FZD₅ Extracellular Domain (human, recombinant)

Frizzled family G protein-coupled receptor 5 (FZD₅) is a Wnt receptor involved in canonical and non-canonical Wnt/β-catenin signaling.¹ It is composed of an extracellular cysteine-rich ligand-binding domain, seven transmembrane domains, and an intracellular C-terminal domain that binds the PDZ domain of dishevelled (Dvl) and G proteins.^2,3,4 Fzd₅ is expressed in the yolk sac, eye, and lung during development and primarily in the eye, kidney, lung, and testis in adults.^5,6 Upon ligand-binding, FZD₅ associates with LDL receptor-related protein 5/6 (LRP5/6) and recruits Dvl, which leads to phosphorylation of LRP5/6, recruitment of Axin, and subsequent accumulation of β-catenin.^3,7 It is involved in ocular development, mesenchymal stem cell senescence, and intestinal crypt homeostasis, and plays pro- and anti-tumorigenic roles in a context-dependent manner.^1,4,5,8,9,10 A frameshift mutation in FZD5 that results in production of a secreted FZD₅ extracellular domain is associated with autosomal dominant coloboma.¹ Cayman’s FZD₅ Extracellular Domain (human, recombinant) protein can be used for binding assays. This protein consists of 152 amino acids, has a calculated molecular weight of 17.6 kDa, and a predicted N-terminus of Ala27 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is 25-30 kDa due to glycosylation.

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1. Liu, C., Widen, S.A., Williamson, K.A., et al. A secreted WNT-ligand-binding domain of FZD5 generated by a frameshift mutation causes autosomal dominant coloboma. Hum. Mol. Genet. 25(7), 1382-1391 (2016).

2. Lagerström, M.C., and Schiöth, H.B. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat. Rev. Drug Discov. 7(4), 339-357 (2008).

3. Hua, Y., Yang, Y., Li, Q., et al. Oligomerization of Frizzled and LRP5/6 protein initiates intracellular signaling for the canonical WNT/β-catenin pathway. The Journal of Biological Chemisty 293(51), 19710-19724 (2018).

4. Dong, D., Na, L., Zhou, K., et al. FZD5 prevents epithelial-mesenchymal transition in gastric cancer. Cell Commun. Signal. 19(1), 21 (2021).

5. Ishikawa, T., Tamai, Y., Zorn, A.M., et al. Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development 128(1), 25-33 (2001).

6. Wang, Y., Macke, J.P., Abella, B.S., et al. A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled. The Journal of Biological Chemisty 271(8), 4468-4476 (1996).

7. MacDonald, B.T., Tamai, K., and He, X. Wnt/β-catenin Signaling: Components, mechanisms, and diseases. Dev. Cell. 17(1), 9-26 (2009).

8. Harada, S., Mabuchi, Y., Kohyama, J., et al. FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells. Stem Cells 39(3), 318-330 (2021).

9. Mu, Q., Ha, A., Santos, A.J.M., et al. FZD5 controls intestinal crypt homeostasis and colonic Wnt surrogate agonist response. Dev. Cell 60(3), 342-351 (2025).

10. Sun, Y., Wang, Z., Na, L., et al. FZD5 contributes to TNBC proliferation, DNA damage repair and stemness. Cell Death Dis. 11(12), 1060 (2020).