FZD4_CHICK
ID FZD4_CHICK Reviewed; 525 AA.
AC Q9IA05; Q9PTW2;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Frizzled-4;
DE Short=Fz-4;
DE Short=cFz-4;
DE Flags: Precursor;
GN Name=FZD4; Synonyms=FZ4;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10781956; DOI=10.1016/s0925-4773(00)00263-x;
RA Stark M.R., Biggs J.J., Schoenwolf G.C., Rao M.S.;
RT "Characterization of avian frizzled genes in cranial placode development.";
RL Mech. Dev. 93:195-200(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 123-310.
RC TISSUE=Limb bud;
RX PubMed=10512196;
RA Nohno T., Kawakami Y., Wada N., Komaguchi C., Nishimatsu S.;
RT "Differential expression of the frizzled family involved in Wnt signaling
RT during chick limb development.";
RL Cell. Mol. Biol. 45:653-659(1999).
RN [3]
RP INTERACTION WITH TSKU.
RX PubMed=21856951; DOI=10.1073/pnas.1100513108;
RA Ohta K., Ito A., Kuriyama S., Lupo G., Kosaka M., Ohnuma S., Nakagawa S.,
RA Tanaka H.;
RT "Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b
RT for binding to transmembrane protein Frizzled4.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:14962-14967(2011).
CC -!- FUNCTION: Receptor for Wnt proteins (By similarity). Most frizzled
CC receptors are coupled to the beta-catenin canonical signaling pathway,
CC which 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 (By similarity). A second signaling pathway involving
CC PKC and calcium fluxes has been seen for some family members, but it is
CC not yet clear if it represents a distinct pathway or if it can be
CC integrated in the canonical pathway, as PKC seems to be required for
CC Wnt-mediated inactivation of GSK-3 kinase (By similarity). Both
CC pathways seem to involve interactions with G-proteins (By similarity).
CC May be involved in transduction and intercellular transmission of
CC polarity information during tissue morphogenesis and/or in
CC differentiated tissues (By similarity). {ECO:0000250|UniProtKB:Q61088,
CC ECO:0000250|UniProtKB:Q9ULV1}.
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:0000269|PubMed:21856951}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ULV1};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the developing kidney, interdigital
CC spaces and optic cup.
CC -!- DEVELOPMENTAL STAGE: Expressed in optic cup at stages 10-19 and in
CC nephric tubules from stage 10 to 20 and more. Expression in
CC interdigital space begins at stage 20.
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; AF224316; AAF61096.1; -; mRNA.
DR EMBL; AB029451; BAA89401.1; -; mRNA.
DR RefSeq; NP_989430.1; NM_204099.1.
DR AlphaFoldDB; Q9IA05; -.
DR SMR; Q9IA05; -.
DR STRING; 9031.ENSGALP00000027820; -.
DR PaxDb; Q9IA05; -.
DR Ensembl; ENSGALT00000027873; ENSGALP00000027820; ENSGALG00000017242.
DR GeneID; 373887; -.
DR KEGG; gga:373887; -.
DR CTD; 8322; -.
DR VEuPathDB; HostDB:geneid_373887; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000157141; -.
DR HOGENOM; CLU_007873_2_1_1; -.
DR InParanoid; Q9IA05; -.
DR OMA; HWGEFRA; -.
DR OrthoDB; 509772at2759; -.
DR PhylomeDB; Q9IA05; -.
DR TreeFam; TF317907; -.
DR Reactome; R-GGA-4086398; Ca2+ pathway.
DR Reactome; R-GGA-4641263; Regulation of FZD by ubiquitination.
DR Reactome; R-GGA-5099900; WNT5A-dependent internalization of FZD4.
DR PRO; PR:Q9IA05; -.
DR Proteomes; UP000000539; Chromosome 1.
DR Bgee; ENSGALG00000017242; Expressed in liver and 13 other tissues.
DR GO; GO:0009986; C:cell surface; ISO:AgBase.
DR GO; GO:0005911; C:cell-cell junction; ISO:AgBase.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; ISO:AgBase.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0019955; F:cytokine binding; ISO:AgBase.
DR GO; GO:0004896; F:cytokine receptor activity; IEA:Ensembl.
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:0044877; F:protein-containing complex binding; IEA:Ensembl.
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:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
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:0090090; P:negative regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; ISO:AgBase.
DR GO; GO:0110135; P:Norrin signaling pathway; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
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:0150012; P:positive regulation of neuron projection arborization; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0061304; P:retinal blood vessel morphogenesis; IEA:Ensembl.
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 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..24
FT /evidence="ECO:0000255"
FT CHAIN 25..525
FT /note="Frizzled-4"
FT /id="PRO_0000012988"
FT TOPO_DOM 25..200
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 201..231
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 232..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 238..263
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 264..287
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 288..321
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 322..324
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 325..353
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 354..371
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 372..406
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 407..419
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 420..448
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 449..461
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 462..483
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 484..525
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DOMAIN 28..149
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT MOTIF 487..492
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 523..525
FT /note="PDZ-binding"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 41..87
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 78..116
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 105..146
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 109..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 169..188
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DISULFID 192..270
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DISULFID 290..365
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
SQ SEQUENCE 525 AA; 58766 MW; 83DD31DDD3345E8D CRC64;
MERRGGGGRM LALLLAGLLG GARGFGDEEE RRCDAIRIAM CQNLGYNVTK MPNLVGHELQ
ADAELQLTTF TPLIQYGCSS QLQFFLCSVY VPMCTEKINI PIGPCGGMCL SVKRRCEPVL
KEFGFAWPDS LNCSKFPPQN DHNHMCMEGP GDEEVPLHSK TSLQPGEECH SMGSNSDQYI
WVKRNLDCVL KCGYDAGLYS RSAKEFTDIW MAVWASLCFI STAFTVLTFL IDSSRFSYPE
RPIIFLSMCY NIYSIAYIVR LTVGRERISC DFEEAAEPVL IQEGLKNTGC AIIFLLMYFF
GMASSIWWVI LTLTWFLAAG LKWGHEAIEM HSSYFHIAAW AIPAVKTIVI LIMRLVDADE
LTGLCYVGNQ NLDALTGFVV APLFTYLVIG TLFIAAGLVA LFKIRSNLQK DGTKTDKLER
LMVKIGVFSV LYTVPATCVI ACYFYEISNW AVFRYSADDS NMAVEMLKIF MSLLVGITSG
MWIWSAKTLH TWQKCSNRLV NSGKVKREKR ADGWVKPGKG NETVV
