FZD4

Frizzled family receptor 4
Identifiers
Symbols	FZD4; CD344; EVR1; FEVR; FZD4S; Fz-4; FzE4; GPCR
External IDs	OMIM: 604579 MGI: 108520 HomoloGene: 7325 IUPHAR: FZD4 GeneCards: FZD4 Gene
Gene Ontology Molecular function • G-protein coupled receptor activity • protein binding • Wnt-protein binding • cytokine binding • PDZ domain binding • ubiquitin protein ligase binding • protein homodimerization activity • Wnt-activated receptor activity • protein heterodimerization activity Cellular component • cytoplasm • plasma membrane • integral to plasma membrane • cell-cell junction • cell surface • cell projection Biological process • vasculogenesis • Wnt receptor signaling pathway, calcium modulating pathway • brain development • sensory perception of sound • embryo development • negative regulation of cell-substrate adhesion • Wnt receptor signaling pathway • neuron differentiation • regulation of vascular endothelial growth factor receptor signaling pathway • locomotion involved in locomotory behavior • substrate adhesion-dependent cell spreading • extracellular matrix-cell signaling • progesterone secretion • positive regulation of JUN kinase activity • positive regulation of transcription, DNA-dependent • positive regulation of sequence-specific DNA binding transcription factor activity • canonical Wnt receptor signaling pathway • retina vasculature morphogenesis in camera-type eye • cerebellum vasculature morphogenesis • retinal blood vessel morphogenesis • cellular response to retinoic acid Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8322	14366
Ensembl	ENSG00000174804	ENSMUSG00000049791
UniProt	Q9ULV1	Q61088
RefSeq (mRNA)	NM_012193.3	NM_008055.4
RefSeq (protein)	NP_036325.2	NP_032081.3
Location (UCSC)	Chr 11: 86.66 – 86.67 Mb	Chr 7: 89.4 – 89.41 Mb
PubMed search	[1]	[2]

Frizzled-4 is a protein that in humans is encoded by the FZD4 gene. FZD4 has also been designated as CD344 (cluster of differentiation 344).

This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Frizzled-4 is the only representative of frizzled family members that binds strongly an additional ligand Norrin that is functionally similar but structurally different from Wingless type proteins. FZD4 signaling induced by Norrin regulates vascular development of vertebrate retina and controls important blood vessels in the ear. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence.

See also

• Frizzled

Further reading

• Li Y, Fuhrmann C, Schwinger E et al. (1992). "The gene for autosomal dominant familial exudative vitreoretinopathy (Criswick-Schepens) on the long arm of chromosome 11". Am. J. Ophthalmol. 113 (6): 712–3. PMID 1598965. 
• Tanaka S, Akiyoshi T, Mori M et al. (1998). "A novel frizzled gene identified in human esophageal carcinoma mediates APC/β-catenin signals". Proc. Natl. Acad. Sci. U.S.A. 95 (17): 10164–9. doi:10.1073/pnas.95.17.10164. PMC 21479. PMID 9707618. //www.ncbi.nlm.nih.gov/pmc/articles/PMC21479/. 
• Sagara N, Kirikoshi H, Terasaki H et al. (2001). "FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway". Biochem. Biophys. Res. Commun. 282 (3): 750–6. doi:10.1006/bbrc.2001.4634. PMID 11401527. 
• Takeda S, Kadowaki S, Haga T et al. (2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Lett. 520 (1–3): 97–101. doi:10.1016/S0014-5793(02)02775-8. PMID 12044878. 
• Hering H, Sheng M (2002). "Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95". FEBS Lett. 521 (1–3): 185–9. doi:10.1016/S0014-5793(02)02831-4. PMID 12067714. 
• Robitaille J, MacDonald ML, Kaykas A et al. (2002). "Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy". Nat. Genet. 32 (2): 326–30. doi:10.1038/ng957. PMID 12172548. 
• Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. //www.ncbi.nlm.nih.gov/pmc/articles/PMC139241/. 
• Chen W, ten Berge D, Brown J et al. (2003). "Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4". Science 301 (5638): 1391–4. doi:10.1126/science.1082808. PMID 12958364. 
• Toomes C, Downey LM, Bottomley HM et al. (2004). "Identification of a fourth locus (EVR4) for familial exudative vitreoretinopathy (FEVR)". Mol. Vis. 10: 37–42. PMID 14737064. 
• Yao R, Natsume Y, Noda T (2005). "MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap". Oncogene 23 (36): 6023–30. doi:10.1038/sj.onc.1207817. PMID 15195140. 
• Toomes C, Bottomley HM, Scott S et al. (2004). "Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy". Invest. Ophthalmol. Vis. Sci. 45 (7): 2083–90. doi:10.1167/iovs.03-1044. PMID 15223780. 
• Omoto S, Hayashi T, Kitahara K et al. (2004). "Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R)". Ophthalmic Genet. 25 (2): 81–90. doi:10.1080/13816810490514270. PMID 15370539. 
• Yoshida S, Arita R, Yoshida A et al. (2004). "Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy". Am. J. Ophthalmol. 138 (4): 670–1. doi:10.1016/j.ajo.2004.05.001. PMID 15488808. 
• Gerhard DS, Wagner L, Feingold EA et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. //www.ncbi.nlm.nih.gov/pmc/articles/PMC528928/. 
• Qin M, Hayashi H, Oshima K et al. (2006). "Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes". Hum. Mutat. 26 (2): 104–12. doi:10.1002/humu.20191. PMID 15981244. 
• Nallathambi J, Shukla D, Rajendran A et al. (2006). "Identification of novel FZD4 mutations in Indian patients with familial exudative vitreoretinopathy". Mol. Vis. 12: 1086–92. PMID 17093393. 
• Planutis K, Planutiene M, Moyer MP et al. (2007). "Regulation of norrin receptor frizzled-4 by Wnt2 in colon-derived cells". BMC Cell Biol. 8: 12. doi:10.1186/1471-2121-8-12. PMC 1847812. PMID 17386109. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1847812/. 

External links

• "Frizzled Receptors: FZD₄". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3062. ]
• GeneReviews/NCBI/NIH/UW entry on Familial Exudative Vitreoretinopathy, Autosomal Dominant

This article incorporates text from the United States National Library of Medicine, which is in the public domain.