ID:EPS15_HUMAN DESCRIPTION: RecName: Full=Epidermal growth factor receptor substrate 15; Short=Protein Eps15; AltName: Full=Protein AF-1p; 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). 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. SUBUNIT: Interacts with SGIP1 (By similarity). 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. Interacts with AP2B1; clathrin competes with EPS15. Binds STON2 and EPN1. Interacts (via its SH3-binding sites) with CRK. Interacts with SH3BP4/TTP. Interacts with ERBB2. Interacts with FCHO1. Interacts with FCHO2. Interacts (via EH domains) with DAB2. INTERACTION: Q0JRZ9:FCHO2; NbExp=3; IntAct=EBI-396684, EBI-2609756; Q3UQN2:Fcho2 (xeno); NbExp=3; IntAct=EBI-396684, EBI-6094986; P16333:NCK1; NbExp=2; IntAct=EBI-396684, EBI-389883; SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Membrane, clathrin-coated pit. Note=Recruited to the plasma membrane upon EGFR activation and localizes to coated pits. SUBCELLULAR LOCATION: Isoform 2: Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Note=Colocalizes with HGS on bilayered clathrin coats on endosomes. TISSUE SPECIFICITY: Ubiquitously expressed. DOMAIN: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins. 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. DISEASE: Note=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. SIMILARITY: Contains 2 EF-hand domains. SIMILARITY: Contains 3 EH domains. SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats. CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR used a siRNA mixture of EPS15 and EPS15L1, and a Dab2 mutant with impaired binding to EH domain-containing proteins EPS15 and ITSN1 suggesting a partially overlapping role of the EH domain- containing proteins (PubMed:22648170). WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AF1pID11.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P42566
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
