FRIZ4_DROME
ID FRIZ4_DROME Reviewed; 705 AA.
AC Q9NBW1; Q9W3S2;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Frizzled-4;
DE Short=dFz4;
DE Flags: Precursor;
GN Name=fz4; ORFNames=CG4626;
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].
RA Xu Y.K., Nusse R.;
RT "Dfz4 acts in the Wg pathway.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
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 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Ovary;
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).
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. May be involved in transduction and
CC intercellular transmission of polarity information during tissue
CC morphogenesis and/or in differentiated tissues. Required to coordinate
CC the cytoskeletons of epidermal cells to produce a parallel array of
CC cuticular hairs and bristles.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
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}.
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DR EMBL; AF241270; AAF81195.1; -; mRNA.
DR EMBL; AE014298; AAN09202.1; -; Genomic_DNA.
DR EMBL; AY118543; AAM49912.1; -; mRNA.
DR RefSeq; NP_511068.2; NM_078513.3.
DR RefSeq; NP_727170.2; NM_167119.3.
DR AlphaFoldDB; Q9NBW1; -.
DR SMR; Q9NBW1; -.
DR BioGRID; 58135; 6.
DR IntAct; Q9NBW1; 1.
DR MINT; Q9NBW1; -.
DR STRING; 7227.FBpp0070976; -.
DR GlyGen; Q9NBW1; 4 sites.
DR PaxDb; Q9NBW1; -.
DR PRIDE; Q9NBW1; -.
DR DNASU; 31659; -.
DR EnsemblMetazoa; FBtr0071017; FBpp0070976; FBgn0027342.
DR EnsemblMetazoa; FBtr0071018; FBpp0070977; FBgn0027342.
DR GeneID; 31659; -.
DR KEGG; dme:Dmel_CG4626; -.
DR CTD; 31659; -.
DR FlyBase; FBgn0027342; fz4.
DR VEuPathDB; VectorBase:FBgn0027342; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000157141; -.
DR HOGENOM; CLU_007873_2_1_1; -.
DR InParanoid; Q9NBW1; -.
DR OMA; HETMCME; -.
DR OrthoDB; 509772at2759; -.
DR PhylomeDB; Q9NBW1; -.
DR Reactome; R-DME-4086398; Ca2+ pathway.
DR Reactome; R-DME-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-DME-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-DME-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-DME-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q9NBW1; -.
DR BioGRID-ORCS; 31659; 0 hits in 1 CRISPR screen.
DR ChiTaRS; fz4; fly.
DR GenomeRNAi; 31659; -.
DR PRO; PR:Q9NBW1; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0027342; Expressed in adult abdomen and 27 other tissues.
DR ExpressionAtlas; Q9NBW1; baseline and differential.
DR Genevisible; Q9NBW1; DM.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; ISS:FlyBase.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISS:FlyBase.
DR GO; GO:0042813; F:Wnt receptor activity; IEA:InterPro.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:FlyBase.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; ISS:FlyBase.
DR CDD; cd07448; CRD_FZ4; 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; IPR041765; FZ4_CRD.
DR InterPro; IPR026551; FZD4.
DR InterPro; IPR017981; GPCR_2-like.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF23; PTHR11309:SF23; 1.
DR Pfam; PF01534; Frizzled; 2.
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 2: Evidence at transcript level;
KW Developmental protein; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Signal; Transducer;
KW Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..705
FT /note="Frizzled-4"
FT /id="PRO_0000013014"
FT TOPO_DOM 23..233
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..322
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 344..386
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 408..430
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 431..451
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 452..483
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..504
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 505..529
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 530..550
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 551..705
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 41..163
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 21..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 635..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 703..705
FT /note="PDZ-binding"
FT COMPBIAS 639..669
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 46..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 54..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 91..130
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 119..160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 123..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
SQ SEQUENCE 705 AA; 77490 MW; 0188DFCE57BB626F CRC64;
MKPTCILCLL VVILLHPRIS KSSTSGNPSA SSSSSSPPEI PAFRQCETIR IEMCRKIGYN
ETSMPNLVGN EMQTDVEYTL QTFAPLIEYD CSSQLKLFLC AAYVPMCTPK APVHAIGPCR
SLCESVRIRC HPVLQGFGFP WPPALDCDKF PRENNHETMC MEGPGELHQP QQEQDLYGLP
GQGIPGGLGG KLPMDCSGLA KSHLYVRLPR SGRCAPLCEA DILFTPAEKH LAEIWVSTWA
YAALGLALVA TVCLLASDGS RLASAKWSRL LSPLIWCHNM VTLGWAVRFM VGRTGTACGT
DPQAPNESLL TVDGLSNASC ASVFLMRYYF GMAACAWWAV LCLGWHRDIR RHSPDSKGHV
VIPSNFGGSP AKRNSAKTAQ QDLTQNNFVC FVAWGLPAFQ TSAVIVARFV DADELLGACF
VGNQSDKALQ ILVATPVFCY WIFGSMNLIS GYLVHCRTKE ILRNSNALSV QQQLQQLSAH
SSSGIGIFLF IYGLACAMLL LAVIYEFANI DVWLGSGDTN TPLWPFLLRA FMELMLGICC
FAWVLGPSIS TLYKRQVSNG KMVKHTSAGA ATGHLDGHSS SRGSHAACNS TVVSYHSVRT
SMASVPLPPS PYKLKTSPGT GSISLNQMSN YSLGRSVHHQ QRHSPHHHHH QQQQHHQFHP
HHNHQHHSTS SHRLYYPPGS YASQKYSQHG SYYPHLQQYG NETLL
