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Q9H461 (FZD8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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-8

Short name=Fz-8
Short name=hFz8
Gene names
Name:FZD8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length694 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. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. The beta-catenin canonical signaling pathway 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. Coreceptor along with RYK of Wnt proteins, such as WNT1. Ref.3

Subunit structure

Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly with LRP5 or LRP6; the interaction is promoted by Wnt-binding and signaling and inhibited by DKK1. Interacts with GPOC, RSPO1 and RSPO3 By similarity. Ref.3 Ref.4

Subcellular location

Membrane; Multi-pass membrane protein. Golgi apparatus By similarity. Cell membrane; Multi-pass membrane protein By similarity. Note: Colocalizes with GOPC at the Golgi apparatus By similarity.

Tissue specificity

Most abundant in fetal kidney, followed by brain and lung. In adult tissues, expressed in kidney, heart, pancreas and skeletal muscle.

Domain

The PDZ-binding motif mediates interaction with GOPC By similarity.

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. Ref.5

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
Golgi apparatus
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_processT cell differentiation in thymus

Inferred from Biological aspect of Ancestor. Source: RefGenome

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

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of JUN kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell projection

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Traceable author statement Ref.1. Source: UniProtKB

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from physical interaction PubMed 18256285. Source: BHF-UCL

Wnt-activated receptor activity

Traceable author statement Ref.1. Source: UniProtKB

Wnt-protein binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction PubMed 22682250. Source: IntAct

ubiquitin protein ligase binding

Inferred from physical interaction Ref.5. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

C1qaP980863EBI-6254212,EBI-299840From a different organism.
WNT3AP567042EBI-6254212,EBI-6173037

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 694667Frizzled-8
PRO_0000013000

Regions

Topological domain28 – 275248Extracellular Potential
Transmembrane276 – 29621Helical; Name=1; Potential
Topological domain297 – 31216Cytoplasmic Potential
Transmembrane313 – 33321Helical; Name=2; Potential
Topological domain334 – 39663Extracellular Potential
Transmembrane397 – 41721Helical; Name=3; Potential
Topological domain418 – 43922Cytoplasmic Potential
Transmembrane440 – 46021Helical; Name=4; Potential
Topological domain461 – 48323Extracellular Potential
Transmembrane484 – 50421Helical; Name=5; Potential
Topological domain505 – 53228Cytoplasmic Potential
Transmembrane533 – 55321Helical; Name=6; Potential
Topological domain554 – 58431Extracellular Potential
Transmembrane585 – 60521Helical; Name=7; Potential
Topological domain606 – 69489Cytoplasmic Potential
Domain30 – 151122FZ
Region71 – 788Palmitate-binding groove By similarity
Region95 – 1006Wnt-binding By similarity
Region147 – 1526Wnt-binding By similarity
Motif608 – 6136Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif692 – 6943PDZ-binding
Compositional bias168 – 1725Poly-Pro
Compositional bias194 – 2029Poly-Gly
Compositional bias211 – 2166Poly-Gly
Compositional bias639 – 66325Poly-Gly

Amino acid modifications

Glycosylation491N-linked (GlcNAc...) Potential
Glycosylation1521N-linked (GlcNAc...) Potential
Glycosylation4751N-linked (GlcNAc...) Potential
Disulfide bond35 ↔ 96 By similarity
Disulfide bond43 ↔ 89 By similarity
Disulfide bond80 ↔ 118 By similarity
Disulfide bond107 ↔ 148 By similarity
Disulfide bond111 ↔ 135 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9H461 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: E740CBFDA2A233EF

FASTA69473,300
        10         20         30         40         50         60 
MEWGYLLEVT SLLAALALLQ RSSGAAAASA KELACQEITV PLCKGIGYNY TYMPNQFNHD 

        70         80         90        100        110        120 
TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY KKPLPPCRSV CERAKAGCAP 

       130        140        150        160        170        180 
LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD YNRTDLTTAA PSPPRRLPPP PPGEQPPSGS 

