FZD4_XENLA
ID FZD4_XENLA Reviewed; 523 AA.
AC Q9PT62;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Frizzled-4;
DE Short=Fz-4;
DE Short=Xfz4;
DE Flags: Precursor;
GN Name=fzd4; Synonyms=fz4;
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].
RC TISSUE=Embryo;
RX PubMed=10842080; DOI=10.1016/s0925-4773(00)00294-x;
RA Shi D.-L., Boucaut J.-C.;
RT "Xenopus frizzled 4 is a maternal mRNA and its zygotic expression is
RT localized to the neuroectoderm and trunk lateral plate mesoderm.";
RL Mech. Dev. 94:243-245(2000).
RN [2]
RP COUPLING TO BETA-CATENIN PATHWAY.
RX PubMed=10990458; DOI=10.1093/emboj/19.18.4944;
RA Umbhauer M., Djiane A., Goisset C., Penzo-Mendez A., Riou J.-F.,
RA Boucaut J.-C., Shi D.-L.;
RT "The C-terminal cytoplasmic Lys-Thr-X-X-X-Trp motif in frizzled receptors
RT mediates Wnt/beta-catenin signalling.";
RL EMBO J. 19:4944-4954(2000).
CC -!- FUNCTION: Receptor for Wnt proteins. Most 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. Activated by Wnt5A.
CC -!- SUBUNIT: Interacts (via FZ domain) with tsku; tsku competes with wnt2b
CC for binding to fzd4, inhibiting Wnt signaling and repressing peripheral
CC eye development. {ECO:0000250|UniProtKB:Q9IA05}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ULV1};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Expression level remains constant during early
CC development. First localized during gastrulation to the dorsal
CC presumptive neuroectoderm. At the end of gastrulation, detected in the
CC dorso-anterior neuroectoderm. During neurulation, expressed as a band
CC on both sides of the forebrain, and in the trunk lateral plate
CC mesoderm. As development proceeds, expression in the trunk lateral
CC plate mesoderm decreases but persists in the forebrain. Also expressed
CC in the posterior unsegmented somitic mesoderm from late tail-bud stage
CC onward.
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.
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; AJ251750; CAB63117.1; -; mRNA.
DR RefSeq; NP_001083922.1; NM_001090453.1.
DR AlphaFoldDB; Q9PT62; -.
DR SMR; Q9PT62; -.
DR GeneID; 399192; -.
DR KEGG; xla:399192; -.
DR CTD; 399192; -.
DR Xenbase; XB-GENE-865153; fzd4.S.
DR OrthoDB; 509772at2759; -.
DR Proteomes; UP000186698; Chromosome 2S.
DR Bgee; 399192; Expressed in internal ear and 18 other tissues.
DR GO; GO:0009986; C:cell surface; ISO:AgBase.
DR GO; GO:0005911; C:cell-cell junction; ISO:AgBase.
DR GO; GO:0070062; C:extracellular exosome; ISO:AgBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0019955; F:cytokine binding; ISO:AgBase.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; ISO:AgBase.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:AgBase.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:AgBase.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:AgBase.
DR GO; GO:0042813; F:Wnt receptor activity; ISO:AgBase.
DR GO; GO:0017147; F:Wnt-protein binding; ISO:AgBase.
DR GO; GO:0001568; P:blood vessel development; ISO:AgBase.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:AgBase.
DR GO; GO:0061301; P:cerebellum vasculature morphogenesis; ISO:AgBase.
DR GO; GO:0035426; P:extracellular matrix-cell signaling; ISO:AgBase.
DR GO; GO:0031987; P:locomotion involved in locomotory behavior; ISO:AgBase.
DR GO; GO:0001553; P:luteinization; ISO:AgBase.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; ISO:AgBase.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:AgBase.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:AgBase.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:AgBase.
DR GO; GO:0042701; P:progesterone secretion; ISO:AgBase.
DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; ISO:AgBase.
DR GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; ISO:AgBase.
DR GO; GO:0061304; P:retinal blood vessel morphogenesis; ISO:AgBase.
DR GO; GO:0007605; P:sensory perception of sound; ISO:AgBase.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:AgBase.
DR GO; GO:0001570; P:vasculogenesis; ISO:AgBase.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:AgBase.
DR GO; GO:0007223; P:Wnt signaling pathway, calcium modulating pathway; ISO:AgBase.
DR CDD; cd07448; CRD_FZ4; 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; IPR041765; FZ4_CRD.
DR InterPro; IPR026551; FZD4.
DR InterPro; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF23; PTHR11309:SF23; 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; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix;
KW Wnt signaling pathway.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..523
FT /note="Frizzled-4"
FT /id="PRO_0000012989"
FT TOPO_DOM 23..198
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 199..229
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 230..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 236..261
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 262..285
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 286..319
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 320..322
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 323..351
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 352..369
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 370..396
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 397..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 418..443
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 444..459
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 460..481
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 482..523
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DOMAIN 26..147
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT MOTIF 485..490
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 521..523
FT /note="PDZ-binding"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..92
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 39..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 76..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 103..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 107..131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 167..186
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DISULFID 190..268
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DISULFID 288..363
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
SQ SEQUENCE 523 AA; 58741 MW; ACCA8D2AFBFC6105 CRC64;
MGARSLTLLY LLCCLVVGLI AGFGEEEERS CDPIRITMCQ NLGYNVTKMP NLVGHELQAD
AELQLTTFTP LIQYGCSSQL QFFLCSVYVP MCTEKINIPI GPCGGMCLSV KRRCEPVLKE
FGFAWPESLN CSKFPPQNDH NHMCMEGPGD DEVPAHSKTP VLPGEDCNSF GPNSDQYTWV
KRSMNCVLKC GYDSGLYNRL SKEFTDIWMA VWASLCFIST AFTVLTFLID SSRFCYPERP
IIFLSMCYNI YSIAYIVRLT VGRERISCDF EEAAEPVLIQ EGLKNTGCAI IFLLMYFFGM
ASSIWWVILT LTWFLAAGLK WGHEAIEMHS SYFHIAAWAI PAVKTIVILI MRLVDADELT
GLCYVGNQNI DALTGFVVAP LFTYLVIGTL FIAAGLVALF KIRSNLQKDG TKTDKLERLM
VKIGVFSVLY TVPATCVIAC YFYEVSNWNV FRYTADDSNM AVEMLNIFMS LLVGITSGMW
IWSAKTLHTW QKCTNRLVNS GKVKRKKRVD GWVKPGKGNE TVV
