Epidermal growth factor receptor substrate 15 (EPS15)

Epidermal growth factor receptor substrate 15 (EPS15) is a cytoplasmic protein that plays a critical role in receptor-mediated endocytosis, especially for receptors such as the epidermal growth factor receptor (EGFR)[5][1][3]. EPS15 is predominantly localized at clathrin-coated pits in the plasma membrane and interacts with adaptor proteins such as AP-2 and accessory proteins like epsin, functioning as a scaffolding protein essential for the assembly of the endocytic machinery[3][4][5]. Structurally, EPS15 has three N-terminal EH (Eps15 homology) domains, a coiled-coil domain mediating dimerization and protein interactions, and C-terminal regions with multiple DPF motifs which mediate interactions with α-adaptin (AP-2 complex)[3][4]. EPS15 is phosphorylated by activated EGFR and cycles through different stages of the endocytic pathway, contributing to the internalization and trafficking of engaged receptors[1][3][4]. Disruption of its function impairs endocytosis of EGF and transferrin receptors[3]. In disease, chromosomal rearrangements involving EPS15 (notably with the HRX/ALL/MLL gene) have been identified in acute myelogenous leukemia, highlighting a role in oncogenesis[5][3]. EPS15 is not a classical receptor, enzyme, or ion channel, but rather a key adaptor in the molecular machinery underlying endocytosis and signal regulation. No known clinical drugs directly target EPS15, but its role in cell proliferation and endocytosis implicates it in cancer biology and intracellular trafficking disorders[3][5].

Other names

AF-1PMLLT5Protein AF-1pALL1 fused gene from chromosome 1protein AF-1pEps15AF1PEpidermal growth factor pathway substrate 15