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FZD1
Not curated in GtoImmuPdb
Target id: 229
Nomenclature: FZD1
Family: Class Frizzled GPCRs
Annotation status:
Annotated and reviewed, awaiting update
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Contents:
- Quaternary Structure
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Selected 3D Structures
- Associated Proteins
- Functional Characteristics
- Natural/Endogenous Ligands
- Rank order lists
- Activators
- Inhibitors
- Gating Inhibitors
- Agonists
- Antagonists
- Channel Blockers
- Allosteric Modulators
- Antibodies
- Other Binding Ligands
- Whole Organism Assay Data
- Large-scale Ligand Screening Data
- Immunopharmacology Comments
- Immuno Cell Type Associations
- Immuno Process Associations
- Immuno Disease Associations
- Malaria Pharmacology Comments
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Xenobiotics Influencing Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Gene Expression and Pathophysiology
- Biologically Significant Variants
- General Comments
- Available Assays
- References
- Contributors
- How to cite this page
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 | 647 | 7q21.13 | FZD1 | frizzled class receptor 1 | 9 |
| Mouse | 7 | 642 | 5 2.61 cM | Fzd1 | frizzled class receptor 1 | 25 |
| Rat | 7 | 641 | 4q13 | Fzd1 | frizzled class receptor 1 | 2 |
| Previous and Unofficial Names |
| Fz1 | Wnt receptor | Drosophila polarity gene homolog 1 | frizzled family receptor 1 | frizzled homolog 1 | Drosophila polarity gene (frizzled) homologue | Frizzled-1 |
| Database Links |
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| Alphafold | Q9UP38 (Hs), O70421 (Mm), Q08463 (Rn) |
| CATH/Gene3D | 1.10.2000.10 |
| ChEMBL Target | CHEMBL2346493 (Hs), CHEMBL4879419 (Mm), CHEMBL4879454 (Rn) |
| Ensembl Gene | ENSG00000157240 (Hs), ENSMUSG00000044674 (Mm), ENSRNOG00000016242 (Rn), ENSRNOG00000062541 (Rn) |
| Entrez Gene | 8321 (Hs), 14362 (Mm), 58868 (Rn) |
| Human Protein Atlas | ENSG00000157240 (Hs) |
| KEGG Gene | hsa:8321 (Hs), mmu:14362 (Mm), rno:58868 (Rn) |
| OMIM | 603408 (Hs) |
| Pharos | Q9UP38 (Hs) |
| RefSeq Nucleotide | NM_003505 (Hs), NM_021457 (Mm), NM_021266 (Rn) |
| RefSeq Protein | NP_003496 (Hs), NP_067432 (Mm), NP_067089 (Rn) |
| UniProtKB | Q9UP38 (Hs), O70421 (Mm), Q08463 (Rn) |
| Wikipedia | FZD1 (Hs) |
| Natural/Endogenous Ligands |
| Wnt-1 {Sp: Human} |
| Wnt-2 {Sp: Human} |
| Wnt-5a {Sp: Human} |
| Wnt-3a {Sp: Human} |
| Wnt-7b {Sp: Human} |
Download all structure-activity data for this target as a CSV file 
| Agonist Comments | ||
| WNT-1, WNT-2, WNT-3A, WNT-5A, WNT-5B and WNT-7B bind to the FZD1 receptor [9,12,23]. 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 FZD1 by individual WNTs. For additional information see [5]. |
| Antagonist Comments | ||
| UM206 is a synthetic peptidic FZD ligand whose sequence is derived from regions of high homology between the ligands Wnt3a and Wnt5a [14]. It acts as an antagonist of FZD1/2 signalling [17], and has shown efficacy in aminal models of cardiovascular disease [14,21]. |
| Allosteric Modulator Comments | ||
| Currently no allosteric modulators are known. |
| Antibodies | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Other - See Comments | |
| Comments: FZD/beta-catenin signalling (also referred to as canonical WNT signalling). | |
| References: 7-9,23 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
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Gi/Go family Gq/G11 family |
Phospholipase C stimulation Other - See Comments |
| Comments: WNT-3A induces a Gq-dependent production of IP5 and a PTX-sensitive activation of casein kinase 2, which are involved in FZD/beta-catenin signalling. In addition, FZD1 was shown to mediate Go activation (GDP/GTP exchange) in membranes from FZD1 overexpressing mammalian cells [12]. | |
| References: 7-8 | |
| 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 |
| The WNTs that are available in purified and active form for a pharmacological characterisation to date are WNT-3A and WNT-5A [20,24]. |
References
1. Borello U, Buffa V, Sonnino C, Melchionna R, Vivarelli E, Cossu G. (1999) Differential expression of the Wnt putative receptors Frizzled during mouse somitogenesis. Mech Dev, 89 (1-2): 173-7. [PMID:10559494]
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. Chen M, Wang J, Lu J, Bond MC, Ren XR, Lyerly HK, Barak LS, Chen W. (2009) The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling. Biochemistry, 48 (43): 10267-74. [PMID:19772353]
4. Daudet N, Ripoll C, Molès JP, Rebillard G. (2002) Expression of members of Wnt and Frizzled gene families in the postnatal rat cochlea. Brain Res Mol Brain Res, 105 (1-2): 98-107. [PMID:12399112]
5. 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]
6. Fischer T, Guimera J, Wurst W, Prakash N. (2007) Distinct but redundant expression of the Frizzled Wnt receptor genes at signaling centers of the developing mouse brain. Neuroscience, 147 (3): 693-711. [PMID:17582687]
7. Gao Y, Wang HY. (2006) Casein kinase 2 Is activated and essential for Wnt/beta-catenin signaling. J Biol Chem, 281 (27): 18394-400. [PMID:16672224]
8. Gao Y, Wang HY. (2007) Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. J Biol Chem, 282 (36): 26490-502. [PMID:17595165]
9. Gazit A, Yaniv A, Bafico A, Pramila T, Igarashi M, Kitajewski J, Aaronson SA. (1999) Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response. Oncogene, 18 (44): 5959-66. [PMID:10557084]
10. 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]
11. Holcombe RF, Marsh JL, Waterman ML, Lin F, Milovanovic T, Truong T. (2002) Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma. MP, Mol Pathol, 55 (4): 220-6. [PMID:12147710]
12. Katanaev VL, Buestorf S. Frizzled Proteins are bona fide G Protein-Coupled Receptors. Accessed on 31/07/2014. Modified on 31/07/2014. Nature Precedings, http://precedings.nature.com/documents/2765/version/1
13. Koval A, Katanaev VL. (2011) Wnt3a stimulation elicits G-protein-coupled receptor properties of mammalian Frizzled proteins. Biochem J, 433 (3): 435-40. [PMID:21128903]
14. 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]
15. Lapointe E, Boyer A, Rico C, Paquet M, Franco HL, Gossen J, DeMayo FJ, Richards JS, Boerboom D. (2012) FZD1 regulates cumulus expansion genes and is required for normal female fertility in mice. Biol Reprod, 87 (5): 104. [PMID:22954793]
16. Liu T, Liu X, Wang Hy, Moon RT, Malbon CC. (1999) Activation of rat frizzled-1 promotes Wnt signaling and differentiation of mouse F9 teratocarcinoma cells via pathways that require Galpha(q) and Galpha(o) function. J Biol Chem, 274 (47): 33539-44. [PMID:10559239]
17. 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]
18. Neumann J, Schaale K, Farhat K, Endermann T, Ulmer AJ, Ehlers S, Reiling N. (2010) Frizzled1 is a marker of inflammatory macrophages, and its ligand Wnt3a is involved in reprogramming Mycobacterium tuberculosis-infected macrophages. FASEB J, 24 (11): 4599-612. [PMID:20667980]
19. 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]
20. 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]
21. 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]
22. van Amerongen R, Berns A. (2006) Knockout mouse models to study Wnt signal transduction. Trends Genet, 22 (12): 678-89. [PMID:17045694]
23. Wang Z, Shu W, Lu MM, Morrisey EE. (2005) Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5. Mol Cell Biol, 25 (12): 5022-30. [PMID:15923619]
24. 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]
25. Xu L, Tan L, Goldring MB, Olsen BR, Li Y. (2001) Expression of frizzled genes in mouse costochondral chondrocytes. Matrix Biol, 20 (2): 147-51. [PMID:11334716]
26. 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]
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