Gene Symbol: EPS15L1
Description: epidermal growth factor receptor pathway substrate 15 like 1
Alias: EPS15R, epidermal growth factor receptor substrate 15-like 1, epidermal growth factor receptor substrate EPS15R, eps15-related protein
Species: human
Products:     EPS15L1

Top Publications

  1. Coda L, Salcini A, Confalonieri S, Pelicci G, Sorkina T, Sorkin A, et al. Eps15R is a tyrosine kinase substrate with characteristics of a docking protein possibly involved in coated pits-mediated internalization. J Biol Chem. 1998;273:3003-12 pubmed
    b>eps15R was identified because of its relatedness to eps15, a gene encoding a tyrosine kinase substrate bearing a novel protein-protein interaction domain, called EH...
  2. Salcini A, Confalonieri S, Doria M, Santolini E, Tassi E, Minenkova O, et al. Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module. Genes Dev. 1997;11:2239-49 pubmed
    EH is a recently identified protein-protein interaction domain found in the signal transducers Eps15 and Eps15R and several other proteins of yeast nematode...
  3. Chen H, Fre S, Slepnev V, Capua M, Takei K, Butler M, et al. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature. 1998;394:793-7 pubmed
    ..We propose that epsin may participate, together with Eps15, in the molecular rearrangement of the clathrin coats that are required for coated-pit invagination and vesicle fission. ..
  4. Rosenthal J, Chen H, Slepnev V, Pellegrini L, Salcini A, Di Fiore P, et al. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module. J Biol Chem. 1999;274:33959-65 pubmed
    ..The epsins define a new protein family implicated in membrane dynamics at the cell surface. ..
  5. Jiang S, Wang X, Song D, Liu X, Gu Y, Xu Z, et al. Cholesterol induces epithelial-to-mesenchymal transition of prostate cancer cells by suppressing degradation of EGFR through APMAP. Cancer Res. 2019;: pubmed publisher
    ..APMAP increases the interaction with epidermal growth factor receptor substrate 15-related protein (EPS15R) to inhibit the endocytosis of EGFR by cholesterol, thus promoting cholesterol-induced EMT...
  6. Milesi C, Alberici P, Pozzi B, Oldani A, Beznoussenko G, Raimondi A, et al. Redundant and nonredundant organismal functions of EPS15 and EPS15L1. Life Sci Alliance. 2019;2: pubmed publisher
    EPS15 and its homologous EPS15L1 are endocytic accessory proteins. Studies in mammalian cell lines suggested that EPS15 and EPS15L1 regulate endocytosis in a redundant manner...
  7. Nalls M, Couper D, Tanaka T, van Rooij F, Chen M, Smith A, et al. Multiple loci are associated with white blood cell phenotypes. PLoS Genet. 2011;7:e1002113 pubmed publisher
    ..and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously ..
  8. Sigismund S, Woelk T, Puri C, Maspero E, Tacchetti C, Transidico P, et al. Clathrin-independent endocytosis of ubiquitinated cargos. Proc Natl Acad Sci U S A. 2005;102:2760-5 pubmed
    ..the Ub-interacting motif, as shown through the ablation of three Ub-interacting motif-containing proteins, eps15, eps15R, and epsin...
  9. Zuidema A, Wang W, Kreft M, Te Molder L, Hoekman L, Bleijerveld O, et al. Mechanisms of integrin αVβ5 clustering in flat clathrin lattices. J Cell Sci. 2018;131: pubmed publisher
    ..as ligand, Ca2+, and the clathrin adaptor proteins ARH (also known as LDLRAP1), Numb and EPS15/EPS15L1. Integrin chimeras, containing the extracellular and transmembrane domains of β5 and the cytoplasmic domains of ..

More Information


  1. Seiler C, Gebhart N, Zhang Y, Shinton S, Li Y, Ross N, et al. Mutagenesis Screen Identifies agtpbp1 and eps15L1 as Essential for T lymphocyte Development in Zebrafish. PLoS ONE. 2015;10:e0131908 pubmed publisher
    ..In two of the lines we identified the disrupted genes, agtpbp1 and eps15L1. Morpholino-mediated knockdown of these genes mimicked the T cell defects in the corresponding mutant embryos, ..
  2. Sprooten E, Fleming K, Thomson P, Bastin M, Whalley H, Hall J, et al. White matter integrity as an intermediate phenotype: exploratory genome-wide association analysis in individuals at high risk of bipolar disorder. Psychiatry Res. 2013;206:223-31 pubmed publisher
  3. Umair M, Ullah A, Abbas S, Ahmad F, Basit S, Ahmad W. First direct evidence of involvement of a homozygous loss-of-function variant in the EPS15L1 gene underlying split-hand/split-foot malformation. Clin Genet. 2017;: pubmed publisher
    ..409delA, p.Ser137Alafs*19) in the EPS15L1 gene located on chromosome 19p13.11...
  4. Poupon V, Polo S, Vecchi M, Martin G, Dautry Varsat A, Cerf Bensussan N, et al. Differential nucleocytoplasmic trafficking between the related endocytic proteins Eps15 and Eps15R. J Biol Chem. 2002;277:8941-8 pubmed
    Eps15 and Eps15R are constitutive components of clathrin-coated pits that are required for clathrin-dependent endocytosis...
  5. Doria M, Salcini A, Colombo E, Parslow T, Pelicci P, Di Fiore P. The eps15 homology (EH) domain-based interaction between eps15 and hrb connects the molecular machinery of endocytosis to that of nucleocytosolic transport. J Cell Biol. 1999;147:1379-84 pubmed
    ..In this study, we demonstrate that Eps15 and Eps15R, two EH-containing proteins, synergize with Hrb and Hrbl to enhance the function of Rev in the export pathway...
  6. Haglund K, Shimokawa N, Szymkiewicz I, Dikic I. Cbl-directed monoubiquitination of CIN85 is involved in regulation of ligand-induced degradation of EGF receptors. Proc Natl Acad Sci U S A. 2002;99:12191-6 pubmed
    ..Thus, our data demonstrate that Cbl/Cbl-b can mediate polyubiquitination of cargo as well as monoubiquitination of CIN85 to control endosomal sorting and degradation of receptor tyrosine kinases. ..
  7. Barriere H, Nemes C, Lechardeur D, Khan Mohammad M, Fruh K, Lukacs G. Molecular basis of oligoubiquitin-dependent internalization of membrane proteins in Mammalian cells. Traffic. 2006;7:282-97 pubmed
    ..These results provide a paradigm for the clathrin-mediated uptake of ubiquitinated membrane proteins in mammalian cells, requiring the assembly of multiple UIM-Ub interactions to overcome the low affinity binding of mono-Ub to UIM. ..
  8. Schmid E, Ford M, Burtey A, Praefcke G, Peak Chew S, Mills I, et al. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol. 2006;4:e262 pubmed
    ..However, proteins such as beta-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors...
  9. Henne W, Boucrot E, Meinecke M, Evergren E, Vallis Y, Mittal R, et al. FCHo proteins are nucleators of clathrin-mediated endocytosis. Science. 2010;328:1281-4 pubmed publisher
    ..The FCHo F-BAR membrane-bending activity was required, leading to the proposal that FCHo1/2 sculpt the initial bud site and recruit the clathrin machinery for CCV formation. ..
  10. Evergren E, Cobbe N, McMahon H. Eps15R and clathrin regulate EphB2-mediated cell repulsion. Traffic. 2017;: pubmed publisher
    ..Here we show that the process is clathrin- and Eps15R-mediated using Co115 colorectal cell lines stably expressing EphB2 and ephrinB1...
  11. Krieger J, Taylor P, Gajadhar A, Guha A, Moran M, McGlade C. Identification and selected reaction monitoring (SRM) quantification of endocytosis factors associated with Numb. Mol Cell Proteomics. 2013;12:499-514 pubmed publisher
    ..Hence, quantitative mass spectrometric analysis of Numb protein-protein interactions has provided new insights into the assembly and regulation of protein complexes important in development and cancer. ..
  12. Regan Klapisz E, Sorokina I, Voortman J, de Keizer P, Roovers R, Verheesen P, et al. Ubiquilin recruits Eps15 into ubiquitin-rich cytoplasmic aggregates via a UIM-UBL interaction. J Cell Sci. 2005;118:4437-50 pubmed
    Eps15 and its related protein Eps15R are key components of the clathrin-mediated endocytic pathway. We searched for new binding partners of Eps15 using a yeast two-hybrid screen...
  13. Bens S, Haake A, Tonnies H, Vater I, Stephani U, Holterhus P, et al. A de novo 1.1Mb microdeletion of chromosome 19p13.11 provides indirect evidence for EPS15L1 to be a strong candidate for split hand split foot malformation. Eur J Med Genet. 2011;54:e501-4 pubmed publisher
    ..difference is that in the previously described patient but not in the patient reported herein the genes EPS15L1 and CALR3 were deleted...
  14. McMahon K, Zajicek H, Li W, Peyton M, Minna J, Hernandez V, et al. SRBC/cavin-3 is a caveolin adapter protein that regulates caveolae function. EMBO J. 2009;28:1001-15 pubmed publisher
    ..We conclude that SRBC (sdr-related gene product that binds to c-kinase) and two other family members [PTRF (Pol I and transcription release factor) and SDPR] function as caveolin adapter molecules that regulate caveolae function. ..
  15. Offenhauser N, Santolini E, Simeone A, Di Fiore P. Differential patterns of expression of Eps15 and Eps15R during mouse embryogenesis. Mech Dev. 2000;95:309-12 pubmed
    Eps15 and Eps15R are related tyrosine kinase substrates, which have been implicated in endocytosis and synaptic vesicle recycling...
  16. Haglund K, Schmidt M, Wong E, Guy G, Dikic I. Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation. EMBO Rep. 2005;6:635-41 pubmed
    ..Sprouty2 therefore acts as an inducible inhibitor of EGFR downregulation by targeting both the Cbl and CIN85 pathways. ..
  17. Martina J, Bonangelino C, Aguilar R, Bonifacino J. Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery. J Cell Biol. 2001;153:1111-20 pubmed
    ..Stonin 2, but not stonin 1, interacts with the endocytic machinery proteins Eps15, Eps15R, and intersectin 1...
  18. Ueki N, Oda T, Kondo M, Yano K, Noguchi T, Muramatsu M. Selection system for genes encoding nuclear-targeted proteins. Nat Biotechnol. 1998;16:1338-42 pubmed
    ..We propose that NTT is an efficient method for isolating cDNAs that encode nuclear targeted proteins that can be applied to the retrieval of novel nuclear proteins and to annotate gene function. ..
  19. Klapisz E, Sorokina I, Lemeer S, Pijnenburg M, Verkleij A, van Bergen en Henegouwen P. A ubiquitin-interacting motif (UIM) is essential for Eps15 and Eps15R ubiquitination. J Biol Chem. 2002;277:30746-53 pubmed
    ..Eps15 and its related partner Eps15R play a key role in clathrin-mediated endocytosis of transmembrane receptors...
  20. Carbone R, Fre S, Iannolo G, Belleudi F, Mancini P, Pelicci P, et al. eps15 and eps15R are essential components of the endocytic pathway. Cancer Res. 1997;57:5498-504 pubmed
    ..Indirect evidence suggests that eps15 and eps15R are involved in endocytosis...