FZD<sub>10</sub> | Class Frizzled GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

FZD10

Target id: 238

Nomenclature: FZD10

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 FZD10 in GtoImmuPdb

Gene and Protein Information
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
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Wnt
Agonist Comments
FZDs are receptors for Wnt proteins. Until now FZD10 is known to bind Wnt7b [9] 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..
Primary Transduction Mechanisms
Comments:  FZD/β-catenin signaling [8] and DVL-RAC-JNK signaling [3].
References: 
Secondary Transduction Mechanisms
Transducer Effector/Response
G12/G13 family
Comments:  Involvement of G proteins likely [2].
References:  4
Tissue Distribution
Placenta
Species:  Human
Technique:  Northern blot
References:  6
Distal airway epithelium in mouse embryon from E12.5-14.5
Species:  Mouse
Technique:  Immunohistochemistry
References:  9
Dorsal CNS and progress zone of the limb in mouse embryo at E11.5
Species:  Mouse
Technique:  Whole mount in situ hybridisation
References:  7
FZD10 expression in mouse brain endothelial cells during embryologic development stages E11.5-E14.5
Species:  Mouse
Technique:  Immunohistochemistry, in situ hybridisation
References:  4
Stroma of the uteri
Species:  Rat
Technique:  In situ hybridisation
References:  1
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
WNT-3A stimulation of L-cells expressing FZD10
Species:  Mouse
Tissue:  L-cells
Response measured:  G protein activation (GDP/GTP exchange)
References:  5
Physiological Functions
Increase of RhoA activity by suppression of FZD10 with siRNA
Species:  Human
Tissue:  SYO-1 cells
References:  3
Knockdown of FZD10 by siRNA supress Rac1 activity
Species:  Human
Tissue:  HS-SY-II cells
References:  3
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Fzd10tm1Dgen Fzd10tm1Dgen/Fzd10tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:2136761  MP:0002169 no abnormal phenotype detected
Clinically-Relevant Mutations and Pathophysiology Comments
Possible correlation of high expression in synovial sacromas [6]. A FZD10 monoclonal antibody is in clinical trails.

References

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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, 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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: 5022-5030. [PMID:15923619]

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: FZD10. Last modified on 05/09/2018. Accessed on 14/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=238.