       190        200        210        220        230        240 
GHGRPPGARP PHRGGGRGGG GGDAAAPPAR GGGGGGKARP PGGGAAPCEP GCQCRAPMVS 

       250        260        270        280        290        300 
VSSERHPLYN RVKTGQIANC ALPCHNPFFS QDERAFTVFW IGLWSVLCFV STFATVSTFL 

       310        320        330        340        350        360 
IDMERFKYPE RPIIFLSACY LFVSVGYLVR LVAGHEKVAC SGGAPGAGGA GGAGGAAAGA 

       370        380        390        400        410        420 
GAAGAGAGGP GGRGEYEELG AVEQHVRYET TGPALCTVVF LLVYFFGMAS SIWWVILSLT 

       430        440        450        460        470        480 
WFLAAGMKWG NEAIAGYSQY FHLAAWLVPS VKSIAVLALS SVDGDPVAGI CYVGNQSLDN 

       490        500        510        520        530        540 
LRGFVLAPLV IYLFIGTMFL LAGFVSLFRI RSVIKQQDGP TKTHKLEKLM IRLGLFTVLY 

       550        560        570        580        590        600 
TVPAAVVVAC LFYEQHNRPR WEATHNCPCL RDLQPDQARR PDYAVFMLKY FMCLVVGITS 

       610        620        630        640        650        660 
GVWVWSGKTL ESWRSLCTRC CWASKGAAVG GGAGATAAGG GGGPGGGGGG GPGGGGGPGG 

       670        680        690 
GGGSLYSDVS TGLTWRSGTA SSVSYPKQMP LSQV 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2."
Saitoh T., Hirai M., Katoh M.
Int. J. Oncol. 18:991-996(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6."
Semenov M.V., Tamai K., Brott B.K., Kuhl M., Sokol S., He X.
Curr. Biol. 11:951-961(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRP5 AND LRP6 IN THE WNT-FZD-LRP5-LRP6 COMPLEX, FUNCTION.
[4]"Solution structure of GOPC PDZ domain and its interaction with the C-terminal motif of neuroligin."
Li X., Zhang J., Cao Z., Wu J., Shi Y.
Protein Sci. 15:2149-2158(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GOPC.
[5]"ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner."
Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H., Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T., Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F.
Nature 485:195-200(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY ZNRF3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB043703 mRNA. Translation: BAB41064.1.
AL121749 Genomic DNA. Translation: CAC10185.1.
CCDSCCDS7192.1.
RefSeqNP_114072.1. NM_031866.2.
UniGeneHs.302634.

3D structure databases

ProteinModelPortalQ9H461.
SMRQ9H461. Positions 35-150, 233-619.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113921. 4 interactions.
IntActQ9H461. 3 interactions.
STRING9606.ENSP00000363826.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ9H461.

Polymorphism databases

DMDM17433053.

Proteomic databases

PaxDbQ9H461.
PRIDEQ9H461.

Protocols and materials databases

DNASU8325.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000374694; ENSP00000363826; ENSG00000177283.
GeneID8325.
KEGGhsa:8325.
UCSCuc001iyz.1. human.

Organism-specific databases

CTD8325.
GeneCardsGC10M035927.
HGNCHGNC:4046. FZD8.
HPAHPA045025.
MIM606146. gene.
neXtProtNX_Q9H461.
PharmGKBPA28463.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG257258.
HOGENOMHOG000233236.
HOVERGENHBG006977.
InParanoidQ9H461.
KOK02375.
OMAHEKVACN.
OrthoDBEOG7M3J01.
PhylomeDBQ9H461.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ9H461.

Gene expression databases

BgeeQ9H461.
CleanExHS_FZD8.
GenevestigatorQ9H461.

Family and domain databases

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

GeneWikiFZD8.
GenomeRNAi8325.
NextBio31175.
PROQ9H461.
SOURCESearch...

Entry information

Entry nameFZD8_HUMAN
AccessionPrimary (citable) accession number: Q9H461
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries