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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 | 581 | 12q24.33 | FZD10 | frizzled class receptor 10 | |
| Mouse | 7 | 582 | 5 G1.3 | Fzd10 | frizzled class receptor 10 | |
| Previous and Unofficial Names |
| CD350 | Fz-10 |
| Database Links |
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| Alphafold | Q9ULW2 (Hs), Q8BKG4 (Mm) |
| CATH/Gene3D | 1.10.2000.10 |
| ChEMBL Target | CHEMBL4523492 (Hs) |
| Ensembl Gene | ENSG00000111432 (Hs), ENSMUSG00000081683 (Mm) |
| Entrez Gene | 11211 (Hs), 93897 (Mm) |
| Human Protein Atlas | ENSG00000111432 (Hs) |
| KEGG Gene | hsa:11211 (Hs), mmu:93897 (Mm) |
| OMIM | 606147 (Hs) |
| Pharos | Q9ULW2 (Hs) |
| RefSeq Nucleotide | NM_007197 (Hs), NM_175284 (Mm) |
| RefSeq Protein | NP_009128 (Hs), NP_780493 (Mm) |
| UniProtKB | Q9ULW2 (Hs), Q8BKG4 (Mm) |
| Wikipedia | FZD10 (Hs) |
| Natural/Endogenous Ligands |
| Wnt |
| Agonist Comments | ||
| FZDs are receptors for Wnt proteins. Until now FZD10 is known to bind Wnt7b [10] and Wnt7a [1]. |
| Antagonist Comments | ||
| A chimeric humanised monoclonal antibody targeting Fzd10 (tabituximab, ONC-005, OTSA101) has been shown to be an antagonist at the human receptor. A version of this antibody conjugated to a Yttrium (Y) chelator (tabituximab barzuxetan) and labelled with the radioisotope 90Y began Phase 1 evaluation in patients with synovial sarcoma (see NCT01469975) but participant accrual was very slow and the trial was terminated as a result.. |
| Antibody Comments | ||
| Radio-labelled murine monoclonal antibody MAb 92-13 has been used to demonstrate the therapeutic potential of targeting FZD10-positive tumours [3]. |
| Primary Transduction Mechanisms
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| Comments: FZD/β-catenin signaling [9] and DVL-RAC-JNK signaling [4]. | |
| References: |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| G12/G13 family | |
| Comments: Involvement of G proteins likely [2]. | |
| References: 5 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology Comments |
| Possible correlation of high expression in synovial sacromas [7]. A FZD10 monoclonal antibody is in clinical trails. |
1. Carmon KS, Loose DS. (2008) Secreted frizzled-related protein 4 regulates two Wnt7a signaling pathways and inhibits proliferation in endometrial cancer cells. Mol Cancer Res, 6 (6): 1017-28. [PMID:18567805]
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. Fukukawa C, Hanaoka H, Nagayama S, Tsunoda T, Toguchida J, Endo K, Nakamura Y, Katagiri T. (2008) Radioimmunotherapy of human synovial sarcoma using a monoclonal antibody against FZD10. Cancer Sci, 99 (2): 432-40. [PMID:18271942]
4. Fukukawa C, Nagayama S, Tsunoda T, Toguchida J, Nakamura Y, Katagiri T. (2009) Activation of the non-canonical Dvl-Rac1-JNK pathway by Frizzled homologue 10 in human synovial sarcoma. Oncogene, 28 (8): 1110-20. [PMID:19137009]
5. Hot B, Valnohova J, Arthofer E, Simon K, Shin J, Uhlén M, Kostenis E, Mulder J, Schulte G. (2017) FZD10-Gα13 signalling axis points to a role of FZD10 in CNS angiogenesis. Cell Signal, 32: 93-103. [PMID:28126591]
6. 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]
7. Nagayama S, Fukukawa C, Katagiri T, Okamoto T, Aoyama T, Oyaizu N, Imamura M, Toguchida J, Nakamura Y. (2005) Therapeutic potential of antibodies against FZD 10, a cell-surface protein, for synovial sarcomas. Oncogene, 24 (41): 6201-12. [PMID:16007199]
8. Summerhurst K, Stark M, Sharpe J, Davidson D, Murphy P. (2008) 3D representation of Wnt and Frizzled gene expression patterns in the mouse embryo at embryonic day 11.5 (Ts19). Gene Expr Patterns, 8 (5): 331-48. [PMID:18364260]
9. Terasaki H, Saitoh T, Shiokawa K, Katoh M. (2002) Frizzled-10, up-regulated in primary colorectal cancer, is a positive regulator of the WNT - beta-catenin - TCF signaling pathway. Int J Mol Med, 9 (2): 107-12. [PMID:11786918]
10. 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]
