FZD8_MOUSE
ID FZD8_MOUSE Reviewed; 685 AA.
AC Q61091; A2RTK9;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Frizzled-8;
DE Short=Fz-8;
DE Short=mFz8;
DE Flags: Precursor;
GN Name=Fzd8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8626800; DOI=10.1074/jbc.271.8.4468;
RA Wang Y., Macke J.P., Abella B.S., Andreasson K., Worley P., Gilbert D.J.,
RA Copeland N.G., Jenkins N.A., Nathans J.;
RT "A large family of putative transmembrane receptors homologous to the
RT product of the Drosophila tissue polarity gene frizzled.";
RL J. Biol. Chem. 271:4468-4476(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION IN BETA-CATENIN SIGNALING.
RX PubMed=10395542; DOI=10.1016/s0960-9822(99)80310-8;
RA Sheldahl L.C., Park M., Malbon C.C., Moon R.T.;
RT "Protein kinase C is differentially stimulated by Wnt and Frizzled homologs
RT in a G-protein-dependent manner.";
RL Curr. Biol. 9:695-698(1999).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10097073; DOI=10.1073/pnas.96.7.3546;
RA Hsieh J.C., Rattner A., Smallwood P.M., Nathans J.;
RT "Biochemical characterization of Wnt-frizzled interactions using a soluble,
RT biologically active vertebrate Wnt protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3546-3551(1999).
RN [6]
RP INTERACTION WITH GOPC, SUBCELLULAR LOCATION, AND MUTAGENESIS OF VAL-685.
RX PubMed=11520064; DOI=10.1006/bbrc.2001.5430;
RA Yao R., Maeda T., Takada S., Noda T.;
RT "Identification of a PDZ domain containing Golgi protein, GOPC, as an
RT interaction partner of frizzled.";
RL Biochem. Biophys. Res. Commun. 286:771-778(2001).
RN [7]
RP FUNCTION.
RX PubMed=15454084; DOI=10.1016/j.cell.2004.09.019;
RA Lu W., Yamamoto V., Ortega B., Baltimore D.;
RT "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite
RT outgrowth.";
RL Cell 119:97-108(2004).
RN [8]
RP INTERACTION WITH RSPO1 AND RSPO3, AND FUNCTION.
RX PubMed=16543246; DOI=10.1074/jbc.m508324200;
RA Nam J.-S., Turcotte T.J., Smith P.F., Choi S., Yoon J.K.;
RT "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled
RT 8 and LRP6 receptors and activate beta-catenin-dependent gene expression.";
RL J. Biol. Chem. 281:13247-13257(2006).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 28-155, AND DISULFIDE BONDS.
RX PubMed=11452312; DOI=10.1038/35083601;
RA Dann C.E., Hsieh J.-C., Rattner A., Sharma D., Nathans J., Leahy D.J.;
RT "Insights into Wnt binding and signalling from the structures of two
RT Frizzled cysteine-rich domains.";
RL Nature 412:86-90(2001).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 28-150 IN COMPLEX WITH XENOPUS
RP WNT8.
RX PubMed=22653731; DOI=10.1126/science.1222879;
RA Janda C.Y., Waghray D., Levin A.M., Thomas C., Garcia K.C.;
RT "Structural basis of Wnt recognition by Frizzled.";
RL Science 337:59-64(2012).
CC -!- FUNCTION: Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6
CC complex that triggers beta-catenin signaling through inducing
CC aggregation of receptor-ligand complexes into ribosome-sized
CC signalsomes (By similarity). The beta-catenin canonical signaling
CC pathway leads to the activation of disheveled proteins, inhibition of
CC GSK-3 kinase, nuclear accumulation of beta-catenin and activation of
CC Wnt target genes. A second signaling pathway involving PKC and calcium
CC fluxes has been seen for some family members, but it is not yet clear
CC if it represents a distinct pathway or if it can be integrated in the
CC canonical pathway, as PKC seems to be required for Wnt-mediated
CC inactivation of GSK-3 kinase. Both pathways seem to involve
CC interactions with G-proteins. May be involved in transduction and
CC intercellular transmission of polarity information during tissue
CC morphogenesis and/or in differentiated tissues. Coreceptor along with
CC RYK of Wnt proteins, such as WNT1. {ECO:0000250,
CC ECO:0000269|PubMed:10097073, ECO:0000269|PubMed:10395542,
CC ECO:0000269|PubMed:15454084, ECO:0000269|PubMed:16543246}.
CC -!- SUBUNIT: Component of a Wnt-signaling complex that contains a WNT
CC protein, a FZD protein and LRP5 or LRP6. Interacts directly with LRP5
CC or LRP6; the interaction is promoted by Wnt-binding and signaling and
CC inhibited by DKK1 (By similarity). Interacts (via the PDZ-binding
CC motif) with GPOC (via its PDZ domain). Interacts with RSPO1 and RSPO3.
CC Interacts with glypican GPC3 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9H461, ECO:0000269|PubMed:11520064,
CC ECO:0000269|PubMed:16543246, ECO:0000269|PubMed:22653731}.
CC -!- INTERACTION:
CC Q61091; Q8BH60: Gopc; NbExp=3; IntAct=EBI-6171689, EBI-296357;
CC Q61091; P47879: Igfbp4; NbExp=3; IntAct=EBI-6171689, EBI-15706768;
CC Q61091; P27467: Wnt3a; NbExp=3; IntAct=EBI-6171689, EBI-2899665;
CC Q61091; O75581: LRP6; Xeno; NbExp=4; IntAct=EBI-6171689, EBI-910915;
CC Q61091; P28026: wnt8; Xeno; NbExp=3; IntAct=EBI-6171689, EBI-6257743;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Golgi
CC apparatus. Cell membrane; Multi-pass membrane protein. Note=Colocalizes
CC with GOPC at the Golgi apparatus.
CC -!- TISSUE SPECIFICITY: Expressed in chondrocytes.
CC -!- DOMAIN: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl
CC (Disheveled) family members and is involved in the activation of the
CC Wnt/beta-catenin signaling pathway. {ECO:0000250}.
CC -!- DOMAIN: The FZ domain is involved in binding with Wnt ligands.
CC -!- PTM: Ubiquitinated by ZNRF3, leading to its degradation by the
CC proteasome. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family.
CC {ECO:0000305}.
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DR EMBL; U43321; AAC52433.1; -; Genomic_DNA.
DR EMBL; CH466592; EDL23012.1; -; Genomic_DNA.
DR EMBL; BC132543; AAI32544.1; -; mRNA.
DR EMBL; BC138062; AAI38063.1; -; mRNA.
DR CCDS; CCDS29048.1; -.
DR RefSeq; NP_032084.2; NM_008058.2.
DR PDB; 1IJY; X-ray; 1.35 A; A/B=28-155.
DR PDB; 4F0A; X-ray; 3.25 A; A=28-150.
DR PDB; 6AHY; X-ray; 2.80 A; A/C/E=28-159.
DR PDB; 6TFB; X-ray; 1.68 A; A/B=28-151.
DR PDB; 6TFM; X-ray; 2.34 A; A/B/C/D=28-151.
DR PDBsum; 1IJY; -.
DR PDBsum; 4F0A; -.
DR PDBsum; 6AHY; -.
DR PDBsum; 6TFB; -.
DR PDBsum; 6TFM; -.
DR AlphaFoldDB; Q61091; -.
DR SMR; Q61091; -.
DR BioGRID; 199781; 4.
DR CORUM; Q61091; -.
DR DIP; DIP-41258N; -.
DR IntAct; Q61091; 12.
DR MINT; Q61091; -.
DR STRING; 10090.ENSMUSP00000039660; -.
DR BindingDB; Q61091; -.
DR ChEMBL; CHEMBL4523332; -.
DR GlyGen; Q61091; 3 sites.
DR iPTMnet; Q61091; -.
DR PhosphoSitePlus; Q61091; -.
DR PaxDb; Q61091; -.
DR PRIDE; Q61091; -.
DR ProteomicsDB; 271621; -.
DR Antibodypedia; 13314; 337 antibodies from 40 providers.
DR DNASU; 14370; -.
DR Ensembl; ENSMUST00000041080; ENSMUSP00000039660; ENSMUSG00000036904.
DR GeneID; 14370; -.
DR KEGG; mmu:14370; -.
DR UCSC; uc008eag.2; mouse.
DR CTD; 8325; -.
DR MGI; MGI:108460; Fzd8.
DR VEuPathDB; HostDB:ENSMUSG00000036904; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000161191; -.
DR HOGENOM; CLU_007873_2_0_1; -.
DR InParanoid; Q61091; -.
DR OMA; MECYLLG; -.
DR OrthoDB; 509772at2759; -.
DR PhylomeDB; Q61091; -.
DR TreeFam; TF317907; -.
DR Reactome; R-MMU-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-MMU-4641263; Regulation of FZD by ubiquitination.
DR BioGRID-ORCS; 14370; 1 hit in 73 CRISPR screens.
DR EvolutionaryTrace; Q61091; -.
DR PRO; PR:Q61091; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q61091; protein.
DR Bgee; ENSMUSG00000036904; Expressed in ventricular zone and 222 other tissues.
DR Genevisible; Q61091; MM.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; IPI:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0042813; F:Wnt receptor activity; IPI:MGI.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0001525; P:angiogenesis; IDA:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0033077; P:T cell differentiation in thymus; IMP:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IDA:ParkinsonsUK-UCL.
DR CDD; cd07461; CRD_FZ8; 1.
DR Gene3D; 1.10.2000.10; -; 1.
DR InterPro; IPR015526; Frizzled/SFRP.
DR InterPro; IPR000539; Frizzled/Smoothened_TM.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR041776; FZ8_CRD.
DR InterPro; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR Pfam; PF01534; Frizzled; 1.
DR Pfam; PF01392; Fz; 1.
DR PRINTS; PR00489; FRIZZLED.
DR SMART; SM00063; FRI; 1.
DR SMART; SM01330; Frizzled; 1.
DR SUPFAM; SSF63501; SSF63501; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Developmental protein; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Golgi apparatus; Membrane;
KW Receptor; Reference proteome; Signal; Transducer; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Wnt signaling pathway.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..685
FT /note="Frizzled-8"
FT /id="PRO_0000013001"
FT TOPO_DOM 28..272
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 273..293
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 294..309
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 310..330
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 331..394
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..415
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 416..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 459..481
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 482..502
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 503..530
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 531..551
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 552..582
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 583..603
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 604..685
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..151
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 95..100
FT /note="Wnt-binding"
FT REGION 147..152
FT /note="Wnt-binding"
FT REGION 155..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 631..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 606..611
FT /note="Lys-Thr-X-X-X-Trp motif, mediates interaction with
FT the PDZ domain of Dvl family members"
FT /evidence="ECO:0000250"
FT MOTIF 683..685
FT /note="PDZ-binding"
FT COMPBIAS 162..180
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 71..78
FT /ligand="hexadecanoate"
FT /ligand_id="ChEBI:CHEBI:7896"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 473
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..96
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:11452312"
FT DISULFID 43..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:11452312"
FT DISULFID 80..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:11452312"
FT DISULFID 107..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:11452312"
FT DISULFID 111..135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090,
FT ECO:0000269|PubMed:11452312"
FT MUTAGEN 685
FT /note="V->A: Reduces interaction with GOPC."
FT /evidence="ECO:0000269|PubMed:11520064"
FT CONFLICT 347
FT /note="A -> R (in Ref. 1; AAC52433)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="A -> R (in Ref. 1; AAC52433)"
FT /evidence="ECO:0000305"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:1IJY"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:4F0A"
FT HELIX 62..69
FT /evidence="ECO:0007829|PDB:1IJY"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:1IJY"
FT HELIX 73..78
FT /evidence="ECO:0007829|PDB:1IJY"
FT HELIX 84..92
FT /evidence="ECO:0007829|PDB:1IJY"
FT HELIX 108..124
FT /evidence="ECO:0007829|PDB:1IJY"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:1IJY"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:1IJY"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:4F0A"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:6TFB"
SQ SEQUENCE 685 AA; 73045 MW; 9DB95F068BC45CD8 CRC64;
MEWGYLLEVT SLLAALAVLQ RSSGAAAASA KELACQEITV PLCKGIGYNY TYMPNQFNHD
TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY KKPLPPCRSV CERAKAGCAP
LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD YNRTDLTTAA PSPPRRLPPP PPPGEQPPSG
SGHSRPPGAR PPHRGGSSRG SGDAAAAPPS RGGKARPPGG GAAPCEPGCQ CRAPMVSVSS
ERHPLYNRVK TGQIANCALP CHNPFFSQDE RAFTVFWIGL WSVLCFVSTF ATVSTFLIDM
ERFKYPERPI IFLSACYLFV SVGYLVRLVA GHEKVACSGG APGAGGAGGA GGAAAAGAGA
AGAGASSPGA RGEYEELGAV EQHVRYETTG PALCTVVFLL VYFFGMASSI WWVILSLTWF
LAAGMKWGNE AIAGYSQYFH LAAWLVPSVK SIAVLALSSV DGDPVAGICY VGNQSLDNLR
GFVLAPLVIY LFIGTMFLLA GFVSLFRIRS VIKQQGGPTK THKLEKLMIR LGLFTVLYTV
PAAVVVACLF YEQHNRPRWE ATHNCPCLRD LQPDQARRPD YAVFMLKYFM CLVVGITSGV
WVWSGKTLES WRALCTRCCW ASKGAAVGAG AGGSGPGGSG PGPGGGGGHG GGGGSLYSDV
STGLTWRSGT ASSVSYPKQM PLSQV
