Epidermal Growth Factor Receptor Pathway Substrate 15 (EPS15)

EPS15 encodes a protein that is part of the EGFR pathway. The protein is present at clathrin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.

Binding of the parkin ubiquitin-like domain to the Eps15 ubiquitin-interacting motifs was required for parkin-mediated Eps15 ubiquitination. Egfr endocytosis and degradation were accelerated in parkin-deficient cells, and Egfr signaling via the PI3K-Akt pathway was reduced in parkin-knockout mouse brain.