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Protein

Frizzled-6

Gene

Fzd6

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

GO - Biological processi

  • canonical Wnt signaling pathway Source: GO_Central
  • cell proliferation in midbrain Source: MGI
  • embryonic nail plate morphogenesis Source: MGI
  • establishment of body hair planar orientation Source: MGI
  • establishment of planar polarity Source: MGI
  • hair follicle development Source: MGI
  • inner ear morphogenesis Source: MGI
  • midbrain development Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of DNA binding transcription factor activity Source: MGI
  • neural tube closure Source: MGI
  • non-canonical Wnt signaling pathway Source: MGI
  • platelet activation Source: MGI
  • Wnt signaling pathway, planar cell polarity pathway Source: MGI

Keywordsi

Molecular functionDevelopmental protein, G-protein coupled receptor, Receptor, Transducer
Biological processNeurogenesis, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-4086398 Ca2+ pathway
R-MMU-4086400 PCP/CE pathway
R-MMU-4641263 Regulation of FZD by ubiquitination

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:108474 Fzd6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 201ExtracellularSequence analysisAdd BLAST183
Transmembranei202 – 222Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini223 – 233CytoplasmicSequence analysisAdd BLAST11
Transmembranei234 – 254Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini255 – 284ExtracellularSequence analysisAdd BLAST30
Transmembranei285 – 305Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini306 – 324CytoplasmicSequence analysisAdd BLAST19
Transmembranei325 – 345Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini346 – 370ExtracellularSequence analysisAdd BLAST25
Transmembranei371 – 391Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini392 – 416CytoplasmicSequence analysisAdd BLAST25
Transmembranei417 – 437Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini438 – 473ExtracellularSequence analysisAdd BLAST36
Transmembranei474 – 494Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini495 – 709CytoplasmicSequence analysisAdd BLAST215

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001299519 – 709Frizzled-6Add BLAST691

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi24 ↔ 85PROSITE-ProRule annotation
Disulfide bondi32 ↔ 78PROSITE-ProRule annotation
Glycosylationi38N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi69 ↔ 106PROSITE-ProRule annotation
Disulfide bondi95 ↔ 129PROSITE-ProRule annotation
Disulfide bondi99 ↔ 123PROSITE-ProRule annotation
Glycosylationi256N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi352N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei656PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ61089
PaxDbiQ61089
PRIDEiQ61089

PTM databases

iPTMnetiQ61089
PhosphoSitePlusiQ61089

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

BgeeiENSMUSG00000022297
CleanExiMM_FZD6
ExpressionAtlasiQ61089 baseline and differential
GenevisibleiQ61089 MM

Interactioni

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: MGI
  • Wnt-protein binding Source: BHF-UCL

Protein-protein interaction databases

IntActiQ61089 1 interactor.
STRINGi10090.ENSMUSP00000022906

Structurei

3D structure databases

ProteinModelPortaliQ61089
SMRiQ61089
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 132FZPROSITE-ProRule annotationAdd BLAST114

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi498 – 503Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6

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.By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOGENOMiHOG000233237
HOVERGENiHBG006977
InParanoidiQ61089
KOiK02376
OMAiCPNMYFK
OrthoDBiEOG091G0N5M
PhylomeDBiQ61089
TreeFamiTF317907

Family and domain databases

Gene3Di1.10.2000.101 hit
InterProiView protein in InterPro
IPR015526 Frizzled/SFRP
IPR000539 Frizzled/Smoothened_TM
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR026543 FZD6
IPR017981 GPCR_2-like
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF75 PTHR11309:SF75, 1 hit
PfamiView protein in Pfam
PF01534 Frizzled, 1 hit
PF01392 Fz, 1 hit
PRINTSiPR00489 FRIZZLED
SMARTiView protein in SMART
SM00063 FRI, 1 hit
SM01330 Frizzled, 1 hit
SUPFAMiSSF63501 SSF63501, 1 hit
PROSITEiView protein in PROSITE
PS50038 FZ, 1 hit
PS50261 G_PROTEIN_RECEP_F2_4, 1 hit

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
XP_017171919.1, XM_017316430.1
UniGeneiMm.4769

Genome annotation databases

EnsembliENSMUST00000022906; ENSMUSP00000022906; ENSMUSG00000022297
ENSMUST00000179165; ENSMUSP00000136328; ENSMUSG00000022297
ENSMUST00000202117; ENSMUSP00000144310; ENSMUSG00000107137
ENSMUST00000202152; ENSMUSP00000144351; ENSMUSG00000107137
GeneIDi14368
KEGGimmu:14368
UCSCiuc007vny.2 mouse

Similar proteinsi

Entry informationi

Entry nameiFZD6_MOUSE
AccessioniPrimary (citable) accession number: Q61089
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: February 28, 2018
This is version 152 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome