Q08464 (FZD2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-2
Short name=Fz-2
Short name=rFz2

Gene names

Name:

Fzd2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	570 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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism.
Subcellular location	Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Widely expressed. Most abundant in kidney, liver, uterus, ovary and heart. Lower levels seen in brain and intestine. Extremely low in calvaria, mammary glands and testis.
Developmental stage	Expressed predominantly in neonatal tissues, at lower levels in adult.
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.
Post-translational modification	Ubiquitinated by ZNRF3, leading to its degradation by the proteasome 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
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Inferred from direct assay PubMed 12471263. Source: RGD Wnt receptor signaling pathway, calcium modulating pathway Inferred from direct assay PubMed 12471263. Source: RGD axonogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome brain development Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome cell activation Inferred from expression pattern PubMed 16780995. Source: RGD cellular response to growth factor stimulus Inferred from expression pattern Ref.1. Source: RGD cellular response to peptide hormone stimulus Inferred from expression pattern Ref.1. Source: RGD cellular response to vitamin D Inferred from expression pattern Ref.1. Source: RGD elevation of cytosolic calcium ion concentration Inferred from direct assay PubMed 12471263. Source: RGD embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome epithelial cell differentiation Inferred from Biological aspect of Ancestor. Source: RefGenome gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	apical part of cell Inferred from Biological aspect of Ancestor. Source: RefGenome cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome integral to membrane Traceable author statement PubMed 12471263. Source: RGD 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 PubMed 12471263. Source: RGD Wnt-protein binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Potential
	Chain	29 – 570	542	Frizzled-2		PRO_0000012980
Regions
	Topological domain	29 – 252	224	Extracellular Potential
	Transmembrane	253 – 273	21	Helical; Name=1; Potential
	Topological domain	274 – 284	11	Cytoplasmic Potential
	Transmembrane	285 – 305	21	Helical; Name=2; Potential
	Topological domain	306 – 332	27	Extracellular Potential
	Transmembrane	333 – 353	21	Helical; Name=3; Potential
	Topological domain	354 – 375	22	Cytoplasmic Potential
	Transmembrane	376 – 396	21	Helical; Name=4; Potential
	Topological domain	397 – 419	23	Extracellular Potential
	Transmembrane	420 – 440	21	Helical; Name=5; Potential
	Topological domain	441 – 466	26	Cytoplasmic Potential
	Transmembrane	467 – 487	21	Helical; Name=6; Potential
	Topological domain	488 – 524	37	Extracellular Potential
	Transmembrane	525 – 545	21	Helical; Name=7; Potential
	Topological domain	546 – 570	25	Cytoplasmic Potential
	Domain	39 – 158	120	FZ
	Motif	548 – 553	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	568 – 570	3	PDZ-binding
	Compositional bias	186 – 192	7	Poly-Gly
Amino acid modifications
	Glycosylation	58	1	N-linked (GlcNAc...) Potential
	Glycosylation	159	1	N-linked (GlcNAc...) Potential
	Disulfide bond	44 ↔ 105		By similarity
	Disulfide bond	52 ↔ 98		By similarity
	Disulfide bond	89 ↔ 126		By similarity
	Disulfide bond	115 ↔ 155		By similarity
	Disulfide bond	119 ↔ 143		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q08464 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 4FB895D9BEAFCA4E	FASTA	570	63,885
	10 20 30 40 50 60 MRARSALPRS ALPRLLLPLL LLPAAGPAQF HGEKGISIPD HGFCQPISIP LCTDIAYNQT 70 80 90 100 110 120 IMPNLLGHTN QEDAGLEVHQ FYPLVKVQCS PELRFFLCSM YAPVCTVLEQ AIPPCRSICE 130 140 150 160 170 180 RARQGCEALM NKFGFQWPER LRCEHFPRHG AEQICVGQNH SEDGTPALLT TAPPSGLQPG 190 200 210 220 230 240 AGGTPGGPGG GGAPPRYATL EHPFHCPRVL KVPSYLSYKF LGERDCAAPC EPARPDGSMF 250 260 270 280 290 300 FSHHHTRFAR LWILTWSVLC CASTFFTVTT SLVAMQRFRY PERPIIFLSG CYTMVSVAYI 310 320 330 340 350 360 AGFVLQERVV CNERFSEDGY RTVGQGTKKE GCTILFMMLY FFSMASSIWW VILSLTWFLA 370 380 390 400 410 420 AGMKWGHAAI EANSQYFHLA AWAVPAVKTI TILAMGQIDG DLLSGVCFVG LNRLDPLRGF 430 440 450 460 470 480 VLAPLFVYLF IGTSFLLAGF VSLFRIRTIM KHDGTKTEPL ERLMVRIGVF SVLYTVPATI 490 500 510 520 530 540 VIACYFYEQA FREHWERSWV SQHCKSLAIP CPAHYTPRTS PDFTVYMIKY LMTLIVGITS 550 560 570 GFWIWSGKTL HSWRKFYTRL TNSRHGETTV

References

[1]	"Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues." Chan S.D.H., Karpf D.B., Fowlkes M.E., Hooks M., Bradley M.S., Vuong V., Bambino T., Liu M.Y.C., Arnaud C.D., Strewler G.J., Nissenson R.A. J. Biol. Chem. 267:25202-25207(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Osteosarcoma.
[2]	"Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner." Sheldahl L.C., Park M., Malbon C.C., Moon R.T. Curr. Biol. 9:695-698(1999) [PubMed] [Europe PMC] [Abstract] Cited for: WNT-MEDIATED PKC ACTIVATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L02530 mRNA. Translation: AAA41172.1.
IPI	IPI00200613.
RefSeq	NP_742032.1. NM_172035.1.
UniGene	Rn.92324.
3D structure databases
ProteinModelPortal	Q08464.
SMR	Q08464. Positions 42-159.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1780823.
STRING	10116.ENSRNOP00000036154.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q08464.
Proteomic databases
PaxDb	Q08464.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	64512.
KEGG	rno:64512.
UCSC	RGD:71012. rat.
Organism-specific databases
CTD	2535.
RGD	71012. Fzd2.
Phylogenomic databases
eggNOG	NOG257258.
HOGENOM	HOG000233237.
HOVERGEN	HBG006977.
InParanoid	Q08464.
KO	K02235.
OrthoDB	EOG4V437C.
Gene expression databases
Genevestigator	Q08464.
GermOnline	ENSRNOG00000021962. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026550. FZD2. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF34. PTHR11309:SF34. 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	613298.

Entry information

Entry name

FZD2_RAT

Accession

Primary (citable) accession number: Q08464

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	November 1, 1996
Last modified:	April 3, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program