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Q61088 (FZD4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. 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·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-4

Short name=Fz-4
Short name=mFz4
Alternative name(s):
CD_antigen=CD344
Gene names
Name:Fzd4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length537 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.7

Subunit structure

Interacts with MAGI3 and NDP. Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP). Ref.5 Ref.6 Ref.7

Subcellular location

Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein Ref.4.

Tissue specificity

Expressed in chondrocytes.

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

Defects in retinal vascularization. Ref.5

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_processWnt signaling pathway, calcium modulating pathway

Inferred from electronic annotation. Source: Ensembl

blood vessel development

Inferred from mutant phenotype PubMed 19837032. Source: MGI

canonical Wnt signaling pathway

Inferred from direct assay Ref.5. Source: BHF-UCL

cerebellum vasculature morphogenesis

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

extracellular matrix-cell signaling

Inferred from direct assay Ref.5. Source: BHF-UCL

locomotion involved in locomotory behavior

Inferred from mutant phenotype PubMed 11425903. Source: MGI

luteinization

Inferred from mutant phenotype PubMed 16093361. Source: MGI

negative regulation of cell-substrate adhesion

Inferred from mutant phenotype PubMed 18156211. Source: BHF-UCL

positive regulation of JUN kinase activity

Inferred from genetic interaction Ref.6. Source: MGI

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.5. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: BHF-UCL

progesterone secretion

Inferred from mutant phenotype PubMed 16093361. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 16093361. Source: MGI

retina vasculature morphogenesis in camera-type eye

Inferred from mutant phenotype PubMed 19837032. Source: MGI

retinal blood vessel morphogenesis

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

sensory perception of sound

Inferred from mutant phenotype PubMed 11425903. Source: MGI

substrate adhesion-dependent cell spreading

Inferred from mutant phenotype PubMed 18156211. Source: MGI

vasculogenesis

Inferred from mutant phenotype PubMed 16093361. Source: MGI

   Cellular_componentcell projection

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell surface

Inferred from electronic annotation. Source: Ensembl

cell-cell junction

Inferred from direct assay Ref.6. Source: MGI

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay Ref.5. Source: BHF-UCL

   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 physical interaction PubMed 16163358. Source: MGI

Wnt-protein binding

Inferred from physical interaction PubMed 12490564. Source: BHF-UCL

cytokine binding

Inferred from physical interaction Ref.5. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 20495530. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

UBCP0CG483EBI-7987880,EBI-3390054From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3636 Potential
Chain37 – 537501Frizzled-4
PRO_0000012986

Regions

Topological domain37 – 222186Extracellular Potential
Transmembrane223 – 24321Helical; Name=1; Potential
Topological domain244 – 25411Cytoplasmic Potential
Transmembrane255 – 27521Helical; Name=2; Potential
Topological domain276 – 30227Extracellular Potential
Transmembrane303 – 32321Helical; Name=3; Potential
Topological domain324 – 34421Cytoplasmic Potential
Transmembrane345 – 36521Helical; Name=4; Potential
Topological domain366 – 38924Extracellular Potential
Transmembrane390 – 41021Helical; Name=5; Potential
Topological domain411 – 43626Cytoplasmic Potential
Transmembrane437 – 45721Helical; Name=6; Potential
Topological domain458 – 47720Extracellular Potential
Transmembrane478 – 49821Helical; Name=7; Potential
Topological domain499 – 53739Cytoplasmic Potential
Domain40 – 161122FZ
Motif499 – 5046Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif535 – 5373PDZ-binding

Amino acid modifications

Glycosylation591N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Disulfide bond45 ↔ 106 By similarity
Disulfide bond53 ↔ 99 By similarity
Disulfide bond90 ↔ 128 By similarity
Disulfide bond117 ↔ 158 By similarity
Disulfide bond121 ↔ 145 By similarity

Experimental info

Sequence conflict271F → L in AAH15256. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q61088 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6641996E6960BCD8

FASTA53760,143
        10         20         30         40         50         60 
MAWPGTGPSS RGAPGGVGLR LGLLLQFLLL LRPTLGFGDE EERRCDPIRI AMCQNLGYNV 

