EPS15
Domain
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.
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 (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.
Involvement in disease
A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1. The result is a rogue activator protein.
Post-translational modifications
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.
Ubiquitinated.
Tissue Specificity
Ubiquitously expressed.
Cellular localization
- Cytoplasm
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Membrane
- Clathrin-coated pit
- 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.
- Isoform 2
- Early endosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Colocalizes with HGS on bilayered clathrin coats on endosomes.
Alternative names
AF1P, EPS15, Epidermal growth factor receptor substrate 15, Protein Eps15, Protein AF-1p