Q9QZH0 (FZD4_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-4
Short name=Fz-4
Short name=rFz4

Alternative name(s):
CD_antigen=CD344

Gene names

Name:

Fzd4

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	538 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 (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. 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 By similarity.
Subunit structure	Interacts with MAGI3 and NDP. Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP) By similarity.
Subcellular location	Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity.
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
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	canonical Wnt receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome progesterone secretion Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of vascular endothelial growth factor receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome substrate adhesion-dependent cell spreading Inferred from Biological aspect of Ancestor. Source: RefGenome vasculogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	cell projection Inferred from Biological aspect of Ancestor. Source: RefGenome cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma 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 Biological aspect of Ancestor. Source: RefGenome Wnt-protein binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 37	37	Potential
	Chain	38 – 538	501	Frizzled-4		PRO_0000012987
Regions
	Topological domain	38 – 223	186	Extracellular Potential
	Transmembrane	224 – 244	21	Helical; Name=1; Potential
	Topological domain	245 – 255	11	Cytoplasmic Potential
	Transmembrane	256 – 276	21	Helical; Name=2; Potential
	Topological domain	277 – 303	27	Extracellular Potential
	Transmembrane	304 – 324	21	Helical; Name=3; Potential
	Topological domain	325 – 345	21	Cytoplasmic Potential
	Transmembrane	346 – 366	21	Helical; Name=4; Potential
	Topological domain	367 – 390	24	Extracellular Potential
	Transmembrane	391 – 411	21	Helical; Name=5; Potential
	Topological domain	412 – 437	26	Cytoplasmic Potential
	Transmembrane	438 – 458	21	Helical; Name=6; Potential
	Topological domain	459 – 478	20	Extracellular Potential
	Transmembrane	479 – 499	21	Helical; Name=7; Potential
	Topological domain	500 – 538	39	Cytoplasmic Potential
	Domain	41 – 162	122	FZ
	Motif	500 – 505	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	536 – 538	3	PDZ-binding
Amino acid modifications
	Glycosylation	60	1	N-linked (GlcNAc...) Potential
	Glycosylation	145	1	N-linked (GlcNAc...) Potential
	Glycosylation	382	1	N-linked (GlcNAc...) Potential
	Disulfide bond	46 ↔ 107		By similarity
	Disulfide bond	54 ↔ 100		By similarity
	Disulfide bond	91 ↔ 129		By similarity
	Disulfide bond	118 ↔ 159		By similarity
	Disulfide bond	122 ↔ 146		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9QZH0 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 07DAAE606B46E005	FASTA	538	60,355
	10 20 30 40 50 60 MAWQGTGPSV RGMPGGVRLR LGLLLLQLLL LQRPALGFGD EEERRCDPIR IAMCQNLGYN 70 80 90 100 110 120 VTKMPNLVGH ELQTDAELQL TTFTPLIQYG CSSQLQFFLC SVYVPMCTEK INIPIGPCGG 130 140 150 160 170 180 MCLSVKRRCE PVLKEFGFAW PDSLNCSKFP PQNDHNHMCM EGPGDEEVPL PHKTPIQPGE 190 200 210 220 230 240 ECHSVGTNSD QYIWVKRSLN CVLKCGYDAG LYSRSAKEFT DIWMAVWASL CFISTTFTVL 250 260 270 280 290 300 TFLIDSSRFS YPERPIIFLS MCYNIYSIAY IVRLTVGRER ISCDFEEAAE PVLIQEGLKN 310 320 330 340 350 360 TGCAIIFLLM YFFGMASSIW WVILTLTWFL AAGLKWGHEA IEMHSSYFHI AAWAIPAVKT 370 380 390 400 410 420 IVILIMRLVD ADELTGLCYV GNQSLDALTG FVVAPLFTYL VIGTLFIAAG LVALFKIRSN 430 440 450 460 470 480 LQKDGTKTDK LERLMVKIGV FSVLYTVPAT CVIACYFYEI SNWALFRYSA DDSNMAVEML 490 500 510 520 530 KIFMSLLVGI TSGMWIWSAK TLHTWQKCSN RLVNSGKVKR EKRGNGWVKP GKGNETVV

References

[1]	"Expression of a putative seven-pass transmembrane frizzled receptor in the Corpus Luteum (CL) of the rat during pregnancy and involution." Walther P.R., Lacher M.D., Saurer S., Friis R.R. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Corpus luteum.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF183910 mRNA. Translation: AAF01036.1.
IPI	IPI00214987.
RefSeq	NP_072145.1. NM_022623.1.
UniGene	Rn.48736.
3D structure databases
ProteinModelPortal	Q9QZH0.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9QZH0.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	Q9QZH0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000023205; ENSRNOP00000023205; ENSRNOG00000016848.
GeneID	64558.
KEGG	rno:64558.
UCSC	NM_022623. rat.
Organism-specific databases
CTD	8322.
RGD	71017. Fzd4.
Phylogenomic databases
eggNOG	roNOG04408.
GeneTree	ENSGT00560000076655.
HOVERGEN	HBG006977.
InParanoid	Q9QZH0.
OMA	GHELQAD.
OrthoDB	EOG4KPT9H.
PhylomeDB	Q9QZH0.
Gene expression databases
ArrayExpress	Q9QZH0.
Genevestigator	Q9QZH0.
GermOnline	ENSRNOG00000016848. Rattus norvegicus.
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	K02354.
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	613472.

Entry information

Entry name

FZD4_RAT

Accession

Primary (citable) accession number: Q9QZH0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	May 1, 2000
Last modified:	November 16, 2011
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program