Epidermal growth factor receptor substrate 15 (EPS15)

The protein contains 896 amino acids for an estimated molecular weight of 98656 Da.

 

Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 0%
Model score: 0
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs17567

The reference OMIM entry for this protein is 600051

Epidermal growth factor receptor pathway substrate 15; eps15
All1-fused gene from chromosome 1; af1p

CLONING

Fazioli et al. (1993) developed an expression cloning approach which, applied to the study of epidermal growth factor receptor (EGFR)-activated signaling, yielded a number of murine cDNA clones, referred to as eps (for egfr-pathway-substrate) clones. One of these clones, eps15, encoded a protein of 140 to 150 kD. Wong et al. (1994) cloned the human EPS15 gene. Bakowska et al. (2005) noted that the full-length 896-amino acid EPS15 protein has 3 N-terminal EPS15 homology (EH) domains, a central coiled-coil region, an adaptor protein-2 (see AP2A1; 601026)-binding domain, and a proline-rich domain. Fallon et al. (2006) noted that the C-terminal region of EPS15 contains 2 ubiquitin-interacting motifs (UIMs).

GENE FUNCTION

Fazioli et al. (1993) found that Eps15 was phosphorylated on tyrosine following activation of the EGFR (131550) and platelet-derived growth factor receptor (PDGFR; 173410). Phosphorylation of eps15 appeared relatively receptor-specific, since the erbB-2 receptor (164870), which is highly related to EGFR, was not able to phosphorylate it efficiently. By yeast 2-hybrid analysis, Bakowska et al. (2005) found that an N-terminal fragment of spartin (SPG20; 607111) interacted with EPS15, which was confirmed by protein pull-down and cellular redistribution assays. Mutation analysis showed that a 99-residue domain near the N terminus of spartin interacted with the C-terminal 65 amino acids of EPS15. Fallon et al. (2006) found that treatment of mammalian cells with human EGF (131530) stimulated parkin (602544) binding to both Eps15 and Egfr (131550) and promoted parkin-mediated ubiquitination of Eps15. Binding of the parkin ubiquitin-like domain to the Eps15 ubiquitin-interacting motifs was required for parkin-mediated Eps15 ubiquitination. Egfr endocytosis and degradation were accelerated in parkin-deficient cells, and Egfr signaling via the PI3K (see 171834)-Akt (164730) pathway was reduced in parkin-knockout mouse brain. Fallon et al. (2006) proposed that by ubiquitinating EPS15, parkin interferes with the ability of the EPS15 UIMs to bind ubiquitinated EGFR, thereby delaying EGFR internalization and degradation, and promoting PI3K-AKT signaling.

CYTOGENETICS

Most of the translocations affecting the chromosome band 11q23 in human acute leukemias involve a restricted area of the MLL gene (159555), which is also known as ALL1. Other partners in the fused gene created by the translocation include AF4 (159557) on chromosome 4, AF9 (159558) on chromosome 9, and ENL (159556) on chromosome 19. Indeed, at least 15 different chromosomal partners have been involved with MLL in leukemia-producing translocations. In 2 myeloid leukemias, the derivative chromosome 11 expressed the 1,368 N-terminal amino acids of MLL fused to almost all the AF1P product. The predicted wildtype AF1P product was a 98-kD acidic protein that exhibited no similarity to AF4, AF9, and ENL gene products. It was highly similar to the murine EPS15 gene product. Bernard et al. (1994) characterized 2 t(1;11)(p32;q11) translocations that fused the MML gene to the AF1P (EPS15) gene on 1p32.

MAPPING

Wong et al. (1994) mapped the EPS15 gene to chromosome 1p32-p31 by analysis of human/rodent hybrids retaining various segments of human chromosome 1. The region of assignment is one involved in deletion in neuroblastoma, translocations in acute lymphoblastic leukemia, and a fragile site. ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600051 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed