14-3-3 protein gamma (YWHAG)
The protein contains 247 amino acids for an estimated molecular weight of 28303 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. (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.
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Biological Process
Apoptotic process
Cellular response to insulin stimulus
Ciliary basal body-plasma membrane docking
G2/M transition of mitotic cell cycle
Intrinsic apoptotic signaling pathway
Membrane organization
Mitotic cell cycle
Negative regulation of protein kinase activity
Negative regulation of protein serine/threonine kinase activity
Organelle organization
Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
Protein targeting
Regulation of G2/M transition of mitotic cell cycle
Regulation of neuron differentiation
Regulation of signal transduction
Regulation of synaptic plasticity
The reference OMIM entry for this protein is 605356
Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma isoform; ywhag
14-3-3-gamma
DESCRIPTION
Members of the 14-3-3 protein family, such as YWHAG, play an important role in signal transduction leading to mitosis and cellular proliferation (Morrison, 1994). For background information on 14-3-3 proteins, see 113508.CLONING
Using PCR primers based on the rat 14-3-3-gamma (YWHAG) sequence to screen human vascular smooth muscle cells (VSMC), Autieri and Carbone (1999) isolated a cDNA encoding YWHAG. The deduced 246-amino acid protein, which shares 98% sequence identity with the rat sequence, has preserved 14-3-3 family signature motifs, a predicted annexin motif, and several potential phosphorylation sites but not the CDK2 (116953) phosphorylation motif. By EST database searching, Horie et al. (1999) also obtained a cDNA encoding YWHAG, which they found to be 100% identical to the 247-amino acid rat sequence. Northern blot analysis revealed ubiquitous expression of a 3.8-kb YWHAG transcript that is relatively strong in brain, skeletal muscle, and heart but weak in peripheral blood leukocytes. By SDS-PAGE and autoradiographic analysis, Autieri and Carbone (1999) found that YWHAG is expressed and phosphorylated by activation with platelet-derived growth factor (190040) and other activators of several isoforms of protein kinase C (PKC; e.g., 176960). Inhibitors of PKC block YWHAG phosphorylation. Western blot analysis showed that YWHAG interacts with PKC and with RAF1 (164760).GENE FUNCTION
Autieri et al. (1995, 1996) found that YWHAG is upregulated in injured rat carotid arteries and that YWHAG mRNA is upregulated in cytokine-stimulated human VSMC.MAPPING
By fluorescence in situ hybridization, Horie et al. (1999) mapped the YWHAG gene to chromosome 7q11.23. By radiation hybrid analysis, they mapped the gene 2.33 cR telomeric to D7S1870, at the most telomeric end of the common deletion region of Williams-Beuren syndrome (194050).ANIMAL MODEL
Komoike et al. (2010) found that knockdown of Ywhag1 in zebrafish resulted in reduced brain size and increased diameter of the heart tube with increased cardiac arrhythmia. Two unrelated human patients with interstitial deletions at chromosome 7q11.23 (613729) including the YWHAG gene had severe infantile seizures and hypertrophic cardiomyopathy, which Komoike et al. (2010) postulated may have resulted from haploinsufficiency of YWHAG. ... 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 605356 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed