FZD4

Frizzled class receptor 4
Identifiers
Symbols	FZD4 ; CD344; EVR1; FEVR; FZD4S; Fz-4; Fz4; FzE4; GPCR; hFz4
External IDs	OMIM: 604579 MGI: 108520 HomoloGene: 7325 IUPHAR: 232 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 • plasma membrane • integral component of plasma membrane • cell-cell junction • cell surface • integral component of membrane • clathrin-coated endocytic vesicle membrane • extracellular exosome Biological process • vasculogenesis • G-protein coupled receptor signaling pathway • Wnt signaling pathway, calcium modulating pathway • sensory perception of sound • negative regulation of cell-substrate adhesion • Wnt 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-templated • positive regulation of sequence-specific DNA binding transcription factor activity • canonical Wnt 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	NM_008055
RefSeq (protein)	NP_036325	NP_032081
Location (UCSC)	Chr 11: 86.95 – 86.96 Mb	Chr 7: 89.4 – 89.41 Mb
PubMed search

Frizzled-4 is a protein that in humans is encoded by the FZD4 gene.^[1][2][3] FZD4 has also been designated as CD344 (cluster of differentiation 344).

Function

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.^[4] 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.^[3]

See also

• Frizzled

References

1. Kirikoshi H, Sagara N, Koike J, Tanaka K, Sekihara H, Hirai M, Katoh M (Nov 1999). "Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21". Biochemical and Biophysical Research Communications 264 (3): 955–61. doi:10.1006/bbrc.1999.1612. PMID 10544037.
2. Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff G, Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF (Apr 2004). "Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q". American Journal of Human Genetics 74 (4): 721–30. doi:10.1086/383202. PMC 1181948. PMID 15024691.
3. "Entrez Gene: FZD4 frizzled homolog 4 (Drosophila)".
4. Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J (March 2004). "Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair". Cell 116 (6): 883–895. doi:10.1016/S0092-8674(04)00216-8. PMID 15035989.

Further reading

• Li Y, Fuhrmann C, Schwinger E, Gal A, Laqua H (Jun 1992). "The gene for autosomal dominant familial exudative vitreoretinopathy (Criswick-Schepens) on the long arm of chromosome 11". American Journal of Ophthalmology 113 (6): 712–3. doi:10.1016/s0002-9394(14)74800-7. PMID 1598965.
• Tanaka S, Akiyoshi T, Mori M, Wands JR, Sugimachi K (Aug 1998). "A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals". Proceedings of the National Academy of Sciences of the United States of America 95 (17): 10164–9. doi:10.1073/pnas.95.17.10164. PMC 21479. PMID 9707618.
• Sagara N, Kirikoshi H, Terasaki H, Yasuhiko Y, Toda G, Shiokawa K, Katoh M (Apr 2001). "FZD4S, a splicing variant of frizzled-4, encodes a soluble-type positive regulator of the WNT signaling pathway". Biochemical and Biophysical Research Communications 282 (3): 750–6. doi:10.1006/bbrc.2001.4634. PMID 11401527.
• Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (Jun 2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Letters 520 (1-3): 97–101. doi:10.1016/S0014-5793(02)02775-8. PMID 12044878.
• Hering H, Sheng M (Jun 2002). "Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95". FEBS Letters 521 (1-3): 185–9. doi:10.1016/S0014-5793(02)02831-4. PMID 12067714.
• Robitaille J, MacDonald ML, Kaykas A, Sheldahl LC, Zeisler J, Dubé MP, Zhang LH, Singaraja RR, Guernsey DL, Zheng B, Siebert LF, Hoskin-Mott A, Trese MT, Pimstone SN, Shastry BS, Moon RT, Hayden MR, Goldberg YP, Samuels ME (Oct 2002). "Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy". Nature Genetics 32 (2): 326–30. doi:10.1038/ng957. PMID 12172548.
• Chen W, ten Berge D, Brown J, Ahn S, Hu LA, Miller WE, Caron MG, Barak LS, Nusse R, Lefkowitz RJ (Sep 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, Scott S, Woodruff G, Trembath RC, Inglehearn CF (Jan 2004). "Identification of a fourth locus (EVR4) for familial exudative vitreoretinopathy (FEVR)". Molecular Vision 10: 37–42. PMID 14737064.
• Yao R, Natsume Y, Noda T (Aug 2004). "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, Mackey DA, Craig JE, Appukuttan B, Stout JT, Flaxel CJ, Zhang K, Black GC, Fryer A, Downey LM, Inglehearn CF (Jul 2004). "Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy". Investigative Ophthalmology & Visual Science 45 (7): 2083–90. doi:10.1167/iovs.03-1044. PMID 15223780.
• Omoto S, Hayashi T, Kitahara K, Takeuchi T, Ueoka Y (Jun 2004). "Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R)". Ophthalmic Genetics 25 (2): 81–90. doi:10.1080/13816810490514270. PMID 15370539.
• Yoshida S, Arita R, Yoshida A, Tada H, Emori A, Noda Y, Nakao S, Fujisawa K, Ishibashi T (Oct 2004). "Novel mutation in FZD4 gene in a Japanese pedigree with familial exudative vitreoretinopathy". American Journal of Ophthalmology 138 (4): 670–1. doi:10.1016/j.ajo.2004.05.001. PMID 15488808.
• Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H (Aug 2005). "Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes". Human Mutation 26 (2): 104–12. doi:10.1002/humu.20191. PMID 15981244.
• Nallathambi J, Shukla D, Rajendran A, Namperumalsamy P, Muthulakshmi R, Sundaresan P (2006). "Identification of novel FZD4 mutations in Indian patients with familial exudative vitreoretinopathy". Molecular Vision 12: 1086–92. PMID 17093393.
• Planutis K, Planutiene M, Moyer MP, Nguyen AV, Pérez CA, Holcombe RF (2007). "Regulation of norrin receptor frizzled-4 by Wnt2 in colon-derived cells". BMC Cell Biology 8: 12. doi:10.1186/1471-2121-8-12. PMC 1847812. PMID 17386109.

External links

• "Frizzled Receptors: FZD₄". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.]
• 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.