FZD<sub>7</sub> | Class Frizzled GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

FZD7

Target id: 235

Nomenclature: FZD7

Family: Class Frizzled GPCRs

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for FZD7 in GtoImmuPdb

Gene and Protein Information
Frizzled family G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 574 2q33 FZD7 frizzled class receptor 7
Mouse 7 572 1 C1.3 Fzd7 frizzled class receptor 7
Rat 7 - 9 Fzd7 frizzled class receptor 7
Previous and Unofficial Names
FzE3 | frizzled family receptor 7 | Fzd7 | Fz7
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Wnt
Agonist Comments
WNT-3, WNT-3A, WNT-5A and WNT-7A bind to FZD7. Due to the lack of purified and biologically active WNTs hardly any information on the specificity and pharmacology of FZD-WNT interaction is available. Extensive and quantitative binding assays have not been performed with mammalian FZDs. The references above contain data showing the direct activation/interaction of FZD7 by individual WNTs. For additional information see [2].
Antagonist Comments
Monoclonal antibody vantictumab (OMP-18R5) was found to act as an antagonist at FZD7, and was also found to bind to FZD1, FZD2, FZD5 and FZD8 [3].
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family
References:  2
Secondary Transduction Mechanisms
Transducer Effector/Response
Other - See Comments
Comments:  WNT/β-catenin signaling.
References:  2
Tissue Distribution
Adult skeletal muscle
Species:  Human
Technique:  Northern blot
References:  9
Fetal kidney
Species:  Human
Technique:  Northern blot
References:  9
Fetal lung
Species:  Human
Technique:  Northern blot
References:  9
Adult heart
Species:  Human
Technique:  Northern blot
References:  9
Adult brain
Species:  Human
Technique:  Northern blot
References:  9
Adult placenta
Species:  Human
Technique:  Northern blot
References:  9
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Activate WNT/PCP pathway to drive the symmetric expansion of satellite stem cells
Species:  Mouse
Tissue:  Satellite stem cells
Response measured:  Increased satellite stem cell numbers and proportion of satellite stem cells.
References:  7
Stabilization of β-catenin in human hepatocellular carcinoma cells
Species:  Human
Tissue:  HCC cells
Response measured:  Accumulation of β-catenin
References:  4
WNT-7a binds to FZD7 and activates the Gαs protein. This is hypothesized to lead to the activation of PI(3)K which in turn activates PDK1. PDK1 then activates Akt, leading to the activation of its downstream targets S6 kinase and S6 and the induction of hypertrophy.
Species:  Mouse
Tissue:  Skeletal muscle
Response measured:  Activatation of the Akt/mTOR growth pathway in myotubes
References:  13
Physiological Functions
Activate anabolic growth pathway in skeletal muscle
Species:  Mouse
Tissue:  Skeletal muscle
References:  13
Activate WNT/PCP pathway to drive the symmetric expansion of satellite stem cells
Species:  Mouse
Tissue:  Satellite stem cells
References:  7
Stabilization of β-catenin in human hepatocellular carcinoma cells
Species:  Human
Tissue:  HCC cells
References:  4
Physiological Consequences of Altering Gene Expression
Mice with Fzd7 knockout exhibit tail truncation and kinking with 100% penetrance and ventricular septal defects (VSDs) with ~15% penetrance
Species:  Mouse
Tissue: 
Technique:  Targeting in embryonic stem cells
References:  15
Clinically-Relevant Mutations and Pathophysiology
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
Role: 
References:  5,14
Disease:  Colorectal cancer
Disease Ontology: DOID:9256
OMIM: 114500
References:  5,12
Disease:  Esophageal cancer
Disease Ontology: DOID:5041
OMIM: 133239
Comments: 
References:  5,10
Disease:  Gastric cancer
Synonyms: Stomach cancer
Disease Ontology: DOID:10534
OMIM: 613659
References:  5-6
Disease:  Hepatocellular carcinoma
Disease Ontology: DOID:684
OMIM: 114550
References:  1,4-5,8
Disease:  Lung cancer
Disease Ontology: DOID:1324
OMIM: 211980
References:  5,9
Disease:  Melanoma
Disease Ontology: DOID:1909
References:  5,9
Disease:  Wilm's tumor
Synonyms: Nephroblastoma [Disease Ontology: DOID:2154] [Orphanet: ORPHA654]
Disease Ontology: DOID:2154
Orphanet: ORPHA654
References:  5,11

References

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1. Bengochea A, de Souza MM, Lefrançois L, Le Roux E, Galy O, Chemin I, Kim M, Wands JR, Trepo C, Hainaut P, Scoazec JY, Vitvitski L, Merle P. (2008) Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma. Br J Cancer, 99: 143-150. [PMID:18577996]

2. Dijksterhuis JP, Petersen J, Schulte G. (2013) WNT/Frizzled signaling: receptor-ligand selectivity with focus on FZD-G protein signaling and its physiological relevance. Br J Pharmacol,. [PMID:24032637]

3. Gurney A, Axelrod F, Bond CJ, Cain J, Chartier C, Donigan L, Fischer M, Chaudhari A, Ji M, Kapoun AM et al.. (2012) Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors. Proc. Natl. Acad. Sci. U.S.A., 109 (29): 11717-22. [PMID:22753465]

4. Kim M, Lee HC, Tsedensodnom O, Hartley R, Lim YS, Yu E, Merle P, Wands JR. (2008) Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells. J. Hepatol., 48 (5): 780-91. [PMID:18313787]

5. King TD, Zhang W, Suto MJ, Li Y. (2012) Frizzled7 as an emerging target for cancer therapy. Cell. Signal., 24 (4): 846-51. [PMID:22182510]

6. Kirikoshi H, Sekihara H, Katoh M. (2001) Up-regulation of Frizzled-7 (FZD7) in human gastric cancer. Int. J. Oncol., 19 (1): 111-5. [PMID:11408930]

7. Le Grand F, Jones AE, Seale V, Scimè A, Rudnicki MA. (2009) Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells. Cell Stem Cell, 4 (6): 535-47. [PMID:19497282]

8. Merle P, de la Monte S, Kim M, Herrmann M, Tanaka S, Von Dem Bussche A, Kew MC, Trepo C, Wands JR. (2004) Functional consequences of frizzled-7 receptor overexpression in human hepatocellular carcinoma. Gastroenterology, 127 (4): 1110-22. [PMID:15480989]

9. Sagara N, Toda G, Hirai M, Terada M, Katoh M. (1998) Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7. Biochem Biophys Res Commun, 252: 117-122. [PMID:9813155]

10. Tanaka S, Akiyoshi T, Mori M, Wands JR, Sugimachi K. (1998) A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals. Proc. Natl. Acad. Sci. U.S.A., 95 (17): 10164-9. [PMID:9707618]

11. Tycko B, Li CM, Buttyan R. (2007) The Wnt/beta-catenin pathway in Wilms tumors and prostate cancers. Curr. Mol. Med., 7 (5): 479-89. [PMID:17691963]

12. Ueno K, Hiura M, Suehiro Y, Hazama S, Hirata H, Oka M, Imai K, Dahiya R, Hinoda Y. (2008) Frizzled-7 as a potential therapeutic target in colorectal cancer. Neoplasia, 10 (7): 697-705. [PMID:18592008]

13. von Maltzahn J, Bentzinger CF, Rudnicki MA. (2012) Wnt7a-Fzd7 signalling directly activates the Akt/mTOR anabolic growth pathway in skeletal muscle. Nat. Cell Biol., 14 (2): 186-91. [PMID:22179044]

14. Yang L, Wu X, Wang Y, Zhang K, Wu J, Yuan YC, Deng X, Chen L, Kim CC, Lau S et al.. (2011) FZD7 has a critical role in cell proliferation in triple negative breast cancer. Oncogene, 30 (43): 4437-46. [PMID:21532620]

15. Yu H, Ye X, Guo N, Nathans J. (2012) Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes. Development, 139 (23): 4383-94. [PMID:23095888]

Contributors

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How to cite this page

Gunnar Schulte, Jacomijn Dijksterhuis, Julian Petersen, Elisa Arthofer, Belma Hot, Katerina Strakova, Shane Wright, Jana Valnohova, Matthias Lauth.
Class Frizzled GPCRs: FZD7. Last modified on 10/07/2015. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=235.