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P18537 (FRIZ_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled
Alternative name(s):
Frizzled-1
Short name=dFz1
Gene names
Name:fz
ORF Names:CG17697
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length581 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Domain

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 similarities

Belongs to the G-protein coupled receptor Fz/Smo family.

Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from genetic interaction PubMed 23524329. Source: FlyBase

R3/R4 cell fate commitment

Inferred from mutant phenotype PubMed 23524329. Source: FlyBase

Wnt signaling pathway

Non-traceable author statement PubMed 12000787. Source: FlyBase

asymmetric cell division

Inferred from mutant phenotype PubMed 16617104. Source: FlyBase

asymmetric protein localization

Traceable author statement PubMed 12231350. Source: FlyBase

axon extension

Inferred from mutant phenotype PubMed 17032066. Source: FlyBase

border follicle cell migration

Inferred from mutant phenotype PubMed 17652348. Source: FlyBase

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from genetic interaction PubMed 16163385. Source: FlyBase

compound eye morphogenesis

Inferred from mutant phenotype PubMed 21811578. Source: FlyBase

establishment of cell polarity

Inferred from mutant phenotype PubMed 11239465. Source: FlyBase

establishment of epithelial cell apical/basal polarity

Inferred from mutant phenotype PubMed 12540853. Source: FlyBase

establishment of imaginal disc-derived wing hair orientation

Inferred from mutant phenotype PubMed 10490098PubMed 11239465PubMed 16824922. Source: FlyBase

establishment of ommatidial planar polarity

Inferred from mutant phenotype PubMed 11893338PubMed 16824921PubMed 16824922PubMed 7555730. Source: FlyBase

establishment of planar polarity

Inferred from mutant phenotype PubMed 10490098. Source: FlyBase

establishment of tissue polarity

Non-traceable author statement PubMed 12000787PubMed 12231350. Source: FlyBase

establishment or maintenance of cell polarity

Inferred from mutant phenotype Ref.1. Source: UniProtKB

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

heart development

Non-traceable author statement PubMed 12027431. Source: FlyBase

homophilic cell adhesion

Inferred from mutant phenotype PubMed 10490098. Source: FlyBase

imaginal disc-derived wing hair organization

Inferred from genetic interaction PubMed 11301004. Source: FlyBase

imaginal disc-derived wing hair site selection

Inferred from mutant phenotype PubMed 7918095. Source: FlyBase

imaginal disc-derived wing morphogenesis

Inferred from mutant phenotype PubMed 21635778. Source: FlyBase

morphogenesis of a polarized epithelium

Inferred from mutant phenotype PubMed 16326392. Source: FlyBase

negative regulation of Notch signaling pathway

Inferred from mutant phenotype PubMed 22736244. Source: FlyBase

ommatidial rotation

Inferred from mutant phenotype PubMed 7555730. Source: FlyBase

protein localization

Traceable author statement PubMed 12000787PubMed 12127767. Source: FlyBase

regulation of actin filament bundle assembly

Inferred from genetic interaction PubMed 11301004. Source: FlyBase

regulation of hemocyte proliferation

Inferred from mutant phenotype PubMed 20688956. Source: FlyBase

regulation of tube length, open tracheal system

Inferred from mutant phenotype PubMed 19956736. Source: FlyBase

salivary gland morphogenesis

Inferred from mutant phenotype PubMed 17507403. Source: FlyBase

sensory organ precursor cell fate determination

Inferred from mutant phenotype PubMed 11146626. Source: FlyBase

signal transduction

Inferred from sequence or structural similarity PubMed 10908591. Source: FlyBase

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcell cortex

Inferred from direct assay PubMed 11239465. Source: FlyBase

integral component of membrane

Non-traceable author statement Ref.2. Source: UniProtKB

integral component of plasma membrane

Traceable author statement PubMed 7555730. Source: FlyBase

neuron projection membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from direct assay PubMed 16163385PubMed 8199049. Source: FlyBase

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-activated receptor activity

Inferred from direct assay PubMed 16163385. Source: FlyBase

Wnt-protein binding

Inferred from physical interaction PubMed 12205098. Source: FlyBase

protein binding

Inferred from physical interaction PubMed 18555784. Source: IntAct

transmembrane signaling receptor activity

Inferred from sequence or structural similarity PubMed 10908591. Source: FlyBase

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

stanQ9V5N83EBI-251576,EBI-119250

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform I (identifier: P18537-1)

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.
Isoform II (identifier: P18537-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 581563Frizzled
PRO_0000013010

Regions

Topological domain19 – 247229Extracellular Probable
Transmembrane248 – 27023Helical; Name=1; Probable
Topological domain271 – 28010Cytoplasmic Probable
Transmembrane281 – 30323Helical; Name=2; Probable
Topological domain304 – 34340Extracellular Probable
Transmembrane344 – 36421Helical; Name=3; Probable
Topological domain365 – 38016Cytoplasmic Probable
Transmembrane381 – 40121Helical; Name=4; Probable
Topological domain402 – 42120Extracellular Probable
Transmembrane422 – 43918Helical; Name=5; Probable
Topological domain440 – 47132Cytoplasmic Probable
Transmembrane472 – 49221Helical; Name=6; Probable
Topological domain493 – 52937Extracellular Probable
Transmembrane530 – 55324Helical; Name=7; Probable
Topological domain554 – 58128Cytoplasmic Probable
Domain48 – 166119FZ
Motif556 – 5616Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif579 – 5813PDZ-binding

Amino acid modifications

Glycosylation671N-linked (GlcNAc...) Potential
Glycosylation1671N-linked (GlcNAc...) Potential
Disulfide bond53 ↔ 114 By similarity
Disulfide bond61 ↔ 107 By similarity
Disulfide bond98 ↔ 134 By similarity
Disulfide bond124 ↔ 163 By similarity
Disulfide bond128 ↔ 151 By similarity

Natural variations

Alternative sequence406 – 41510DILSGVCFVG → MYLWQFHTIN in isoform II.
VSP_002013
Alternative sequence416 – 581166Missing in isoform II.
VSP_002014

Sequences

Sequence LengthMass (Da)Tools
Isoform I [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: 486721D84DA0D0A1

FASTA58164,847
        10         20         30         40         50         60 
MWRQILFILP TLIQGVQRYD QSPLDASPYY RSGGGLMASS GTELDGLPHH NRCEPITISI 

        70         80         90        100        110        120 
CKNIPYNMTI MPNLIGHTKQ EEAGLEVHQF APLVKIGCSD DLQLFLCSLY VPVCTILERP 

       130        140        150        160        170        180 
IPPCRSLCES ARVCEKLMKT YNFNWPENLE CSKFPVHGGE DLCVAENTTS SASTAATPTR 

       190        200        210        220        230        240 
SVAKVTTRKH QTGVESPHRN IGFVCPVQLK TPLGMGYELK VGGKDLHDCG APCHAMFFPE 

       250        260        270        280        290        300 
RERTVLRYWV GSWAAVCVAS CLFTVLTFLI DSSRFRYPER AIVFLAVCYL VVGCAYVAGL 

       310        320        330        340        350        360 
GAGDSVSCRE PFPPPVKLGR LQMMSTITQG HRQTTSCTVL FMALYFCCMA AFAWWSCLAF 

       370        380        390        400        410        420 
AWFLAAGLKW GHEAIENKSH LFHLVAWAVP ALQTISVLAL AKVEGDILSG VCFVGQLDTH 

       430        440        450        460        470        480 
SLGAFLILPL CIYLSIGALF LLAGFISLFR IRTVMKTDGK RTDKLERLML RIGFFSGLFI 

       490        500        510        520        530        540 
LPAVGLLGCL FYEYYNFDEW MIQWHRDICK PFSIPCPAAR APGSPEARPI FQIFMVKYLC 

       550        560        570        580 
SMLVGVTSSV WLYSSKTMVS WRNFVERLQG KEPRTRAQAY V 

« Hide

Isoform II [UniParc].

Checksum: F0A0A5AA080BAAE7
Show »

FASTA41546,118

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review."
Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. expand/collapse author list , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
Strain: Berkeley.
[5]"A Drosophila full-length cDNA resource."
Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E.
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X54648 expand/collapse EMBL AC list , X54649, X54650, X54651 Genomic DNA. Translation: CAA38460.1.
X54648 expand/collapse EMBL AC list , 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.
PIRS03540.
RefSeqNP_524812.1. NM_080073.3. [P18537-1]
NP_729970.1. NM_168587.2. [P18537-2]
UniGeneDm.1456.

3D structure databases

ProteinModelPortalP18537.
SMRP18537. Positions 53-164, 208-562.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid69580. 25 interactions.
DIPDIP-22727N.
IntActP18537. 3 interactions.
MINTMINT-1663972.

Protein family/group databases

GPCRDBSearch...

Proteomic databases

PaxDbP18537.
PRIDEP18537.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaFBtr0075743; FBpp0075485; FBgn0001085. [P18537-1]
GeneID45307.
KEGGdme:Dmel_CG17697.

Organism-specific databases

CTD45307.
FlyBaseFBgn0001085. fz.

Phylogenomic databases

eggNOGNOG257258.
GeneTreeENSGT00740000114899.
InParanoidP18537.
KOK02432.
OrthoDBEOG7M3J01.
PhylomeDBP18537.

Enzyme and pathway databases

SignaLinkP18537.

Gene expression databases

BgeeP18537.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR026561. dFz1.
IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF47. PTHR11309:SF47. 1 hit.
PfamPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSPR00489. FRIZZLED.
SMARTSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi45307.
NextBio837994.

Entry information

Entry nameFRIZ_DROME
AccessionPrimary (citable) accession number: P18537
Secondary accession number(s): Q9VUE0, Q9VUE2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: July 9, 2014
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries