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Gene and Protein Information  |
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| Frizzled family G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 565 | 17q21.31 | FZD2 | frizzled class receptor 2 | 19 |
| Mouse | 7 | 570 | 11 E1 | Fzd2 | frizzled class receptor 2 | 8 |
| Rat | 7 | 570 | 10q32.1 | Fzd2 | frizzled class receptor 2 | 2 |
| Previous and Unofficial Names |
| Fz2 | Frizzled-2 | Drosophila polarity gene homolog 2 | frizzled family receptor 2 | Fzd10 | Fz10 |
| Database Links |
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| Alphafold | Q14332 (Hs), Q9JIP6 (Mm), Q08464 (Rn) |
| CATH/Gene3D | 1.10.2000.10 |
| ChEMBL Target | CHEMBL3559686 (Hs), CHEMBL4879521 (Mm), CHEMBL4879455 (Rn) |
| Ensembl Gene | ENSG00000180340 (Hs), ENSMUSG00000050288 (Mm), ENSRNOG00000021962 (Rn) |
| Entrez Gene | 2535 (Hs), 57265 (Mm), 64512 (Rn) |
| Human Protein Atlas | ENSG00000180340 (Hs) |
| KEGG Gene | hsa:2535 (Hs), mmu:57265 (Mm), rno:64512 (Rn) |
| OMIM | 600667 (Hs) |
| Pharos | Q14332 (Hs) |
| RefSeq Nucleotide | NM_001466 (Hs), NM_020510 (Mm), NM_172035 (Rn) |
| RefSeq Protein | NP_001457 (Hs), NP_065256 (Mm), NP_742032 (Rn) |
| UniProtKB | Q14332 (Hs), Q9JIP6 (Mm), Q08464 (Rn) |
| Wikipedia | FZD2 (Hs) |
| Natural/Endogenous Ligands |
| Wnt-5a {Sp: Human} |
Download all structure-activity data for this target as a CSV file 
| Agonist Comments | ||
| FZDs are receptors for WNT proteins. Until now FZD2 has been proven to bind to WNT 2, 3, 3A, 5A, 6, 7A and 8B. For more detail information see [3]. |
| Antagonist Comments | ||
| UM206 is a synthetic peptidic FZD ligand whose sequence is derived from regions of high homology between the ligands Wnt3a and Wnt5a [5]. It acts as an antagonist of FZD1/2 signalling [9], and has shown efficacy in aminal models of cardiovascular disease [5,13]. |
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
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Gi/Go family G protein (identity unknown) |
Calcium channel Other - See Comments |
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Comments:
Even though data argue strongly for FZD2 signalling via heterotrimeric G proteins, no direct interaction between FZD2 and the G protein has been shown yet. Thus direct proof for G protein-coupling of this receptor is still not available. WNT-5A/FZD2 binding in F9 cells induced a PTX-sensitive and PDE6-dependent decrease in cGMP and increase in Ca2+ suggesting a very likely involvement of heterotrimeric G proteins [1]. |
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| References: 1,6-7 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| General Comments |
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The WNTs that are available in purified and active form for a pharmacological characterisation to date are WNT-3A and WNT-5A [11,17]. FZD2 (mouse) shows high homology to FZD10 (mouse). Since these receptors are encoded by two genes on different chromosomes, they should be seen as two receptor subtypes. |
1. Ahumada A, Slusarski DC, Liu X, Moon RT, Malbon CC, Wang HY. (2002) Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP. Science, 298 (5600): 2006-10. [PMID:12471263]
2. Chan SD, Karpf DB, Fowlkes ME, Hooks M, Bradley MS, Vuong V, Bambino T, Liu MY, Arnaud CD, Strewler GJ et al.. (1992) Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues. J Biol Chem, 267 (35): 25202-7. [PMID:1334084]
3. 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]
4. 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 USA, 109 (29): 11717-22. [PMID:22753465]
5. Laeremans H, Hackeng TM, van Zandvoort MA, Thijssen VL, Janssen BJ, Ottenheijm HC, Smits JF, Blankesteijn WM. (2011) Blocking of frizzled signaling with a homologous peptide fragment of wnt3a/wnt5a reduces infarct expansion and prevents the development of heart failure after myocardial infarction. Circulation, 124 (15): 1626-35. [PMID:21931076]
6. Ma L, Wang HY. (2006) Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/cGMP/Ca2+ pathway. J Biol Chem, 281 (41): 30990-1001. [PMID:16920709]
7. Ma L, Wang HY. (2007) Mitogen-activated protein kinase p38 regulates the Wnt/cyclic GMP/Ca2+ non-canonical pathway. J Biol Chem, 282 (39): 28980-90. [PMID:17684012]
8. Malik TH, Shivdasani RA. (2000) Structure and expression of a novel frizzled gene isolated from the developing mouse gut. Biochem J, 349 Pt 3: 829-34. [PMID:10903145]
9. Moyes KW, Sip CG, Obenza W, Yang E, Horst C, Welikson RE, Hauschka SD, Folch A, Laflamme MA. (2013) Human embryonic stem cell-derived cardiomyocytes migrate in response to gradients of fibronectin and Wnt5a. Stem Cells Dev, 22 (16): 2315-25. [PMID:23517131]
10. 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 (1): 117-22. [PMID:9813155]
11. Schulte G, Bryja V, Rawal N, Castelo-Branco G, Sousa KM, Arenas E. (2005) Purified Wnt-5a increases differentiation of midbrain dopaminergic cells and dishevelled phosphorylation. J Neurochem, 92 (6): 1550-3. [PMID:15748172]
12. Sen M, Lauterbach K, El-Gabalawy H, Firestein GS, Corr M, Carson DA. (2000) Expression and function of wingless and frizzled homologs in rheumatoid arthritis. Proc Natl Acad Sci USA, 97 (6): 2791-6. [PMID:10688908]
13. Uitterdijk A, Hermans KC, de Wijs-Meijler DP, Daskalopoulos EP, Reiss IK, Duncker DJ, Matthijs Blankesteijn W, Merkus D. (2016) UM206, a selective Frizzled antagonist, attenuates adverse remodeling after myocardial infarction in swine. Lab Invest, 96 (2): 168-76. [PMID:26658451]
14. van Amerongen R, Berns A. (2006) Knockout mouse models to study Wnt signal transduction. Trends Genet, 22 (12): 678-89. [PMID:17045694]
15. van Gijn ME, Blankesteijn WM, Smits JF, Hierck B, Gittenberger-de Groot AC. (2001) Frizzled 2 is transiently expressed in neural crest-containing areas during development of the heart and great arteries in the mouse. Anat Embryol, 203 (3): 185-92. [PMID:11303904]
16. Wang Y, Macke JP, Abella BS, Andreasson K, Worley P, Gilbert DJ, Copeland NG, Jenkins NA, Nathans J. (1996) A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled. J Biol Chem, 271 (8): 4468-76. [PMID:8626800]
17. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates 3rd JR, Nusse R. (2003) Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature, 423 (6938): 448-52. [PMID:12717451]
18. Yu H, Smallwood PM, Wang Y, Vidaltamayo R, Reed R, Nathans J. (2010) Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes. Development, 137 (21): 3707-17. [PMID:20940229]
19. Zhao Z, Lee CC, Baldini A, Caskey CT. (1995) A human homologue of the Drosophila polarity gene frizzled has been identified and mapped to 17q21.1. Genomics, 27 (2): 370-3. [PMID:7558010]
