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. ,
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