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-4

Gene

Fzd4

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 (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

  • amyloid-beta binding Source: MGI
  • cytokine binding Source: BHF-UCL
  • G-protein coupled receptor activity Source: GO_Central
  • PDZ domain binding Source: MGI
  • protein-containing complex binding Source: Ensembl
  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: MGI
  • signaling receptor activity Source: ARUK-UCL
  • 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
  • cellular response to leukemia inhibitory factor Source: MGI
  • 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 DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of JUN kinase activity Source: MGI
  • positive regulation of neuron projection arborization Source: ARUK-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: ARUK-UCL
  • Wnt signaling pathway, calcium modulating pathway Source: MGI

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-4086398 Ca2+ pathway
R-MMU-4608870 Asymmetric localization of PCP proteins
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:108520 Fzd4

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 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

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...) asparagineSequence analysis1
Disulfide bondi90 ↔ 128PROSITE-ProRule annotation
Disulfide bondi117 ↔ 158PROSITE-ProRule annotation
Disulfide bondi121 ↔ 145PROSITE-ProRule annotation
Glycosylationi144N-linked (GlcNAc...) asparagineSequence 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 (PubMed:15035989, PubMed:15195140). Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP) (PubMed:19837033). Interacts (via FZ domain) with TSKU (PubMed:21856951).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
UBCP0CG483EBI-7987880,EBI-3390054From Homo sapiens.

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
CORUMiQ61088
DIPiDIP-41623N
IntActiQ61088, 8 interactors
MINTiQ61088
STRINGi10090.ENSMUSP00000049852

Structurei

3D structure databases

ProteinModelPortaliQ61088
SMRiQ61088
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

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
InterProiView protein in InterPro
IPR015526 Frizzled/SFRP
IPR000539 Frizzled/Smoothened_TM
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR026551 FZD4
IPR017981 GPCR_2-like
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF23 PTHR11309:SF23, 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.

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

Similar proteinsi

Entry informationi

Entry nameiFZD4_MOUSE
AccessioniPrimary (citable) accession number: Q61088
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: July 18, 2018
This is version 159 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

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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health