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P18537

- FRIZ_DROME

UniProt

P18537 - FRIZ_DROME

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Protein
Frizzled
Gene
fz, CG17697
Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed - 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: UniProtKB-KW
  2. PDZ domain binding Source: RefGenome
  3. Wnt-activated receptor activity Source: FlyBase
  4. Wnt-protein binding Source: FlyBase
  5. protein binding Source: IntAct
  6. transmembrane signaling receptor activity Source: FlyBase

GO - Biological processi

  1. G-protein coupled receptor signaling pathway Source: FlyBase
  2. R3/R4 cell fate commitment Source: FlyBase
  3. Wnt signaling pathway Source: FlyBase
  4. asymmetric cell division Source: FlyBase
  5. asymmetric protein localization Source: FlyBase
  6. axon extension Source: FlyBase
  7. border follicle cell migration Source: FlyBase
  8. brain development Source: RefGenome
  9. canonical Wnt signaling pathway Source: FlyBase
  10. compound eye morphogenesis Source: FlyBase
  11. establishment of cell polarity Source: FlyBase
  12. establishment of epithelial cell apical/basal polarity Source: FlyBase
  13. establishment of imaginal disc-derived wing hair orientation Source: FlyBase
  14. establishment of ommatidial planar polarity Source: FlyBase
  15. establishment of planar polarity Source: FlyBase
  16. establishment of tissue polarity Source: FlyBase
  17. establishment or maintenance of cell polarity Source: UniProtKB
  18. gonad development Source: RefGenome
  19. heart development Source: FlyBase
  20. homophilic cell adhesion Source: FlyBase
  21. imaginal disc-derived wing hair organization Source: FlyBase
  22. imaginal disc-derived wing hair site selection Source: FlyBase
  23. imaginal disc-derived wing morphogenesis Source: FlyBase
  24. morphogenesis of a polarized epithelium Source: FlyBase
  25. negative regulation of Notch signaling pathway Source: FlyBase
  26. ommatidial rotation Source: FlyBase
  27. protein localization Source: FlyBase
  28. regulation of actin filament bundle assembly Source: FlyBase
  29. regulation of hemocyte proliferation Source: FlyBase
  30. regulation of tube length, open tracheal system Source: FlyBase
  31. salivary gland morphogenesis Source: FlyBase
  32. sensory organ precursor cell fate determination Source: FlyBase
  33. signal transduction Source: FlyBase
  34. vasculature development Source: RefGenome
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.
SignaLinkiP18537.

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 – 247229Extracellular Inferred
Add
BLAST
Transmembranei248 – 27023Helical; Name=1; Inferred
Add
BLAST
Topological domaini271 – 28010Cytoplasmic Inferred
Transmembranei281 – 30323Helical; Name=2; Inferred
Add
BLAST
Topological domaini304 – 34340Extracellular Inferred
Add
BLAST
Transmembranei344 – 36421Helical; Name=3; Inferred
Add
BLAST
Topological domaini365 – 38016Cytoplasmic Inferred
Add
BLAST
Transmembranei381 – 40121Helical; Name=4; Inferred
Add
BLAST
Topological domaini402 – 42120Extracellular Inferred
Add
BLAST
Transmembranei422 – 43918Helical; Name=5; Inferred
Add
BLAST
Topological domaini440 – 47132Cytoplasmic Inferred
Add
BLAST
Transmembranei472 – 49221Helical; Name=6; Inferred
Add
BLAST
Topological domaini493 – 52937Extracellular Inferred
Add
BLAST
Transmembranei530 – 55324Helical; Name=7; Inferred
Add
BLAST
Topological domaini554 – 58128Cytoplasmic Inferred
Add
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. neuron projection membrane Source: RefGenome
  5. 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 – 1818 Reviewed prediction
Add
BLAST
Chaini19 – 581563Frizzled
PRO_0000013010Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi53 ↔ 114 By similarity
Disulfide bondi61 ↔ 107 By similarity
Glycosylationi67 – 671N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi98 ↔ 134 By similarity
Disulfide bondi124 ↔ 163 By similarity
Disulfide bondi128 ↔ 151 By similarity
Glycosylationi167 – 1671N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP18537.
PRIDEiP18537.

