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Q61088

- FZD4_MOUSE

UniProt

Q61088 - FZD4_MOUSE

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Protein

Frizzled-4

Gene
Fzd4
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. cytokine binding Source: BHF-UCL
  2. G-protein coupled receptor activity Source: UniProtKB-KW
  3. PDZ domain binding Source: RefGenome
  4. protein binding Source: IntAct
  5. Wnt-activated receptor activity Source: MGI
  6. Wnt-protein binding Source: BHF-UCL

GO - Biological processi

  1. blood vessel development Source: MGI
  2. canonical Wnt signaling pathway Source: BHF-UCL
  3. cerebellum vasculature morphogenesis Source: BHF-UCL
  4. extracellular matrix-cell signaling Source: BHF-UCL
  5. locomotion involved in locomotory behavior Source: MGI
  6. luteinization Source: MGI
  7. negative regulation of cell-substrate adhesion Source: BHF-UCL
  8. positive regulation of JUN kinase activity Source: MGI
  9. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  10. positive regulation of transcription, DNA-templated Source: BHF-UCL
  11. progesterone secretion Source: MGI
  12. regulation of transcription from RNA polymerase II promoter Source: RefGenome
  13. regulation of vascular endothelial growth factor receptor signaling pathway Source: MGI
  14. retinal blood vessel morphogenesis Source: BHF-UCL
  15. retina vasculature morphogenesis in camera-type eye Source: MGI
  16. sensory perception of sound Source: MGI
  17. substrate adhesion-dependent cell spreading Source: MGI
  18. vasculogenesis Source: MGI
  19. Wnt signaling pathway, calcium modulating pathway Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_213035. regulation of FZD by ubiquitination.
REACT_221970. Ca2+ pathway.
REACT_222404. WNT5A-dependent internalization of FZD4.

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
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:108520. Fzd4.

Subcellular locationi

Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini37 – 222186Extracellular Reviewed predictionAdd
BLAST
Transmembranei223 – 24321Helical; Name=1; Reviewed predictionAdd
BLAST
Topological domaini244 – 25411Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei255 – 27521Helical; Name=2; Reviewed predictionAdd
BLAST
Topological domaini276 – 30227Extracellular Reviewed predictionAdd
BLAST
Transmembranei303 – 32321Helical; Name=3; Reviewed predictionAdd
BLAST
Topological domaini324 – 34421Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei345 – 36521Helical; Name=4; Reviewed predictionAdd
BLAST
Topological domaini366 – 38924Extracellular Reviewed predictionAdd
BLAST
Transmembranei390 – 41021Helical; Name=5; Reviewed predictionAdd
BLAST
Topological domaini411 – 43626Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei437 – 45721Helical; Name=6; Reviewed predictionAdd
BLAST
Topological domaini458 – 47720Extracellular Reviewed predictionAdd
BLAST
Transmembranei478 – 49821Helical; Name=7; Reviewed predictionAdd
BLAST
Topological domaini499 – 53739Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. cell-cell junction Source: MGI
  2. cell projection Source: RefGenome
  3. cell surface Source: Ensembl
  4. cytoplasm Source: RefGenome
  5. integral component of membrane Source: UniProtKB-KW
  6. plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Defects in retinal vascularization.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3636 Reviewed predictionAdd
BLAST
Chaini37 – 537501Frizzled-4PRO_0000012986Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi45 ↔ 106 By similarity
Disulfide bondi53 ↔ 99 By similarity
Glycosylationi59 – 591N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi90 ↔ 128 By similarity
Disulfide bondi117 ↔ 158 By similarity
Disulfide bondi121 ↔ 145 By similarity
Glycosylationi144 – 1441N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ61088.
PRIDEiQ61088.

PTM databases

PhosphoSiteiQ61088.

Expressioni

Tissue specificityi

Expressed in chondrocytes.

Gene expression databases

ArrayExpressiQ61088.
BgeeiQ61088.
CleanExiMM_FZD4.
GenevestigatoriQ61088.

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.

Protein-protein interaction databases

BioGridi199777. 3 interactions.
DIPiDIP-41623N.
IntActiQ61088. 7 interactions.
MINTiMINT-1779328.

Structurei

3D structure databases

ProteinModelPortaliQ61088.
SMRiQ61088. Positions 45-161, 193-511.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini40 – 161122FZAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi499 – 5046Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motifi535 – 5373PDZ-binding

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG284049.
GeneTreeiENSGT00750000117488.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ61088.
KOiK02354.
OMAiSMCLSVK.
OrthoDBiEOG7M3J01.
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.
[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

MAWPGTGPSS RGAPGGVGLR LGLLLQFLLL LRPTLGFGDE EERRCDPIRI    50
AMCQNLGYNV TKMPNLVGHE LQTDAELQLT TFTPLIQYGC SSQLQFFLCS 100
VYVPMCTEKI NIPIGPCGGM CLSVKRRCEP VLREFGFAWP DTLNCSKFPP 150
QNDHNHMCME GPGDEEVPLP HKTPIQPGEE CHSVGSNSDQ YIWVKRSLNC 200
VLKCGYDAGL YSRSAKEFTD IWMAVWASLC FISTTFTVLT FLIDSSRFSY 250
PERPIIFLSM CYNIYSIAYI VRLTVGRERI SCDFEEAAEP VLIQEGLKNT 300
GCAIIFLLMY FFGMASSIWW VILTLTWFLA AGLKWGHEAI EMHSSYFHIA 350
AWAIPAVKTI VILIMRLVDA DELTGLCYVG NQNLDALTGF VVAPLFTYLV 400
IGTLFIAAGL VALFKIRSNL QKDGTKTDKL ERLMVKIGVF SVLYTVPATC 450
VIACYFYEIS NWALFRYSAD DSNMAVEMLK IFMSLLVGIT SGMWIWSAKT 500
LHTWQKCSNR LVNSGKVKRE KRGNGWVKPG KGNETVV 537
Length:537
Mass (Da):60,143
Last modified:November 1, 1996 - v1
Checksum:i6641996E6960BCD8
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti27 – 271F → L in AAH15256. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
U43317 mRNA. Translation: AAC52430.1 .
BC015256 mRNA. Translation: AAH15256.1 .
CCDSi CCDS21441.1.
RefSeqi NP_032081.3. NM_008055.4.
UniGenei Mm.86755.

3D structure databases

ProteinModelPortali Q61088.
SMRi Q61088. Positions 45-161, 193-511.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 199777. 3 interactions.
DIPi DIP-41623N.
IntActi Q61088. 7 interactions.
MINTi MINT-1779328.

Chemistry

GuidetoPHARMACOLOGYi 232.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei Q61088.

Proteomic databases

PaxDbi Q61088.
PRIDEi Q61088.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000058755 ; ENSMUSP00000049852 ; ENSMUSG00000049791 .
GeneIDi 14366.
KEGGi mmu:14366.
UCSCi uc009ifx.2. mouse.

Organism-specific databases

CTDi 8322.
MGIi MGI:108520. Fzd4.

Phylogenomic databases

eggNOGi NOG284049.
GeneTreei ENSGT00750000117488.
HOGENOMi HOG000233236.
HOVERGENi HBG006977.
InParanoidi Q61088.
KOi K02354.
OMAi SMCLSVK.
OrthoDBi EOG7M3J01.
PhylomeDBi Q61088.
TreeFami TF317907.

Enzyme and pathway databases

Reactomei REACT_213035. regulation of FZD by ubiquitination.
REACT_221970. Ca2+ pathway.
REACT_222404. WNT5A-dependent internalization of FZD4.

Miscellaneous databases

NextBioi 285835.
PROi Q61088.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q61088.
Bgeei Q61088.
CleanExi MM_FZD4.
Genevestigatori Q61088.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026551. FZD4.
IPR017981. GPCR_2-like.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF23. PTHR11309:SF23. 1 hit.
Pfami PF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view ]
PRINTSi PR00489. FRIZZLED.
SMARTi SM00063. FRI. 1 hit.
[Graphical view ]
SUPFAMi SSF63501. SSF63501. 1 hit.
PROSITEi PS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

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: September 3, 2014
This is version 128 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