Human Gene EPS15 (uc001csq.1) Description and Page Index
Description: Homo sapiens epidermal growth factor receptor pathway substrate 15 (EPS15), transcript variant 1, mRNA. RefSeq Summary (NM_001981): 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]. Transcript (Including UTRs) Position: hg19 chr1:51,819,935-51,984,995 Size: 165,061 Total Exon Count: 25 Strand: - Coding Region Position: hg19 chr1:51,822,372-51,984,903 Size: 162,532 Coding Exon Count: 25
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";
Genetic Association Studies of Complex Diseases and Disorders
Rhinitis, Allergic, Seasonal Adaikalavan Ramasamy et al. The Journal of allergy and clinical immunology 2011, A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order., The Journal of allergy and clinical immunology.
This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses.
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
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
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.