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Epidermal growth factor receptor pathway substrate 15
Protein EPS15 PDB 1c07.png
PDB rendering based on 1c07.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols EPS15 ; AF-1P; AF1P; MLLT5
External IDs OMIM600051 MGI104583 HomoloGene128359 GeneCards: EPS15 Gene
RNA expression pattern
PBB GE EPS15 217887 s at tn.png
PBB GE EPS15 217886 at tn.png
More reference expression data
Species Human Mouse
Entrez 2060 13858
Ensembl ENSG00000085832 ENSMUSG00000028552
UniProt P42566 P42567
RefSeq (mRNA) NM_001159969 NM_001159964
RefSeq (protein) NP_001153441 NP_001153436
Location (UCSC) Chr 1:
51.82 – 51.99 Mb
Chr 4:
109.28 – 109.39 Mb
PubMed search [1] [2]

Epidermal growth factor receptor substrate 15 is a protein that in humans is encoded by the EPS15 gene.[1]

This gene encodes a protein that is part of the EGFR pathway. The protein is present at clathrin-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. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.[2]

Model organisms[edit]

Model organisms have been used in the study of EPS15 function. A conditional knockout mouse line, called Eps15tm1a(KOMP)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[9][10][11]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty six tests were carried out on mutant mice and one significant abnormality was observed: homozygous mutant animals had a decreased mean corpuscular hemoglobin concentration.[5]


EPS15 has been shown to interact with REPS2,[13] HGS,[14][15] EPN1,[16] CRK[17] and HRB.[18]


  1. ^ Wong WT, Kraus MH, Carlomagno F, Zelano A, Druck T, Croce CM, Huebner K, Di Fiore PP (Jun 1994). "The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32". Oncogene 9 (6): 1591–7. PMID 8183552. 
  2. ^ "Entrez Gene: EPS15 epidermal growth factor receptor pathway substrate 15". 
  3. ^ "Salmonella infection data for Eps15". Wellcome Trust Sanger Institute. 
  4. ^ "Citrobacter infection data for Eps15". Wellcome Trust Sanger Institute. 
  5. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. 
  6. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  7. ^ "International Knockout Mouse Consortium". 
  8. ^ "Mouse Genome Informatics". 
  9. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  10. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  11. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  12. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  13. ^ Nakashima, S; Morinaka K; Koyama S; Ikeda M; Kishida M; Okawa K; Iwamatsu A; Kishida S; Kikuchi A (July 1999). "Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors". EMBO J. (ENGLAND) 18 (13): 3629–42. doi:10.1093/emboj/18.13.3629. ISSN 0261-4189. PMC 1171441. PMID 10393179. 
  14. ^ Bean, A J; Davanger S; Chou M F; Gerhardt B; Tsujimoto S; Chang Y (May 2000). "Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15". J. Biol. Chem. (UNITED STATES) 275 (20): 15271–8. doi:10.1074/jbc.275.20.15271. ISSN 0021-9258. PMID 10809762. 
  15. ^ Bache, Kristi G; Raiborg Camilla; Mehlum Anja; Stenmark Harald (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". J. Biol. Chem. (United States) 278 (14): 12513–21. doi:10.1074/jbc.M210843200. ISSN 0021-9258. PMID 12551915. 
  16. ^ Chen, H; Fre S; Slepnev V I; Capua M R; Takei K; Butler M H; Di Fiore P P; De Camilli P (August 1998). "Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis". Nature (ENGLAND) 394 (6695): 793–7. doi:10.1038/29555. ISSN 0028-0836. PMID 9723620. 
  17. ^ Schumacher, C; Knudsen B S; Ohuchi T; Di Fiore P P; Glassman R H; Hanafusa H (June 1995). "The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R". J. Biol. Chem. (UNITED STATES) 270 (25): 15341–7. doi:10.1074/jbc.270.25.15341. ISSN 0021-9258. PMID 7797522. 
  18. ^ Doria, M; Salcini A E; Colombo E; Parslow T G; Pelicci P G; Di Fiore P P (December 1999). "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. (UNITED STATES) 147 (7): 1379–84. doi:10.1083/jcb.147.7.1379. ISSN 0021-9525. PMC 2174238. PMID 10613896. 

Further reading[edit]