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Protein

Frizzled-8

Gene

Fzd8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

  • G-protein coupled receptor activity Source: GO_Central
  • PDZ domain binding Source: BHF-UCL
  • receptor binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: MGI
  • Wnt-activated receptor activity Source: MGI
  • Wnt-protein binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • angiogenesis Source: MGI
  • canonical Wnt signaling pathway Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • non-canonical Wnt signaling pathway Source: GO_Central
  • positive regulation of JUN kinase activity Source: MGI
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • T cell differentiation in thymus Source: MGI
  • Wnt signaling pathway Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

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
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:108460. Fzd8.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 272ExtracellularSequence analysisAdd BLAST245
Transmembranei273 – 293Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini294 – 309CytoplasmicSequence analysisAdd BLAST16
Transmembranei310 – 330Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini331 – 394ExtracellularSequence analysisAdd BLAST64
Transmembranei395 – 415Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini416 – 437CytoplasmicSequence analysisAdd BLAST22
Transmembranei438 – 458Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini459 – 481ExtracellularSequence analysisAdd BLAST23
Transmembranei482 – 502Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini503 – 530CytoplasmicSequence analysisAdd BLAST28
Transmembranei531 – 551Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini552 – 582ExtracellularSequence analysisAdd BLAST31
Transmembranei583 – 603Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini604 – 685CytoplasmicSequence analysisAdd BLAST82

GO - Cellular componenti

  • extracellular region Source: Reactome
  • Golgi apparatus Source: UniProtKB-SubCell
  • integral component of membrane Source: GO_Central
  • plasma membrane Source: BHF-UCL
  • Wnt-Frizzled-LRP5/6 complex Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi685V → A: Reduces interaction with GOPC. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001300128 – 685Frizzled-8Add BLAST658

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 96PROSITE-ProRule annotation1 Publication
Disulfide bondi43 ↔ 89PROSITE-ProRule annotation1 Publication
Glycosylationi49N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi80 ↔ 118PROSITE-ProRule annotation1 Publication
Disulfide bondi107 ↔ 148PROSITE-ProRule annotation1 Publication
Disulfide bondi111 ↔ 135PROSITE-ProRule annotation1 Publication
Glycosylationi152N-linked (GlcNAc...)Sequence analysis1
Glycosylationi473N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ61091.
PRIDEiQ61091.

PTM databases

iPTMnetiQ61091.
PhosphoSitePlusiQ61091.

Expressioni

Tissue specificityi

Expressed in chondrocytes.

Gene expression databases

BgeeiENSMUSG00000036904.
CleanExiMM_FZD8.
GenevisibleiQ61091. MM.

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.

GO - Molecular functioni

  • PDZ domain binding Source: BHF-UCL
  • receptor binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: MGI
  • Wnt-protein binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

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

Structurei

Secondary structure

1685
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi41 – 43Combined sources3
Beta strandi49 – 51Combined sources3
Helixi62 – 69Combined sources8
Helixi70 – 72Combined sources3
Helixi73 – 78Combined sources6
Helixi84 – 92Combined sources9
Helixi108 – 124Combined sources17
Helixi131 – 133Combined sources3
Helixi135 – 137Combined sources3
Beta strandi144 – 146Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IJYX-ray1.35A/B28-155[»]
4F0AX-ray3.25A28-150[»]
ProteinModelPortaliQ61091.
SMRiQ61091.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61091.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 151FZPROSITE-ProRule annotationAdd BLAST122

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni71 – 78Palmitate-binding groove8
Regioni95 – 100Wnt-binding6
Regioni147 – 152Wnt-binding6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi606 – 611Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi683 – 685PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi168 – 173Poly-Pro6
Compositional biasi353 – 361Poly-Ala9
Compositional biasi640 – 654Poly-GlyAdd BLAST15

Domaini

Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain 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

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ61091.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG091G0N5M.
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. 3 hits.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
SM01330. Frizzled. 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)DescriptionActionsGraphical viewLength
Sequence conflicti347A → R in AAC52433 (PubMed:8626800).Curated1
Sequence conflicti363A → R in AAC52433 (PubMed:8626800).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IJYX-ray1.35A/B28-155[»]
4F0AX-ray3.25A28-150[»]
ProteinModelPortaliQ61091.
SMRiQ61091.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ61091.
PhosphoSitePlusiQ61091.

Proteomic databases

PaxDbiQ61091.
PRIDEiQ61091.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8325.
MGIiMGI:108460. Fzd8.

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ61091.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG091G0N5M.
TreeFamiTF317907.

Miscellaneous databases

EvolutionaryTraceiQ61091.
PROiQ61091.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036904.
CleanExiMM_FZD8.
GenevisibleiQ61091. MM.

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. 3 hits.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
SM01330. Frizzled. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 152 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.