Tryptophan--tRNA ligase, cytoplasmic (WARS)
The protein contains 471 amino acids for an estimated molecular weight of 53165 Da.
Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression. (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
Angiogenesis
Gene expression
Negative regulation of cell population proliferation
Negative regulation of protein kinase activity
Negative regulation of protein phosphorylation
Positive regulation of gene expression
Positive regulation of protein-containing complex assembly
Regulation of angiogenesis
Regulation of protein ADP-ribosylation
Translation
TRNA aminoacylation for protein translation
Tryptophanyl-tRNA aminoacylation
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Nucleus
Protein complex
Protein-containing complex
The reference OMIM entry for this protein is 191050
Tryptophanyl-trna synthetase; wars
Tryptophanyl-trna synthetase, cytoplasmic
Trprs
DESCRIPTION
Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis. Human tyrosyl-tRNA synthetase (YARS; 603623) can be split into 2 fragments having distinct cytokine activities, thereby linking protein synthesis to cytokine signaling pathways. Tryptophanyl-tRNA synthetase (WARS) is a close homolog of tyrosyl-tRNA synthetase. It catalyzes the aminoacylation of tRNA(trp) with tryptophan, an essential function of the cell's protein synthesis machinery.CLONING
Frolova et al. (1991) cloned the human gene and reported its nucleotide sequence. Shimizu et al. (1976) and Denney et al. (1978) located the structural gene for tryptophanyl-tRNA synthetase on chromosome 14. Lo et al. (2014) reported the discovery of a large number of natural catalytic nulls for each human aminoacyl tRNA synthetase. Splicing events retain noncatalytic domains while ablating the catalytic domain to create catalytic nulls with diverse functions. Each synthetase is converted into several new signaling proteins with biologic activities 'orthogonal' to that of the catalytic parent. The recombinant aminoacyl tRNA synthetase variants had specific biologic activities across a spectrum of cell-based assays: about 46% across all species affect transcriptional regulation, 22% cell differentiation, 10% immunomodulation, 10% cytoprotection, and 4% each for proliferation, adipogenesis/cholesterol transport, and inflammatory response. Lo et al. (2014) identified in-frame splice variants of cytoplasmic aminoacyl tRNA synthetases. They identified 2 catalytic-null splice variants for TrpRS.GENE FUNCTION
In normal cells, human tryptophanyl-tRNA synthetase exists in 2 forms. The major form is the full-length protein, and the other is a truncated form in which most of the extra-NH2-terminal domain is deleted because of alternative splicing of the pre-mRNA (Tolstrup et al., 1995; Turpaev et al., 1996), with met48 being deduced as the NH2-terminal residue of the truncated form. The expression of the short form of WARS is highly stimulated in human cells by the addition of interferon-gamma (IFNG; 147570). Wakasugi et al. (2002) showed that the truncated form of WARS is angiostatic in several different systems and assays, whereas the full-length enzyme is inactive. Thus, protein synthesis may be linked to the regulation of angiogenesis by a natural fragment of tryptophanyl-tRNA synthetase. Otani et al. (2002) showed that a recombinant form of a COOH-terminal fragment of tryptophanyl-tRNA synthetase is a potent antagonist of vascular endothelial growth factor (VEGF; 192240)-induced angiogenesis in a mouse model and of naturally occurring retinal angiogenesis in the neonatal mouse. Angiostatic activity was dose-dependent in both systems. The full-length protein was inactive as an antagonist of angiogenesis. The results suggested that fragments of tryptophanyl-tRNA synthetase, as naturally occurring and potentially nonimmunogenic anti-angiogenics, can be used for the treatment of neovascular eye diseases.MAPPING
Francke et al. (1977) assigned WARS to 14q21-qter. Graphodatsky et al. (1993) confirmed the assignment to chromosome 14 and regionalized it by isotopic in situ hybridization to 14q23-q31. The gene may be in the 14q24 band where one-third of the grains were localized. Borglum et al. (1996) mapped a cDNA probe of the WARS gene by a combination of somatic cell hybrid analysis, fluorescence in situ hybridization (FISH), and li ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 191050 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed