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Protein

Frizzled-2

Gene

Fzd2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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 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.

GO - Molecular functioni

  • G-protein coupled receptor activity Source: GO_Central
  • protein heterodimerization activity Source: BHF-UCL
  • Wnt-activated receptor activity Source: RGD
  • Wnt-protein binding Source: GO_Central

GO - Biological processi

  • canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • cell activation Source: RGD
  • cellular response to growth factor stimulus Source: RGD
  • cellular response to peptide hormone stimulus Source: RGD
  • cellular response to vitamin D Source: RGD
  • G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RGD
  • multicellular organism development Source: UniProtKB-KW
  • positive regulation of cytosolic calcium ion concentration Source: RGD
  • Wnt signaling pathway, calcium modulating pathway Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Wnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-2
Short name:
Fz-2
Short name:
rFz2
Gene namesi
Name:Fzd2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi71012. Fzd2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 252ExtracellularSequence analysisAdd BLAST224
Transmembranei253 – 273Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini274 – 284CytoplasmicSequence analysisAdd BLAST11
Transmembranei285 – 305Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini306 – 332ExtracellularSequence analysisAdd BLAST27
Transmembranei333 – 353Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini354 – 375CytoplasmicSequence analysisAdd BLAST22
Transmembranei376 – 396Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini397 – 419ExtracellularSequence analysisAdd BLAST23
Transmembranei420 – 440Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini441 – 466CytoplasmicSequence analysisAdd BLAST26
Transmembranei467 – 487Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini488 – 524ExtracellularSequence analysisAdd BLAST37
Transmembranei525 – 545Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini546 – 570CytoplasmicSequence analysisAdd BLAST25

GO - Cellular componenti

  • integral component of membrane Source: RGD
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000001298029 – 570Frizzled-2Add BLAST542

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi44 ↔ 105PROSITE-ProRule annotation
Disulfide bondi52 ↔ 98PROSITE-ProRule annotation
Glycosylationi58N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi89 ↔ 126PROSITE-ProRule annotation
Disulfide bondi115 ↔ 155PROSITE-ProRule annotation
Disulfide bondi119 ↔ 143PROSITE-ProRule annotation
Glycosylationi159N-linked (GlcNAc...)Sequence 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

PaxDbiQ08464.

PTM databases

PhosphoSitePlusiQ08464.

Expressioni

Tissue specificityi

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 stagei

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

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-7402050,EBI-7402050
Fzd1Q084636EBI-7402050,EBI-8766455

GO - Molecular functioni

  • protein heterodimerization activity Source: BHF-UCL
  • Wnt-protein binding Source: GO_Central

Protein-protein interaction databases

BioGridi249097. 1 interactor.
IntActiQ08464. 3 interactors.
MINTiMINT-1780823.
STRINGi10116.ENSRNOP00000036154.

Structurei

3D structure databases

ProteinModelPortaliQ08464.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 158FZPROSITE-ProRule annotationAdd BLAST120

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi548 – 553Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi568 – 570PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi186 – 192Poly-Gly7

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

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
HOGENOMiHOG000233237.
HOVERGENiHBG006977.
InParanoidiQ08464.
KOiK02235.
PhylomeDBiQ08464.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026550. FZD2.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF34. PTHR11309:SF34. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
SM01330. Frizzled. 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.

Q08464-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRARSALPRS ALPRLLLPLL LLPAAGPAQF HGEKGISIPD HGFCQPISIP
60 70 80 90 100
LCTDIAYNQT IMPNLLGHTN QEDAGLEVHQ FYPLVKVQCS PELRFFLCSM
110 120 130 140 150
YAPVCTVLEQ AIPPCRSICE RARQGCEALM NKFGFQWPER LRCEHFPRHG
160 170 180 190 200
AEQICVGQNH SEDGTPALLT TAPPSGLQPG AGGTPGGPGG GGAPPRYATL
210 220 230 240 250
EHPFHCPRVL KVPSYLSYKF LGERDCAAPC EPARPDGSMF FSHHHTRFAR
260 270 280 290 300
LWILTWSVLC CASTFFTVTT SLVAMQRFRY PERPIIFLSG CYTMVSVAYI
310 320 330 340 350
AGFVLQERVV CNERFSEDGY RTVGQGTKKE GCTILFMMLY FFSMASSIWW
360 370 380 390 400
VILSLTWFLA AGMKWGHAAI EANSQYFHLA AWAVPAVKTI TILAMGQIDG
410 420 430 440 450
DLLSGVCFVG LNRLDPLRGF VLAPLFVYLF IGTSFLLAGF VSLFRIRTIM
460 470 480 490 500
KHDGTKTEPL ERLMVRIGVF SVLYTVPATI VIACYFYEQA FREHWERSWV
510 520 530 540 550
SQHCKSLAIP CPAHYTPRTS PDFTVYMIKY LMTLIVGITS GFWIWSGKTL
560 570
HSWRKFYTRL TNSRHGETTV
Length:570
Mass (Da):63,885
Last modified:November 1, 1996 - v1
Checksum:i4FB895D9BEAFCA4E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L02530 mRNA. Translation: AAA41172.1.
RefSeqiNP_742032.1. NM_172035.1.
UniGeneiRn.92324.

Genome annotation databases

GeneIDi64512.
KEGGirno:64512.
UCSCiRGD:71012. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L02530 mRNA. Translation: AAA41172.1.
RefSeqiNP_742032.1. NM_172035.1.
UniGeneiRn.92324.

3D structure databases

ProteinModelPortaliQ08464.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249097. 1 interactor.
IntActiQ08464. 3 interactors.
MINTiMINT-1780823.
STRINGi10116.ENSRNOP00000036154.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiQ08464.

Proteomic databases

PaxDbiQ08464.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi64512.
KEGGirno:64512.
UCSCiRGD:71012. rat.

Organism-specific databases

CTDi2535.
RGDi71012. Fzd2.

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
HOGENOMiHOG000233237.
HOVERGENiHBG006977.
InParanoidiQ08464.
KOiK02235.
PhylomeDBiQ08464.

Miscellaneous databases

PROiQ08464.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026550. FZD2.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF34. PTHR11309:SF34. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
SM01330. Frizzled. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFZD2_RAT
AccessioniPrimary (citable) accession number: Q08464
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 133 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

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 one 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.