GPC3

Function

GPC3 interacts with both Wnt and frizzled (FZD) to form a complex and triggers downstream signaling. The core protein of GPC3 may serve as a co-receptor or a receiver for Wnt. A cysteine-rich domain at the N-lobe of GPC3 has been identified as a hydrophobic groove that interacts with Wnt3a. Blocking the Wnt binding domain on GPC3 using the HN3 single domain antibody can inhibit Wnt activation. Wnt also recognizes a heparan sulfate structure on GPC3, which contains IdoA2S and GlcNS6S, and that the 3-O-sulfation in GlcNS6S3S significantly enhances the binding of Wnt to heparan sulfate. GPC3 also modulates Yap signaling. It interacts with FAT1, a potential upstream cell surface receptor of YAP1 in human cells. GPC3 is also found to bind Alpha-fetoprotein in liver cancer.