FZD2_RAT
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 03-AUG-2022, entry version 160.
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 GlyGen; Q08464; 2 sites.
DR PhosphoSitePlus; Q08464; -.
DR PaxDb; Q08464; -.
DR GeneID; 64512; -.
DR KEGG; rno:64512; -.
DR UCSC; RGD:71012; rat.
DR CTD; 2535; -.
DR RGD; 71012; Fzd2.
DR eggNOG; KOG3577; Eukaryota.
DR InParanoid; Q08464; -.
DR OrthoDB; 330751at2759; -.
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:0016021; C:integral component of membrane; IBA:GO_Central.
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:0001775; P:cell activation; IEP:RGD.
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:0030855; P:epithelial 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: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:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; 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; -; 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; IPR041778; FZ2_CRD.
DR InterPro; IPR026550; FZD1/2.
DR InterPro; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF34; PTHR11309:SF34; 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 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
