reduces interaction with GOPC. Ref.6
Sequence conflict3471A → R in AAC52433. Ref.1
Sequence conflict3631A → R in AAC52433. Ref.1

Secondary structure

................... 685
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q61091 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 9DB95F068BC45CD8

FASTA68573,045
        10         20         30         40         50         60 
MEWGYLLEVT SLLAALAVLQ RSSGAAAASA KELACQEITV PLCKGIGYNY TYMPNQFNHD 

        70         80         90        100        110        120 
TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY KKPLPPCRSV CERAKAGCAP 

       130        140        150        160        170        180 
LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD YNRTDLTTAA PSPPRRLPPP PPPGEQPPSG 

       190        200        210        220        230        240 
SGHSRPPGAR PPHRGGSSRG SGDAAAAPPS RGGKARPPGG GAAPCEPGCQ CRAPMVSVSS 

       250        260        270        280        290        300 
ERHPLYNRVK TGQIANCALP CHNPFFSQDE RAFTVFWIGL WSVLCFVSTF ATVSTFLIDM 

       310        320        330        340        350        360 
ERFKYPERPI IFLSACYLFV SVGYLVRLVA GHEKVACSGG APGAGGAGGA GGAAAAGAGA 

       370        380        390        400        410        420 
AGAGASSPGA RGEYEELGAV EQHVRYETTG PALCTVVFLL VYFFGMASSI WWVILSLTWF 

       430        440        450        460        470        480 
LAAGMKWGNE AIAGYSQYFH LAAWLVPSVK SIAVLALSSV DGDPVAGICY VGNQSLDNLR 

       490        500        510        520        530        540 
GFVLAPLVIY LFIGTMFLLA GFVSLFRIRS VIKQQGGPTK THKLEKLMIR LGLFTVLYTV 

       550        560        570        580        590        600 
PAAVVVACLF YEQHNRPRWE ATHNCPCLRD LQPDQARRPD YAVFMLKYFM CLVVGITSGV 

       610        620        630        640        650        660 
WVWSGKTLES WRALCTRCCW ASKGAAVGAG AGGSGPGGSG PGPGGGGGHG GGGGSLYSDV 

       670        680 
STGLTWRSGT ASSVSYPKQM PLSQV 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U43321 Genomic DNA. Translation: AAC52433.1.
CH466592 Genomic DNA. Translation: EDL23012.1.
BC132543 mRNA. Translation: AAI32544.1.
BC138062 mRNA. Translation: AAI38063.1.
RefSeqNP_032084.2. NM_008058.2.
UniGeneMm.184289.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IJYX-ray1.35A/B28-155[»]
4F0AX-ray3.25A28-150[»]
ProteinModelPortalQ61091.
SMRQ61091. Positions 35-150, 230-612.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199781. 4 interactions.
DIPDIP-41258N.
IntActQ61091. 4 interactions.
MINTMINT-1782989.
STRING10090.ENSMUSP00000039660.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ61091.

Proteomic databases

PRIDEQ61091.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000041080; ENSMUSP00000039660; ENSMUSG00000036904.
GeneID14370.
KEGGmmu:14370.
UCSCuc008eag.2. mouse.

Organism-specific databases

CTD8325.
MGIMGI:108460. Fzd8.

Phylogenomic databases

eggNOGNOG257258.
GeneTreeENSGT00750000117488.
HOGENOMHOG000233236.
HOVERGENHBG006977.
InParanoidA2RTK9.
KOK02375.
OMAFRIRNVI.
OrthoDBEOG7M3J01.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.

Gene expression databases

BgeeQ61091.
CleanExMM_FZD8.
GenevestigatorQ61091.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026547. FZD5/FZD8.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF29. PTHR11309:SF29. 1 hit.
PfamPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSPR00489. FRIZZLED.
SMARTSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ61091.
NextBio285853.
PROQ61091.
SOURCESearch...

Entry information

Entry nameFZD8_MOUSE
AccessionPrimary (citable) accession number: Q61091
Secondary accession number(s): A2RTK9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries