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Protein

Frizzled-4

Gene

Fzd4

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 (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. 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.2 Publications

GO - Molecular functioni

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

GO - Biological processi

  • blood vessel development Source: MGI
  • canonical Wnt signaling pathway Source: BHF-UCL
  • cerebellum vasculature morphogenesis Source: BHF-UCL
  • extracellular matrix-cell signaling Source: BHF-UCL
  • locomotion involved in locomotory behavior Source: MGI
  • luteinization Source: MGI
  • negative regulation of cell-substrate adhesion Source: BHF-UCL
  • non-canonical Wnt signaling pathway Source: GO_Central
  • positive regulation of JUN kinase activity Source: MGI
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • progesterone secretion Source: MGI
  • regulation of vascular endothelial growth factor receptor signaling pathway Source: MGI
  • retinal blood vessel morphogenesis Source: BHF-UCL
  • retina vasculature morphogenesis in camera-type eye Source: MGI
  • sensory perception of sound Source: MGI
  • substrate adhesion-dependent cell spreading Source: MGI
  • vasculogenesis Source: MGI
  • Wnt signaling pathway Source: MGI
  • Wnt signaling pathway, calcium modulating pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-4086398. Ca2+ pathway.
R-MMU-4641263. Regulation of FZD by ubiquitination.
R-MMU-5099900. WNT5A-dependent internalization of FZD4.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-MMU-8856828. Clathrin-mediated endocytosis.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-4
Short name:
Fz-4
Short name:
mFz4
Alternative name(s):
CD_antigen: CD344
Gene namesi
Name:Fzd4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:108520. Fzd4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini37 – 222ExtracellularSequence analysisAdd BLAST186
Transmembranei223 – 243Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini244 – 254CytoplasmicSequence analysisAdd BLAST11
Transmembranei255 – 275Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini276 – 302ExtracellularSequence analysisAdd BLAST27
Transmembranei303 – 323Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini324 – 344CytoplasmicSequence analysisAdd BLAST21
Transmembranei345 – 365Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini366 – 389ExtracellularSequence analysisAdd BLAST24
Transmembranei390 – 410Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini411 – 436CytoplasmicSequence analysisAdd BLAST26
Transmembranei437 – 457Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini458 – 477ExtracellularSequence analysisAdd BLAST20
Transmembranei478 – 498Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini499 – 537CytoplasmicSequence analysisAdd BLAST39

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • cell surface Source: MGI
  • extracellular exosome Source: MGI
  • integral component of membrane Source: GO_Central
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Defects in retinal vascularization.1 Publication

Chemistry databases

GuidetoPHARMACOLOGYi232.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 36Sequence analysisAdd BLAST36
ChainiPRO_000001298637 – 537Frizzled-4Add BLAST501

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi45 ↔ 106PROSITE-ProRule annotation
Disulfide bondi53 ↔ 99PROSITE-ProRule annotation
Glycosylationi59N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi90 ↔ 128PROSITE-ProRule annotation
Disulfide bondi117 ↔ 158PROSITE-ProRule annotation
Disulfide bondi121 ↔ 145PROSITE-ProRule annotation
Glycosylationi144N-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

MaxQBiQ61088.
PaxDbiQ61088.
PRIDEiQ61088.

PTM databases

PhosphoSitePlusiQ61088.

Expressioni

Tissue specificityi

Expressed in chondrocytes.

Gene expression databases

BgeeiENSMUSG00000049791.
CleanExiMM_FZD4.
ExpressionAtlasiQ61088. baseline and differential.
GenevisibleiQ61088. MM.

Interactioni

Subunit structurei

Interacts with MAGI3 and NDP. Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
UBCP0CG483EBI-7987880,EBI-3390054From a different organism.

GO - Molecular functioni

  • cytokine binding Source: BHF-UCL
  • PDZ domain binding Source: MGI
  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: MGI
  • ubiquitin protein ligase binding Source: MGI
  • Wnt-protein binding Source: AgBase

Protein-protein interaction databases

BioGridi199777. 3 interactors.
DIPiDIP-41623N.
IntActiQ61088. 7 interactors.
MINTiMINT-1779328.
STRINGi10090.ENSMUSP00000049852.

