FRIZ2_DROME
ID FRIZ2_DROME Reviewed; 694 AA.
AC Q9VVX3; A8JNV7; Q494J1; Q94916; Q9VVX2;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Frizzled-2;
DE Short=dFz2;
DE Flags: Precursor;
GN Name=fz2; ORFNames=CG9739;
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 [GENOMIC DNA], AND INTERACTION WITH WG THROUGH FZ
RP DOMAIN.
RX PubMed=8717036; DOI=10.1038/382225a0;
RA Bhanot P., Brink M., Samos C.H., Hsieh J.C., Wang Y., Macke J.P.,
RA Andrew D., Nathans J., Nusse R.;
RT "A new member of the frizzled family from Drosophila functions as a
RT Wingless receptor.";
RL Nature 382:225-230(1996).
RN [2]
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 [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10097073; DOI=10.1073/pnas.96.7.3546;
RA Hsieh J.C., Rattner A., Smallwood P.M., Nathans J.;
RT "Biochemical characterization of Wnt-frizzled interactions using a soluble,
RT biologically active vertebrate Wnt protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3546-3551(1999).
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;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
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. {ECO:0000269|PubMed:10097073}.
CC -!- SUBUNIT: Interacts with ATP6AP2. {ECO:0000269|PubMed:20579883}.
CC -!- INTERACTION:
CC Q9VVX3; Q9W450: Grip; NbExp=3; IntAct=EBI-118222, EBI-149374;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10097073};
CC Multi-pass membrane protein {ECO:0000269|PubMed:10097073}.
CC -!- DEVELOPMENTAL STAGE: Expression starts at stage 6 in all cells between
CC 15 and 70 per cent of egg length, including the invaginating cells of
CC the ventral furrow. Stripe pattern is emerging by early stage 8. From
CC stage 9 and continuing throughout embryogenesis, expression is seen in
CC the developing CNS. At stage 10, expressed in 15 stripes in the
CC presumptive head and trunk regions, in the posterior midgut primordium,
CC in a subset of cells of anterior midgut invagination and in the
CC procephalic lobe. At stage 12, expression declines in epidermis and
CC increases in the midgut and visceral mesoderm. At stage 17, only
CC expressed in the CNS, hindgut and dorsal vessel.
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:0000269|PubMed:8717036}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family.
CC {ECO:0000305}.
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DR EMBL; U65589; AAC47273.1; -; Genomic_DNA.
DR EMBL; AE014296; AAF49184.1; -; Genomic_DNA.
DR EMBL; AE014296; ABW08569.1; -; Genomic_DNA.
DR EMBL; BT023785; AAZ41794.1; -; mRNA.
DR PIR; S71786; S71786.
DR RefSeq; NP_001097643.1; NM_001104173.3.
DR RefSeq; NP_001137971.1; NM_001144499.3.
DR RefSeq; NP_001262036.1; NM_001275107.1.
DR RefSeq; NP_001262038.1; NM_001275109.1.
DR RefSeq; NP_524155.1; NM_079431.2.
DR RefSeq; NP_730389.1; NM_168787.3.
DR AlphaFoldDB; Q9VVX3; -.
DR SMR; Q9VVX3; -.
DR BioGRID; 65366; 30.
DR DIP; DIP-17196N; -.
DR IntAct; Q9VVX3; 60.
DR STRING; 7227.FBpp0304981; -.
DR TCDB; 9.A.14.16.2; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; Q9VVX3; 2 sites.
DR PaxDb; Q9VVX3; -.
DR DNASU; 40090; -.
DR EnsemblMetazoa; FBtr0075028; FBpp0074795; FBgn0016797.
DR EnsemblMetazoa; FBtr0075029; FBpp0074796; FBgn0016797.
DR EnsemblMetazoa; FBtr0112890; FBpp0111803; FBgn0016797.
DR EnsemblMetazoa; FBtr0299586; FBpp0288861; FBgn0016797.
DR EnsemblMetazoa; FBtr0330194; FBpp0303227; FBgn0016797.
DR EnsemblMetazoa; FBtr0332735; FBpp0304981; FBgn0016797.
DR GeneID; 40090; -.
DR KEGG; dme:Dmel_CG9739; -.
DR UCSC; CG9739-RC; d. melanogaster.
DR CTD; 40090; -.
DR FlyBase; FBgn0016797; fz2.
DR VEuPathDB; VectorBase:FBgn0016797; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000166857; -.
DR HOGENOM; CLU_007873_2_0_1; -.
DR InParanoid; Q9VVX3; -.
DR OMA; MECYLLG; -.
