14-3-3 protein epsilon (YWHAE)
The protein contains 255 amino acids for an estimated molecular weight of 29174 Da.
Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). (updated: Jan. 31, 2018)
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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
| 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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Biological Process
Apoptotic process
Apoptotic signaling pathway
Cellular response to heat
Cerebral cortex development
Ciliary basal body-plasma membrane docking
G2/M transition of mitotic cell cycle
Hippo signaling
Hippocampus development
Intracellular signal transduction
Intrinsic apoptotic signaling pathway
MAPK cascade
Membrane organization
Membrane repolarization during cardiac muscle cell action potential
Mitotic cell cycle
Negative regulation of calcium ion export across plasma membrane
Negative regulation of calcium ion transmembrane transporter activity
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of peptidyl-serine dephosphorylation
Neuron migration
Neurotrophin TRK receptor signaling pathway
Organelle organization
Positive regulation of protein export from nucleus
Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
Protein localization to nucleus
Protein targeting
Regulation of cellular response to heat
Regulation of cysteine-type endopeptidase activity involved in apoptotic process
Regulation of cytosolic calcium ion concentration
Regulation of G2/M transition of mitotic cell cycle
Regulation of heart rate by cardiac conduction
Regulation of heart rate by hormone
Regulation of membrane repolarization
Regulation of postsynaptic membrane neurotransmitter receptor levels
Regulation of potassium ion transmembrane transporter activity
Substantia nigra development
Viral process
Cellular Component
Axon
Central region of growth cone
Cytoplasm
Cytoplasmic vesicle membrane
Cytosol
Extracellular exosome
Focal adhesion
Glutamatergic synapse
Kinesin complex
Melanosome
Membrane
Mitochondrion
Nucleus
Obsolete cell
Molecular Function
Cadherin binding
Calcium channel regulator activity
Enzyme binding
Histone deacetylase binding
Identical protein binding
Ion channel binding
MHC class II protein complex binding
Phosphoprotein binding
Phosphoserine residue binding
Poly(A) RNA binding
Potassium channel regulator activity
Protein domain specific binding
Protein heterodimerization activity
Protein phosphatase binding
Rab guanyl-nucleotide exchange factor activity
RNA binding
Scaffold protein binding
Ubiquitin protein ligase binding
The reference OMIM entry for this protein is 605066
Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon isoform; ywhae
14-3-3 protein, epsilon isoform
14-3-3-epsilon
CLONING
Cell division cycle (CDC) proteins and cyclin-dependent kinases (CDK) regulate the progression of cells through mitosis, and their activities are regulated by phosphorylation and dephosphorylation. Interacting proteins can also affect CDC and CDK activity. Using a yeast 2-hybrid screen to probe a HeLa cell library with CDC25A (116947) and CDC25B (116949) as bait, Conklin et al. (1995) isolated cDNAs encoding YWHAB (601289), which they called 14-3-3-beta, and YWHAE, which they called 14-3-3-epsilon. The deduced YWHAE contains 260-amino acids that are 100% identical to those of the mouse protein. Chong et al. (1996) isolated a full-length YWHAE cDNA. Sequence analysis predicted a 255-amino acid protein. Northern blot analysis revealed nearly ubiquitous expression of an approximately 2.0-kb transcript.GENE STRUCTURE
Jin et al. (1996) obtained a YWHAE cDNA containing the previously unreported 3-prime untranslated region (UTR), which is perfectly conserved with rodent sequences. The 3-prime UTR included a 285-bp match with the 8-1 probe for Miller-Dieker lissencephaly syndrome (MDLS; 247200). The authors concluded that the 3-prime YWHAE UTR and the 5-prime end of the MDLS region overlap. However, Chong et al. (1996) determined that the 8.1 probe was a chimeric cDNA and did not include the 5-prime end of the LIS1 (PAFAH2B1; 601545) gene.MAPPING
By radiation hybrid, PCR, and FISH analyses, Chong et al. (1996) mapped the human YWHAE gene to 17p13.3, telomeric to LIS1 (PAFAH1B1), in a region frequently deleted in several types of cancer. Luk et al. (1997) confirmed this localization by FISH. Using RFLP analysis, Jin et al. (1996) mapped the mouse Ywhae gene to a position in tight linkage with Evi2 (158380).GENE FUNCTION
Conklin et al. (1995) found that both YWHAB and YWHAE interacted with CDC25A and CDC25B but did not affect their phosphatase activities. Like YWHAB, YWHAE interacted with RAF1 (164760) but not RAS (190020) in yeast 2-hybrid screens and may facilitate the association of CDC25 with RAF1. The binding of insulin (176730) to its receptor induces the phosphorylation of the cytosolic substrates IRS1 (147545) and IRS2 (600797), which associate with several Src homology-2 (SH2) domain-containing proteins. To identify unique IRS1-binding proteins, Ogihara et al. (1997) screened a human heart cDNA expression library with recombinant IRS1. They obtained 2 isoforms of the 14-3-3 protein family, 14-3-3-zeta (YWHAZ; 601288) and -epsilon. 14-3-3 protein has been shown to associate with IRS1 in L6 myotubes, HepG2 hepatoma cells, Chinese hamster ovary cells, and bovine brain tissue. IRS2, a protein structurally similar to IRS1, was also shown to form a complex with 14-3-3 protein using a baculovirus expression system. The amount of 14-3-3 protein associated with IRS1 was not affected by insulin stimulation but was increased significantly by treatment with okadaic acid, a potent serine/threonine phosphatase inhibitor. The authors identified a putative 14-3-3 protein-binding site within the phosphotyrosine-binding (PTB) domain of IRS1. Ogihara et al. (1997) suggested that the association with 14-3-3 protein may play a role in the regulation of insulin sensitivity by interrupting the association between the insulin receptor and IRS1. Using 2-hybrid experiments, Han et al. (1997) demonstrated interaction between murine Ywhae and the RAS-binding domain of RIN1 (605965). Toyo-oka et al. (2003) repor ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
March 15, 2016: Protein entry updated
Automatic update: OMIM entry 605066 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed