FZD8_RAT
ID FZD8_RAT Reviewed; 684 AA.
AC Q498S8;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Frizzled-8;
DE Short=Fz-8;
DE Flags: Precursor;
GN Name=Fzd8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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).
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. The beta-catenin canonical signaling pathway leads to the
CC activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear
CC accumulation of beta-catenin and activation of Wnt target genes. A
CC second signaling pathway involving PKC and calcium fluxes has been seen
CC for some family members, but it is not yet clear if it represents a
CC distinct pathway or if it can be integrated in the canonical pathway,
CC as PKC seems to be required for Wnt-mediated inactivation of GSK-3
CC kinase. Both pathways seem to involve interactions with G-proteins. May
CC be involved in transduction and intercellular transmission of polarity
CC information during tissue morphogenesis and/or in differentiated
CC tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1 (By
CC similarity). {ECO:0000250}.
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. Interacts (via the PDZ-binding motif) with GPOC (via
CC its PDZ domain). Interacts with RSPO1 and RSPO3 (By similarity).
CC Interacts with glypican GPC3 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9H461}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Golgi
CC apparatus {ECO:0000250}. Cell membrane {ECO:0000250}; Multi-pass
CC membrane protein {ECO:0000250}. Note=Colocalizes with GOPC at the Golgi
CC apparatus. {ECO:0000250}.
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 {ECO:0000250}.
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; BC100088; AAI00089.1; -; mRNA.
DR RefSeq; NP_001037716.1; NM_001044251.2.
DR RefSeq; XP_003751769.1; XM_003751721.4.
DR RefSeq; XP_006254204.1; XM_006254142.3.
DR AlphaFoldDB; Q498S8; -.
DR SMR; Q498S8; -.
DR STRING; 10116.ENSRNOP00000055627; -.
DR GlyGen; Q498S8; 3 sites.
DR PhosphoSitePlus; Q498S8; -.
DR PaxDb; Q498S8; -.
DR Ensembl; ENSRNOT00000116071; ENSRNOP00000093389; ENSRNOG00000069521.
DR GeneID; 364754; -.
DR KEGG; rno:364754; -.
DR UCSC; RGD:1560525; rat.
DR CTD; 8325; -.
DR RGD; 1560525; Fzd8.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000161191; -.
DR HOGENOM; CLU_007873_2_0_1; -.
DR InParanoid; Q498S8; -.
DR OMA; MECYLLG; -.
DR OrthoDB; 509772at2759; -.
DR PhylomeDB; Q498S8; -.
DR TreeFam; TF317907; -.
DR Reactome; R-RNO-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-RNO-4641263; Regulation of FZD by ubiquitination.
DR PRO; PR:Q498S8; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000059244; Expressed in liver and 17 other tissues.
DR Genevisible; Q498S8; RN.
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; ISO:RGD.
DR GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; ISO:RGD.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0042813; F:Wnt receptor activity; ISO:RGD.
DR GO; GO:0017147; F:Wnt-protein binding; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
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 2: Evidence at transcript level;
KW 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..684
FT /note="Frizzled-8"
FT /id="PRO_0000278650"
FT TOPO_DOM 28..271
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 309..329
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 330..393
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 394..414
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 415..436
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 437..457
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 458..480
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..529
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 530..550
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 551..581
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 582..602
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 603..684
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 /evidence="ECO:0000250"
FT REGION 147..152
FT /note="Wnt-binding"
FT /evidence="ECO:0000250"
FT REGION 155..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 605..610
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 682..684
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 162..176
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 /evidence="ECO:0000250"
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 472
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..96
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 43..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 80..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 107..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 111..135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
SQ SEQUENCE 684 AA; 73009 MW; EEBA871326749B69 CRC64;
MEWGYLLEVT SLLAALAVLQ RSSGAAAASA KELACQEITV PLCKGIGYNY TYMPNQFNHD
TQDEAGLEVH QFWPLVEIQC SPDLKFFLCS MYTPICLEDY KKPLPPCRSV CERAKAGCAP
LMRQYGFAWP DRMRCDRLPE QGNPDTLCMD YNRTDLTTAA PSPPRRLPPP QPGEQPPSGS
GHSRPPGARP PHRGGSSRGS GDTAAAPPSR GGKARPPGGG AAPCEPGCQC RAPMVSVSSE
RHPLYNRVKT GQIANCALPC HNPFFSQDER AFTVFWIGLW SVLCFVSTFA TVSTFLIDME
RFKYPERPII FLSACYLFVS VGYLVRLVAG HEKVACSGGA PGAGGAGGAG GAATAGAGAA
GAGASSPGAR GEYEELGAVE QHVRYETTGP ALCTVVFLLV YFFGMASSIW WVILSLTWFL
AAGMKWGNEA IAGYSQYFHL AAWLVPSVKS IAVLALSSVD GDPVAGICYV GNQSLDNLRG
FVLAPLVIYL FIGTMFLLAG FVSLFRIRSV IKQQGGPTKT HKLEKLMIRL GLFTVLYTVP
AAVVVACLFY EQHNRPRWEA THNCPCLRDL QPDQARRPDY AVFMLKYFMC LVVGITSGVW
VWSGKTLESW RALCTRCCWA SKGAAVGAGA GGSGPGGGGP GPGGGGGHGG GGGSLYSDVS
TGLTWRSGTA SSVSYPKQMP LSQV
