FZD6

Frizzled class receptor 6
Identifiers
Symbols	FZD6 ; FZ-6; FZ6; HFZ6; NDNC10
External IDs	OMIM: 603409 MGI: 108474 HomoloGene: 2617 IUPHAR: 234 GeneCards: FZD6 Gene
Gene ontology Molecular function • G-protein coupled receptor activity • protein binding • Wnt-protein binding • ubiquitin protein ligase binding • Wnt-activated receptor activity Cellular component • plasma membrane • integral component of plasma membrane • cell surface • integral component of membrane • apical plasma membrane • apicolateral plasma membrane • cytoplasmic vesicle membrane Biological process • establishment of planar polarity • neural tube closure • hair follicle development • G-protein coupled receptor signaling pathway • platelet activation • cell proliferation in midbrain • non-canonical Wnt signaling pathway • embryonic nail plate morphogenesis • inner ear morphogenesis • negative regulation of sequence-specific DNA binding transcription factor activity • canonical Wnt signaling pathway • Wnt signaling pathway, planar cell polarity pathway • negative regulation of canonical Wnt signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8323	14368
Ensembl	ENSG00000164930	ENSMUSG00000022297
UniProt	O60353	Q61089
RefSeq (mRNA)	NM_001164615	NM_001162494
RefSeq (protein)	NP_001158087	NP_001155966
Location (UCSC)	Chr 8: 103.3 – 103.33 Mb	Chr 15: 39.01 – 39.04 Mb
PubMed search

Frizzled-6 is a protein that in humans is encoded by the FZD6 gene.^[1][2][3]

Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for WNT signaling proteins. The FZD6 protein contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, and 7 transmembrane domains. However, unlike many other FZD family members, FDZ6 does not contain a C-terminal PDZ domain-binding motif.^[3] The FZD6 protein is believed to be the receptor for the WNT4 ligand.^[4]

Interactions

FZD6 has been shown to interact with Secreted frizzled-related protein 1.^[5]

See also

• Frizzled

Model organisms

Model organisms have been used in the study of FXYD3 function. In 2004, researchers at the Howard Hughes Medical Institute showed that FZD6 controls hair patterning in mice,^[6] and its human homologue is understood to play a part in the formation of hair whorls and cowlicks. A conditional knockout mouse line called Fxyd3^{tm1a(KOMP)Wtsi} was generated at the Wellcome Trust Sanger Institute.^[7] Male and female animals underwent a standardized phenotypic screen^[8] to determine the effects of deletion.^{[9][10][11][12]} Additional screens performed: - In-depth immunological phenotyping^[13]

Fxyd3 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[8][13]
Peripheral blood leukocytes 6 Weeks	Normal
Insulin	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Trichuris Challenge	Normal

References

1. Tokuhara M, Hirai M, Atomi Y, Terada M, Katoh M (Feb 1998). "Molecular cloning of human Frizzled-6". Biochemical and Biophysical Research Communications 243 (2): 622–7. doi:10.1006/bbrc.1998.8143. PMID 9480858.
2. Golan T, Yaniv A, Bafico A, Liu G, Gazit A (Apr 2004). "The human Frizzled 6 (HFz6) acts as a negative regulator of the canonical Wnt. beta-catenin signaling cascade". The Journal of Biological Chemistry 279 (15): 14879–88. doi:10.1074/jbc.M306421200. PMID 14747478.
3. "Entrez Gene: FZD6 frizzled homolog 6 (Drosophila)".
4. Lyons JP, Mueller UW, Ji H, Everett C, Fang X, Hsieh JC, Barth AM, McCrea PD (Aug 2004). "Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds Frizzled-6 CRD: functional implications of Wnt/beta-catenin activity in kidney epithelial cells". Experimental Cell Research 298 (2): 369–87. doi:10.1016/j.yexcr.2004.04.036. PMID 15265686.
5. Bafico A, Gazit A, Pramila T, Finch PW, Yaniv A, Aaronson SA (Jun 1999). "Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling". The Journal of Biological Chemistry 274 (23): 16180–7. doi:10.1074/jbc.274.23.16180. PMID 10347172.
6. "Frizzled6 controls hair patterning in mice".
7. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
8. "International Mouse Phenotyping Consortium".
9. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
10. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
11. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
12. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
13. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Wang Y, Macke JP, Abella BS, Andreasson K, Worley P, Gilbert DJ, Copeland NG, Jenkins NA, Nathans J (Feb 1996). "A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled". The Journal of Biological Chemistry 271 (8): 4468–76. doi:10.1074/jbc.271.8.4468. PMID 8626800.
• Finch PW, He X, Kelley MJ, Uren A, Schaudies RP, Popescu NC, Rudikoff S, Aaronson SA, Varmus HE, Rubin JS (Jun 1997). "Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action". Proceedings of the National Academy of Sciences of the United States of America 94 (13): 6770–5. doi:10.1073/pnas.94.13.6770. PMC 21233. PMID 9192640.
• Bafico A, Gazit A, Pramila T, Finch PW, Yaniv A, Aaronson SA (Jun 1999). "Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling". The Journal of Biological Chemistry 274 (23): 16180–7. doi:10.1074/jbc.274.23.16180. PMID 10347172.
• 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.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Sirchia R, Luparello C (May 2007). "Mid-region parathyroid hormone-related protein (PTHrP) and gene expression of MDA-MB231 breast cancer cells". Biological Chemistry 388 (5): 457–65. doi:10.1515/BC.2007.059. PMID 17516841.

External links

• "Frizzled Receptors: FZD₆". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

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