UniProtKB - Q9H461 (FZD8_HUMAN)
Protein
Frizzled-8
Gene
FZD8
Organism
Homo sapiens (Human)
Status
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: UniProtKB-KW
- PDZ domain binding Source: BHF-UCL
- ubiquitin protein ligase binding Source: UniProtKB
- Wnt-activated receptor activity Source: WormBase
- Wnt-protein binding Source: GO_Central
GO - Biological processi
- canonical Wnt signaling pathway Source: WormBase
- neuron differentiation Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, G-protein coupled receptor, Receptor, Transducer |
Biological process | Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | Q9H461 |
Reactomei | R-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, Signaling by RNF43 mutants |
SignaLinki | Q9H461 |
SIGNORi | Q9H461 |
Names & Taxonomyi
Protein namesi | Recommended name: Frizzled-8Short name: Fz-8 Short name: hFz8 |
Gene namesi | Name:FZD8 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4046, FZD8 |
MIMi | 606146, gene |
neXtProti | NX_Q9H461 |
VEuPathDBi | HostDB:ENSG00000177283.5 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Multi-pass membrane protein By similarity
Golgi apparatus
- Golgi apparatus By similarity
Other locations
Note: Colocalizes with GOPC at the Golgi apparatus.By similarity
Golgi apparatus
- Golgi apparatus Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- integral component of membrane Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 28 – 275 | ExtracellularSequence analysisAdd BLAST | 248 | |
Transmembranei | 276 – 296 | Helical; Name=1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 297 – 312 | CytoplasmicSequence analysisAdd BLAST | 16 | |
Transmembranei | 313 – 333 | Helical; Name=2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 334 – 396 | ExtracellularSequence analysisAdd BLAST | 63 | |
Transmembranei | 397 – 417 | Helical; Name=3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 418 – 439 | CytoplasmicSequence analysisAdd BLAST | 22 | |
Transmembranei | 440 – 460 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 461 – 483 | ExtracellularSequence analysisAdd BLAST | 23 | |
Transmembranei | 484 – 504 | Helical; Name=5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 505 – 532 | CytoplasmicSequence analysisAdd BLAST | 28 | |
Transmembranei | 533 – 553 | Helical; Name=6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 554 – 584 | ExtracellularSequence analysisAdd BLAST | 31 | |
Transmembranei | 585 – 605 | Helical; Name=7Sequence analysisAdd BLAST | 21 | |
Topological domaini | 606 – 694 | CytoplasmicSequence analysisAdd BLAST | 89 |
Keywords - Cellular componenti
Cell membrane, Golgi apparatus, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 8325 |
OpenTargetsi | ENSG00000177283 |
PharmGKBi | PA28463 |
Miscellaneous databases
Pharosi | Q9H461, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3559689 |
GuidetoPHARMACOLOGYi | 236 |
Genetic variation databases
BioMutai | FZD8 |
DMDMi | 17433053 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 27 | Sequence analysisAdd BLAST | 27 | |
ChainiPRO_0000013000 | 28 – 694 | Frizzled-8Add BLAST | 667 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 35 ↔ 96 | PROSITE-ProRule annotation | ||
Disulfide bondi | 43 ↔ 89 | PROSITE-ProRule annotation | ||
Glycosylationi | 49 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 80 ↔ 118 | PROSITE-ProRule annotation | ||
Disulfide bondi | 107 ↔ 148 | PROSITE-ProRule annotation | ||
Disulfide bondi | 111 ↔ 135 | PROSITE-ProRule annotation | ||
Glycosylationi | 152 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 475 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.1 Publication
Keywords - PTMi
Disulfide bond, Glycoprotein, Ubl conjugationProteomic databases
jPOSTi | Q9H461 |
MassIVEi | Q9H461 |
PaxDbi | Q9H461 |
PeptideAtlasi | Q9H461 |
PRIDEi | Q9H461 |
ProteomicsDBi | 80787 |
PTM databases
GlyGeni | Q9H461, 3 sites |
iPTMneti | Q9H461 |
PhosphoSitePlusi | Q9H461 |
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
Bgeei | ENSG00000177283, Expressed in ventricular zone and 201 other tissues |
Genevisiblei | Q9H461, HS |
Organism-specific databases
HPAi | ENSG00000177283, Low tissue specificity |
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).
Interacts with glypican GPC3 (PubMed:24496449).
By similarity1 PublicationBinary interactionsi
Hide detailsQ9H461
With | #Exp. | IntAct |
---|---|---|
WNT3A [P56704] | 2 | EBI-6254212,EBI-6173037 |
C1qa [P98086] from Mus musculus. | 3 | EBI-6254212,EBI-299840 |
GO - Molecular functioni
- PDZ domain binding Source: BHF-UCL
- ubiquitin protein ligase binding Source: UniProtKB
- Wnt-protein binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 113921, 12 interactors |
IntActi | Q9H461, 6 interactors |
STRINGi | 9606.ENSP00000363826 |
Miscellaneous databases
RNActi | Q9H461, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9H461 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 30 – 151 | FZPROSITE-ProRule annotationAdd BLAST | 122 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 71 – 78 | Palmitate-binding grooveBy similarity | 8 | |
Regioni | 95 – 100 | Wnt-bindingBy similarity | 6 | |
Regioni | 147 – 152 | Wnt-bindingBy similarity | 6 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 608 – 613 | Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity | 6 | |
Motifi | 692 – 694 | PDZ-binding | 3 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 168 – 172 | Poly-Pro | 5 | |
Compositional biasi | 194 – 202 | Poly-Gly | 9 | |
Compositional biasi | 211 – 216 | Poly-Gly | 6 | |
Compositional biasi | 639 – 663 | Poly-GlyAdd BLAST | 25 |
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
Belongs to the G-protein coupled receptor Fz/Smo family.Curated
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3577, Eukaryota |
GeneTreei | ENSGT00940000161191 |
HOGENOMi | CLU_007873_2_0_1 |
InParanoidi | Q9H461 |
OMAi | HEKVACN |
OrthoDBi | 509772at2759 |
PhylomeDBi | Q9H461 |
TreeFami | TF317907 |
Family and domain databases
CDDi | cd07461, CRD_FZ8, 1 hit |
Gene3Di | 1.10.2000.10, 1 hit |
InterProi | View protein in InterPro IPR015526, Frizzled/SFRP IPR000539, Frizzled/Smoothened_TM IPR020067, Frizzled_dom IPR036790, Frizzled_dom_sf IPR041776, FZ8_CRD IPR017981, GPCR_2-like |
PANTHERi | PTHR11309, PTHR11309, 1 hit |
Pfami | View protein in Pfam PF01534, Frizzled, 1 hit PF01392, Fz, 1 hit |
PRINTSi | PR00489, FRIZZLED |
SMARTi | View protein in SMART SM00063, FRI, 1 hit SM01330, Frizzled, 1 hit |
SUPFAMi | SSF63501, SSF63501, 1 hit |
PROSITEi | View protein in PROSITE PS50038, FZ, 1 hit PS50261, G_PROTEIN_RECEP_F2_4, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q9H461-1 [UniParc]FASTAAdd to basket
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
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB043703 mRNA Translation: BAB41064.1 AL121749 Genomic DNA No translation available. |
CCDSi | CCDS7192.1 |
RefSeqi | NP_114072.1, NM_031866.2 |
Genome annotation databases
Ensembli | ENST00000374694; ENSP00000363826; ENSG00000177283 |
GeneIDi | 8325 |
KEGGi | hsa:8325 |
UCSCi | uc001iyz.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB043703 mRNA Translation: BAB41064.1 AL121749 Genomic DNA No translation available. |
CCDSi | CCDS7192.1 |
RefSeqi | NP_114072.1, NM_031866.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5UN5 | X-ray | 2.99 | A/B | 28-150 | [»] | |
