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Protein

Frizzled

Gene

fz

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. Required to coordinate the cytoskeletons of epidermal cells to produce a parallel array of cuticular hairs and bristles.

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: GO_Central
  2. transmembrane signaling receptor activity Source: FlyBase
  3. Wnt-activated receptor activity Source: FlyBase
  4. Wnt-protein binding Source: FlyBase

GO - Biological processi

  1. asymmetric cell division Source: FlyBase
  2. asymmetric protein localization Source: FlyBase
  3. axon extension Source: FlyBase
  4. border follicle cell migration Source: FlyBase
  5. canonical Wnt signaling pathway Source: FlyBase
  6. compound eye morphogenesis Source: FlyBase
  7. establishment of cell polarity Source: FlyBase
  8. establishment of epithelial cell apical/basal polarity Source: FlyBase
  9. establishment of imaginal disc-derived wing hair orientation Source: FlyBase
  10. establishment of ommatidial planar polarity Source: FlyBase
  11. establishment of planar polarity Source: FlyBase
  12. establishment of tissue polarity Source: FlyBase
  13. establishment or maintenance of cell polarity Source: UniProtKB
  14. G-protein coupled receptor signaling pathway Source: FlyBase
  15. heart development Source: FlyBase
  16. homophilic cell adhesion via plasma membrane adhesion molecules Source: FlyBase
  17. imaginal disc-derived wing hair organization Source: FlyBase
  18. imaginal disc-derived wing hair site selection Source: FlyBase
  19. imaginal disc-derived wing morphogenesis Source: FlyBase
  20. morphogenesis of a polarized epithelium Source: FlyBase
  21. negative regulation of Notch signaling pathway Source: FlyBase
  22. non-canonical Wnt signaling pathway Source: GO_Central
  23. ommatidial rotation Source: FlyBase
  24. protein localization Source: FlyBase
  25. R3/R4 cell fate commitment Source: FlyBase
  26. regulation of actin filament bundle assembly Source: FlyBase
  27. regulation of hemocyte proliferation Source: FlyBase
  28. regulation of tube length, open tracheal system Source: FlyBase
  29. salivary gland morphogenesis Source: FlyBase
  30. sensory organ precursor cell fate determination Source: FlyBase
  31. signal transduction Source: FlyBase
  32. Wnt signaling pathway Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_184329. PCP/CE pathway.
REACT_207070. TCF dependent signaling in response to WNT.
REACT_218761. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
REACT_220429. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_253948. Class B/2 (Secretin family receptors).
SignaLinkiP18537.

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled
Alternative name(s):
Frizzled-1
Short name:
dFz1
Gene namesi
Name:fz
ORF Names:CG17697
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
ProteomesiUP000000803: Chromosome 3L

Organism-specific databases

FlyBaseiFBgn0001085. fz.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 247229Extracellular1 PublicationAdd
BLAST
Transmembranei248 – 27023Helical; Name=1CuratedAdd
BLAST
Topological domaini271 – 28010Cytoplasmic1 Publication
Transmembranei281 – 30323Helical; Name=2CuratedAdd
BLAST
Topological domaini304 – 34340Extracellular1 PublicationAdd
BLAST
Transmembranei344 – 36421Helical; Name=3CuratedAdd
BLAST
Topological domaini365 – 38016Cytoplasmic1 PublicationAdd
BLAST
Transmembranei381 – 40121Helical; Name=4CuratedAdd
BLAST
Topological domaini402 – 42120Extracellular1 PublicationAdd
BLAST
Transmembranei422 – 43918Helical; Name=5CuratedAdd
BLAST
Topological domaini440 – 47132Cytoplasmic1 PublicationAdd
BLAST
Transmembranei472 – 49221Helical; Name=6CuratedAdd
BLAST
Topological domaini493 – 52937Extracellular1 PublicationAdd
BLAST
Transmembranei530 – 55324Helical; Name=7CuratedAdd
BLAST
Topological domaini554 – 58128Cytoplasmic1 PublicationAdd
BLAST

GO - Cellular componenti

  1. cell cortex Source: FlyBase
  2. integral component of membrane Source: UniProtKB
  3. integral component of plasma membrane Source: FlyBase
  4. plasma membrane Source: FlyBase
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 581563FrizzledPRO_0000013010Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi53 ↔ 114PROSITE-ProRule annotation
Disulfide bondi61 ↔ 107PROSITE-ProRule annotation
Glycosylationi67 – 671N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi98 ↔ 134PROSITE-ProRule annotation
Disulfide bondi124 ↔ 163PROSITE-ProRule annotation
Disulfide bondi128 ↔ 151PROSITE-ProRule annotation
Glycosylationi167 – 1671N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP18537.
PRIDEiP18537.

Expressioni

Gene expression databases

BgeeiP18537.
ExpressionAtlasiP18537. differential.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
stanQ9V5N83EBI-251576,EBI-119250

Protein-protein interaction databases

BioGridi69580. 25 interactions.
DIPiDIP-22727N.
IntActiP18537. 3 interactions.
MINTiMINT-1663972.

Structurei

3D structure databases

ProteinModelPortaliP18537.
SMRiP18537. Positions 53-164, 208-562.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini48 – 166119FZPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi556 – 5616Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family membersBy similarity
Motifi579 – 5813PDZ-binding

Domaini

Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.By similarity
The FZ domain is involved in binding with Wnt ligands.By similarity

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
InParanoidiP18537.
KOiK02432.
OrthoDBiEOG7M3J01.
PhylomeDBiP18537.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR026561. dFz1.
IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF47. PTHR11309:SF47. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform I (identifier: P18537-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MWRQILFILP TLIQGVQRYD QSPLDASPYY RSGGGLMASS GTELDGLPHH
60 70 80 90 100
NRCEPITISI CKNIPYNMTI MPNLIGHTKQ EEAGLEVHQF APLVKIGCSD
110 120 130 140 150
DLQLFLCSLY VPVCTILERP IPPCRSLCES ARVCEKLMKT YNFNWPENLE
160 170 180 190 200
CSKFPVHGGE DLCVAENTTS SASTAATPTR SVAKVTTRKH QTGVESPHRN
210 220 230 240 250
IGFVCPVQLK TPLGMGYELK VGGKDLHDCG APCHAMFFPE RERTVLRYWV
260 270 280 290 300
GSWAAVCVAS CLFTVLTFLI DSSRFRYPER AIVFLAVCYL VVGCAYVAGL
310 320 330 340 350
GAGDSVSCRE PFPPPVKLGR LQMMSTITQG HRQTTSCTVL FMALYFCCMA
360 370 380 390 400
AFAWWSCLAF AWFLAAGLKW GHEAIENKSH LFHLVAWAVP ALQTISVLAL
410 420 430 440 450
AKVEGDILSG VCFVGQLDTH SLGAFLILPL CIYLSIGALF LLAGFISLFR
460 470 480 490 500
IRTVMKTDGK RTDKLERLML RIGFFSGLFI LPAVGLLGCL FYEYYNFDEW
510 520 530 540 550
MIQWHRDICK PFSIPCPAAR APGSPEARPI FQIFMVKYLC SMLVGVTSSV
560 570 580
WLYSSKTMVS WRNFVERLQG KEPRTRAQAY V
Length:581
Mass (Da):64,847
Last modified:November 1, 1990 - v1
Checksum:i486721D84DA0D0A1
GO
Isoform II (identifier: P18537-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     406-415: DILSGVCFVG → MYLWQFHTIN
     416-581: Missing.

Show »
Length:415
Mass (Da):46,118
Checksum:iF0A0A5AA080BAAE7
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei406 – 41510DILSGVCFVG → MYLWQFHTIN in isoform II. 1 PublicationVSP_002013
Alternative sequencei416 – 581166Missing in isoform II. 1 PublicationVSP_002014Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54648
, X54649, X54650, X54651 Genomic DNA. Translation: CAA38460.1.
X54648
, X54649, X54650, X54652 Genomic DNA. Translation: CAA38461.1.
X54646 mRNA. Translation: CAA38458.1.
X54647 mRNA. Translation: CAA38459.1. Sequence problems.
AE014296 Genomic DNA. Translation: AAF49746.3.
AE014296 Genomic DNA. Translation: AAN11810.1.
AY051808 mRNA. Translation: AAK93232.1.
PIRiS03540.
RefSeqiNP_524812.1. NM_080073.3. [P18537-1]
UniGeneiDm.1456.

Genome annotation databases

EnsemblMetazoaiFBtr0075743; FBpp0075485; FBgn0001085. [P18537-1]
GeneIDi45307.
KEGGidme:Dmel_CG17697.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54648
, X54649, X54650, X54651 Genomic DNA. Translation: CAA38460.1.
X54648
, X54649, X54650, X54652 Genomic DNA. Translation: CAA38461.1.
X54646 mRNA. Translation: CAA38458.1.
X54647 mRNA. Translation: CAA38459.1. Sequence problems.
AE014296 Genomic DNA. Translation: AAF49746.3.
AE014296 Genomic DNA. Translation: AAN11810.1.
AY051808 mRNA. Translation: AAK93232.1.
PIRiS03540.
RefSeqiNP_524812.1. NM_080073.3. [P18537-1]
UniGeneiDm.1456.

3D structure databases

ProteinModelPortaliP18537.
SMRiP18537. Positions 53-164, 208-562.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi69580. 25 interactions.
DIPiDIP-22727N.
IntActiP18537. 3 interactions.
MINTiMINT-1663972.

Protein family/group databases

MEROPSiI93.001.
GPCRDBiSearch...

Proteomic databases

PaxDbiP18537.
PRIDEiP18537.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0075743; FBpp0075485; FBgn0001085. [P18537-1]
GeneIDi45307.
KEGGidme:Dmel_CG17697.

Organism-specific databases

CTDi45307.
FlyBaseiFBgn0001085. fz.

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00760000118864.
InParanoidiP18537.
KOiK02432.
OrthoDBiEOG7M3J01.
PhylomeDBiP18537.

Enzyme and pathway databases

ReactomeiREACT_184329. PCP/CE pathway.
REACT_207070. TCF dependent signaling in response to WNT.
REACT_218761. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
REACT_220429. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_253948. Class B/2 (Secretin family receptors).
SignaLinkiP18537.

Miscellaneous databases

GenomeRNAii45307.
NextBioi837994.

Gene expression databases

BgeeiP18537.
ExpressionAtlasiP18537. differential.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR026561. dFz1.
IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF47. PTHR11309:SF47. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains."
    Vinson C.R., Conover S., Adler P.N.
    Nature 338:263-264(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORM I).
  2. "Molecular structure of frizzled, a Drosophila tissue polarity gene."
    Adler P.N., Vinson C., Park W.J., Conover S., Klein L.
    Genetics 126:401-416(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS I AND II).
    Strain: Canton-S.
    Tissue: Embryo.
  3. "The genome sequence of Drosophila melanogaster."
    Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D.
    , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
    Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Berkeley.
  4. Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
    Strain: Berkeley.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I).
    Strain: Berkeley.
    Tissue: Embryo.
  6. "Frizzled-suc2 fusion gene studies in Saccharomyces cerevisiae."
    Goo J.H., Ahn Y., Park W.J.
    DNA Cell Biol. 18:429-434(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY.

Entry informationi

Entry nameiFRIZ_DROME
AccessioniPrimary (citable) accession number: P18537
Secondary accession number(s): Q9VUE0, Q9VUE2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: February 4, 2015
This is version 166 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.