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Q08464 (FZD2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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-2

Short name=Fz-2
Short name=rFz2
Gene names
Name:Fzd2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length570 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 canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. 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.

Subcellular location

Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Widely expressed. Most abundant in kidney, liver, uterus, ovary and heart. Lower levels seen in brain and intestine. Extremely low in calvaria, mammary glands and testis.

Developmental stage

Expressed predominantly in neonatal tissues, at lower levels in adult.

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.

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_processG-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger

Inferred from direct assay PubMed 12471263. Source: RGD

Wnt signaling pathway, calcium modulating pathway

Inferred from direct assay PubMed 12471263. Source: RGD

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell activation

Inferred from expression pattern PubMed 16780995. Source: RGD

cellular response to growth factor stimulus

Inferred from expression pattern Ref.1. Source: RGD

cellular response to peptide hormone stimulus

Inferred from expression pattern Ref.1. Source: RGD

cellular response to vitamin D

Inferred from expression pattern Ref.1. Source: RGD

embryo development

Inferred from Biological aspect of Ancestor. Source: RefGenome

epithelial cell differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of cytosolic calcium ion concentration

Inferred from direct assay PubMed 12471263. Source: RGD

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentapical part of cell

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Traceable author statement PubMed 12471263. Source: RGD

neuron projection membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from direct assay PubMed 14688793. 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 direct assay PubMed 12471263. Source: RGD

Wnt-protein binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

identical protein binding

Inferred from physical interaction PubMed 14688793. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 14688793. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself3EBI-7402050,EBI-7402050
Fzd1Q084636EBI-7402050,EBI-8766455

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 570542Frizzled-2
PRO_0000012980

Regions

Topological domain29 – 252224Extracellular Potential
Transmembrane253 – 27321Helical; Name=1; Potential
Topological domain274 – 28411Cytoplasmic Potential
Transmembrane285 – 30521Helical; Name=2; Potential
Topological domain306 – 33227Extracellular Potential
Transmembrane333 – 35321Helical; Name=3; Potential
Topological domain354 – 37522Cytoplasmic Potential
Transmembrane376 – 39621Helical; Name=4; Potential
Topological domain397 – 41923Extracellular Potential
Transmembrane420 – 44021Helical; Name=5; Potential
Topological domain441 – 46626Cytoplasmic Potential
Transmembrane467 – 48721Helical; Name=6; Potential
Topological domain488 – 52437Extracellular Potential
Transmembrane525 – 54521Helical; Name=7; Potential
Topological domain546 – 57025Cytoplasmic Potential
Domain39 – 158120FZ
Motif548 – 5536Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif568 – 5703PDZ-binding
Compositional bias186 – 1927Poly-Gly

Amino acid modifications

Glycosylation581N-linked (GlcNAc...) Potential
Glycosylation1591N-linked (GlcNAc...) Potential
Disulfide bond44 ↔ 105 By similarity
Disulfide bond52 ↔ 98 By similarity
Disulfide bond89 ↔ 126 By similarity
Disulfide bond115 ↔ 155 By similarity
Disulfide bond119 ↔ 143 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q08464 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 4FB895D9BEAFCA4E

FASTA57063,885
        10         20         30         40         50         60 
MRARSALPRS ALPRLLLPLL LLPAAGPAQF HGEKGISIPD HGFCQPISIP LCTDIAYNQT 

        70         80         90        100        110        120 
IMPNLLGHTN QEDAGLEVHQ FYPLVKVQCS PELRFFLCSM YAPVCTVLEQ AIPPCRSICE 

       130        140        150        160        170        180 
RARQGCEALM NKFGFQWPER LRCEHFPRHG AEQICVGQNH SEDGTPALLT TAPPSGLQPG 

       190        200        210        220        230        240 
AGGTPGGPGG GGAPPRYATL EHPFHCPRVL KVPSYLSYKF LGERDCAAPC EPARPDGSMF 

       250        260        270        280        290        300 
FSHHHTRFAR LWILTWSVLC CASTFFTVTT SLVAMQRFRY PERPIIFLSG CYTMVSVAYI 

       310        320        330        340        350        360 
AGFVLQERVV CNERFSEDGY RTVGQGTKKE GCTILFMMLY FFSMASSIWW VILSLTWFLA 

       370        380        390        400        410        420 
AGMKWGHAAI EANSQYFHLA AWAVPAVKTI TILAMGQIDG DLLSGVCFVG LNRLDPLRGF 

       430        440        450        460        470        480 
VLAPLFVYLF IGTSFLLAGF VSLFRIRTIM KHDGTKTEPL ERLMVRIGVF SVLYTVPATI 

       490        500        510        520        530        540 
VIACYFYEQA FREHWERSWV SQHCKSLAIP CPAHYTPRTS PDFTVYMIKY LMTLIVGITS 

       550        560        570 
GFWIWSGKTL HSWRKFYTRL TNSRHGETTV 

« Hide

References

[1]"Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues."
Chan S.D.H., Karpf D.B., Fowlkes M.E., Hooks M., Bradley M.S., Vuong V., Bambino T., Liu M.Y.C., Arnaud C.D., Strewler G.J., Nissenson R.A.
J. Biol. Chem. 267:25202-25207(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Osteosarcoma.
[2]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L02530 mRNA. Translation: AAA41172.1.
RefSeqNP_742032.1. NM_172035.1.
UniGeneRn.92324.

3D structure databases

ProteinModelPortalQ08464.
SMRQ08464. Positions 42-159.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249097. 1 interaction.
IntActQ08464. 3 interactions.
MINTMINT-1780823.
STRING10116.ENSRNOP00000036154.

Chemistry

GuidetoPHARMACOLOGY230.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ08464.

Proteomic databases

PaxDbQ08464.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID64512.
KEGGrno:64512.
UCSCRGD:71012. rat.

Organism-specific databases

CTD2535.
RGD71012. Fzd2.

Phylogenomic databases

eggNOGNOG257258.
HOGENOMHOG000233237.
HOVERGENHBG006977.
InParanoidQ08464.
KOK02235.
PhylomeDBQ08464.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.

Gene expression databases

GenevestigatorQ08464.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026550. FZD2.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF34. PTHR11309:SF34. 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

NextBio613298.
PROQ08464.

Entry information

Entry nameFZD2_RAT
AccessionPrimary (citable) accession number: Q08464
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 115 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

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries