ID   FZD2_RAT                Reviewed;         570 AA.
AC   Q08464;
DT   05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   08-NOV-2023, entry version 166.
DE   RecName: Full=Frizzled-2;
DE            Short=Fz-2;
DE            Short=rFz2;
DE   Flags: Precursor;
GN   Name=Fzd2;
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   STRAIN=Sprague-Dawley; TISSUE=Osteosarcoma;
RX   PubMed=1334084; DOI=10.1016/s0021-9258(19)74025-3;
RA   Chan S.D.H., Karpf D.B., Fowlkes M.E., Hooks M., Bradley M.S., Vuong V.,
RA   Bambino T., Liu M.Y.C., Arnaud C.D., Strewler G.J., Nissenson R.A.;
RT   "Two homologs of the Drosophila polarity gene frizzled (fz) are widely
RT   expressed in mammalian tissues.";
RL   J. Biol. Chem. 267:25202-25207(1992).
RN   [2]
RP   WNT-MEDIATED PKC ACTIVATION.
RX   PubMed=10395542; DOI=10.1016/s0960-9822(99)80310-8;
RA   Sheldahl L.C., Park M., Malbon C.C., Moon R.T.;
RT   "Protein kinase C is differentially stimulated by Wnt and Frizzled homologs
RT   in a G-protein-dependent manner.";
RL   Curr. Biol. 9:695-698(1999).
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 genes
CC       (By similarity). A second signaling pathway involving PKC and calcium
CC       fluxes has been seen for some family members, but it is not yet clear
CC       if it 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 Wnt5A
CC       stimulates PKC activity via a G-protein-dependent mechanism.
CC       {ECO:0000250|UniProtKB:Q14332}.
CC   -!- INTERACTION:
CC       Q08464; Q08463: Fzd1; NbExp=6; IntAct=EBI-7402050, EBI-8766455;
CC       Q08464; Q08464: Fzd2; NbExp=3; IntAct=EBI-7402050, EBI-7402050;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell
CC       membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. Most abundant in kidney, liver,
CC       uterus, ovary and heart. Lower levels seen in brain and intestine.
CC       Extremely low in calvaria, mammary glands and testis.
CC   -!- DEVELOPMENTAL STAGE: Expressed predominantly in neonatal tissues, at
CC       lower levels in adult.
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; L02530; AAA41172.1; -; mRNA.
DR   RefSeq; NP_742032.1; NM_172035.1.
DR   AlphaFoldDB; Q08464; -.
DR   SMR; Q08464; -.
DR   BioGRID; 249097; 1.
DR   IntAct; Q08464; 3.
DR   MINT; Q08464; -.
DR   STRING; 10116.ENSRNOP00000036154; -.
DR   ChEMBL; CHEMBL4879455; -.
DR   GlyCosmos; Q08464; 2 sites, No reported glycans.
DR   GlyGen; Q08464; 2 sites.
DR   PhosphoSitePlus; Q08464; -.
DR   PaxDb; 10116-ENSRNOP00000036154; -.
DR   GeneID; 64512; -.
DR   KEGG; rno:64512; -.
DR   UCSC; RGD:71012; rat.
DR   AGR; RGD:71012; -.
DR   CTD; 2535; -.
DR   RGD; 71012; Fzd2.
DR   eggNOG; KOG3577; Eukaryota.
DR   InParanoid; Q08464; -.
DR   OrthoDB; 5483535at2759; -.
DR   PhylomeDB; Q08464; -.
DR   Reactome; R-RNO-4086398; Ca2+ pathway.
DR   Reactome; R-RNO-4608870; Asymmetric localization of PCP proteins.
DR   Reactome; R-RNO-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR   Reactome; R-RNO-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR   PRO; PR:Q08464; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0030165; F:PDZ domain binding; ISO:RGD.
DR   GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR   GO; GO:0042813; F:Wnt receptor activity; IDA:RGD.
DR   GO; GO:0017147; F:Wnt-protein binding; IBA:GO_Central.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0007267; P:cell-cell signaling; ISO:RGD.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR   GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEP:RGD.
DR   GO; GO:0071305; P:cellular response to vitamin D; IEP:RGD.
DR   GO; GO:0090103; P:cochlea morphogenesis; ISO:RGD.
DR   GO; GO:0045446; P:endothelial cell differentiation; ISO:RGD.
DR   GO; GO:0007199; P:G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger; IDA:RGD.
DR   GO; GO:0060022; P:hard palate development; ISO:RGD.
DR   GO; GO:0060119; P:inner ear receptor cell development; ISO:RGD.
DR   GO; GO:0003149; P:membranous septum morphogenesis; ISO:RGD.
DR   GO; GO:0003150; P:muscular septum morphogenesis; ISO:RGD.
DR   GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:0003151; P:outflow tract morphogenesis; ISO:RGD.
DR   GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; ISO:RGD.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:0007608; P:sensory perception of smell; ISO:RGD.
DR   GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD.
DR   GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
DR   GO; GO:0007223; P:Wnt signaling pathway, calcium modulating pathway; IDA:RGD.
DR   CDD; cd07464; CRD_FZ2; 1.
DR   Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR015526; Frizzled/SFRP.
DR   InterPro; IPR000539; Frizzled/Smoothened_7TM.
DR   InterPro; IPR020067; Frizzled_dom.
DR   InterPro; IPR036790; Frizzled_dom_sf.
DR   InterPro; IPR041778; FZ2_CRD.
DR   InterPro; IPR017981; GPCR_2-like_7TM.
DR   PANTHER; PTHR11309; FRIZZLED; 1.
DR   PANTHER; PTHR11309:SF34; FRIZZLED-2; 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; Frizzled cysteine-rich domain; 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   Ubl conjugation; Wnt signaling pathway.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..570
FT                   /note="Frizzled-2"
FT                   /id="PRO_0000012980"
FT   TOPO_DOM        29..252
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        253..273
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        274..284
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        285..305
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        306..332
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        333..353
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        354..375
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        376..396
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        397..419
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        420..440
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        441..466
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        467..487
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        488..524
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        525..545
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        546..570
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          39..158
FT                   /note="FZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   REGION          166..194
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           548..553
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           568..570
FT                   /note="PDZ-binding"
FT   CARBOHYD        58
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        159
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        44..105
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DISULFID        52..98
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DISULFID        89..126
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DISULFID        115..155
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DISULFID        119..143
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
SQ   SEQUENCE   570 AA;  63885 MW;  4FB895D9BEAFCA4E CRC64;
     MRARSALPRS ALPRLLLPLL LLPAAGPAQF HGEKGISIPD HGFCQPISIP LCTDIAYNQT
     IMPNLLGHTN QEDAGLEVHQ FYPLVKVQCS PELRFFLCSM YAPVCTVLEQ AIPPCRSICE
     RARQGCEALM NKFGFQWPER LRCEHFPRHG AEQICVGQNH SEDGTPALLT TAPPSGLQPG
     AGGTPGGPGG GGAPPRYATL EHPFHCPRVL KVPSYLSYKF LGERDCAAPC EPARPDGSMF
     FSHHHTRFAR LWILTWSVLC CASTFFTVTT SLVAMQRFRY PERPIIFLSG CYTMVSVAYI
     AGFVLQERVV CNERFSEDGY RTVGQGTKKE GCTILFMMLY FFSMASSIWW VILSLTWFLA
     AGMKWGHAAI EANSQYFHLA AWAVPAVKTI TILAMGQIDG DLLSGVCFVG LNRLDPLRGF
     VLAPLFVYLF IGTSFLLAGF VSLFRIRTIM KHDGTKTEPL ERLMVRIGVF SVLYTVPATI
     VIACYFYEQA FREHWERSWV SQHCKSLAIP CPAHYTPRTS PDFTVYMIKY LMTLIVGITS
     GFWIWSGKTL HSWRKFYTRL TNSRHGETTV
//