SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q9H461

- FZD8_HUMAN

UniProt

Q9H461 - FZD8_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Frizzled-8

Gene
FZD8
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 WNT1.1 Publication

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: UniProtKB-KW
  2. PDZ domain binding Source: BHF-UCL
  3. protein binding Source: IntAct
  4. ubiquitin protein ligase binding Source: UniProtKB
  5. Wnt-activated receptor activity Source: UniProtKB
  6. Wnt-protein binding Source: RefGenome

GO - Biological processi

  1. axonogenesis Source: RefGenome
  2. brain development Source: RefGenome
  3. canonical Wnt signaling pathway Source: RefGenome
  4. gonad development Source: RefGenome
  5. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  6. neuron differentiation Source: UniProtKB
  7. positive regulation of JUN kinase activity Source: Ensembl
  8. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  9. T cell differentiation in thymus Source: RefGenome
  10. vasculature development Source: RefGenome
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_18372. Class B/2 (Secretin family receptors).
REACT_200716. regulation of FZD by ubiquitination.
SignaLinkiQ9H461.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-8
Short name:
Fz-8
Short name:
hFz8
Gene namesi
Name:FZD8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:4046. FZD8.

Subcellular locationi

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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 275248Extracellular Reviewed predictionAdd
BLAST
Transmembranei276 – 29621Helical; Name=1; Reviewed predictionAdd
BLAST
Topological domaini297 – 31216Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei313 – 33321Helical; Name=2; Reviewed predictionAdd
BLAST
Topological domaini334 – 39663Extracellular Reviewed predictionAdd
BLAST
Transmembranei397 – 41721Helical; Name=3; Reviewed predictionAdd
BLAST
Topological domaini418 – 43922Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei440 – 46021Helical; Name=4; Reviewed predictionAdd
BLAST
Topological domaini461 – 48323Extracellular Reviewed predictionAdd
BLAST
Transmembranei484 – 50421Helical; Name=5; Reviewed predictionAdd
BLAST
Topological domaini505 – 53228Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei533 – 55321Helical; Name=6; Reviewed predictionAdd
BLAST
Topological domaini554 – 58431Extracellular Reviewed predictionAdd
BLAST
Transmembranei585 – 60521Helical; Name=7; Reviewed predictionAdd
BLAST
Topological domaini606 – 69489Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. cell projection Source: RefGenome
  2. cytoplasm Source: RefGenome
  3. Golgi apparatus Source: UniProtKB-SubCell
  4. integral component of membrane Source: UniProtKB
  5. plasma membrane Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28463.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727 Reviewed predictionAdd
BLAST
Chaini28 – 694667Frizzled-8PRO_0000013000Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 96 By similarity
Disulfide bondi43 ↔ 89 By similarity
Glycosylationi49 – 491N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi80 ↔ 118 By similarity
Disulfide bondi107 ↔ 148 By similarity
Disulfide bondi111 ↔ 135 By similarity
Glycosylationi152 – 1521N-linked (GlcNAc...) Reviewed prediction
Glycosylationi475 – 4751N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9H461.
PRIDEiQ9H461.

PTM databases

PhosphoSiteiQ9H461.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ9H461.
CleanExiHS_FZD8.
GenevestigatoriQ9H461.

Organism-specific databases

HPAiHPA045025.

Interactioni

Subunit structurei

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.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
C1qaP980863EBI-6254212,EBI-299840From a different organism.
WNT3AP567042EBI-6254212,EBI-6173037

Protein-protein interaction databases

BioGridi113921. 4 interactions.
IntActiQ9H461. 3 interactions.
STRINGi9606.ENSP00000363826.

Structurei

3D structure databases

ProteinModelPortaliQ9H461.
SMRiQ9H461. Positions 35-150, 233-619.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 151122FZAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni71 – 788Palmitate-binding groove By similarity
Regioni95 – 1006Wnt-binding By similarity
Regioni147 – 1526Wnt-binding By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi608 – 6136Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motifi692 – 6943PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi168 – 1725Poly-Pro
Compositional biasi194 – 2029Poly-Gly
Compositional biasi211 – 2166Poly-Gly
Compositional biasi639 – 66325Poly-GlyAdd
BLAST

Domaini

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.

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ9H461.
KOiK02375.
OMAiHEKVACN.
OrthoDBiEOG7M3J01.
PhylomeDBiQ9H461.
TreeFamiTF317907.

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.

