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 (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. 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 STAM or STAM2. Binds AP2A2. Interacts with AP2B1; clathrin competes with EPS15. Binds STON2. Interacts (via its SH3-binding sites) with CRK. Interacts with SH3BP4/TTP. Interacts with ERBB2. Interacts (via UIM repeats) with CORO7 (when ubiquitinated at 'Lys-472') (By similarity). Interacts with FCHO1 (By similarity). Interacts with FCHO2. Interacts with SGIP1. Interacts (via EH domains) with DAB2. Interacts (via UIM domains) with UBQLN1 (via ubiquitin-like domain) and can interact with both the ubiquitinated and the non-ubiquitinated forms of UBQLN1. Interacts with UBQLN2 (By similarity). Interacts with REPS2; the interaction is direct (PubMed:10393179). Interacts with EPN1; the interaction is direct (By similarity). Recruited to the plasma membrane upon EGFR activation and localizes to coated pits. Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments and in cytoplasmic juxtanuclear structures called aggresomes. Colocalizes with HGS on bilayered clathrin coats on endosomes. The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins. The UIM (ubiquitin-interacting motif) repeats specifically bind 'Lys-33'-linked ubiquitin. Phosphorylated on serine upon DNA damage, probably by ATM or ATR (By similarity). Phosphorylation on Tyr-850 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. Ubiquitinated.