Reviewed, UniProtKB/Swiss-Prot Q9NBW1 (FRIZ4_DROME)

Names and origin

Protein names

Recommended name:
    Frizzled-4
Alternative name(s):
    dFz4

Gene names

Name:	fz4
ORF Names:	CG4626

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

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	705 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Required to coordinate the cytoskeletons of epidermal cells to produce a parallel array of cuticular hairs and bristles.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Domain	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	Membrane
Domain	Signal Transmembrane
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Non-traceable author statement. Source: UniProtKB
Molecular function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW non-G-protein coupled 7TM receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 705	683	Frizzled-4		PRO_0000013014
Regions
	Topological domain	23 – 233	211	Extracellular Potential
	Transmembrane	234 – 254	21	1 Potential
	Topological domain	255 – 270	16	Cytoplasmic Potential
	Transmembrane	271 – 291	21	2 Potential
	Topological domain	292 – 322	31	Extracellular Potential
	Transmembrane	323 – 343	21	3 Potential
	Topological domain	344 – 386	43	Cytoplasmic Potential
	Transmembrane	387 – 407	21	4 Potential
	Topological domain	408 – 430	23	Extracellular Potential
	Transmembrane	431 – 451	21	5 Potential
	Topological domain	452 – 483	32	Cytoplasmic Potential
	Transmembrane	484 – 504	21	6 Potential
	Topological domain	505 – 529	25	Extracellular Potential
	Transmembrane	530 – 550	21	7 Potential
	Topological domain	551 – 705	155	Cytoplasmic Potential
	Domain	41 – 163	123	FZ
	Motif	703 – 705	3	PDZ-binding
	Compositional bias	29 – 36	8	Poly-Ser
	Compositional bias	646 – 650	5	Poly-His
	Compositional bias	651 – 654	4	Poly-Gln
Amino acid modifications
	Glycosylation	60	1	N-linked (GlcNAc...) Potential
	Glycosylation	306	1	N-linked (GlcNAc...) Potential
	Glycosylation	317	1	N-linked (GlcNAc...) Potential
	Glycosylation	423	1	N-linked (GlcNAc...) Potential
	Disulfide bond	46 ↔ 107		By similarity
	Disulfide bond	54 ↔ 100		By similarity
	Disulfide bond	91 ↔ 130		By similarity
	Disulfide bond	119 ↔ 160		By similarity
	Disulfide bond	123 ↔ 147		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9NBW1-1 [UniParc]. Last modified May 2, 2002. Version 2. Checksum: 0188DFCE57BB626F	FASTA	705	77,490
	10 20 30 40 50 60 MKPTCILCLL VVILLHPRIS KSSTSGNPSA SSSSSSPPEI PAFRQCETIR IEMCRKIGYN 70 80 90 100 110 120 ETSMPNLVGN EMQTDVEYTL QTFAPLIEYD CSSQLKLFLC AAYVPMCTPK APVHAIGPCR 130 140 150 160 170 180 SLCESVRIRC HPVLQGFGFP WPPALDCDKF PRENNHETMC MEGPGELHQP QQEQDLYGLP 190 200 210 220 230 240 GQGIPGGLGG KLPMDCSGLA KSHLYVRLPR SGRCAPLCEA DILFTPAEKH LAEIWVSTWA 250 260 270 280 290 300 YAALGLALVA TVCLLASDGS RLASAKWSRL LSPLIWCHNM VTLGWAVRFM VGRTGTACGT 310 320 330 340 350 360 DPQAPNESLL TVDGLSNASC ASVFLMRYYF GMAACAWWAV LCLGWHRDIR RHSPDSKGHV 370 380 390 400 410 420 VIPSNFGGSP AKRNSAKTAQ QDLTQNNFVC FVAWGLPAFQ TSAVIVARFV DADELLGACF 430 440 450 460 470 480 VGNQSDKALQ ILVATPVFCY WIFGSMNLIS GYLVHCRTKE ILRNSNALSV QQQLQQLSAH 490 500 510 520 530 540 SSSGIGIFLF IYGLACAMLL LAVIYEFANI DVWLGSGDTN TPLWPFLLRA FMELMLGICC 550 560 570 580 590 600 FAWVLGPSIS TLYKRQVSNG KMVKHTSAGA ATGHLDGHSS SRGSHAACNS TVVSYHSVRT 610 620 630 640 650 660 SMASVPLPPS PYKLKTSPGT GSISLNQMSN YSLGRSVHHQ QRHSPHHHHH QQQQHHQFHP 670 680 690 700 HHNHQHHSTS SHRLYYPPGS YASQKYSQHG SYYPHLQQYG NETLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Dfz4 acts in the Wg pathway." Xu Y.K., Nusse R. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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.
[3]	"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.
[4]	"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]. Strain: Berkeley. Tissue: Ovary.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF241270 mRNA. Translation: AAF81195.1. AE014298 Genomic DNA. Translation: AAN09202.1. AY118543 mRNA. Translation: AAM49912.1.
RefSeq	NP_511068.2. NP_727170.2.
UniGene	Dm.92
3D structure databases
HSSP	HSSP built from PDB template 1IJY based on UniProtKB Q61091.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NBW1. 1 interaction.
Protein family/group databases
GPCRDB	Search...
Genome annotation databases
Ensembl	FBgn0027342. Drosophila melanogaster. [Contig view]
GeneID	31659.
KEGG	dme:Dmel_CG4626.
Organism-specific databases
FlyBase	FBgn0027342. fz4.
Phylogenomic databases
HOGENOM	Q9NBW1.
OMA	Q9NBW1. APLCEAD.
Enzyme and pathway databases
BioCyc	DMEL-XXX-02:DMEL-XXX-02-000935-MON.
Gene expression databases
ArrayExpress	Q9NBW1.
GermOnline	CG4626. Drosophila melanogaster.
Family and domain databases
InterPro	IPR000539. Frizzled. IPR000024. Frizzled_Cys-rich. IPR015526. Frizzled_related. IPR017981. GPCR_2-like. [Graphical view]
Gene3D	G3DSA:1.10.2000.10. Frizzled_Cys-rich. 1 hit.
PANTHER	PTHR11309. Fz_related. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	774689.

Entry information

Entry name

FRIZ4_DROME

Accession

Primary (citable) accession number: Q9NBW1
Secondary accession number(s): Q9W3S2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	May 2, 2002
Last modified:	June 16, 2009
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project