Description
TPBG, also known as Trophoblast glycoprotein and Wnt-activated inhibitory factor 1 (WAIF1), is a single-pass transmembrane protein which may function as an inhibitor of Wnt/beta-catenin signaling (1). Distinct regions on the 5T4 ectodomain which contains eight leucine-rich repeats are thought to antagonize Wnt signaling (2). 5T4 has limited expression in normal adult tissues and in some solid tumors, while expression is elevated in human carcinomas which have been correlated with poor survival and prognosis (3-5). Human 5T4 is a 420 amino acid (aa) protein that includes a 31 aa signal peptide, a 324 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 44 aa cytoplasmic tail. Within the ECD, human 5T4 shares 78% and 77% aa sequence identity with mouse and rat 5T4, respectively. It has been identified that TIP-2/GIPC, a common interacting protein involved in cancer, interacts with 5T4 through its PDZ domain (6). 5T4 inhibits Wnt/β-catenin signaling by binding to LRP6 and inhibit Wnt-induced LRP6 internalization into endocytic vesicles (1). Conversely, 5T4 can activate noncanonical Wnt signaling through DKK1 (1). In addition to LRP6, in-house data indicates 5T4 can also interact with Frizzled-8