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Protein

Frizzled-4

Gene

Fzd4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: GO_Central
  2. Wnt-activated receptor activity Source: GO_Central
  3. Wnt-protein binding Source: RGD

GO - Biological processi

  1. canonical Wnt signaling pathway Source: GO_Central
  2. cerebellum vasculature morphogenesis Source: Ensembl
  3. extracellular matrix-cell signaling Source: Ensembl
  4. locomotion involved in locomotory behavior Source: Ensembl
  5. negative regulation of cell-substrate adhesion Source: Ensembl
  6. non-canonical Wnt signaling pathway Source: GO_Central
  7. positive regulation of JUN kinase activity Source: Ensembl
  8. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  9. positive regulation of transcription, DNA-templated Source: Ensembl
  10. progesterone secretion Source: Ensembl
  11. regulation of vascular endothelial growth factor receptor signaling pathway Source: Ensembl
  12. retinal blood vessel morphogenesis Source: Ensembl
  13. sensory perception of sound Source: Ensembl
  14. substrate adhesion-dependent cell spreading Source: Ensembl
  15. vasculogenesis Source: Ensembl
  16. 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_275454. Ca2+ pathway.
REACT_276957. RNF mutants show enhanced WNT signaling and proliferation.
REACT_318736. regulation of FZD by ubiquitination.
REACT_323768. Class B/2 (Secretin family receptors).
REACT_332836. WNT5A-dependent internalization of FZD4.

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-4
Short name:
Fz-4
Short name:
rFz4
Alternative name(s):
CD_antigen: CD344
Gene namesi
Name:Fzd4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi71017. Fzd4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini38 – 223186ExtracellularSequence AnalysisAdd
BLAST
Transmembranei224 – 24421Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini245 – 25511CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei256 – 27621Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini277 – 30327ExtracellularSequence AnalysisAdd
BLAST
Transmembranei304 – 32421Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini325 – 34521CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei346 – 36621Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini367 – 39024ExtracellularSequence AnalysisAdd
BLAST
Transmembranei391 – 41121Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini412 – 43726CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei438 – 45821Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini459 – 47820ExtracellularSequence AnalysisAdd
BLAST
Transmembranei479 – 49921Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini500 – 53839CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell-cell junction Source: Ensembl
  2. cell surface Source: Ensembl
  3. extracellular vesicular exosome Source: Ensembl
  4. integral component of membrane Source: GO_Central
  5. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3737Sequence AnalysisAdd
BLAST
Chaini38 – 538501Frizzled-4PRO_0000012987Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi46 ↔ 107PROSITE-ProRule annotation
Disulfide bondi54 ↔ 100PROSITE-ProRule annotation
Glycosylationi60 – 601N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi91 ↔ 129PROSITE-ProRule annotation
Disulfide bondi118 ↔ 159PROSITE-ProRule annotation
Disulfide bondi122 ↔ 146PROSITE-ProRule annotation
Glycosylationi145 – 1451N-linked (GlcNAc...)Sequence Analysis
Glycosylationi382 – 3821N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9QZH0.
PRIDEiQ9QZH0.

PTM databases

PhosphoSiteiQ9QZH0.

Expressioni

Gene expression databases

GenevestigatoriQ9QZH0.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000023205.

Structurei

3D structure databases

ProteinModelPortaliQ9QZH0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini41 – 162122FZPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi500 – 5056Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
Motifi536 – 5383PDZ-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

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG284049.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ9QZH0.
KOiK02354.
OMAiSMCLSVK.
OrthoDBiEOG7M3J01.
PhylomeDBiQ9QZH0.
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.

Q9QZH0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAWQGTGPSV RGMPGGVRLR LGLLLLQLLL LQRPALGFGD EEERRCDPIR
60 70 80 90 100
IAMCQNLGYN VTKMPNLVGH ELQTDAELQL TTFTPLIQYG CSSQLQFFLC
110 120 130 140 150
SVYVPMCTEK INIPIGPCGG MCLSVKRRCE PVLKEFGFAW PDSLNCSKFP
160 170 180 190 200
PQNDHNHMCM EGPGDEEVPL PHKTPIQPGE ECHSVGTNSD QYIWVKRSLN
210 220 230 240 250
CVLKCGYDAG LYSRSAKEFT DIWMAVWASL CFISTTFTVL TFLIDSSRFS
260 270 280 290 300
YPERPIIFLS MCYNIYSIAY IVRLTVGRER ISCDFEEAAE PVLIQEGLKN
310 320 330 340 350
TGCAIIFLLM YFFGMASSIW WVILTLTWFL AAGLKWGHEA IEMHSSYFHI
360 370 380 390 400
AAWAIPAVKT IVILIMRLVD ADELTGLCYV GNQSLDALTG FVVAPLFTYL
410 420 430 440 450
VIGTLFIAAG LVALFKIRSN LQKDGTKTDK LERLMVKIGV FSVLYTVPAT
460 470 480 490 500
CVIACYFYEI SNWALFRYSA DDSNMAVEML KIFMSLLVGI TSGMWIWSAK
510 520 530
TLHTWQKCSN RLVNSGKVKR EKRGNGWVKP GKGNETVV
Length:538
Mass (Da):60,355
Last modified:May 1, 2000 - v1
Checksum:i07DAAE606B46E005
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF183910 mRNA. Translation: AAF01036.1.
RefSeqiNP_072145.1. NM_022623.2.
UniGeneiRn.18388.
Rn.48736.

Genome annotation databases

EnsembliENSRNOT00000023205; ENSRNOP00000023205; ENSRNOG00000016848.
GeneIDi64558.
KEGGirno:64558.
UCSCiRGD:71017. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF183910 mRNA. Translation: AAF01036.1.
RefSeqiNP_072145.1. NM_022623.2.
UniGeneiRn.18388.
Rn.48736.

3D structure databases

ProteinModelPortaliQ9QZH0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000023205.

Protein family/group databases

MEROPSiI93.001.
GPCRDBiSearch...

PTM databases

PhosphoSiteiQ9QZH0.

Proteomic databases

PaxDbiQ9QZH0.
PRIDEiQ9QZH0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000023205; ENSRNOP00000023205; ENSRNOG00000016848.
GeneIDi64558.
KEGGirno:64558.
UCSCiRGD:71017. rat.

Organism-specific databases

CTDi8322.
RGDi71017. Fzd4.

Phylogenomic databases

eggNOGiNOG284049.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ9QZH0.
KOiK02354.
OMAiSMCLSVK.
OrthoDBiEOG7M3J01.
PhylomeDBiQ9QZH0.
TreeFamiTF317907.

Enzyme and pathway databases

ReactomeiREACT_275454. Ca2+ pathway.
REACT_276957. RNF mutants show enhanced WNT signaling and proliferation.
REACT_318736. regulation of FZD by ubiquitination.
REACT_323768. Class B/2 (Secretin family receptors).
REACT_332836. WNT5A-dependent internalization of FZD4.

Miscellaneous databases

NextBioi613472.
PROiQ9QZH0.

Gene expression databases

GenevestigatoriQ9QZH0.

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]
ProtoNetiSearch...

Publicationsi

  1. "Expression of a putative seven-pass transmembrane frizzled receptor in the Corpus Luteum (CL) of the rat during pregnancy and involution."
    Walther P.R., Lacher M.D., Saurer S., Friis R.R.
    Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Corpus luteum.

Entry informationi

Entry nameiFZD4_RAT
AccessioniPrimary (citable) accession number: Q9QZH0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: May 1, 2000
Last modified: April 1, 2015
This is version 111 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.