5UN6 | X-ray | 3.20 | A/B/C/D | 28-150 | [»] | |
6NDZ | X-ray | 2.26 | A/C/E | 32-150 | [»] | |
SMRi | Q9H461 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 113921, 12 interactors |
IntActi | Q9H461, 6 interactors |
STRINGi | 9606.ENSP00000363826 |
Chemistry databases
ChEMBLi | CHEMBL3559689 |
GuidetoPHARMACOLOGYi | 236 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | Q9H461, 3 sites |
iPTMneti | Q9H461 |
PhosphoSitePlusi | Q9H461 |
Genetic variation databases
BioMutai | FZD8 |
DMDMi | 17433053 |
Proteomic databases
jPOSTi | Q9H461 |
MassIVEi | Q9H461 |
PaxDbi | Q9H461 |
PeptideAtlasi | Q9H461 |
PRIDEi | Q9H461 |
ProteomicsDBi | 80787 |
Protocols and materials databases
ABCDi | Q9H461, 39 sequenced antibodies |
Antibodypediai | 13314, 322 antibodies |
DNASUi | 8325 |
Genome annotation databases
Ensembli | ENST00000374694; ENSP00000363826; ENSG00000177283 |
GeneIDi | 8325 |
KEGGi | hsa:8325 |
UCSCi | uc001iyz.2, human |
Organism-specific databases
CTDi | 8325 |
DisGeNETi | 8325 |
GeneCardsi | FZD8 |
HGNCi | HGNC:4046, FZD8 |
HPAi | ENSG00000177283, Low tissue specificity |
MIMi | 606146, gene |
neXtProti | NX_Q9H461 |
OpenTargetsi | ENSG00000177283 |
PharmGKBi | PA28463 |
VEuPathDBi | HostDB:ENSG00000177283.5 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3577, Eukaryota |
GeneTreei | ENSGT00940000161191 |
HOGENOMi | CLU_007873_2_0_1 |
InParanoidi | Q9H461 |
OMAi | HEKVACN |
OrthoDBi | 509772at2759 |
PhylomeDBi | Q9H461 |
TreeFami | TF317907 |
Enzyme and pathway databases
PathwayCommonsi | Q9H461 |
Reactomei | R-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, Signaling by RNF43 mutants |
SignaLinki | Q9H461 |
SIGNORi | Q9H461 |
Miscellaneous databases
BioGRID-ORCSi | 8325, 9 hits in 983 CRISPR screens |
GeneWikii | FZD8 |
GenomeRNAii | 8325 |
Pharosi | Q9H461, Tbio |
PROi | PR:Q9H461 |
RNActi | Q9H461, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000177283, Expressed in ventricular zone and 201 other tissues |
Genevisiblei | Q9H461, HS |
Family and domain databases
CDDi | cd07461, CRD_FZ8, 1 hit |
Gene3Di | 1.10.2000.10, 1 hit |
InterProi | View protein in InterPro IPR015526, Frizzled/SFRP IPR000539, Frizzled/Smoothened_TM IPR020067, Frizzled_dom IPR036790, Frizzled_dom_sf IPR041776, FZ8_CRD IPR017981, GPCR_2-like |
PANTHERi | PTHR11309, PTHR11309, 1 hit |
Pfami | View protein in Pfam PF01534, Frizzled, 1 hit PF01392, Fz, 1 hit |
PRINTSi | PR00489, FRIZZLED |
SMARTi | View protein in SMART SM00063, FRI, 1 hit SM01330, Frizzled, 1 hit |
SUPFAMi | SSF63501, SSF63501, 1 hit |
PROSITEi | View protein in PROSITE PS50038, FZ, 1 hit PS50261, G_PROTEIN_RECEP_F2_4, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | FZD8_HUMAN | |
Accessioni | Q9H461Primary (citable) accession number: Q9H461 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 5, 2001 |
Last sequence update: | March 1, 2001 | |
Last modified: | April 7, 2021 | |
This is version 178 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries - Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families