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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 | 694 | 10p11.21 | FZD8 | frizzled class receptor 8 | 15 |
| Mouse | 7 | 685 | 18 4.91 cM | Fzd8 | frizzled class receptor 8 | |
| Rat | 7 | 684 | 17q12.1 | Fzd8 | frizzled class receptor 8 | |
| Previous and Unofficial Names |
| frizzled family receptor 8 | Fz8 |
| Database Links |
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| Alphafold | Q9H461 (Hs), Q61091 (Mm), Q498S8 (Rn) |
| CATH/Gene3D | 1.10.2000.10 |
| ChEMBL Target | CHEMBL3559689 (Hs), CHEMBL4523332 (Mm) |
| Ensembl Gene | ENSG00000177283 (Hs), ENSMUSG00000036904 (Mm), ENSRNOG00000069521 (Rn) |
| Entrez Gene | 8325 (Hs), 14370 (Mm), 364754 (Rn) |
| Human Protein Atlas | ENSG00000177283 (Hs) |
| KEGG Gene | hsa:8325 (Hs), mmu:14370 (Mm), rno:364754 (Rn) |
| OMIM | 606146 (Hs) |
| Pharos | Q9H461 (Hs) |
| RefSeq Nucleotide | NM_031866 (Hs), NM_008058 (Mm), NM_001044251 (Rn) |
| RefSeq Protein | NP_114072 (Hs), NP_032084 (Mm), NP_001037716 (Rn) |
| UniProtKB | Q9H461 (Hs), Q61091 (Mm), Q498S8 (Rn) |
| Wikipedia | FZD8 (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| Wnt |
Download all structure-activity data for this target as a CSV file 
| Agonist Comments | ||
| FZDs are receptors for WNT proteins. Until now FZD8 has been proven to bind to WNT-2 [2] WNT-3A [11,13] WNT-9B [14] and Xenopus WNT-8 (XWNT-8 or mini-WNT) [8]. For more detail information see [4]. |
| Antagonist Comments | ||
| FZD8-Fc/OMP-54F28 is a FZD8 antagonist [3]. |
| Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Antibodies | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| G protein (identity unknown) | Other - See Comments |
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Comments:
Involvement of G proteins likely. Effector/response: β-catenin translocation to the nucleus shown by TOPflash activity after WNT-9B and WNT-2 activation of FZD8 ([14] and [2] respectively), although it is also reported that FZD8 receptor activation will inhibit β-catenin signaling [12,18]. |
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| References: | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Functional Assay Comments | ||||||||||
| Pinpointing one of the FZD isoforms in relationship to functional assays is compromised due to the high endogenous expression of various FZD isoforms in many cellular systems. |
| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| No abnormal phenotype was detected in whole animal knockout mice [20]. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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1. Bethge N, Honne H, Hilden V, Trøen G, Eknæs M, Liestøl K, Holte H, Delabie J, Smeland EB, Lind GE. (2013) Identification of highly methylated genes across various types of B-cell non-hodgkin lymphoma. PLoS ONE, 8 (11): e79602. [PMID:24260260]
2. Bravo DT, Yang YL, Kuchenbecker K, Hung MS, Xu Z, Jablons DM, You L. (2013) Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer. BMC Cancer, 13: 316. [PMID:23815780]
3. DeAlmeida VI, Miao L, Ernst JA, Koeppen H, Polakis P, Rubinfeld B. (2007) The soluble wnt receptor Frizzled8CRD-hFc inhibits the growth of teratocarcinomas in vivo. Cancer Res, 67 (11): 5371-9. [PMID:17545618]
4. 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]
5. Gregory MA, Phang TL, Neviani P, Alvarez-Calderon F, Eide CA, O'Hare T, Zaberezhnyy V, Williams RT, Druker BJ, Perrotti D et al.. (2010) Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr-Abl. Cancer Cell, 18 (1): 74-87. [PMID:20609354]
6. 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]
7. Hughes KR, Sablitzky F, Mahida YR. (2011) Expression profiling of Wnt family of genes in normal and inflammatory bowel disease primary human intestinal myofibroblasts and normal human colonic crypt epithelial cells. Inflamm Bowel Dis, 17 (1): 213-20. [PMID:20848536]
8. Janda CY, Waghray D, Levin AM, Thomas C, Garcia KC. (2012) Structural basis of Wnt recognition by Frizzled. Science, 337 (6090): 59-64. [PMID:22653731]
9. Janssens N, Andries L, Janicot M, Perera T, Bakker A. (2004) Alteration of frizzled expression in renal cell carcinoma. Tumour Biol, 25 (4): 161-71. [PMID:15557753]
10. Keay SK, Szekely Z, Conrads TP, Veenstra TD, Barchi Jr JJ, Zhang CO, Koch KR, Michejda CJ. (2004) An antiproliferative factor from interstitial cystitis patients is a frizzled 8 protein-related sialoglycopeptide. Proc Natl Acad Sci USA, 101 (32): 11803-8. [PMID:15282374]
11. Kemp CR, Willems E, Wawrzak D, Hendrickx M, Agbor Agbor T, Leyns L. (2007) Expression of Frizzled5, Frizzled7, and Frizzled10 during early mouse development and interactions with canonical Wnt signaling. Dev Dyn, 236 (7): 2011-9. [PMID:17576136]
12. Kolben T, Peröbner I, Fernsebner K, Lechner F, Geissler C, Ruiz-Heinrich L, Capovilla S, Jochum M, Neth P. (2012) Dissecting the impact of Frizzled receptors in Wnt/β-catenin signaling of human mesenchymal stem cells. Biol Chem, 393 (12): 1433-47. [PMID:23152409]
13. Kumar S, Zigman M, Patel TR, Trageser B, Gross JC, Rahm K, Boutros M, Gradl D, Steinbeisser H, Holstein T et al.. (2014) Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and modulatory determinants of Wnt signaling activity. BMC Biol, 12 (1): 44. [PMID:24885675]
14. Liu C, Wang Y, Smallwood PM, Nathans J. (2008) An essential role for Frizzled5 in neuronal survival in the parafascicular nucleus of the thalamus. J Neurosci, 28 (22): 5641-53. [PMID:18509025]
15. Saitoh T, Hirai M, Katoh M. (2001) Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2. Int J Oncol, 18 (5): 991-6. [PMID:11295046]
16. Salsano E, Paterra R, Figus M, Menghi F, Maderna E, Pollo B, Solero CL, Massimi L, Finocchiaro G. (2012) Expression profile of frizzled receptors in human medulloblastomas. J Neurooncol, 106 (2): 271-80. [PMID:21850537]
17. Sonnet M, Claus R, Becker N, Zucknick M, Petersen J, Lipka DB, Oakes CC, Andrulis M, Lier A, Milsom MD et al.. (2014) Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia. Genome Med, 6 (4): 34. [PMID:24944583]
18. Sugimura R, He XC, Venkatraman A, Arai F, Box A, Semerad C, Haug JS, Peng L, Zhong XB, Suda T et al.. (2012) Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche. Cell, 150 (2): 351-65. [PMID:22817897]
19. Uhlen M, Oksvold P, Fagerberg L, Lundberg E, Jonasson K, Forsberg M, Zwahlen M, Kampf C, Wester K, Hober S et al.. (2010) Towards a knowledge-based Human Protein Atlas. Nat Biotechnol, 28 (12): 1248-50. [PMID:21139605]
20. van Amerongen R, Berns A. (2006) Knockout mouse models to study Wnt signal transduction. Trends Genet, 22 (12): 678-89. [PMID:17045694]
21. Wang HQ, Xu ML, Ma J, Zhang Y, Xie CH. (2012) Frizzled-8 as a putative therapeutic target in human lung cancer. Biochem Biophys Res Commun, 417 (1): 62-6. [PMID:22138402]
22. Ye X, Wang Y, Rattner A, Nathans J. (2011) Genetic mosaic analysis reveals a major role for frizzled 4 and frizzled 8 in controlling ureteric growth in the developing kidney. Development, 138 (6): 1161-72. [PMID:21343368]
23. Zhao Y, Ren J, Hillier J, Lu W, Jones EY. (2020) Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8. J Med Chem, 63 (6): 3252-3260. [PMID:32049522]
