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Protein

Frizzled-8

Gene

FZD8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • G-protein coupled receptor activity Source: GO_Central
  • PDZ domain binding Source: BHF-UCL
  • receptor binding Source: Ensembl
  • ubiquitin protein ligase binding Source: UniProtKB
  • Wnt-activated receptor activity Source: WormBase
  • Wnt-protein binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, G-protein coupled receptor, Receptor, Transducer
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-4608870. Asymmetric localization of PCP proteins.
R-HSA-4641263. Regulation of FZD by ubiquitination.
R-HSA-5340588. RNF mutants show enhanced WNT signaling and proliferation.
SignaLinkiQ9H461.
SIGNORiQ9H461.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000177283.5.
HGNCiHGNC:4046. FZD8.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 275ExtracellularSequence analysisAdd BLAST248
Transmembranei276 – 296Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini297 – 312CytoplasmicSequence analysisAdd BLAST16
Transmembranei313 – 333Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini334 – 396ExtracellularSequence analysisAdd BLAST63
Transmembranei397 – 417Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini418 – 439CytoplasmicSequence analysisAdd BLAST22
Transmembranei440 – 460Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini461 – 483ExtracellularSequence analysisAdd BLAST23
Transmembranei484 – 504Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini505 – 532CytoplasmicSequence analysisAdd BLAST28
Transmembranei533 – 553Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini554 – 584ExtracellularSequence analysisAdd BLAST31
Transmembranei585 – 605Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini606 – 694CytoplasmicSequence analysisAdd BLAST89

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8325.
OpenTargetsiENSG00000177283.
PharmGKBiPA28463.

Chemistry databases

ChEMBLiCHEMBL3559689.

Polymorphism and mutation databases

BioMutaiFZD8.
DMDMi17433053.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001300028 – 694Frizzled-8Add BLAST667

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 96PROSITE-ProRule annotation
Disulfide bondi43 ↔ 89PROSITE-ProRule annotation
Glycosylationi49N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi80 ↔ 118PROSITE-ProRule annotation
Disulfide bondi107 ↔ 148PROSITE-ProRule annotation
Disulfide bondi111 ↔ 135PROSITE-ProRule annotation
Glycosylationi152N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi475N-linked (GlcNAc...) asparagineSequence analysis1

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.
PeptideAtlasiQ9H461.
PRIDEiQ9H461.

PTM databases

iPTMnetiQ9H461.
PhosphoSitePlusiQ9H461.

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

BgeeiENSG00000177283.
CleanExiHS_FZD8.
GenevisibleiQ9H461. HS.

Organism-specific databases

HPAiHPA045025.
HPA071142.

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

Show more details

GO - Molecular functioni

  • PDZ domain binding Source: BHF-UCL
  • receptor binding Source: Ensembl
  • ubiquitin protein ligase binding Source: UniProtKB
  • Wnt-protein binding Source: GO_Central

Protein-protein interaction databases

BioGridi113921. 7 interactors.
IntActiQ9H461. 3 interactors.
STRINGi9606.ENSP00000363826.

Structurei

Secondary structure

1694
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 37Combined sources3
Helixi41 – 43Combined sources3
Beta strandi50 – 54Combined sources5
Helixi62 – 69Combined sources8
Helixi70 – 72Combined sources3
Helixi73 – 78Combined sources6
Helixi84 – 92Combined sources9
Helixi108 – 124Combined sources17
Helixi131 – 133Combined sources3
Helixi135 – 137Combined sources3
Beta strandi144 – 146Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5UN5X-ray2.99A/B28-150[»]
5UN6X-ray3.20A/B/C/D28-150[»]
ProteinModelPortaliQ9H461.
SMRiQ9H461.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 151FZPROSITE-ProRule annotationAdd BLAST122

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni71 – 78Palmitate-binding grooveBy similarity8
Regioni95 – 100Wnt-bindingBy similarity6
Regioni147 – 152Wnt-bindingBy similarity6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi608 – 613Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity6
Motifi692 – 694PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi168 – 172Poly-Pro5
Compositional biasi194 – 202Poly-Gly9
Compositional biasi211 – 216Poly-Gly6
Compositional biasi639 – 663Poly-GlyAdd BLAST25

Domaini

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ9H461.
KOiK02375.
OMAiAPCEPGC.
OrthoDBiEOG091G0N5M.
PhylomeDBiQ9H461.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiView protein in InterPro
IPR015526. Frizzled/SFRP.
IPR000539. Frizzled/Smoothened_TM.
IPR020067. Frizzled_dom.
IPR036790. Frizzled_dom_sf.
IPR017981. GPCR_2-like.
PANTHERiPTHR11309. PTHR11309. 2 hits.
PfamiView protein in Pfam
PF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
PRINTSiPR00489. FRIZZLED.
SMARTiView protein in SMART
SM00063. FRI. 1 hit.
SM01330. Frizzled. 1 hit.
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiView protein in PROSITE
PS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.

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. No translation available.
CCDSiCCDS7192.1.
RefSeqiNP_114072.1. NM_031866.2.
UniGeneiHs.302634.

Genome annotation databases

EnsembliENST00000374694; ENSP00000363826; ENSG00000177283.
GeneIDi8325.
KEGGihsa:8325.
UCSCiuc001iyz.2. human.

Similar proteinsi

Entry informationi

Entry nameiFZD8_HUMAN
AccessioniPrimary (citable) accession number: Q9H461
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 1, 2001
Last modified: October 25, 2017
This is version 154 of the entry and version 1 of the sequence. See 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families