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Q61089 (FZD6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-6

Short name=Fz-6
Short name=mFz6
Gene names
Name:Fzd6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length709 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism.

Subcellular location

Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein Ref.3.

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 By similarity.

Post-translational modification

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

Disruption phenotype

Half of the males without the gene, but not females, display abnormal claw morphology or absent claws compared to wild-type. At the age of 2 to 3 months, the claws disappear or become rudimentary on the hind limbs. Ref.4

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
Membrane
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt signaling pathway, planar cell polarity pathway

Inferred from direct assay PubMed 18606138. Source: MGI

angiogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell proliferation in midbrain

Inferred from genetic interaction PubMed 19842188. Source: MGI

embryonic nail plate morphogenesis

Inferred from mutant phenotype PubMed 23439395. Source: MGI

establishment of planar polarity

Inferred from genetic interaction PubMed 16495441. Source: MGI

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

hair follicle development

Inferred from mutant phenotype PubMed 15169958PubMed 17172440. Source: MGI

inner ear morphogenesis

Inferred from genetic interaction PubMed 16495441. Source: MGI

midbrain development

Inferred from genetic interaction PubMed 19842188. Source: MGI

negative regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

neural tube closure

Inferred from genetic interaction PubMed 16495441. Source: MGI

platelet activation

Inferred from mutant phenotype PubMed 19901330. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentapical part of cell

Inferred from direct assay PubMed 16495441. Source: MGI

apicolateral plasma membrane

Inferred from direct assay PubMed 17376975. Source: MGI

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuron projection membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionG-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 Biological aspect of Ancestor. Source: RefGenome

Wnt-protein binding

Inferred from physical interaction PubMed 15265686. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 18606138. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 709691Frizzled-6
PRO_0000012995

Regions

Topological domain19 – 201183Extracellular Potential
Transmembrane202 – 22221Helical; Name=1; Potential
Topological domain223 – 23311Cytoplasmic Potential
Transmembrane234 – 25421Helical; Name=2; Potential
Topological domain255 – 28430Extracellular Potential
Transmembrane285 – 30521Helical; Name=3; Potential
Topological domain306 – 32419Cytoplasmic Potential
Transmembrane325 – 34521Helical; Name=4; Potential
Topological domain346 – 37025Extracellular Potential
Transmembrane371 – 39121Helical; Name=5; Potential
Topological domain392 – 41625Cytoplasmic Potential
Transmembrane417 – 43721Helical; Name=6; Potential
Topological domain438 – 47336Extracellular Potential
Transmembrane474 – 49421Helical; Name=7; Potential
Topological domain495 – 709215Cytoplasmic Potential
Domain19 – 132114FZ
Motif498 – 5036Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity

Amino acid modifications

Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation2561N-linked (GlcNAc...) Potential
Glycosylation3521N-linked (GlcNAc...) Potential
Disulfide bond24 ↔ 85 By similarity
Disulfide bond32 ↔ 78 By similarity
Disulfide bond69 ↔ 106 By similarity
Disulfide bond95 ↔ 129 By similarity
Disulfide bond99 ↔ 123 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q61089 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 01374A9EC9122484

FASTA70979,082
        10         20         30         40         50         60 
MERSPFLLAC ILLPLVRGHS LFTCEPITVP RCMKMTYNMT FFPNLMGHYD QGIAAVEMGH 

        70         80         90        100        110        120 
FLHLANLECS PNIEMFLCQA FIPTCTEQIH VVLPCRKLCE KIVSDCKKLM DTFGIRWPEE 

       130        140        150        160        170        180 
LECNRLPHCD DTVPVTSHPH TELSGPQKKS DQVPRDIGFW CPKHLRTSGD QGYRFLGIEQ 

       190        200        210        220        230        240 
CAPPCPNMYF KSDELDFAKS FIGIVSIFCL CATLFTFLTF LIDVRRFRYP ERPIIYYSVC 

       250        260        270        280        290        300 
YSIVSLMYFV GFLLGNSTAC NKADEKLELG DTVVLGSKNK ACSVVFMFLY FFTMAGTVWW 

       310        320        330        340        350        360 
VILTITWFLA AGRKWSCEAI EQKAVWFHAV AWGAPGFLTV MLLAMNKVEG DNISGVCFVG 

       370        380        390        400        410        420 
LYDLDASRYF VLLPLCLCVF VGLSLLLAGI ISLNHVRQVI QHDGRNQEKL KKFMIRIGVF 

       430        440        450        460        470        480 
SGLYLVPLVT LLGCYVYELV NRITWEMTWF SDHCHQYRIP CPYQANPKAR PELALFMIKY 

       490        500        510        520        530        540 
LMTLIVGISA VFWVGSKKTC TEWAGFFKRN RKRDPISESR RVLQESCEFF LKHNSKVKHK 

       550        560        570        580        590        600 
KKHGAPGPHR LKVISKSMGT STGATTNHGT SAMAIADHDY LGQETSTEVH TSPEASVKEG 

       610        620        630        640        650        660 
RADRANTPSA KDRDCGESAG PSSKLSGNRN GRESRAGGLK ERSNGSEGAP SEGRVSPKSS 

       670        680        690        700 
VPETGLIDCS TSQAASSPEP TSLKGSTSLP VHSASRARKE QGAGSHSDA 

« Hide

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 [MRNA].
[2]"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: WNT-MEDIATED PKC ACTIVATION.
[3]"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: SUBCELLULAR LOCATION.
[4]"Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia."
Frojmark A.S., Schuster J., Sobol M., Entesarian M., Kilander M.B., Gabrikova D., Nawaz S., Baig S.M., Schulte G., Klar J., Dahl N.
Am. J. Hum. Genet. 88:852-860(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U43319 mRNA. Translation: AAC52431.1.
CCDSCCDS27441.1.
RefSeqNP_001155966.1. NM_001162494.1.
NP_032082.3. NM_008056.3.
UniGeneMm.4769.

3D structure databases

ProteinModelPortalQ61089.
SMRQ61089. Positions 24-127, 178-503.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ61089. 1 interaction.

Chemistry

GuidetoPHARMACOLOGY234.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ61089.

Proteomic databases

PRIDEQ61089.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022906; ENSMUSP00000022906; ENSMUSG00000022297.
ENSMUST00000179165; ENSMUSP00000136328; ENSMUSG00000022297.
GeneID14368.
KEGGmmu:14368.
UCSCuc007vny.2. mouse.

Organism-specific databases

CTD8323.
MGIMGI:108474. Fzd6.

Phylogenomic databases

eggNOGNOG262811.
GeneTreeENSGT00740000114899.
HOGENOMHOG000233237.
HOVERGENHBG006977.
InParanoidQ61089.
KOK02376.
OMACPYQAKA.
OrthoDBEOG7M3J01.
PhylomeDBQ61089.
TreeFamTF317907.

Gene expression databases

ArrayExpressQ61089.
BgeeQ61089.
CleanExMM_FZD6.
GenevestigatorQ61089.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026543. FZD6.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF75. PTHR11309:SF75. 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

ChiTaRSFZD6. mouse.
NextBio285845.
PROQ61089.
SOURCESearch...

Entry information

Entry nameFZD6_MOUSE
AccessionPrimary (citable) accession number: Q61089
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 119 of the entry and version 1 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

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