Q61091 (FZD8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-8
Short name=Fz-8
Short name=mFz8

Gene names

Name:

Fzd8

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	685 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Wnt signaling pathway
Cellular component	Cell membrane Golgi apparatus Membrane
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T 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 receptor 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 transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17360443. Source: MGI vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	Golgi 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 to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay PubMed 15035989. Source: BHF-UCL
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW PDZ domain binding Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt-activated receptor activity Inferred from physical interaction Ref.7. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Potential

Chain

28 – 685

658

Frizzled-8

PRO_0000013001

Regions

Topological domain

28 – 272

245

Extracellular Potential

Transmembrane

273 – 293

21

Helical; Name=1; Potential

Topological domain

294 – 309

16

Cytoplasmic Potential

Transmembrane

310 – 330

21

Helical; Name=2; Potential

Topological domain

331 – 394

64

Extracellular Potential

Transmembrane

395 – 415

21

Helical; Name=3; Potential

Topological domain

416 – 437

22

Cytoplasmic Potential

Transmembrane

438 – 458

21

Helical; Name=4; Potential

Topological domain

459 – 481

23

Extracellular Potential

Transmembrane

482 – 502

21

Helical; Name=5; Potential

Topological domain

503 – 530

28

Cytoplasmic Potential

Transmembrane

531 – 551

21

Helical; Name=6; Potential

Topological domain

552 – 582

31

Extracellular Potential

Transmembrane

583 – 603

21

Helical; Name=7; Potential

Topological domain

604 – 685

82

Cytoplasmic Potential

Domain

30 – 151

122

FZ

Region

71 – 78

8

Palmitate-binding groove

Region

95 – 100

6

Wnt-binding

Region

147 – 152

6

Wnt-binding

Motif

606 – 611

6

Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity

Motif

683 – 685

3

PDZ-binding

Compositional bias

168 – 173

6

Poly-Pro

Compositional bias

353 – 361

9

Poly-Ala

Compositional bias

640 – 654

15

Poly-Gly

Amino acid modifications

Glycosylation

49

1

N-linked (GlcNAc...) Potential

Glycosylation

152

1

N-linked (GlcNAc...) Potential

Glycosylation

473

1

N-linked (GlcNAc...) Potential

Disulfide bond

35 ↔ 96

Ref.9

Disulfide bond

43 ↔ 89

Ref.9

Disulfide bond

80 ↔ 118

Ref.9

Disulfide bond

107 ↔ 148

Ref.9

Disulfide bond

111 ↔ 135

Ref.9

Experimental info

Mutagenesis

685

1

V → A: Reduces interaction with GOPC. Ref.6

Sequence conflict

347

1

A → R in AAC52433. Ref.1

Sequence conflict

363

1

A → R in AAC52433. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

685

Helix Strand Turn

Details...

Helix

41 – 43

3

Beta strand

49 – 51

3

Helix

62 – 69

8

Helix

70 – 72

3

Helix

73 – 78

6

Helix

84 – 92

9

Helix

108 – 124

17

Helix

131 – 133

3

Helix

135 – 137

3

Beta strand

144 – 146

3

Sequences

	Sequence		Length	Mass (Da)
	Q61091 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 9DB95F068BC45CD8	FASTA	685	73,045
	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

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00117114.

RefSeq

NP_032084.2. NM_008058.2.

UniGene

Mm.184289.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IJY	X-ray	1.35	A/B	28-155	[»]
4F0A	X-ray	3.25	A	28-150	[»]

ProteinModelPortal

Q61091.

SMR

Q61091. Positions 35-150.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41258N.

IntAct

Q61091. 1 interaction.

MINT

MINT-1782989.

STRING

10090.ENSMUSP00000039660.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

Q61091.

Proteomic databases

PRIDE

Q61091.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000041080; ENSMUSP00000039660; ENSMUSG00000036904.

GeneID

14370.

KEGG

mmu:14370.

Organism-specific databases

CTD

8325.

MGI

MGI:108460. Fzd8.

Phylogenomic databases

eggNOG

NOG257258.

GeneTree

ENSGT00660000095421.

HOGENOM

HOG000233236.

HOVERGEN

HBG006977.

InParanoid

A2RTK9.

KO

K02375.

OMA

CHNPYFT.

OrthoDB

EOG4B5P5T.

Gene expression databases

Bgee

Q61091.

CleanEx

MM_FZD8.

Genevestigator

Q61091.

GermOnline

ENSMUSG00000036904. Mus musculus.

Family and domain databases

Gene3D

1.10.2000.10. 1 hit.

InterPro

IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026545. FZD8.
IPR017981. GPCR_2-like.
[Graphical view]

PANTHER

PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF28. PTHR11309:SF28. 1 hit.

Pfam

PF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]

PRINTS

PR00489. FRIZZLED.

SMART

SM00063. FRI. 1 hit.
[Graphical view]

SUPFAM

SSF63501. Frizzled_Cys-rich. 1 hit.

PROSITE

PS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q61091.

NextBio

285853.

SOURCE

Search...

Entry information

Entry name

FZD8_MOUSE

Accession

Primary (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 3, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program