FZD4_RAT
ID FZD4_RAT Reviewed; 538 AA.
AC Q9QZH0;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Frizzled-4;
DE Short=Fz-4;
DE Short=rFz4;
DE AltName: CD_antigen=CD344;
DE Flags: Precursor;
GN Name=Fzd4;
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 [MRNA].
RC TISSUE=Corpus luteum;
RA Walther P.R., Lacher M.D., Saurer S., Friis R.R.;
RT "Expression of a putative seven-pass transmembrane frizzled receptor in the
RT Corpus Luteum (CL) of the rat during pregnancy and involution.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Receptor for Wnt proteins (By similarity). Most of frizzled
CC receptors are coupled to the beta-catenin (CTNNB1) canonical signaling
CC pathway, which leads to the activation of disheveled proteins,
CC inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin
CC (CTNNB1) and activation of Wnt target genes (By similarity). Plays a
CC critical role in retinal vascularization by acting as a receptor for
CC Wnt proteins and norrin (NDP) (By similarity). In retina, it can be
CC both activated by Wnt protein-binding, but also by a Wnt-independent
CC signaling via binding of norrin (NDP), promoting in both cases beta-
CC catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated
CC transcriptional programs (By similarity). A second signaling pathway
CC involving PKC and calcium fluxes has been seen for some family members,
CC but it is not yet clear if it represents a distinct pathway or if it
CC can be integrated in the canonical pathway, as PKC seems to be required
CC for 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 with MAGI3 and NDP. Component of a complex, at least
CC composed of TSPAN12, FZD4 and norrin (NDP). Interacts (via FZ domain)
CC with TSKU; TSKU competes with WNT2B for binding to FZD4, inhibiting Wnt
CC signaling and repressing peripheral eye development. Interacts with
CC glypican GPC3. {ECO:0000250|UniProtKB:Q61088,
CC ECO:0000250|UniProtKB:Q9ULV1}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ULV1};
CC Multi-pass membrane protein {ECO:0000255}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF183910; AAF01036.1; -; mRNA.
DR RefSeq; NP_072145.1; NM_022623.2.
DR AlphaFoldDB; Q9QZH0; -.
DR SMR; Q9QZH0; -.
DR STRING; 10116.ENSRNOP00000023205; -.
DR GlyGen; Q9QZH0; 3 sites.
DR PhosphoSitePlus; Q9QZH0; -.
DR PaxDb; Q9QZH0; -.
DR Ensembl; ENSRNOT00000106139; ENSRNOP00000088712; ENSRNOG00000063590.
DR GeneID; 64558; -.
DR KEGG; rno:64558; -.
DR UCSC; RGD:71017; rat.
DR CTD; 8322; -.
DR RGD; 71017; Fzd4.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000157141; -.
DR HOGENOM; CLU_007873_2_1_1; -.
DR InParanoid; Q9QZH0; -.
DR OMA; HWGEFRA; -.
DR OrthoDB; 509772at2759; -.
DR PhylomeDB; Q9QZH0; -.
DR TreeFam; TF317907; -.
DR Reactome; R-RNO-4086398; Ca2+ pathway.
DR Reactome; R-RNO-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-RNO-4641263; Regulation of FZD by ubiquitination.
DR Reactome; R-RNO-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR PRO; PR:Q9QZH0; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016848; Expressed in skeletal muscle tissue and 18 other tissues.
DR Genevisible; Q9QZH0; RN.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005911; C:cell-cell junction; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:RGD.
DR GO; GO:0019955; F:cytokine binding; ISO:RGD.
DR GO; GO:0004896; F:cytokine receptor activity; 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:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0038023; F:signaling receptor activity; IGI:ARUK-UCL.
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; IPI:RGD.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0061301; P:cerebellum vasculature morphogenesis; ISO:RGD.
DR GO; GO:0035426; P:extracellular matrix-cell signaling; ISO:RGD.
DR GO; GO:0031987; P:locomotion involved in locomotory behavior; ISO:RGD.
DR GO; GO:0001553; P:luteinization; ISO:RGD.
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:RGD.
DR GO; GO:0110135; P:Norrin signaling pathway; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0150012; P:positive regulation of neuron projection arborization; IGI:ARUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0042701; P:progesterone secretion; ISO:RGD.
DR GO; GO:0030947; P:regulation of vascular endothelial growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; ISO:RGD.
DR GO; GO:0061304; P:retinal blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:RGD.
DR GO; GO:0001570; P:vasculogenesis; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0007223; P:Wnt signaling pathway, calcium modulating pathway; ISO:RGD.
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 Ubl conjugation; Wnt signaling pathway.
FT SIGNAL 1..37
FT /evidence="ECO:0000255"
FT CHAIN 38..538
FT /note="Frizzled-4"
FT /id="PRO_0000012987"
FT TOPO_DOM 38..213
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 214..244
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 245..250
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 251..276
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 277..300
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 301..334
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 335..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 338..366
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 367..384
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 385..419
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 420..432
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 433..461
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 462..474
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TRANSMEM 475..496
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT TOPO_DOM 497..538
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DOMAIN 41..162
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT MOTIF 500..505
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 536..538
FT /note="PDZ-binding"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 46..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 54..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 91..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 118..159
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 122..146
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 182..201
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DISULFID 205..283
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
FT DISULFID 303..378
FT /evidence="ECO:0000250|UniProtKB:Q9ULV1"
SQ SEQUENCE 538 AA; 60355 MW; 07DAAE606B46E005 CRC64;
MAWQGTGPSV RGMPGGVRLR LGLLLLQLLL LQRPALGFGD EEERRCDPIR IAMCQNLGYN
VTKMPNLVGH ELQTDAELQL TTFTPLIQYG CSSQLQFFLC SVYVPMCTEK INIPIGPCGG
MCLSVKRRCE PVLKEFGFAW PDSLNCSKFP PQNDHNHMCM EGPGDEEVPL PHKTPIQPGE
ECHSVGTNSD QYIWVKRSLN CVLKCGYDAG LYSRSAKEFT DIWMAVWASL CFISTTFTVL
TFLIDSSRFS YPERPIIFLS MCYNIYSIAY IVRLTVGRER ISCDFEEAAE PVLIQEGLKN
TGCAIIFLLM YFFGMASSIW WVILTLTWFL AAGLKWGHEA IEMHSSYFHI AAWAIPAVKT
IVILIMRLVD ADELTGLCYV GNQSLDALTG FVVAPLFTYL VIGTLFIAAG LVALFKIRSN
LQKDGTKTDK LERLMVKIGV FSVLYTVPAT CVIACYFYEI SNWALFRYSA DDSNMAVEML
KIFMSLLVGI TSGMWIWSAK TLHTWQKCSN RLVNSGKVKR EKRGNGWVKP GKGNETVV
