FRIZ_DROME
ID FRIZ_DROME Reviewed; 581 AA.
AC P18537; Q9VUE0; Q9VUE2;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Frizzled;
DE AltName: Full=Frizzled-1;
DE Short=dFz1;
DE Flags: Precursor;
GN Name=fz; ORFNames=CG17697;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2493583; DOI=10.1038/338263a0;
RA Vinson C.R., Conover S., Adler P.N.;
RT "A Drosophila tissue polarity locus encodes a protein containing seven
RT potential transmembrane domains.";
RL Nature 338:263-264(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=Canton-S; TISSUE=Embryo;
RX PubMed=2174014; DOI=10.1093/genetics/126.2.401;
RA Adler P.N., Vinson C., Park W.J., Conover S., Klein L.;
RT "Molecular structure of frizzled, a Drosophila tissue polarity gene.";
RL Genetics 126:401-416(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP TOPOLOGY.
RX PubMed=10360843; DOI=10.1089/104454999315312;
RA Goo J.H., Ahn Y., Park W.J.;
RT "Frizzled-suc2 fusion gene studies in Saccharomyces cerevisiae.";
RL DNA Cell Biol. 18:429-434(1999).
RN [7]
RP INTERACTION WITH ATP6AP2.
RX PubMed=20579883; DOI=10.1016/j.cub.2010.05.028;
RA Buechling T., Bartscherer K., Ohkawara B., Chaudhary V., Spirohn K.,
RA Niehrs C., Boutros M.;
RT "Wnt/Frizzled signaling requires dPRR, the Drosophila homolog of the
RT prorenin receptor.";
RL Curr. Biol. 20:1263-1268(2010).
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
CC genes. A second signaling pathway involving PKC and calcium fluxes has
CC been seen for some family members, but it is not yet clear if it
CC 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. Required to coordinate the cytoskeletons
CC of epidermal cells to produce a parallel array of cuticular hairs and
CC bristles.
CC -!- SUBUNIT: Interacts with ATP6AP2. {ECO:0000269|PubMed:20579883}.
CC -!- INTERACTION:
CC P18537; Q9V5N8: stan; NbExp=3; IntAct=EBI-251576, EBI-119250;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA38459.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=CAA38461.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; X54648; CAA38460.1; -; Genomic_DNA.
DR EMBL; X54649; CAA38460.1; JOINED; Genomic_DNA.
DR EMBL; X54650; CAA38460.1; JOINED; Genomic_DNA.
DR EMBL; X54651; CAA38460.1; JOINED; Genomic_DNA.
DR EMBL; X54648; CAA38461.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X54649; CAA38461.1; JOINED; Genomic_DNA.
DR EMBL; X54650; CAA38461.1; JOINED; Genomic_DNA.
DR EMBL; X54652; CAA38461.1; JOINED; Genomic_DNA.
DR EMBL; X54646; CAA38458.1; -; mRNA.
DR EMBL; X54647; CAA38459.1; ALT_SEQ; mRNA.
DR EMBL; AE014296; AAF49746.3; -; Genomic_DNA.
DR EMBL; AY051808; AAK93232.1; -; mRNA.
DR PIR; S03540; S03540.
DR RefSeq; NP_524812.1; NM_080073.3.
DR AlphaFoldDB; P18537; -.
DR SMR; P18537; -.
DR BioGRID; 69580; 59.
DR DIP; DIP-22727N; -.
DR IntAct; P18537; 3.
DR STRING; 7227.FBpp0075485; -.
DR TCDB; 9.A.14.16.5; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P18537; 2 sites.
DR PaxDb; P18537; -.
DR DNASU; 45307; -.
DR EnsemblMetazoa; FBtr0075743; FBpp0075485; FBgn0001085.
DR GeneID; 45307; -.
DR KEGG; dme:Dmel_CG17697; -.
DR CTD; 45307; -.
DR FlyBase; FBgn0001085; fz.
DR VEuPathDB; VectorBase:FBgn0001085; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000166686; -.
DR HOGENOM; CLU_007873_2_1_1; -.
DR InParanoid; P18537; -.
DR OMA; RSHGMMY; -.
DR OrthoDB; 330751at2759; -.
DR PhylomeDB; P18537; -.
DR Reactome; R-DME-209387; Phosphorylation of ARR.
DR Reactome; R-DME-209440; Recruitment of the 'destruction complex' to the receptor complex, the degradation of AXN and release of ARM.
DR Reactome; R-DME-209472; Assembly of receptor complex.
DR Reactome; R-DME-350368; Activation of RHO1 by FZ:DSH complex.
DR Reactome; R-DME-350376; Activation of RAC1:GTP by FZ:DSH complex.
DR Reactome; R-DME-350379; Homo-/heterophilic binding of transmembrane components.
DR Reactome; R-DME-350411; Formation and asymmetric localisation of transmembrane complexes.
DR Reactome; R-DME-350480; Activation of non-muscle Myosin II.
DR Reactome; R-DME-4086398; Ca2+ pathway.
DR Reactome; R-DME-4086400; PCP/CE pathway.
DR Reactome; R-DME-450728; Inhibition of actin polymerisation.
DR Reactome; R-DME-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-DME-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-DME-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR SignaLink; P18537; -.
DR BioGRID-ORCS; 45307; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 45307; -.
DR PRO; PR:P18537; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0001085; Expressed in wing disc and 20 other tissues.
DR ExpressionAtlas; P18537; baseline and differential.
DR Genevisible; P18537; DM.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0042813; F:Wnt receptor activity; IDA:FlyBase.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:FlyBase.
DR GO; GO:0008356; P:asymmetric cell division; IMP:FlyBase.
DR GO; GO:0048675; P:axon extension; IMP:FlyBase.
DR GO; GO:0007298; P:border follicle cell migration; IMP:FlyBase.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:FlyBase.
DR GO; GO:0042685; P:cardioblast cell fate specification; IGI:FlyBase.
DR GO; GO:0035293; P:chitin-based larval cuticle pattern formation; IGI:FlyBase.
DR GO; GO:0001745; P:compound eye morphogenesis; IMP:FlyBase.
DR GO; GO:0030010; P:establishment of cell polarity; IMP:FlyBase.
DR GO; GO:0001737; P:establishment of imaginal disc-derived wing hair orientation; IMP:FlyBase.
DR GO; GO:0042067; P:establishment of ommatidial planar polarity; IMP:FlyBase.
DR GO; GO:0001736; P:establishment of planar polarity; IMP:FlyBase.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IGI:FlyBase.
DR GO; GO:0060250; P:germ-line stem-cell niche homeostasis; IMP:FlyBase.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IMP:FlyBase.
DR GO; GO:0035317; P:imaginal disc-derived wing hair organization; IGI:FlyBase.
DR GO; GO:0035320; P:imaginal disc-derived wing hair site selection; IMP:FlyBase.
DR GO; GO:0008587; P:imaginal disc-derived wing margin morphogenesis; IGI:FlyBase.
DR GO; GO:0007494; P:midgut development; IGI:FlyBase.
DR GO; GO:0001738; P:morphogenesis of a polarized epithelium; IMP:FlyBase.
DR GO; GO:0048665; P:neuron fate specification; IGI:FlyBase.
DR GO; GO:0016318; P:ommatidial rotation; IMP:FlyBase.
DR GO; GO:0045773; P:positive regulation of axon extension; IGI:FlyBase.
DR GO; GO:1902669; P:positive regulation of axon guidance; IMP:FlyBase.
DR GO; GO:0048056; P:R3/R4 cell differentiation; IMP:FlyBase.
DR GO; GO:0007464; P:R3/R4 cell fate commitment; IMP:FlyBase.
DR GO; GO:0032231; P:regulation of actin filament bundle assembly; IGI:FlyBase.
DR GO; GO:0035206; P:regulation of hemocyte proliferation; IMP:FlyBase.
DR GO; GO:0035159; P:regulation of tube length, open tracheal system; IMP:FlyBase.
DR GO; GO:0007435; P:salivary gland morphogenesis; IMP:FlyBase.
DR GO; GO:0007367; P:segment polarity determination; IGI:FlyBase.
DR GO; GO:0016360; P:sensory organ precursor cell fate determination; IMP:FlyBase.
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; IPR026552; FZD7.
DR InterPro; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF31; PTHR11309:SF31; 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..18
FT /evidence="ECO:0000255"
FT CHAIN 19..581
FT /note="Frizzled"
FT /id="PRO_0000013010"
FT TOPO_DOM 19..247
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:10360843"
FT TRANSMEM 248..270
FT /note="Helical; Name=1"
FT /evidence="ECO:0000305"
FT TOPO_DOM 271..280
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10360843"
FT TRANSMEM 281..303
FT /note="Helical; Name=2"
FT /evidence="ECO:0000305"
FT TOPO_DOM 304..343
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:10360843"
FT TRANSMEM 344..364
FT /note="Helical; Name=3"
FT /evidence="ECO:0000305"
FT TOPO_DOM 365..380
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10360843"
FT TRANSMEM 381..401
FT /note="Helical; Name=4"
FT /evidence="ECO:0000305"
FT TOPO_DOM 402..421
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:10360843"
FT TRANSMEM 422..439
FT /note="Helical; Name=5"
FT /evidence="ECO:0000305"
FT TOPO_DOM 440..471
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10360843"
FT TRANSMEM 472..492
FT /note="Helical; Name=6"
FT /evidence="ECO:0000305"
FT TOPO_DOM 493..529
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:10360843"
FT TRANSMEM 530..553
FT /note="Helical; Name=7"
FT /evidence="ECO:0000305"
FT TOPO_DOM 554..581
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10360843"
FT DOMAIN 48..166
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT MOTIF 556..561
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 579..581
FT /note="PDZ-binding"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 53..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 61..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 98..134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 124..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 128..151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
SQ SEQUENCE 581 AA; 64847 MW; 486721D84DA0D0A1 CRC64;
MWRQILFILP TLIQGVQRYD QSPLDASPYY RSGGGLMASS GTELDGLPHH NRCEPITISI
CKNIPYNMTI MPNLIGHTKQ EEAGLEVHQF APLVKIGCSD DLQLFLCSLY VPVCTILERP
IPPCRSLCES ARVCEKLMKT YNFNWPENLE CSKFPVHGGE DLCVAENTTS SASTAATPTR
SVAKVTTRKH QTGVESPHRN IGFVCPVQLK TPLGMGYELK VGGKDLHDCG APCHAMFFPE
RERTVLRYWV GSWAAVCVAS CLFTVLTFLI DSSRFRYPER AIVFLAVCYL VVGCAYVAGL
GAGDSVSCRE PFPPPVKLGR LQMMSTITQG HRQTTSCTVL FMALYFCCMA AFAWWSCLAF
AWFLAAGLKW GHEAIENKSH LFHLVAWAVP ALQTISVLAL AKVEGDILSG VCFVGQLDTH
SLGAFLILPL CIYLSIGALF LLAGFISLFR IRTVMKTDGK RTDKLERLML RIGFFSGLFI
LPAVGLLGCL FYEYYNFDEW MIQWHRDICK PFSIPCPAAR APGSPEARPI FQIFMVKYLC
SMLVGVTSSV WLYSSKTMVS WRNFVERLQG KEPRTRAQAY V
