14-3-3 protein eta (YWHAH)
The protein contains 246 amino acids for an estimated molecular weight of 28219 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. Negatively regulates the kinase activity of PDPK1. (updated: April 1, 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.
- 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.
- 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.
- 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.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Apoptotic process
Glucocorticoid catabolic process
Glucocorticoid receptor signaling pathway
Intracellular protein transport
Intrinsic apoptotic signaling pathway
Membrane depolarization during action potential
Membrane organization
Negative regulation of dendrite morphogenesis
Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
Positive regulation of transcription, DNA-templated
Regulation of neuron differentiation
Regulation of sodium ion transmembrane transporter activity
Regulation of sodium ion transport
Regulation of synaptic plasticity
Substantia nigra development
The reference OMIM entry for this protein is 113508
Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta isoform; ywhah
Brain protein 14-3-3, eta isoform
Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein 1; ywha1
14-3-3-eta
DESCRIPTION
Protein 14-3-3 is a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases (191290, 191060) and an endogenous inhibitor of protein kinase C (176960). The 14-3-3 protein exists in several distinct forms: e.g., beta (YWHAB; 601289), gamma (YWHAG; 605356), epsilon (YWHAE; 605066), zeta (YWHAZ; 601288), theta (YWHAQ; 609009), sigma (SFN; 601290), and eta (YWHAH).CLONING
Ichimura-Ohshima et al. (1992) reported a cDNA clone of mRNA encoding human 14-3-3 protein. The 1,730-nucleotide sequence of the cDNA contained a 191-bp 5-prime noncoding region, the complete 738-bp coding region, and an 801-bp 3-prime noncoding region with 3 canonical polyadenylation signals. The eta chain encoded by the cDNA is a 246-amino acid polypeptide with a predicted molecular weight of 28,196. The predicted amino acid sequence of the human 14-3-3 protein eta was highly homologous to that of previously reported bovine and rat proteins with only 2 amino acid differences. Northern blot analysis demonstrated widespread expression of the eta chain in cultured cell lines derived from various human tumors.GENE STRUCTURE
Muratake et al. (1996) determined that the human YWHAH gene has 2 exons separated by an intron of approximately 8 kb. Using S1 nuclease mapping, primer extension, and RACE PCR, Muratake et al. (1996) identified the transcription initiation site. They also identified several regulatory element sequences, including CRE, in the 5-prime noncoding region. Muratake et al. (1996) noted that the presence of a CRE binding element may indicate that this gene is involved in brain responses to narcotics. The authors also found changes in a 7-bp repeat sequence (GCCTGCA) located in the noncoding region of exon 1 and they speculated that these changes, or other changes in the sequence of this gene, may be associated with neuropsychiatric disorders.MAPPING
Ichimura-Ohshima et al. (1992) used spot blot hybridization analysis with flow sorted chromosomes to show that the eta chain is located on chromosome 22. Tommerup and Leffers (1996) mapped the YWHAH gene to 22q12 by fluorescence in situ hybridization (FISH). Muratake et al. (1996) used FISH to refine the mapping of the YWHAH gene to 22q12.1-q13.1.GENE FUNCTION
The 14-3-3 family of proteins mediates signal transduction by binding to phosphoserine-containing proteins. Using phosphoserine-oriented peptide libraries to probe all mammalian and yeast 14-3-3s, Yaffe et al. (1997) identified 2 different binding motifs, RSXpSXP and RXY/FXpSXP, present in nearly all known 14-3-3 binding proteins. The crystal structure of YWHAZ (601288) complexed with the phosphoserine motif in polyoma middle-T was determined to 2.6-angstrom resolution. The authors showed that the 14-3-3 dimer binds tightly to single molecules containing tandem repeats of phosphoserine motifs, implicating bidentate association as a signaling mechanism with molecules such as Raf, BAD (603167), and Cbl. Simsek-Duran et al. (2004) found that a 14-3-3 protein from rodent brain lysate bound phosphorylated residue ser413 of the Rim1 (606629) protein, whereas it did not bind to nonphosphorylatable Rim1 mutants. Presynaptic transfection with a dominant-negative 14-3-3-eta mutant protein, which showed reduced binding to Rim1, inhibited mouse cerebellar long-term potentiation (LTP). The authors concluded that 14-3-3 is a necessary downstream component of the ser413-Rim1 pathway involv ... More on the omim web site
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 113508 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed