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Description

Frizzled-2 (UniProt: Q14332, also known as Fz-2, hFz2, FzE2) is encoded by the FZD2 gene (Gene ID: 2535) in human. Frizzled-2 is a multi-pass membrane protein that is widely expressed in adult tissues. In fetus, higher levels are expressed in the brain, lung, and kidney and lower levels are observed in liver. Frizzled serves as a receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. In the presence of Wnt the Frizzled receptor is activated, which along with low-density lipoprotein receptor-related proteins (LRP) 5 and 6 stabilizes beta-catenin. The formation of Wnt-Frizzled-LRP6 complex, together with the recruitment of the scaffolding protein Dishevelled (Dvl), results in LRP6 phosphorylation and activation and the recruitment of the Axin complex to the receptors. This leads to the inhibition of Axin-mediated beta-catenin phosphorylation, which stabilizes beta-catenin. Frizzled-2 is synthesized with a signal peptide (aa 1-23), which is subsequently cleaved off in the mature form. Its Fz domain is localized to amino acids 34-153 and this domain is involved in its binding with Wnt ligands. Frizzled-2 can be ubiquitinated by RING-type E3 ubiquitin transferase ZNRF3 leading to its proteasomal degradation. Abnormalities in Wnt signaling are reported to promote birth defects, degenerative diseases, and cancer.