Q9H461-1 [UniParc]FASTAAdd to Basket

« Hide

MEWGYLLEVT SLLAALALLQ RSSGAAAASA KELACQEITV PLCKGIGYNY    50
TYMPNQFNHD TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY 100
KKPLPPCRSV CERAKAGCAP LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD 150
YNRTDLTTAA PSPPRRLPPP PPGEQPPSGS GHGRPPGARP PHRGGGRGGG 200
GGDAAAPPAR GGGGGGKARP PGGGAAPCEP GCQCRAPMVS VSSERHPLYN 250
RVKTGQIANC ALPCHNPFFS QDERAFTVFW IGLWSVLCFV STFATVSTFL 300
IDMERFKYPE RPIIFLSACY LFVSVGYLVR LVAGHEKVAC SGGAPGAGGA 350
GGAGGAAAGA GAAGAGAGGP GGRGEYEELG AVEQHVRYET TGPALCTVVF 400
LLVYFFGMAS SIWWVILSLT WFLAAGMKWG NEAIAGYSQY FHLAAWLVPS 450
VKSIAVLALS SVDGDPVAGI CYVGNQSLDN LRGFVLAPLV IYLFIGTMFL 500
LAGFVSLFRI RSVIKQQDGP TKTHKLEKLM IRLGLFTVLY TVPAAVVVAC 550
LFYEQHNRPR WEATHNCPCL RDLQPDQARR PDYAVFMLKY FMCLVVGITS 600
GVWVWSGKTL ESWRSLCTRC CWASKGAAVG GGAGATAAGG GGGPGGGGGG 650
GPGGGGGPGG GGGSLYSDVS TGLTWRSGTA SSVSYPKQMP LSQV 694
Length:694
Mass (Da):73,300
Last modified:March 1, 2001 - v1
Checksum:iE740CBFDA2A233EF
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB043703 mRNA. Translation: BAB41064.1.
AL121749 Genomic DNA. Translation: CAC10185.1.
CCDSiCCDS7192.1.
RefSeqiNP_114072.1. NM_031866.2.
UniGeneiHs.302634.

Genome annotation databases

EnsembliENST00000374694; ENSP00000363826; ENSG00000177283.
GeneIDi8325.
KEGGihsa:8325.
UCSCiuc001iyz.1. human.

Polymorphism databases

DMDMi17433053.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB043703 mRNA. Translation: BAB41064.1 .
AL121749 Genomic DNA. Translation: CAC10185.1 .
CCDSi CCDS7192.1.
RefSeqi NP_114072.1. NM_031866.2.
UniGenei Hs.302634.

3D structure databases

ProteinModelPortali Q9H461.
SMRi Q9H461. Positions 35-150, 233-619.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113921. 4 interactions.
IntActi Q9H461. 3 interactions.
STRINGi 9606.ENSP00000363826.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei Q9H461.

Polymorphism databases

DMDMi 17433053.

Proteomic databases

PaxDbi Q9H461.
PRIDEi Q9H461.

Protocols and materials databases

DNASUi 8325.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000374694 ; ENSP00000363826 ; ENSG00000177283 .
GeneIDi 8325.
KEGGi hsa:8325.
UCSCi uc001iyz.1. human.

Organism-specific databases

CTDi 8325.
GeneCardsi GC10M035927.
HGNCi HGNC:4046. FZD8.
HPAi HPA045025.
MIMi 606146. gene.
neXtProti NX_Q9H461.
PharmGKBi PA28463.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG257258.
HOGENOMi HOG000233236.
HOVERGENi HBG006977.
InParanoidi Q9H461.
KOi K02375.
OMAi HEKVACN.
OrthoDBi EOG7M3J01.
PhylomeDBi Q9H461.
TreeFami TF317907.

Enzyme and pathway databases

Reactomei REACT_18372. Class B/2 (Secretin family receptors).
REACT_200716. regulation of FZD by ubiquitination.
SignaLinki Q9H461.

Miscellaneous databases

GeneWikii FZD8.
GenomeRNAii 8325.
NextBioi 31175.
PROi Q9H461.
SOURCEi Search...

Gene expression databases

Bgeei Q9H461.
CleanExi HS_FZD8.
Genevestigatori Q9H461.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 1 hit.
Pfami PF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view ]
PRINTSi PR00489. FRIZZLED.
SMARTi SM00063. FRI. 1 hit.
[Graphical view ]
SUPFAMi SSF63501. SSF63501. 1 hit.
PROSITEi PS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: UBIQUITINATION BY ZNRF3.

Entry informationi

Entry nameiFZD8_HUMAN
AccessioniPrimary (citable) accession number: Q9H461
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 1, 2001
Last modified: September 3, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi