Early endosome antigen 1 (EEA1)
The protein contains 1411 amino acids for an estimated molecular weight of 162466 Da.
Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking. (updated: March 4, 2015)
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.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs10745623 |
Biological Process
Early endosome to late endosome transport
Endocytosis
Synaptic vesicle to endosome fusion
Vesicle fusion
Viral RNA genome replication
The reference OMIM entry for this protein is 605070
Early endosome antigen 1; eea1
Early endosome antigen, 162-kd
Early endosomes are cellular compartments that receive endocytosed materials and sort them for vesicular transport to late endosomes and lysosomes or for recycling to the plasma membrane.
CLONING
By screening a HeLa cell expression library with autoimmune serum, Mu et al. (1995) obtained a cDNA encoding EEA1. Sequence analysis predicted that the 1,411-amino acid EEA1 protein is largely hydrophilic with short amphiphilic regions in the 15 N-terminal amino acids and in segments centered around amino acids 515 and 645. EEA1 contains an N-terminal zinc finger motif, a cys-rich C-terminal metal-binding finger, and multiple sites for N-glycosylation, phosphorylation, N-myristoylation, and for a leucine zipper structure. Northern blot analysis detected a 9.0-kb EEA1 transcript in skeletal muscle, heart, brain, lung, liver, and pancreas. Immunoblot analysis determined that EEA1 is expressed as a 180-kD protein in membrane and cytosolic fractions. Immunofluorescence microscopy showed that EEA1 colocalizes with transferrin (TF; 190000) and with RAB5 (RAB5A; 179512), which localizes in early endosomes, but not with RAB7 (602298), which localizes in late endosomes.BIOCHEMICAL FEATURES
Using yeast 2-hybrid analysis, Simonsen et al. (1998) found that the N-terminal zinc finger and the C-terminal FYVE finger of EEA1 bind to RAB5 or RAB5-GTP and to phosphatidylinositol 3-phosphate (PtdIns(3)P), respectively. Each of these interactions stabilizes the binding of EEA1 to the endosomal membrane. Kutateladze and Overduin (2001) determined the solution structure of the FYVE domain of EEA1 protein in the free state and compared it with the structures of the domain complexed with phosphatidylinositol 3-phosphate and mixed micelles. The multistep binding mechanism involved nonspecific insertion of a hydrophobic loop into the lipid bilayer, positioning and activating the binding pocket. Ligation of phosphatidylinositol 3-phosphate then induced a global structural change, drawing the protein termini over the bound phosphoinositide by extension of a hinge. Specific recognition of the 3-phosphate was determined indirectly and directly by 2 clusters of conserved arginines. To determine the structural basis for selective PtdIns(3)P recognition by FYVE domains and the role of domain organization, dimerization, and quaternary structure with respect to EEA1 localization and endosome tethering, Dumas et al. (2001) characterized the binding of soluble phosphoinositides to monomeric and homodimeric constructs of EEA1 and determined the crystal structure of the homodimeric C-terminal region as a complex with the head group of PtdIns(3)P. A specific head group binding mode showed how FYVE domains selectively recognize PtdIns(3)P and discriminate against other mono- or polyphosphorylated species. The EEA1 homodimer was found to be ideally configured for multivalent membrane engagement. The simplest thermodynamic model for bivalent recognition of PtdIns(3)P in a lipid bilayer quantitatively accounted for the large amplification of the weak affinity and moderate specificity of soluble PtdIns(3)P binding to the EEA1 FYVE domain and explained why the region preceding the FYVE domain is required for localization to early endosomes.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the EEA1 gene to chromosome 12 (TMAP sts-X78998). ... More on the omim web siteFeb. 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605070 was added.