Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Frizzled-6

Gene

Fzd6

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

Functioni

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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues (By similarity). Together with FZD3, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear.By similarity1 Publication

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: GO_Central
  2. Wnt-activated receptor activity Source: GO_Central
  3. Wnt-protein binding Source: BHF-UCL

GO - Biological processi

  1. canonical Wnt signaling pathway Source: GO_Central
  2. cell proliferation in midbrain Source: MGI
  3. embryonic nail plate morphogenesis Source: MGI
  4. establishment of planar polarity Source: MGI
  5. hair follicle development Source: MGI
  6. inner ear morphogenesis Source: MGI
  7. midbrain development Source: MGI
  8. negative regulation of canonical Wnt signaling pathway Source: Ensembl
  9. negative regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  10. neural tube closure Source: MGI
  11. platelet activation Source: MGI
  12. Wnt signaling pathway, planar cell polarity pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Neurogenesis, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_221970. Ca2+ pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-6
Short name:
Fz-6
Short name:
mFz6
Gene namesi
Name:Fzd6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 15

Organism-specific databases

MGIiMGI:108474. Fzd6.

Subcellular locationi

Membrane 1 Publication; Multi-pass membrane protein Sequence Analysis. Cell membrane 1 Publication; Multi-pass membrane protein Sequence Analysis. Cell surface 1 Publication. Apical cell membrane 1 Publication; Multi-pass membrane protein Sequence Analysis. Cytoplasmic vesicle membrane 1 Publication; Multi-pass membrane protein Sequence Analysis
Note: Colocalizes with FZD3 at the apical face of cells (PubMed:16495441).1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 201183ExtracellularSequence AnalysisAdd
BLAST
Transmembranei202 – 22221Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini223 – 23311CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei234 – 25421Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini255 – 28430ExtracellularSequence AnalysisAdd
BLAST
Transmembranei285 – 30521Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini306 – 32419CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei325 – 34521Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini346 – 37025ExtracellularSequence AnalysisAdd
BLAST
Transmembranei371 – 39121Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini392 – 41625CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei417 – 43721Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini438 – 47336ExtracellularSequence AnalysisAdd
BLAST
Transmembranei474 – 49421Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini495 – 709215CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. apical part of cell Source: MGI
  2. apicolateral plasma membrane Source: MGI
  3. integral component of membrane Source: GO_Central
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Disruption phenotypei

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 (PubMed:21665003). FZD3 and FZD6 double knockout embryos have a curled tail, exhibit defects in neural tube and eyelids closure, in the orientation of hair bundles on inner-ear sensory cells and die at birth (PubMed:16495441).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 709691Frizzled-6PRO_0000012995Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi24 ↔ 85PROSITE-ProRule annotation
Disulfide bondi32 ↔ 78PROSITE-ProRule annotation
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi69 ↔ 106PROSITE-ProRule annotation
Disulfide bondi95 ↔ 129PROSITE-ProRule annotation
Disulfide bondi99 ↔ 123PROSITE-ProRule annotation
Glycosylationi256 – 2561N-linked (GlcNAc...)Sequence Analysis
Glycosylationi352 – 3521N-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

PRIDEiQ61089.

PTM databases

PhosphoSiteiQ61089.

Expressioni

Tissue specificityi

Expressed in both hair cells and supporting cells in the utricle, saccule, cristae and the organ of Corti in the inner ear (at protein level).1 Publication

Gene expression databases

BgeeiQ61089.
CleanExiMM_FZD6.
ExpressionAtlasiQ61089. baseline and differential.
GenevestigatoriQ61089.

Interactioni

Protein-protein interaction databases

IntActiQ61089. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ61089.
SMRiQ61089. Positions 22-127.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 132114FZPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi498 – 5036Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity

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.By similarity

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG262811.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233237.
HOVERGENiHBG006977.
InParanoidiQ61089.
KOiK02376.
OMAiKKTCSEW.
OrthoDBiEOG7M3J01.
PhylomeDBiQ61089.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026543. FZD6.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF75. PTHR11309:SF75. 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.

Q61089-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MERSPFLLAC ILLPLVRGHS LFTCEPITVP RCMKMTYNMT FFPNLMGHYD
60 70 80 90 100
QGIAAVEMGH FLHLANLECS PNIEMFLCQA FIPTCTEQIH VVLPCRKLCE
110 120 130 140 150
KIVSDCKKLM DTFGIRWPEE LECNRLPHCD DTVPVTSHPH TELSGPQKKS
160 170 180 190 200
DQVPRDIGFW CPKHLRTSGD QGYRFLGIEQ CAPPCPNMYF KSDELDFAKS
210 220 230 240 250
FIGIVSIFCL CATLFTFLTF LIDVRRFRYP ERPIIYYSVC YSIVSLMYFV
260 270 280 290 300
GFLLGNSTAC NKADEKLELG DTVVLGSKNK ACSVVFMFLY FFTMAGTVWW
310 320 330 340 350
VILTITWFLA AGRKWSCEAI EQKAVWFHAV AWGAPGFLTV MLLAMNKVEG
360 370 380 390 400
DNISGVCFVG LYDLDASRYF VLLPLCLCVF VGLSLLLAGI ISLNHVRQVI
410 420 430 440 450
QHDGRNQEKL KKFMIRIGVF SGLYLVPLVT LLGCYVYELV NRITWEMTWF
460 470 480 490 500
SDHCHQYRIP CPYQANPKAR PELALFMIKY LMTLIVGISA VFWVGSKKTC
510 520 530 540 550
TEWAGFFKRN RKRDPISESR RVLQESCEFF LKHNSKVKHK KKHGAPGPHR
560 570 580 590 600
LKVISKSMGT STGATTNHGT SAMAIADHDY LGQETSTEVH TSPEASVKEG
610 620 630 640 650
RADRANTPSA KDRDCGESAG PSSKLSGNRN GRESRAGGLK ERSNGSEGAP
660 670 680 690 700
SEGRVSPKSS VPETGLIDCS TSQAASSPEP TSLKGSTSLP VHSASRARKE

QGAGSHSDA
Length:709
Mass (Da):79,082
Last modified:November 1, 1996 - v1
Checksum:i01374A9EC9122484
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43319 mRNA. Translation: AAC52431.1.
CCDSiCCDS27441.1.
RefSeqiNP_001155966.1. NM_001162494.1.
NP_032082.3. NM_008056.3.
UniGeneiMm.4769.

Genome annotation databases

EnsembliENSMUST00000022906; ENSMUSP00000022906; ENSMUSG00000022297.
ENSMUST00000179165; ENSMUSP00000136328; ENSMUSG00000022297.
GeneIDi14368.
KEGGimmu:14368.
UCSCiuc007vny.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43319 mRNA. Translation: AAC52431.1.
CCDSiCCDS27441.1.
RefSeqiNP_001155966.1. NM_001162494.1.
NP_032082.3. NM_008056.3.
UniGeneiMm.4769.

3D structure databases

ProteinModelPortaliQ61089.
SMRiQ61089. Positions 22-127.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ61089. 1 interaction.

Chemistry

GuidetoPHARMACOLOGYi234.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ61089.

Proteomic databases

PRIDEiQ61089.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022906; ENSMUSP00000022906; ENSMUSG00000022297.
ENSMUST00000179165; ENSMUSP00000136328; ENSMUSG00000022297.
GeneIDi14368.
KEGGimmu:14368.
UCSCiuc007vny.2. mouse.

Organism-specific databases

CTDi8323.
MGIiMGI:108474. Fzd6.

Phylogenomic databases

eggNOGiNOG262811.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233237.
HOVERGENiHBG006977.
InParanoidiQ61089.
KOiK02376.
OMAiKKTCSEW.
OrthoDBiEOG7M3J01.
PhylomeDBiQ61089.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiREACT_221970. Ca2+ pathway.

Miscellaneous databases

ChiTaRSiFzd6. mouse.
NextBioi285845.
PROiQ61089.
SOURCEiSearch...

Gene expression databases

BgeeiQ61089.
CleanExiMM_FZD6.
ExpressionAtlasiQ61089. baseline and differential.
GenevestigatoriQ61089.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026543. FZD6.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF75. PTHR11309:SF75. 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]
ProtoNetiSearch...

Publicationsi

  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. Cited for: DISRUPTION PHENOTYPE.
  5. "The role of Frizzled3 and Frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells."
    Wang Y., Guo N., Nathans J.
    J. Neurosci. 26:2147-2156(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiFZD6_MOUSE
AccessioniPrimary (citable) accession number: Q61089
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: February 4, 2015
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.