EPS15 explained

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

Function

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]

Interactions

EPS15 has been shown to interact with:

• CRK^[3]
• EPN1,^[4]
• HGS,^{[5] [6]}
• HRB,^[7] and
• REPS2.^[8]

Further reading

• Schumacher C, Knudsen BS, Ohuchi T, Di Fiore PP, Glassman RH, Hanafusa H . The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R. . J. Biol. Chem. . 270 . 25 . 15341–7 . 1995 . 7797522 . 10.1074/jbc.270.25.15341 . free .
• Bernard OA, Mauchauffe M, Mecucci C, Van den Berghe H, Berger R . 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 . 1994 . 8134107 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction. . Anal. Biochem. . 236 . 1 . 107–13 . 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Benmerah A, Bégue B, Dautry-Varsat A, Cerf-Bensussan N . The ear of alpha-adaptin interacts with the COOH-terminal domain of the Eps 15 protein. . J. Biol. Chem. . 271 . 20 . 12111–6 . 1996 . 8662627 . 10.1074/jbc.271.20.12111 . free .
• Matsuda M, Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T, Nagashima K, Kurata T . Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins. . J. Biol. Chem. . 271 . 24 . 14468–72 . 1996 . 8662907 . 10.1074/jbc.271.24.14468 . free .
• van Delft S, Schumacher C, Hage W, Verkleij AJ, van Bergen en Henegouwen PM . Association and colocalization of Eps15 with adaptor protein-2 and clathrin. . J. Cell Biol. . 136 . 4 . 811–21 . 1997 . 9049247 . 2132490 . 10.1083/jcb.136.4.811 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing. . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Tebar F, Confalonieri S, Carter RE, Di Fiore PP, Sorkin A . Eps15 is constitutively oligomerized due to homophilic interaction of its coiled-coil region. . J. Biol. Chem. . 272 . 24 . 15413–8 . 1997 . 9182572 . 10.1074/jbc.272.24.15413 . free .
• Salcini AE, Confalonieri S, Doria M, Santolini E, Tassi E, Minenkova O, Cesareni G, Pelicci PG, Di Fiore PP . Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module. . Genes Dev. . 11 . 17 . 2239–49 . 1997 . 9303539 . 275390 . 10.1101/gad.11.17.2239 .
• Cupers P, ter Haar E, Boll W, Kirchhausen T . Parallel dimers and anti-parallel tetramers formed by epidermal growth factor receptor pathway substrate clone 15. . J. Biol. Chem. . 272 . 52 . 33430–4 . 1998 . 9407139 . 10.1074/jbc.272.52.33430 . free .
• Haffner C, Takei K, Chen H, Ringstad N, Hudson A, Butler MH, Salcini AE, Di Fiore PP, De Camilli P . 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 . 1998 . 9428629 . 10.1016/S0014-5793(97)01451-8 . 45186831 .
• Benmerah A, Lamaze C, Bègue B, Schmid SL, Dautry-Varsat A, Cerf-Bensussan N . AP-2/Eps15 interaction is required for receptor-mediated endocytosis . J. Cell Biol. . 140 . 5 . 1055–62 . 1998 . 9490719 . 2132690 . 10.1083/jcb.140.5.1055 .
• de Beer T, Carter RE, Lobel-Rice KE, Sorkin A, Overduin M . Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain . Science . 281 . 5381 . 1357–60 . 1998 . 9721102 . 10.1126/science.281.5381.1357 . 1998Sci...281.1357D .
• Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore PP, De Camilli P . Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis . Nature . 394 . 6695 . 793–7 . 1998 . 9723620 . 10.1038/29555 . 1998Natur.394..793C . 4430975 .
• Lewin DA, Sheff D, Ooi CE, Whitney JA, Yamamoto E, Chicione LM, Webster P, Bonifacino JS, Mellman I . Cloning, expression, and localization of a novel gamma-adaptin-like molecule . FEBS Lett. . 435 . 2–3 . 263–8 . 1998 . 9762922 . 10.1016/S0014-5793(98)01083-7 . 83518205 .
• Sengar AS, Wang W, Bishay J, Cohen S, Egan SE . The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15 . EMBO J. . 18 . 5 . 1159–71 . 1999 . 10064583 . 1171207 . 10.1093/emboj/18.5.1159 .
• Poupon V, Bègue B, Gagnon J, Dautry-Varsat A, Cerf-Bensussan N, Benmerah A . Molecular cloning and characterization of MT-ACT48, a novel mitochondrial acyl-CoA thioesterase . J. Biol. Chem. . 274 . 27 . 19188–94 . 1999 . 10383425 . 10.1074/jbc.274.27.19188 . free.
• Nakashima S, Morinaka K, Koyama S, Ikeda M, Kishida M, Okawa K, Iwamatsu A, Kishida S, Kikuchi A . Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors . EMBO J. . 18 . 13 . 3629–42 . 1999 . 10393179 . 1171441 . 10.1093/emboj/18.13.3629 .
• Stephens DJ, Banting G . Direct interaction of the trans-Golgi network membrane protein, TGN38, with the F-actin binding protein, neurabin . J. Biol. Chem. . 274 . 42 . 30080–6 . 1999 . 10514494 . 10.1074/jbc.274.42.30080 . free .

Notes and References

1. Wong WT, Kraus MH, Carlomagno F, Zelano A, Druck T, Croce CM, Huebner K, Di Fiore PP . The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32 . Oncogene . 9 . 6 . 1591–7 . Jun 1994 . 8183552 .
2. Web site: Entrez Gene: EPS15 epidermal growth factor receptor pathway substrate 15.
3. Schumacher C, Knudsen BS, Ohuchi T, Di Fiore PP, Glassman RH, Hanafusa H . The SH3 domain of Crk binds specifically to a conserved proline-rich motif in Eps15 and Eps15R . J. Biol. Chem. . 270 . 25 . 15341–7 . June 1995 . 7797522 . 10.1074/jbc.270.25.15341. free .
4. Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore PP, De Camilli P . Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis . Nature . 394 . 6695 . 793–7 . August 1998 . 9723620 . 10.1038/29555 . 1998Natur.394..793C . 4430975 .
5. Bean AJ, Davanger S, Chou MF, Gerhardt B, Tsujimoto S, Chang Y . Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15 . J. Biol. Chem. . 275 . 20 . 15271–8 . May 2000 . 10809762 . 10.1074/jbc.275.20.15271. free .
6. Bache KG, Raiborg C, Mehlum A, Stenmark H . STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes . J. Biol. Chem. . 278 . 14 . 12513–21 . April 2003 . 12551915 . 10.1074/jbc.M210843200 . free .
7. Doria M, Salcini AE, Colombo E, Parslow TG, Pelicci PG, Di Fiore PP . 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. . 147 . 7 . 1379–84 . December 1999 . 10613896 . 2174238 . 10.1083/jcb.147.7.1379.
8. Nakashima S, Morinaka K, Koyama S, Ikeda M, Kishida M, Okawa K, Iwamatsu A, Kishida S, Kikuchi A . Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors . EMBO J. . 18 . 13 . 3629–42 . July 1999 . 10393179 . 1171441 . 10.1093/emboj/18.13.3629 .