EPS15

EPS15
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1C07, 1EH2, 1F8H, 1FF1, 2IV9, 2JXC, 4RH5, 4RH9, 4RHG, 4S0G, 5JP2
Identifiers
Aliases	EPS15 , AF-1P, AF1P, MLLT5, epidermal growth factor receptor pathway substrate 15
External IDs	OMIM: 600051 MGI: 104583 HomoloGene: 128359 GeneCards: EPS15
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p32.3 Start 51,354,263 bp [1] End 51,519,266 bp [1]
Gene location (Mouse) Chr. Chromosome 4 (mouse) [2] Band 4|4 C7 Start 109,137,465 bp [2] End 109,245,014 bp [2]
RNA expression pattern Bgee Top expressed in brain ovary substantia nigra internal globus pallidus corpus callosum middle temporal gyrus Brodmann area 46 globus pallidus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding SH3 domain binding metal ion binding polyubiquitin modification-dependent protein binding GO:0001948 protein binding cadherin binding identical protein binding cargo receptor activity Cellular component endosome clathrin coat of coated pit early endosome membrane membrane intracellular membrane-bounded organelle plasma membrane aggresome ciliary membrane clathrin-coated pit AP-2 adaptor complex clathrin-coated vesicle basal plasma membrane apical plasma membrane early endosome cytoplasm cytosol synapse postsynapse glutamatergic synapse Biological process negative regulation of epidermal growth factor receptor signaling pathway endocytosis epidermal growth factor receptor signaling pathway vesicle organization Golgi to endosome transport clathrin coat assembly protein transport viral entry into host cell receptor-mediated endocytosis of virus by host cell cell population proliferation positive regulation of receptor recycling regulation of cell population proliferation endocytic recycling membrane organization GO:0022415 viral process transport postsynaptic neurotransmitter receptor internalization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2060	13858
Ensembl	ENSG00000085832	ENSMUSG00000028552
UniProt	P42566	P42567
RefSeq (mRNA)	NM_001159969 NM_001981	NM_001159964 NM_007943
RefSeq (protein)	NP_001153441 NP_001972	NP_001153436 NP_031969
Location (UCSC)	Chr 1: 51.35 – 51.52 Mb	Chr 4: 109.14 – 109.25 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Epidermal growth factor receptor substrate 15 is a protein that in humans is encoded by the EPS15 gene. ^[5]

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. ^[6]

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 [7]
Citrobacter infection	Normal [8]
All tests and analysis from [9] [10]

Model organisms have been used in the study of EPS15 function. A conditional knockout mouse line, called Eps15^{tm1a(KOMP)Wtsi [11] [12]} 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. ^{[13] [14] [15]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[9] [16]} 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. ^[9]

Interactions

EPS15 has been shown to interact with:

• CRK ^[17]
• EPN1, ^[18]
• HGS, ^{[19] [20]}
• HRB, ^[21] and
• REPS2. ^[22]

References

1. GRCh38: Ensembl release 89: ENSG00000085832 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028552 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: EPS15 epidermal growth factor receptor pathway substrate 15".
7. "Salmonella infection data for Eps15". Wellcome Trust Sanger Institute.
8. "Citrobacter infection data for Eps15". Wellcome Trust Sanger Institute.
9. 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. S2CID   85911512.
10. Mouse Resources Portal, Wellcome Trust Sanger Institute.
11. "International Knockout Mouse Consortium".
12. "Mouse Genome Informatics".
13. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, 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.
14. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
15. 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. S2CID   18872015.
16. 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.
17. Schumacher C, Knudsen BS, Ohuchi T, Di Fiore PP, Glassman RH, Hanafusa H (June 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.
18. Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore PP, De Camilli P (August 1998). "Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis". Nature. 394 (6695): 793–7. Bibcode:1998Natur.394..793C. doi:10.1038/29555. PMID   9723620. S2CID   4430975.
19. Bean AJ, Davanger S, Chou MF, Gerhardt B, Tsujimoto S, Chang Y (May 2000). "Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15". J. Biol. Chem. 275 (20): 15271–8. doi: 10.1074/jbc.275.20.15271 . PMID   10809762.
20. Bache KG, Raiborg C, Mehlum A, Stenmark H (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". J. Biol. Chem. 278 (14): 12513–21. doi: 10.1074/jbc.M210843200 . PMID   12551915.
21. Doria M, Salcini AE, Colombo E, Parslow TG, Pelicci PG, Di Fiore PP (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. 147 (7): 1379–84. doi:10.1083/jcb.147.7.1379. PMC   2174238 . PMID   10613896.
22. 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. 18 (13): 3629–42. doi:10.1093/emboj/18.13.3629. PMC   1171441 . PMID   10393179.

Further reading

• Schumacher C, Knudsen BS, Ohuchi T, Di Fiore PP, Glassman RH, Hanafusa H (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, Van den Berghe H, Berger R (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, Liu W, Gibbs RA (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, Nakamura H, Matuoka K, Takenawa T, Nagashima K, Kurata T (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, Verkleij AJ, van Bergen en Henegouwen PM (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.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC   139146 . PMID   9110174.
• Tebar F, Confalonieri S, Carter RE, Di Fiore PP, Sorkin A (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, Santolini E, Tassi E, Minenkova O, Cesareni G, Pelicci PG, Di Fiore PP (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.
• 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, Ringstad N, Hudson A, Butler MH, Salcini AE, Di Fiore PP, De Camilli P (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. S2CID   45186831.
• Benmerah A, Lamaze C, Bègue B, Schmid SL, Dautry-Varsat A, Cerf-Bensussan N (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.
• de Beer T, Carter RE, Lobel-Rice KE, Sorkin A, Overduin M (1998). "Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain". Science. 281 (5381): 1357–60. Bibcode:1998Sci...281.1357D. doi:10.1126/science.281.5381.1357. PMID   9721102.
• Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore PP, De Camilli P (1998). "Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis". Nature. 394 (6695): 793–7. Bibcode:1998Natur.394..793C. doi:10.1038/29555. PMID   9723620. S2CID   4430975.
• Lewin DA, Sheff D, Ooi CE, Whitney JA, Yamamoto E, Chicione LM, Webster P, Bonifacino JS, Mellman I (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. S2CID   83518205.
• Sengar AS, Wang W, Bishay J, Cohen S, Egan SE (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.
• Poupon V, Bègue B, Gagnon J, Dautry-Varsat A, Cerf-Bensussan N, Benmerah A (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, Ikeda M, Kishida M, Okawa K, Iwamatsu A, Kishida S, Kikuchi A (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.
• 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.