FZD8_XENLA
ID FZD8_XENLA Reviewed; 581 AA.
AC O93274; Q9YI55;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Frizzled-8;
DE Short=Fz-8;
DE Short=Xfz8;
DE Flags: Precursor;
GN Name=fzd8; Synonyms=fz8;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND COUPLING TO BETA-CATENIN PATHWAY.
RC TISSUE=Embryo;
RX PubMed=9651509; DOI=10.1016/s0925-4773(98)00076-8;
RA Itoh K., Jacob J., Sokol S.Y.;
RT "A role for Xenopus Frizzled 8 in dorsal development.";
RL Mech. Dev. 74:145-157(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RX PubMed=9636083; DOI=10.1242/dev.125.14.2687;
RA Deardorff M.A., Tan C., Conrad L.J., Klein P.S.;
RT "Frizzled-8 is expressed in the Spemann organizer and plays a role in early
RT morphogenesis.";
RL Development 125:2687-2700(1998).
RN [3]
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 [4]
RP INTERACTION WITH LYPD6.
RX PubMed=23987510; DOI=10.1016/j.devcel.2013.07.020;
RA Oezhan G., Sezgin E., Wehner D., Pfister A.S., Kuehl S.J.,
RA Kagermeier-Schenk B., Kuehl M., Schwille P., Weidinger G.;
RT "Lypd6 enhances Wnt/beta-catenin signaling by promoting Lrp6
RT phosphorylation in raft plasma membrane domains.";
RL Dev. Cell 26:331-345(2013).
CC -!- FUNCTION: Receptor for Wnt proteins. Most of frizzled receptors are
CC coupled to the beta-catenin canonical signaling pathway, which leads to
CC the activation of disheveled proteins, inhibition of GSK-3 kinase,
CC nuclear accumulation of beta-catenin and activation of Wnt target
CC genes. A second signaling pathway involving PKC and calcium fluxes has
CC been seen for some family members, but it is not yet clear if it
CC 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. Activation by Wnt8,
CC Wnt5A or Wnt3A induces expression of beta-catenin target genes.
CC Displays an axis-inducing activity. {ECO:0000269|PubMed:10097073}.
CC -!- SUBUNIT: Interacts with lypd6 and the interaction is strongly enhanced
CC by wnt3a (PubMed:23987510). {ECO:0000269|PubMed:23987510}.
CC -!- INTERACTION:
CC O93274; Q6EHH9: FRIED; NbExp=2; IntAct=EBI-7735236, EBI-7735259;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10097073}; Multi-
CC pass membrane protein {ECO:0000269|PubMed:10097073}. Cell membrane
CC {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: First expressed at high levels in the late
CC blastula stages. At early gastrula, expressed in the deep cells of the
CC Spemann organizer prior to involution of the dorsal blastopore lip.
CC Detected in presumptive neurectoderm as gastrulation proceeds. Becomes
CC restricted to the anterior ectoderm by the end of gastrulation. At
CC neurula stages, localized in the most anterior region of the embryo,
CC mainly in the anterior ectoderm including telencephalic and cement
CC gland regions.
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 -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family.
CC {ECO:0000305}.
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DR EMBL; AF017177; AAC31121.1; -; mRNA.
DR EMBL; AF033110; AAC77361.1; -; mRNA.
DR RefSeq; NP_001079144.1; NM_001085675.1.
DR RefSeq; NP_001084206.1; NM_001090737.1.
DR AlphaFoldDB; O93274; -.
DR SMR; O93274; -.
DR IntAct; O93274; 1.
DR MINT; O93274; -.
DR GeneID; 373690; -.
DR GeneID; 399367; -.
DR KEGG; xla:373690; -.
DR KEGG; xla:399367; -.
DR CTD; 373690; -.
DR CTD; 399367; -.
DR Xenbase; XB-GENE-865411; fzd8.L.
DR Xenbase; XB-GENE-6254029; fzd8.S.
DR OrthoDB; 509772at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Proteomes; UP000186698; Chromosome 6S.
DR Bgee; 373690; Expressed in liver and 14 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-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 Cell membrane; Developmental protein; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix;
KW Wnt signaling pathway.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..581
FT /note="Frizzled-8"
FT /id="PRO_0000013002"
FT TOPO_DOM 24..239
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..320
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..341
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 342..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..407
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 408..428
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 429..454
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 455..475
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 476..505
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 506..526
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..581
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..144
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 88..93
FT /note="Wnt-binding"
FT /evidence="ECO:0000250"
FT REGION 140..146
FT /note="Wnt-binding"
FT /evidence="ECO:0000250"
FT REGION 151..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 529..534
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 579..581
FT /note="PDZ-binding"
FT BINDING 64..71
FT /ligand="hexadecanoate"
FT /ligand_id="ChEBI:CHEBI:7896"
FT /evidence="ECO:0000250"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 36..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 73..111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 100..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 104..128
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT CONFLICT 1..3
FT /note="MES -> MECPY (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 7
FT /note="S -> L (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 10
FT /note="L -> V (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 14
FT /note="W -> G (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="C -> S (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="G -> S (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="G -> S (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="V -> A (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="T -> P (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="I -> T (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="E -> D (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 494..496
FT /note="PEM -> SEG (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 500
FT /note="H -> R (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 547
FT /note="A -> T (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 565
FT /note="G -> A (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
FT CONFLICT 572
FT /note="C -> Y (in Ref. 2; AAC77361)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 581 AA; 65379 MW; 80890C408AB21E23 CRC64;
MESLSLSLLL LVSWLQGSQC AAAKELSCQE ITVPLCKDIG YNYTYMPNQF NHDTQDEAGM
EVHQFWPLVV IHCSPDLKFF LCSMYTPICL EDYKKPLPPC RSVCERARAG CAPLMRQYGF
AWPDRMRCDR LPEQGNPDTL CMDYYNRTEQ TTAAPSHPEP PKPPARSVPK GRTRVEPPRS
RSRATGCESG CQCRAPMVQV SNERHPLYNR VRTGQIPNCA MPCHNPFFSP EERTFTEFWI
GLWSVLCFAS TFATVSTFLI DMERFKYPER PIIFLSACYL LVSTGYLIRL IAGHEKVACS
RGELDLEHII HYETTGPALC TLVFLLIYFF GMASSIWWVI LSLTWFLAAG MKWGNEAIAG
YSQYFHLAAW LVPSIKSIAV LALSSVDGDP VAGICFVGNQ NLDNLRGFVL APLVIYLFIG
SMFLLAGFVS LFRIRSVIKQ GGTKTDKLEK LMIRIGIFSV LYTVPATIVV ACFFYEQHNR
QGWEVAHNCN SCQPEMAQPH RPDYAVFMLK YFMCLVVGIT SGVWIWSGKT LESWRAFCTR
CCWGSKATGG SMYSDVSTGL TWRSGTGSSV SCPKQMPLSQ V
