EPS15

Epidermal growth factor receptor pathway substrate 15
PDB rendering based on 1c07.
Available structures PDB 1C07, 1EH2, 1F8H, 1FF1, 2IV9, 2JXC
Identifiers
Symbols	EPS15; AF-1P; AF1P; MLLT5
External IDs	OMIM: 600051 MGI: 104583 HomoloGene: 100716 GeneCards: EPS15 Gene
Gene Ontology Molecular function • calcium ion binding • protein binding • SH3 domain binding Cellular component • cytoplasm • endosome • cytosol • cytosol • plasma membrane • coated pit • AP-2 adaptor complex • clathrin-coated vesicle • early endosome membrane • intracellular membrane-bounded organelle Biological process • epidermal growth factor receptor signaling pathway • cell proliferation • protein transport • vesicle organization • endocytic recycling • negative regulation of epidermal growth factor receptor signaling pathway • clathrin coat assembly Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2060	13858
Ensembl	ENSG00000085832	ENSMUSG00000028552
UniProt	P42566	Q8C431
RefSeq (mRNA)	NM_001159969.1	NM_007943
RefSeq (protein)	NP_001153441.1	NP_031969
Location (UCSC)	Chr 1: 51.82 – 51.99 Mb	Chr 4: 108.95 – 109.06 Mb
PubMed search	[1]	[2]

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

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.

Model organisms

Eps15 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Abnormal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of EPS15 function. A conditional knockout mouse line, called Eps15^{tm1a(KOMP)Wtsi} 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.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. 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.

Interactions

EPS15 has been shown to interact with REPS2, HGS, EPN1, CRK and HRB.

Further reading

• Schumacher C, Knudsen BS, Ohuchi T, et al. (1995). "The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R.". J. Biol. Chem. 270 (25): 15341–7. doi:10.1074/jbc.270.25.15341. PMID 7797522. 
• Bernard OA, Mauchauffe M, Mecucci C, et al. (1994). "A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL.". Oncogene 9 (4): 1039–45. PMID 8134107. 
• Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474. 
• Benmerah A, Bégue B, Dautry-Varsat A, Cerf-Bensussan N (1996). "The ear of alpha-adaptin interacts with the COOH-terminal domain of the Eps 15 protein.". J. Biol. Chem. 271 (20): 12111–6. doi:10.1074/jbc.271.20.12111. PMID 8662627. 
• Matsuda M, Ota S, Tanimura R, et al. (1996). "Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins.". J. Biol. Chem. 271 (24): 14468–72. doi:10.1074/jbc.271.24.14468. PMID 8662907. 
• van Delft S, Schumacher C, Hage W, et al. (1997). "Association and colocalization of Eps15 with adaptor protein-2 and clathrin.". J. Cell Biol. 136 (4): 811–21. doi:10.1083/jcb.136.4.811. PMC 2132490. PMID 9049247. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132490. 
• Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139146. 
• Tebar F, Confalonieri S, Carter RE, et al. (1997). "Eps15 is constitutively oligomerized due to homophilic interaction of its coiled-coil region.". J. Biol. Chem. 272 (24): 15413–8. doi:10.1074/jbc.272.24.15413. PMID 9182572. 
• Salcini AE, Confalonieri S, Doria M, et al. (1997). "Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module.". Genes Dev. 11 (17): 2239–49. doi:10.1101/gad.11.17.2239. PMC 275390. PMID 9303539. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=275390. 
• Cupers P, ter Haar E, Boll W, Kirchhausen T (1998). "Parallel dimers and anti-parallel tetramers formed by epidermal growth factor receptor pathway substrate clone 15.". J. Biol. Chem. 272 (52): 33430–4. doi:10.1074/jbc.272.52.33430. PMID 9407139. 
• Haffner C, Takei K, Chen H, et al. (1998). "Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15.". FEBS Lett. 419 (2–3): 175–80. doi:10.1016/S0014-5793(97)01451-8. PMID 9428629. 
• Benmerah A, Lamaze C, Bègue B, et al. (1998). "AP-2/Eps15 interaction is required for receptor-mediated endocytosis". J. Cell Biol. 140 (5): 1055–62. doi:10.1083/jcb.140.5.1055. PMC 2132690. PMID 9490719. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132690. 
• de Beer T, Carter RE, Lobel-Rice KE, et al. (1998). "Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain". Science 281 (5381): 1357–60. doi:10.1126/science.281.5381.1357. PMID 9721102. 
• Chen H, Fre S, Slepnev VI, et al. (1998). "Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis". Nature 394 (6695): 793–7. doi:10.1038/29555. PMID 9723620. 
• Lewin DA, Sheff D, Ooi CE, et al. (1998). "Cloning, expression, and localization of a novel gamma-adaptin-like molecule". FEBS Lett. 435 (2–3): 263–8. doi:10.1016/S0014-5793(98)01083-7. PMID 9762922. 
• Sengar AS, Wang W, Bishay J, et al. (1999). "The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15". EMBO J. 18 (5): 1159–71. doi:10.1093/emboj/18.5.1159. PMC 1171207. PMID 10064583. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171207. 
• Poupon V, Bègue B, Gagnon J, et al. (1999). "Molecular cloning and characterization of MT-ACT48, a novel mitochondrial acyl-CoA thioesterase". J. Biol. Chem. 274 (27): 19188–94. doi:10.1074/jbc.274.27.19188. PMID 10383425. 
• Nakashima S, Morinaka K, Koyama S, et al. (1999). "Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors". EMBO J. 18 (13): 3629–42. doi:10.1093/emboj/18.13.3629. PMC 1171441. PMID 10393179. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171441. 
• Stephens DJ, Banting G (1999). "Direct interaction of the trans-Golgi network membrane protein, TGN38, with the F-actin binding protein, neurabin". J. Biol. Chem. 274 (42): 30080–6. doi:10.1074/jbc.274.42.30080. PMID 10514494.