P18537 (FRIZ_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled

Alternative name(s):
Frizzled-1
Short name=dFz1

Gene names

Name:	fz
ORF Names:	CG17697

Organism

Drosophila melanogaster (Fruit fly)

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	581 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Wnt signaling pathway
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	R3/R4 cell fate commitment Non-traceable author statement. Source: FlyBase asymmetric cell division Inferred from mutant phenotype. Source: FlyBase asymmetric protein localization Traceable author statement. Source: FlyBase axon extension Inferred from mutant phenotype. Source: FlyBase border follicle cell migration Inferred from mutant phenotype. Source: FlyBase brain development Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor signaling pathway Inferred from genetic interaction. Source: FlyBase embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome establishment of epithelial cell apical/basal polarity Inferred from mutant phenotype. Source: FlyBase gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome heart development Non-traceable author statement. Source: FlyBase homophilic cell adhesion Inferred from mutant phenotype. Source: FlyBase imaginal disc-derived wing hair site selection Inferred from mutant phenotype. Source: FlyBase ommatidial rotation Inferred from mutant phenotype. Source: FlyBase regulation of actin filament bundle assembly Inferred from genetic interaction. Source: FlyBase regulation of tube length, open tracheal system Inferred from mutant phenotype. Source: FlyBase salivary gland morphogenesis Inferred from mutant phenotype. Source: FlyBase sensory organ precursor cell fate determination Inferred from mutant phenotype. Source: FlyBase vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	cell cortex Inferred from direct assay. Source: FlyBase integral to plasma membrane Traceable author statement. Source: FlyBase neuron projection membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular function	G-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. Source: FlyBase Wnt-protein binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
stan	Q9V5N8	3	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 581	563	Frizzled		PRO_0000013010
Regions
	Topological domain	19 – 247	229	Extracellular Probable
	Transmembrane	248 – 270	23	Helical; Name=1; Probable
	Topological domain	271 – 280	10	Cytoplasmic Probable
	Transmembrane	281 – 303	23	Helical; Name=2; Probable
	Topological domain	304 – 343	40	Extracellular Probable
	Transmembrane	344 – 364	21	Helical; Name=3; Probable
	Topological domain	365 – 380	16	Cytoplasmic Probable
	Transmembrane	381 – 401	21	Helical; Name=4; Probable
	Topological domain	402 – 421	20	Extracellular Probable
	Transmembrane	422 – 439	18	Helical; Name=5; Probable
	Topological domain	440 – 471	32	Cytoplasmic Probable
	Transmembrane	472 – 492	21	Helical; Name=6; Probable
	Topological domain	493 – 529	37	Extracellular Probable
	Transmembrane	530 – 553	24	Helical; Name=7; Probable
	Topological domain	554 – 581	28	Cytoplasmic Probable
	Domain	48 – 166	119	FZ
	Motif	556 – 561	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	579 – 581	3	PDZ-binding
Amino acid modifications
	Glycosylation	67	1	N-linked (GlcNAc...) Potential
	Glycosylation	167	1	N-linked (GlcNAc...) Potential
	Disulfide bond	53 ↔ 114		By similarity
	Disulfide bond	61 ↔ 107		By similarity
	Disulfide bond	98 ↔ 134		By similarity
	Disulfide bond	124 ↔ 163		By similarity
	Disulfide bond	128 ↔ 151		By similarity
Natural variations
	Alternative sequence	406 – 415	10	DILSGVCFVG → MYLWQFHTIN in isoform II.		VSP_002013
	Alternative sequence	416 – 581	166	Missing in isoform II.		VSP_002014

Sequences

	Sequence		Length	Mass (Da)
	Isoform I [UniParc]. Last modified November 1, 1990. Version 1. Checksum: 486721D84DA0D0A1	FASTA	581	64,847
	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
	Isoform II [UniParc]. Checksum: F0A0A5AA080BAAE7	FASTA	415	46,118
	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 AWFLAAGLKW GHEAIENKSH LFHLVAWAVP ALQTISVLAL AKVEGMYLWQ FHTIN

References

	« Hide 'large scale' referencesShow '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: 2493583] [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: 2174014] [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: 10731132] [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. , 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: 12537572] [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: 12537569] [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: 10360843] [Abstract] Cited for: TOPOLOGY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
PIR	S03540.
RefSeq	NP_524812.1. NM_080073.2. NP_729970.1. NM_168587.1.
UniGene	Dm.1456.
3D structure databases
ProteinModelPortal	P18537.
SMR	P18537. Positions 51-167.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-22727N.
IntAct	P18537. 3 interactions.
MINT	MINT-1663972.
STRING	P18537.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	P18537.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0075743; FBpp0075485; FBgn0001085.
GeneID	45307.
KEGG	dme:Dmel_CG17697.
NMPDR	fig|7227.3.peg.9807.
Organism-specific databases
CTD	45307.
FlyBase	FBgn0001085. fz.
Phylogenomic databases
eggNOG	inNOG09413.
GeneTree	EMGT00050000001357.
InParanoid	P18537.
OMA	PITISIC.
OrthoDB	EOG44MW73.
PhylomeDB	P18537.
Gene expression databases
Bgee	P18537.
GermOnline	CG17697. Drosophila melanogaster.
Family and domain databases
InterPro	IPR000539. Frizzled. IPR015526. Frizzled-related. IPR020067. Frizzled_dom. IPR017981. GPCR_2-like. [Graphical view]
Gene3D	G3DSA:1.10.2000.10. Frizzled_Cys-rich. 1 hit.
KO	K02432.
PANTHER	PTHR11309. Fz_related. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
SMART	SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	837994.

Entry information

Entry name

FRIZ_DROME

Accession

Primary (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:	January 25, 2012
This is version 138 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project