FZD1_RAT
ID FZD1_RAT Reviewed; 641 AA.
AC Q08463;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Frizzled-1;
DE Short=Fz-1;
DE Short=rFz1;
DE Flags: Precursor;
GN Name=Fzd1;
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 COUPLING TO BETA-CATENIN PATHWAY.
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. Activated by WNT3A, WNT3, WNT1 and
CC to a lesser extent WNT2, but apparently not by WNT4, WNT5A, WNT5B, WNT6
CC or WNT7A. Contradictory results have been reported for activation by
CC WNT7B. Functions in the canonical Wnt/beta-catenin signaling pathway.
CC The canonical Wnt/beta-catenin signaling pathway leads to the
CC activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear
CC accumulation of beta-catenin and activation of Wnt target genes (By
CC 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 (Probable).
CC {ECO:0000250|UniProtKB:O70421, ECO:0000250|UniProtKB:Q9UP38,
CC ECO:0000305}.
CC -!- SUBUNIT: Interacts with MYOC (By similarity). Interacts with WNT7B (By
CC similarity). {ECO:0000250|UniProtKB:O70421,
CC ECO:0000250|UniProtKB:Q9UP38}.
CC -!- INTERACTION:
CC Q08463; Q08463: Fzd1; NbExp=4; IntAct=EBI-8766455, EBI-8766455;
CC Q08463; Q08464: Fzd2; NbExp=6; IntAct=EBI-8766455, EBI-7402050;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UP38};
CC Multi-pass membrane protein {ECO:0000255}.
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 {ECO:0000269|PubMed:1334084}.
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}.
CC -!- CAUTION: Activation by specific Wnt family members may depend on the
CC cells used for the experiment. Contradictory results have been reported
CC for activation by WNT7B in human and mouse. {ECO:0000305}.
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DR EMBL; L02529; AAA41173.1; -; mRNA.
DR PIR; A45054; A45054.
DR AlphaFoldDB; Q08463; -.
DR SMR; Q08463; -.
DR IntAct; Q08463; 1.
DR STRING; 10116.ENSRNOP00000021979; -.
DR GlyGen; Q08463; 2 sites.
DR PhosphoSitePlus; Q08463; -.
DR PaxDb; Q08463; -.
DR UCSC; RGD:61916; rat.
DR RGD; 61916; Fzd1.
DR eggNOG; KOG3577; Eukaryota.
DR InParanoid; Q08463; -.
DR PhylomeDB; Q08463; -.
DR Reactome; R-RNO-4086400; PCP/CE 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 PRO; PR:Q08463; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005109; F:frizzled binding; ISO:RGD.
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:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0042813; F:Wnt receptor activity; ISO:RGD.
DR GO; GO:0017147; F:Wnt-protein binding; ISO:RGD.
DR GO; GO:0036520; P:astrocyte-dopaminergic neuron signaling; ISO:RGD.
DR GO; GO:0035425; P:autocrine signaling; ISO:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0044338; P:canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation; ISO:RGD.
DR GO; GO:0044339; P:canonical Wnt signaling pathway involved in osteoblast differentiation; ISO: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:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0060022; P:hard palate development; ISO:RGD.
DR GO; GO:0048286; P:lung alveolus development; IEP:RGD.
DR GO; GO:0003149; P:membranous septum morphogenesis; ISO:RGD.
DR GO; GO:0003150; P:muscular septum morphogenesis; ISO:RGD.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:1903204; P:negative regulation of oxidative stress-induced neuron death; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; 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:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:ParkinsonsUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; IEP:RGD.
DR GO; GO:1905606; P:regulation of presynapse assembly; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; IDA:RGD.
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; 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..68
FT /evidence="ECO:0000255"
FT CHAIN 69..641
FT /note="Frizzled-1"
FT /id="PRO_0000012975"
FT TOPO_DOM 69..316
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 317..337
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 338..348
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 349..369
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 370..396
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 397..417
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 418..439
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 440..460
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 461..483
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..504
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 505..530
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 531..551
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 552..595
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 596..616
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 617..641
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 106..224
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 74..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 619..624
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 639..641
FT /note="PDZ-binding"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 111..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 119..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 156..192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 182..221
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 186..209
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
SQ SEQUENCE 641 AA; 71027 MW; D82E2C113E81B8B6 CRC64;
MAEEAVPSES RAAGRPSLEL CAVALPGRRE EVGHQDTAGH RRPRAHSRCW ARGLLLLLWL
LEAPLLLGVR AQPAGQVSGP GQQRPPPPQP QQGGQQYNGE RGISIPDHGY CQPISIPLCT
DIAYNQTIMP NLLGHTNQED AGLEVHQFYP LVKVQCSAEL KFFLCSMYAP VCTVLEQALP
PCRSLCERAQ GCEALMNKFG FQWPDTLKCE KFPVHGAGEL CVGQNTSDKG TPTPSLLPEF
WTSNPQHGGG GYRGGYPGGA GPVERGKFSC PRALRVPSYL NYHFLGEKDC GAPCEPTKVY
GLMYFGPEEL RFSRTWIGIW SVLCCASTLF TVLTYLVDMR RFSYPERPII FLSGCYTAVA
VAYIAGFLLE DRVVCNDKFA EDGARTVAQG TKKEGCTILF MMLYFFSMAS SIWWVILSLT
WFLAAGMKWG HEAIEANSQY FHLAAWAVPA IKTITILALG QVDGDVLSGV CFVGLNNVDA
LRGFVLAPLF VYLFIGTSFL LAGFVSLFRI RTIMKHDGTK TEKLEKLMVR IGVFSVLYTV
PATIVIACYF YEQAFRDQWE RSWVAQSCKS YAIPCPHLQG GGGVPPHPPM SPDFTVFMIK
YLMTLIVGIT SGFWIWSGKT LNSWRKFYTR LTNSKQGETT V
