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Q9H461

- FZD8_HUMAN

UniProt

Q9H461 - FZD8_HUMAN

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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. ubiquitin protein ligase binding Source: UniProtKB
  4. Wnt-activated receptor activity Source: UniProtKB
  5. 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_172638. Asymmetric localization of PCP proteins.
REACT_18372. Class B/2 (Secretin family receptors).
REACT_200716. regulation of FZD by ubiquitination.
REACT_228188. RNF mutants show enhanced WNT signaling and proliferation.
SignaLinkiQ9H461.

Protein family/group databases

MEROPSiI93.001.

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 By similarity; 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 – 275248ExtracellularSequence AnalysisAdd
BLAST
Transmembranei276 – 29621Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini297 – 31216CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei313 – 33321Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini334 – 39663ExtracellularSequence AnalysisAdd
BLAST
Transmembranei397 – 41721Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini418 – 43922CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei440 – 46021Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini461 – 48323ExtracellularSequence AnalysisAdd
BLAST
Transmembranei484 – 50421Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini505 – 53228CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei533 – 55321Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini554 – 58431ExtracellularSequence AnalysisAdd
BLAST
Transmembranei585 – 60521Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini606 – 69489CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell projection Source: RefGenome
  2. cytoplasm Source: RefGenome
  3. Golgi apparatus Source: UniProtKB-KW
  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 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 694667Frizzled-8PRO_0000013000Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 96PROSITE-ProRule annotation
Disulfide bondi43 ↔ 89PROSITE-ProRule annotation
Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi80 ↔ 118PROSITE-ProRule annotation
Disulfide bondi107 ↔ 148PROSITE-ProRule annotation
Disulfide bondi111 ↔ 135PROSITE-ProRule annotation
Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence Analysis
Glycosylationi475 – 4751N-linked (GlcNAc...)Sequence Analysis

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).By similarity

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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 151122FZPROSITE-ProRule annotationAdd
BLAST

Region

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

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
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

        10         20         30         40         50
MEWGYLLEVT SLLAALALLQ RSSGAAAASA KELACQEITV PLCKGIGYNY
60 70 80 90 100
TYMPNQFNHD TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY
110 120 130 140 150
KKPLPPCRSV CERAKAGCAP LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD
160 170 180 190 200
YNRTDLTTAA PSPPRRLPPP PPGEQPPSGS GHGRPPGARP PHRGGGRGGG
210 220 230 240 250
GGDAAAPPAR GGGGGGKARP PGGGAAPCEP GCQCRAPMVS VSSERHPLYN
260 270 280 290 300
RVKTGQIANC ALPCHNPFFS QDERAFTVFW IGLWSVLCFV STFATVSTFL
310 320 330 340 350
IDMERFKYPE RPIIFLSACY LFVSVGYLVR LVAGHEKVAC SGGAPGAGGA
360 370 380 390 400
GGAGGAAAGA GAAGAGAGGP GGRGEYEELG AVEQHVRYET TGPALCTVVF
410 420 430 440 450
LLVYFFGMAS SIWWVILSLT WFLAAGMKWG NEAIAGYSQY FHLAAWLVPS
460 470 480 490 500
VKSIAVLALS SVDGDPVAGI CYVGNQSLDN LRGFVLAPLV IYLFIGTMFL
510 520 530 540 550
LAGFVSLFRI RSVIKQQDGP TKTHKLEKLM IRLGLFTVLY TVPAAVVVAC
560 570 580 590 600
LFYEQHNRPR WEATHNCPCL RDLQPDQARR PDYAVFMLKY FMCLVVGITS
610 620 630 640 650
GVWVWSGKTL ESWRSLCTRC CWASKGAAVG GGAGATAAGG GGGPGGGGGG
660 670 680 690
GPGGGGGPGG GGGSLYSDVS TGLTWRSGTA SSVSYPKQMP LSQV
Length:694
Mass (Da):73,300
Last modified:March 1, 2001 - v1
Checksum:iE740CBFDA2A233EF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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

MEROPSi I93.001.
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.
GeneTreei ENSGT00760000118864.
HOGENOMi HOG000233236.
HOVERGENi HBG006977.
InParanoidi Q9H461.
KOi K02375.
OMAi HEKVACN.
OrthoDBi EOG7M3J01.
PhylomeDBi Q9H461.
TreeFami TF317907.

Enzyme and pathway databases

Reactomei REACT_172638. Asymmetric localization of PCP proteins.
REACT_18372. Class B/2 (Secretin family receptors).
REACT_200716. regulation of FZD by ubiquitination.
REACT_228188. RNF mutants show enhanced WNT signaling and proliferation.
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: November 26, 2014
This is version 126 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