APC membrane recruitment protein 1 (AMER1)

APC membrane recruitment protein 1 (AMER1, also known as WTX or FAM123B) is a multifunctional scaffold protein that plays a key role as a tumor suppressor and negative regulator of the canonical Wnt/β‐catenin signaling pathway. AMER1 binds directly to APC (adenomatous polyposis coli), Axin, and β-catenin, orchestrating the assembly of the β‐catenin destruction complex at the plasma membrane, which leads to β-catenin ubiquitination and degradation. It acts via distinct membrane-binding domains and contains multiple APC interaction motifs (A1-A4), which are crucial for its recruitment and regulatory functions. Mutations in AMER1 underlie the developmental disorder osteopathia striata with cranial sclerosis (OSCS) and predispose to certain cancers, including Wilms tumor. In some cellular contexts, AMER1 can also act as a positive regulator of Wnt signaling, for example by promoting LRP6 phosphorylation. The protein is essential for normal kidney and bone development, and its tumor suppressive activity is context- and localization-dependent.

Other names

AMER1WTXFAM123BWilms tumor gene on the X chromosome proteinosteopathia striata with cranial sclerosis proteinOSCSfamily with sequence similarity 123BRP11-403E24.2FLJ39827protein FAM123Badenomatous polyposis coli membrane recruitment 1

Scaffold assembly promoting β-catenin ubiquitination and degradation; Inhibition of Wnt/β-catenin signaling by recruiting destruction complex to plasma membrane; Promotion of LRP6 phosphorylation (context-dependent upregulation of Wnt signaling)