DR OrthoDB; 509772at2759; -.
DR PhylomeDB; Q9VVX3; -.
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-4086398; Ca2+ pathway.
DR Reactome; R-DME-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-DME-5140745; WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
DR SignaLink; Q9VVX3; -.
DR BioGRID-ORCS; 40090; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 40090; -.
DR PRO; PR:Q9VVX3; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0016797; Expressed in wing disc and 45 other tissues.
DR ExpressionAtlas; Q9VVX3; baseline and differential.
DR Genevisible; Q9VVX3; 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:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:1990909; C:Wnt signalosome; IDA:FlyBase.
DR GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; ISS:FlyBase.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; IPI:FlyBase.
DR GO; GO:0042813; F:Wnt receptor activity; IDA:FlyBase.
DR GO; GO:0017147; F:Wnt-protein binding; IDA:UniProtKB.
DR GO; GO:0048675; P:axon extension; IMP:FlyBase.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:FlyBase.
DR GO; GO:0042685; P:cardioblast cell fate specification; IGI:FlyBase.
DR GO; GO:0016477; P:cell migration; IMP:FlyBase.
DR GO; GO:0035293; P:chitin-based larval cuticle pattern formation; IGI:FlyBase.
DR GO; GO:0008585; P:female gonad development; IMP:FlyBase.
DR GO; GO:0060250; P:germ-line stem-cell niche homeostasis; IMP:FlyBase.
DR GO; GO:0008587; P:imaginal disc-derived wing margin morphogenesis; IMP:FlyBase.
DR GO; GO:0007494; P:midgut development; IGI:FlyBase.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:FlyBase.
DR GO; GO:0048665; P:neuron fate specification; IGI:FlyBase.
DR GO; GO:0050770; P:regulation of axonogenesis; IMP:FlyBase.
DR GO; GO:0035206; P:regulation of hemocyte proliferation; IMP:FlyBase.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; 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:0050808; P:synapse organization; IPI:FlyBase.
DR GO; GO:0016201; P:synaptic target inhibition; IMP:FlyBase.
DR GO; GO:0016055; P:Wnt signaling pathway; IDA:UniProtKB.
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; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 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..22
FT /evidence="ECO:0000255"
FT CHAIN 23..694
FT /note="Frizzled-2"
FT /id="PRO_0000013012"
FT TOPO_DOM 23..315
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 316..336
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 337..352
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 353..373
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 374..397
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 398..418
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 419..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..482
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..534
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 535..555
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 556..584
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 585..605
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 606..694
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 59..180
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 175..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 608..613
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 692..694
FT /note="PDZ-binding"
FT COMPBIAS 181..249
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 64..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 72..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 109..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 136..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 140..164
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT CONFLICT 55
FT /note="V -> A (in Ref. 1; AAC47273)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="S -> T (in Ref. 1; AAC47273)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 694 AA; 75451 MW; 6C510F13CBAFB096 CRC64;
MRHNRLKVLI LGLVLLLTSC RADGPLHSAD HGMGGMGMGG HGLDASPAPG YGVPVIPKDP
NLRCEEITIP MCRGIGYNMT SFPNEMNHET QDEAGLEVHQ FWPLVEIKCS PDLKFFLCSM
YTPICLEDYH KPLPVCRSVC ERARSGCAPI MQQYSFEWPE RMACEHLPLH GDPDNLCMEQ
PSYTEAGSGG SSGGSGGSGS GSGSGGKRKQ GGSGSGGSGA GGSSGSTSTK PCRGRNSKNC
QNPQGEKASG KECSCSCRSP LIFLGKEQLL QQQSQMPMMH HPHHWYMNLT VQRIAGVPNC
GIPCKGPFFS NDEKDFAGLW IALWSGLCFC STLMTLTTFI IDTERFKYPE RPIVFLSACY
FMVAVGYLSR NFLQNEEIAC DGLLLRESST GPHSCTLVFL LTYFFGMASS IWWVILSFTW
FLAAGLKWGN EAITKHSQYF HLAAWLIPTV QSVAVLLLSA VDGDPILGIC YVGNLNPDHL
KTFVLAPLFV YLVIGTTFLM AGFVSLFRIR SVIKQQGGVG AGVKADKLEK LMIRIGIFSV
LYTVPATIVI GCYLYEAAYF EDWIKALACP CAQVKGPGKK PLYSVLMLKY FMALAVGITS
GVWIWSGKTL ESWRRFWRRL LGAPDRTGAN QALIKQRPPI PHPYAGSGMG MPVGSAAGSL
LATPYTQAGG ASVASTSHHH LHHHVLKQPA ASHV
