Eps15

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]

Full Name

Epidermal Growth Factor Receptor Pathway Substrate 15

Research Area

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.

Biological Process

Clathrin coat assembly Source: BHF-UCL
Endocytic recycling Source: BHF-UCL
Endocytosis Source: GO_Central
Endosomal transport Source: GO_Central
Golgi to endosome transport Source: UniProtKB
Positive regulation of receptor recycling Source: Ensembl
Postsynaptic neurotransmitter receptor internalization Source: Ensembl
Protein transport Source: UniProtKB-KW
Receptor-mediated endocytosis of virus by host cell Source: CACAO
Regulation of cell population proliferation Source: Ensembl
Vesicle organization Source: UniProtKB
Viral entry into host cell Source: CACAO

Cellular Location

Cytoplasm; Cell 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. Colocalizes with HGS on bilayered clathrin coats on endosomes.

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.

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.By similarity
Ubiquitinated.By similarity