        70         80         90        100        110        120 
TKMPNLVGHE LQTDAELQLT TFTPLIQYGC SSQLQFFLCS VYVPMCTEKI NIPIGPCGGM 

       130        140        150        160        170        180 
CLSVKRRCEP VLREFGFAWP DTLNCSKFPP QNDHNHMCME GPGDEEVPLP HKTPIQPGEE 

       190        200        210        220        230        240 
CHSVGSNSDQ YIWVKRSLNC VLKCGYDAGL YSRSAKEFTD IWMAVWASLC FISTTFTVLT 

       250        260        270        280        290        300 
FLIDSSRFSY PERPIIFLSM CYNIYSIAYI VRLTVGRERI SCDFEEAAEP VLIQEGLKNT 

       310        320        330        340        350        360 
GCAIIFLLMY FFGMASSIWW VILTLTWFLA AGLKWGHEAI EMHSSYFHIA AWAIPAVKTI 

       370        380        390        400        410        420 
VILIMRLVDA DELTGLCYVG NQNLDALTGF VVAPLFTYLV IGTLFIAAGL VALFKIRSNL 

       430        440        450        460        470        480 
QKDGTKTDKL ERLMVKIGVF SVLYTVPATC VIACYFYEIS NWALFRYSAD DSNMAVEMLK 

       490        500        510        520        530 
IFMSLLVGIT SGMWIWSAKT LHTWQKCSNR LVNSGKVKRE KRGNGWVKPG KGNETVV 

« Hide

References

« Hide 'large scale' 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]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[3]"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.
[4]"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: FUNCTION, SUBCELLULAR LOCATION.
[5]"Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair."
Xu Q., Wang Y., Dabdoub A., Smallwood P.M., Williams J., Woods C., Kelley M.W., Jiang L., Tasman W., Zhang K., Nathans J.
Cell 116:883-895(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NDP, DISRUPTION PHENOTYPE.
[6]"MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap."
Yao R., Natsume Y., Noda T.
Oncogene 23:6023-6030(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAGI3.
[7]"TSPAN12 regulates retinal vascular development by promoting Norrin-but not Wnt-induced FZD4/beta-catenin signaling."
Junge H.J., Yang S., Burton J.B., Paes K., Shu X., French D.M., Costa M., Rice D.S., Ye W.
Cell 139:299-311(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH NDP AND TSPAN12.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U43317 mRNA. Translation: AAC52430.1.
BC015256 mRNA. Translation: AAH15256.1.
CCDSCCDS21441.1.
RefSeqNP_032081.3. NM_008055.4.
UniGeneMm.86755.

3D structure databases

ProteinModelPortalQ61088.
SMRQ61088. Positions 45-161, 193-511.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199777. 3 interactions.
DIPDIP-41623N.
IntActQ61088. 7 interactions.
MINTMINT-1779328.

Chemistry

GuidetoPHARMACOLOGY232.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ61088.

Proteomic databases

PaxDbQ61088.
PRIDEQ61088.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000058755; ENSMUSP00000049852; ENSMUSG00000049791.
GeneID14366.
KEGGmmu:14366.
UCSCuc009ifx.2. mouse.

Organism-specific databases

CTD8322.
MGIMGI:108520. Fzd4.

Phylogenomic databases

eggNOGNOG284049.
GeneTreeENSGT00750000117488.
HOGENOMHOG000233236.
HOVERGENHBG006977.
InParanoidQ61088.
KOK02354.
OMASMCLSVK.
OrthoDBEOG7M3J01.
PhylomeDBQ61088.
TreeFamTF317907.

Gene expression databases

ArrayExpressQ61088.
BgeeQ61088.
CleanExMM_FZD4.
GenevestigatorQ61088.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026551. FZD4.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF23. PTHR11309:SF23. 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

NextBio285835.
PROQ61088.
SOURCESearch...

Entry information

Entry nameFZD4_MOUSE
AccessionPrimary (citable) accession number: Q61088
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 127 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