Expressioni

Gene expression databases

BgeeiP18537.

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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini48 – 166119FZ
Add
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 members By 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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
GeneTreeiENSGT00740000114899.
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

MWRQILFILP TLIQGVQRYD QSPLDASPYY RSGGGLMASS GTELDGLPHH    50
NRCEPITISI CKNIPYNMTI MPNLIGHTKQ EEAGLEVHQF APLVKIGCSD 100
DLQLFLCSLY VPVCTILERP IPPCRSLCES ARVCEKLMKT YNFNWPENLE 150
CSKFPVHGGE DLCVAENTTS SASTAATPTR SVAKVTTRKH QTGVESPHRN 200
IGFVCPVQLK TPLGMGYELK VGGKDLHDCG APCHAMFFPE RERTVLRYWV 250
GSWAAVCVAS CLFTVLTFLI DSSRFRYPER AIVFLAVCYL VVGCAYVAGL 300
GAGDSVSCRE PFPPPVKLGR LQMMSTITQG HRQTTSCTVL FMALYFCCMA 350
AFAWWSCLAF AWFLAAGLKW GHEAIENKSH LFHLVAWAVP ALQTISVLAL 400
AKVEGDILSG VCFVGQLDTH SLGAFLILPL CIYLSIGALF LLAGFISLFR 450
IRTVMKTDGK RTDKLERLML RIGFFSGLFI LPAVGLLGCL FYEYYNFDEW 500
MIQWHRDICK PFSIPCPAAR APGSPEARPI FQIFMVKYLC SMLVGVTSSV 550
WLYSSKTMVS WRNFVERLQG KEPRTRAQAY V 581
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.
VSP_002013
Alternative sequencei416 – 581166Missing in isoform II.
VSP_002014Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
NP_729970.1. NM_168587.2. [P18537-2]
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:
EMBL
GenBank
DDBJ
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 .
PIRi S03540.
RefSeqi NP_524812.1. NM_080073.3. [P18537-1 ]
NP_729970.1. NM_168587.2. [P18537-2 ]
UniGenei Dm.1456.

3D structure databases

ProteinModelPortali P18537.
SMRi P18537. Positions 53-164, 208-562.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 69580. 25 interactions.
DIPi DIP-22727N.
IntActi P18537. 3 interactions.
MINTi MINT-1663972.

Protein family/group databases

GPCRDBi Search...

Proteomic databases

PaxDbi P18537.
PRIDEi P18537.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblMetazoai FBtr0075743 ; FBpp0075485 ; FBgn0001085 . [P18537-1 ]
GeneIDi 45307.
KEGGi dme:Dmel_CG17697.

Organism-specific databases

CTDi 45307.
FlyBasei FBgn0001085. fz.

Phylogenomic databases

eggNOGi NOG257258.
GeneTreei ENSGT00740000114899.
InParanoidi P18537.
KOi K02432.
OrthoDBi EOG7M3J01.
PhylomeDBi P18537.

Enzyme and pathway databases

Reactomei REACT_184329. PCP/CE pathway.
REACT_207070. TCF dependent signaling in response to WNT.
REACT_218761. WNT5A-dependent internalization of FZD2, FZD5 and ROR2.
SignaLinki P18537.

Miscellaneous databases

GenomeRNAii 45307.
NextBioi 837994.

Gene expression databases

Bgeei P18537.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR026561. dFz1.
IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF47. PTHR11309:SF47. 1 hit.
Pfami PF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view ]
PRINTSi PR00489. FRIZZLED.
SMARTi SM00063. FRI. 1 hit.
[Graphical view ]
SUPFAMi SSF63501. SSF63501. 1 hit.
PROSITEi PS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 161 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

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