EPS15
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]
Model organisms
| 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[3] |
| Citrobacter infection | Normal[4] |
| All tests and analysis from[5][6] |
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]
Interactions
EPS15 has been shown to interact with:
References
- ↑ Wong WT, Kraus MH, Carlomagno F, Zelano A, Druck T, Croce CM et al. (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.
- ↑ "Entrez Gene: EPS15 epidermal growth factor receptor pathway substrate 15".
- ↑ "Salmonella infection data for Eps15". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Eps15". Wellcome Trust Sanger Institute.
- ↑ 5.0 5.1 5.2 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.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (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.
- ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH et al. (August 1998). "Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis". Nature 394 (6695): 793–7. doi:10.1038/29555. PMID 9723620.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Nakashima S, Morinaka K, Koyama S, Ikeda M, Kishida M, Okawa K et al. (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. Vancouver style error (help)
- Matsuda M, Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T 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, 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 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.
- 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 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.
- 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 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, 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. Vancouver style error (help)
- 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. doi:10.1126/science.281.5381.1357. PMID 9721102.
- Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH 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, Whitney JA, Yamamoto E, Chicione LM 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, 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. Vancouver style error (help)
- Nakashima S, Morinaka K, Koyama S, Ikeda M, Kishida M, Okawa K 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.
- 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.
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