Structurei

3D structure databases

ProteinModelPortaliQ61088.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 161FZPROSITE-ProRule annotationAdd BLAST122

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi499 – 504Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi535 – 537PDZ-binding3

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

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ61088.
KOiK02354.
OMAiSMCLSVK.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ61088.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026551. FZD4.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF23. PTHR11309:SF23. 1 hit.
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.

Q61088-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAWPGTGPSS RGAPGGVGLR LGLLLQFLLL LRPTLGFGDE EERRCDPIRI
60 70 80 90 100
AMCQNLGYNV TKMPNLVGHE LQTDAELQLT TFTPLIQYGC SSQLQFFLCS
110 120 130 140 150
VYVPMCTEKI NIPIGPCGGM CLSVKRRCEP VLREFGFAWP DTLNCSKFPP
160 170 180 190 200
QNDHNHMCME GPGDEEVPLP HKTPIQPGEE CHSVGSNSDQ YIWVKRSLNC
210 220 230 240 250
VLKCGYDAGL YSRSAKEFTD IWMAVWASLC FISTTFTVLT FLIDSSRFSY
260 270 280 290 300
PERPIIFLSM CYNIYSIAYI VRLTVGRERI SCDFEEAAEP VLIQEGLKNT
310 320 330 340 350
GCAIIFLLMY FFGMASSIWW VILTLTWFLA AGLKWGHEAI EMHSSYFHIA
360 370 380 390 400
AWAIPAVKTI VILIMRLVDA DELTGLCYVG NQNLDALTGF VVAPLFTYLV
410 420 430 440 450
IGTLFIAAGL VALFKIRSNL QKDGTKTDKL ERLMVKIGVF SVLYTVPATC
460 470 480 490 500
VIACYFYEIS NWALFRYSAD DSNMAVEMLK IFMSLLVGIT SGMWIWSAKT
510 520 530
LHTWQKCSNR LVNSGKVKRE KRGNGWVKPG KGNETVV
Length:537
Mass (Da):60,143
Last modified:November 1, 1996 - v1
Checksum:i6641996E6960BCD8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti27F → L in AAH15256 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43317 mRNA. Translation: AAC52430.1.
BC015256 mRNA. Translation: AAH15256.1.
CCDSiCCDS21441.1.
RefSeqiNP_032081.3. NM_008055.4.
UniGeneiMm.86755.

Genome annotation databases

EnsembliENSMUST00000058755; ENSMUSP00000049852; ENSMUSG00000049791.
GeneIDi14366.
KEGGimmu:14366.
UCSCiuc009ifx.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43317 mRNA. Translation: AAC52430.1.
BC015256 mRNA. Translation: AAH15256.1.
CCDSiCCDS21441.1.
RefSeqiNP_032081.3. NM_008055.4.
UniGeneiMm.86755.

3D structure databases

ProteinModelPortaliQ61088.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199777. 3 interactors.
DIPiDIP-41623N.
IntActiQ61088. 7 interactors.
MINTiMINT-1779328.
STRINGi10090.ENSMUSP00000049852.

Chemistry databases

GuidetoPHARMACOLOGYi232.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiQ61088.

Proteomic databases

MaxQBiQ61088.
PaxDbiQ61088.
PRIDEiQ61088.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000058755; ENSMUSP00000049852; ENSMUSG00000049791.
GeneIDi14366.
KEGGimmu:14366.
UCSCiuc009ifx.2. mouse.

Organism-specific databases

CTDi8322.
MGIiMGI:108520. Fzd4.

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ61088.
KOiK02354.
OMAiSMCLSVK.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ61088.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiR-MMU-4086398. Ca2+ pathway.
R-MMU-4641263. Regulation of FZD by ubiquitination.
R-MMU-5099900. WNT5A-dependent internalization of FZD4.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-MMU-8856828. Clathrin-mediated endocytosis.

Miscellaneous databases

PROiQ61088.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000049791.
CleanExiMM_FZD4.
ExpressionAtlasiQ61088. baseline and differential.
GenevisibleiQ61088. MM.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026551. FZD4.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF23. PTHR11309:SF23. 1 hit.
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 nameiFZD4_MOUSE
AccessioniPrimary (citable) accession number: Q61088
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 146 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

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.