Epsin-1 (EPN1)
The protein contains 576 amino acids for an estimated molecular weight of 60293 Da.
Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regulates receptor-mediated endocytosis (PubMed:10557078, PubMed:10393179). (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Embryonic organ development
Endocytosis
Epidermal growth factor receptor signaling pathway
Female pregnancy
In utero embryonic development
Membrane organization
Negative regulation of epidermal growth factor receptor signaling pathway
Negative regulation of sprouting angiogenesis
Notch signaling pathway
The reference OMIM entry for this protein is 607262
Epsin 1; epn1
Epsin
DESCRIPTION
EPN1 is an endocytic accessory protein that interacts with EPS15 (600051), the alpha subunit of the clathrin adaptor AP2 (AP2A1; 601026), and clathrin (see 118960), as well as with other accessory proteins for the endocytosis of clathrin-coated vesicles.CLONING
Chen et al. (1998) cloned rat Epn1 from a rat brain cDNA library. The deduced 576-amino acid protein contains several conserved asp-pro-trp (DPW) repeats in its central region, a Cdc2 (116940) phosphorylation site, and 3 arg-pro-phe (NPF) repeats in its C-terminal region. Northern blot analysis detected a 2.6-kb transcript in all rat tissues tested, and Western blot analysis confirmed ubiquitous expression. Immunofluorescence localization using rat brain frozen sections revealed colocalization of Epn1 with Eps15, synaptophysin (313475), and clathrin in nerve terminals. Morinaka et al. (1999) identified EPN1 as an 84-kD protein that binds bovine brain Pob1 (REPS2; 300317). By searching an EST database, PCR, and 5-prime and 3-prime RACE of a brain cDNA library, they cloned human EPN1. The deduced 551-amino acid protein contains an epsin N-terminal homology (ENTH) region, which includes 1 DPW sequence, followed by 8 central DPW repeats, a single LVDLD sequence, and 3 NPF repeats at the C terminus. The LVDLD sequence is a clathrin-binding motif, and NPF is the core motif of an EPS15 homology (EH) domain-binding domain.GENE FUNCTION
Using truncation mutants of rat brain Epn1, Chen et al. (1998) determined that the central region of Epn1, which contains the DPW repeats, binds AP2, and the C-terminal region binds Eps15. Rat Epn1 associated with clathrin coats in situ and could be coprecipitated with AP2 and Eps15. It did not copurify with mature clathrin-coated vesicles. Chen et al. (1998) concluded that EPN1 may participate with EPS15 in the molecular rearrangement of the clathrin coats that are required for coated-pit invagination and vesicle fission. Using in vitro pull-down assays, Morinaka et al. (1999) determined that the EH domain of REPS2 interacts specifically with a 10-amino acid C-terminal peptide of EPN1 containing the NPF sequence. Expression of EPN1 in CHO cells overexpressing insulin receptor (INSR; 147670) inhibited internalization of insulin, but it did not affect insulin-binding or autophosphorylation of INSR. Kariya et al. (2000) found that EPN1, RALA-binding protein-1 (RALBP1; 605801), REPS2, and EPS15 formed a complex with AP2A1 in CHO cells. They noted that EPN1 contains a single putative phosphorylation site at ser357, and they transfected human EPN1 containing a point mutation (ser357 to asp) at this site into CHO cells overexpressing INSR. Phosphorylated EPN1 and the ser357-to-asp mutant formed a complex with AP2A1 less efficiently than nonphosphorylated wildtype EPN1. Phosphorylation of EPN1 also inhibited binding with the EH domain of REPS2, suggesting that phosphorylation of EPN1 inhibits receptor-mediated endocytosis by disassembly of its complex with REPS2 and AP2A1. Ford et al. (2002) found that EPN1 expressed in transfected COS cells showed a general cytoplasmic distribution or accumulation in puncta on the plasma membrane. EPN1 colocalized with AP2, clathrin, EPS15, and dynamin (see 602377). The presence of dynamin suggested that the puncta represent endocytically incompetent coated pits. Ford et al. (2002) determined that the ENTH domain of EPN1 binds the membrane lipid phosphatidylinositol-4,5-bisphosphate ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 607262 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed