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Protein

Frizzled-8

Gene

fzd8

Organism
Xenopus laevis (African clawed frog)
Status
Reviewed-Annotation score: Annotation score: 4 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 Wnt8, Wnt5A or Wnt3A induces expression of beta-catenin target genes. Displays an axis-inducing activity.1 Publication

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: UniProtKB-KW

GO - Biological processi

  1. canonical Wnt signaling pathway Source: BHF-UCL
  2. multicellular organismal development Source: UniProtKB-KW
  3. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
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-8
Short name:
Fz-8
Short name:
Xfz8
Gene namesi
Name:fzd8
Synonyms:fz8
OrganismiXenopus laevis (African clawed frog)
Taxonomic identifieri8355 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

Organism-specific databases

XenbaseiXB-GENE-865411. fzd8.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 239216ExtracellularSequence AnalysisAdd
BLAST
Transmembranei240 – 26021Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini261 – 27111CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei272 – 29221Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini293 – 32028ExtracellularSequence AnalysisAdd
BLAST
Transmembranei321 – 34121Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini342 – 37736CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei378 – 39821Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini399 – 4079ExtracellularSequence Analysis
Transmembranei408 – 42821Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini429 – 45426CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei455 – 47521Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini476 – 50530ExtracellularSequence AnalysisAdd
BLAST
Transmembranei506 – 52621Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini527 – 58155CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. 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 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 581558Frizzled-8PRO_0000013002Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi28 ↔ 89PROSITE-ProRule annotation
Disulfide bondi36 ↔ 82PROSITE-ProRule annotation
Glycosylationi42 – 421N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi73 ↔ 111PROSITE-ProRule annotation
Disulfide bondi100 ↔ 141PROSITE-ProRule annotation
Disulfide bondi104 ↔ 128PROSITE-ProRule annotation
Glycosylationi146 – 1461N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Expressioni

Developmental stagei

First expressed at high levels in the late blastula stages. At early gastrula, expressed in the deep cells of the Spemann organizer prior to involution of the dorsal blastopore lip. Detected in presumptive neurectoderm as gastrulation proceeds. Becomes restricted to the anterior ectoderm by the end of gastrulation. At neurula stages, localized in the most anterior region of the embryo, mainly in the anterior ectoderm including telencephalic and cement gland regions.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
FRIEDQ6EHH92EBI-7735236,EBI-7735259

Protein-protein interaction databases

IntActiO93274. 1 interaction.
MINTiMINT-1893946.

Structurei

3D structure databases

ProteinModelPortaliO93274.
SMRiO93274. Positions 25-144.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 144121FZPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni64 – 718Palmitate-binding grooveBy similarity
Regioni88 – 936Wnt-bindingBy similarity
Regioni140 – 1467Wnt-bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi529 – 5346Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
Motifi579 – 5813PDZ-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

HOVERGENiHBG006977.
KOiK02375.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 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.

O93274-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MESLSLSLLL LVSWLQGSQC AAAKELSCQE ITVPLCKDIG YNYTYMPNQF
60 70 80 90 100
NHDTQDEAGM EVHQFWPLVV IHCSPDLKFF LCSMYTPICL EDYKKPLPPC
110 120 130 140 150
RSVCERARAG CAPLMRQYGF AWPDRMRCDR LPEQGNPDTL CMDYYNRTEQ
160 170 180 190 200
TTAAPSHPEP PKPPARSVPK GRTRVEPPRS RSRATGCESG CQCRAPMVQV
210 220 230 240 250
SNERHPLYNR VRTGQIPNCA MPCHNPFFSP EERTFTEFWI GLWSVLCFAS
260 270 280 290 300
TFATVSTFLI DMERFKYPER PIIFLSACYL LVSTGYLIRL IAGHEKVACS
310 320 330 340 350
RGELDLEHII HYETTGPALC TLVFLLIYFF GMASSIWWVI LSLTWFLAAG
360 370 380 390 400
MKWGNEAIAG YSQYFHLAAW LVPSIKSIAV LALSSVDGDP VAGICFVGNQ
410 420 430 440 450
NLDNLRGFVL APLVIYLFIG SMFLLAGFVS LFRIRSVIKQ GGTKTDKLEK
460 470 480 490 500
LMIRIGIFSV LYTVPATIVV ACFFYEQHNR QGWEVAHNCN SCQPEMAQPH
510 520 530 540 550
RPDYAVFMLK YFMCLVVGIT SGVWIWSGKT LESWRAFCTR CCWGSKATGG
560 570 580
SMYSDVSTGL TWRSGTGSSV SCPKQMPLSQ V
Length:581
Mass (Da):65,379
Last modified:November 1, 1998 - v1
Checksum:i80890C408AB21E23
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 33MES → MECPY(PubMed:9636083)Curated
Sequence conflicti7 – 71S → L in AAC77361. (PubMed:9636083)Curated
Sequence conflicti10 – 101L → V in AAC77361. (PubMed:9636083)Curated
Sequence conflicti14 – 141W → G in AAC77361. (PubMed:9636083)Curated
Sequence conflicti20 – 201C → S in AAC77361. (PubMed:9636083)Curated
Sequence conflicti135 – 1351G → S in AAC77361. (PubMed:9636083)Curated
Sequence conflicti171 – 1711G → S in AAC77361. (PubMed:9636083)Curated
Sequence conflicti175 – 1751V → A in AAC77361. (PubMed:9636083)Curated
Sequence conflicti185 – 1851T → P in AAC77361. (PubMed:9636083)Curated
Sequence conflicti216 – 2161I → T in AAC77361. (PubMed:9636083)Curated
Sequence conflicti237 – 2371E → D in AAC77361. (PubMed:9636083)Curated
Sequence conflicti494 – 4963PEM → SEG in AAC77361. (PubMed:9636083)Curated
Sequence conflicti500 – 5001H → R in AAC77361. (PubMed:9636083)Curated
Sequence conflicti547 – 5471A → T in AAC77361. (PubMed:9636083)Curated
Sequence conflicti565 – 5651G → A in AAC77361. (PubMed:9636083)Curated
Sequence conflicti572 – 5721C → Y in AAC77361. (PubMed:9636083)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017177 mRNA. Translation: AAC31121.1.
AF033110 mRNA. Translation: AAC77361.1.
RefSeqiNP_001079144.1. NM_001085675.1.
NP_001084206.1. NM_001090737.1.
UniGeneiXl.293.
Xl.412.

Genome annotation databases

GeneIDi373690.
399367.
KEGGixla:373690.
xla:399367.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017177 mRNA. Translation: AAC31121.1.
AF033110 mRNA. Translation: AAC77361.1.
RefSeqiNP_001079144.1. NM_001085675.1.
NP_001084206.1. NM_001090737.1.
UniGeneiXl.293.
Xl.412.

3D structure databases

ProteinModelPortaliO93274.
SMRiO93274. Positions 25-144.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO93274. 1 interaction.
MINTiMINT-1893946.

Protein family/group databases

GPCRDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi373690.
399367.
KEGGixla:373690.
xla:399367.

Organism-specific databases

CTDi373690.
399367.
XenbaseiXB-GENE-865411. fzd8.

Phylogenomic databases

HOVERGENiHBG006977.
KOiK02375.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 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. "A role for Xenopus Frizzled 8 in dorsal development."
    Itoh K., Jacob J., Sokol S.Y.
    Mech. Dev. 74:145-157(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], COUPLING TO BETA-CATENIN PATHWAY.
    Tissue: Embryo.
  2. "Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis."
    Deardorff M.A., Tan C., Conrad L.J., Klein P.S.
    Development 125:2687-2700(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Embryo.
  3. "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.

Entry informationi

Entry nameiFZD8_XENLA
AccessioniPrimary (citable) accession number: O93274
Secondary accession number(s): Q9YI55
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: November 1, 1998
Last modified: January 7, 2015
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.