Trophoblast glycoprotein (5T4) (5T4)

Trophoblast glycoprotein (5T4) is a 72-kDa type I transmembrane glycoprotein with a highly glycosylated extracellular domain containing seven leucine-rich repeats (LRRs) flanked by LRR-N and LRR-C regions, and an intracellular domain with potential phosphorylation sites.[1][2][3] It functions primarily to inhibit Wnt/β-catenin signaling through conserved surface residues like Tyr325 and Phe97 in the LRR1 domain, influencing cytoskeletal organization, cell motility, and epithelial-to-mesenchymal transition during development.[1][2] In the nervous system, 5T4 regulates dendritic branching in olfactory bulb granule cells and retinal bipolar/amacrine cells via interactions with Rab11 and PKCα phosphorylation, supporting synaptic circuit formation.[2] The protein is an oncofetal antigen with restricted normal expression (high in brain/ovaries, low elsewhere) but overexpressed in carcinomas like colorectal, ovarian, and gastric, promoting invasive properties and poor prognosis.[1][2][6] It is actively pursued as a therapeutic target in multiple cancer immunotherapy trials due to its tumor-specific surface expression, with structural insights aiding development of modulators that preserve or block its Wnt inhibitory role.[1][6]

Other names

Antigen 5T4Wnt-activated inhibitory factor 1 (WAIF1)TPBGTpbg

Inhibition of Wnt/β-catenin signaling via extracellular LRR domain (Tyr325 and Phe97 residues essential)