Tyrosine--tRNA ligase, cytoplasmic (YARS)
The protein contains 528 amino acids for an estimated molecular weight of 59143 Da.
Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr). (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
Gene expression
Signal transduction
TRNA aminoacylation for protein translation
Tyrosyl-tRNA aminoacylation
The reference OMIM entry for this protein is 603623
Tyrosyl-trna synthetase; yars
Tyrrs
Yts
Yrs
CLONING
Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Kleeman et al. (1997) cloned cDNAs encoding tyrosyl-tRNA synthetase (YARS) from several different human cDNA libraries. The YARS cDNA sequence encodes a 528-amino acid polypeptide. Sequence analysis revealed that the carboxyl end of the protein contains a region with 49% identity to endothelial monocyte-activating polypeptide II (EMAP II; 603605). 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 5 catalytic-null and 1 catalytic domain-retained splice variants for TyrRS.GENE FUNCTION
While native human tyrosyl-tRNA synthetase is inactive as a cell-signaling molecule, it can be split into 2 distinct cytokines. The enzyme is secreted under apoptotic conditions in culture, where it is cleaved into an N-terminal fragment that harbors the catalytic site and into a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8 (IL8; 146930)-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine. Wakasugi and Schimmel (1999) found that the cytokine activities of split human tyrosyl-tRNA synthetase depend on highly differentiated motifs that are idiosyncratic to the mammalian system. Jordanova et al. (2006) determined that YARS is expressed ubiquitously, including in brain and spinal cord.BIOCHEMICAL FEATURES
- Crystal Structure Sajish and Schimmel (2015) presented a 2.1-angstrom cocrystal structure of resveratrol bound to the active site of TYRRS. Resveratrol nullifies the catalytic activity and redirects TYRRS to a nuclear function, stimulating NAD(+)-dependent auto-poly-ADP-ribosylation of PARP1 (173870). Downstream activation of key stress signaling pathways are causally connected to TYRRS-PARP1-NAD+ collaboration. This collaboration is also demonstrated in the mouse, and is specifically blocked in vivo by a resveratrol-displacing tyrosyl adenylate analog. Sajish and Schimmel (2015) concluded that, in contrast to functionally diverse tRNA synthetase catalytic nulls created by alternative splicing events that ablate active sites, a nonspliced TYRRS catalytic null revealed a novel PARP1- and NAD(+)-dependent dimension to the physiologic mechanism of resveratrol.MAPPING
The YARS gene resides on chromosome 1p35-p34 (Jordanova et al., 2003).MOLECULAR GENETICS
Dominant intermediate Charcot-Marie-Tooth (DI-CMT
) neuropathy is a genetic ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603623 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed