EPS15, AF1P, Epidermal growth factor receptor substrate 15, Protein Eps15, Protein AF-1p
This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-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. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009],disease:A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1,11)(p32,q23) with MLL/HRX. The result is a rogue activator protein.,domain:The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.,function:Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits.,PTM:Phosphorylation on Tyr-849 is involved in the internalization of EGFR. Not required for membrane translocation after EGF treatment or for targeting to coated pits, but essential for a subsequent step in EGFR endocytosis (By similarity). Phosphorylated on serine upon DNA damage, probably by ATM or ATR.,similarity:Contains 2 EF-hand domains.,similarity:Contains 2 UIM (ubiquitin-interacting motif) repeats.,similarity:Contains 3 EH domains.,subcellular location:Colocalizes with HGS on bilayered clathrin coats on endosomes.,subcellular location:Recruited to the plasma membrane upon EGFR activation and localizes to coated pits.,subunit:Interacts with HGS, the interaction bridges the interaction of STAM or STAM2 with EPS15. Isoform 2 interacts with HGS and AP2A2. Part of a complex at least composed of EPS15, HGS, and either STAM1 or STAM2. Binds AP2A2 and AP2B1. Binds STON2 and EPN1. Interacts (via its SH3-binding sites) with CRK. Interacts with SH3BP4/TTP.,tissue specificity:Ubiquitously expressed.,
