Aspartate--tRNA ligase, cytoplasmic (DARS)
The protein contains 501 amino acids for an estimated molecular weight of 57136 Da.
Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. (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.
Biological Process
Aspartyl-tRNA aminoacylation
Gene expression
Protein complex assembly
Protein-containing complex assembly
Translation
TRNA aminoacylation for protein translation
Cellular Component
Aminoacyl-tRNA synthetase multienzyme complex
Cytoplasm
Cytosol
Extracellular exosome
Membrane
Synapse
Molecular Function
Aminoacylase activity
Aspartate-tRNA ligase activity
ATP binding
Poly(A) RNA binding
RNA binding
The reference OMIM entry for this protein is 603084
Aspartyl-trna synthetase; dars
Asprs
DESCRIPTION
The DARS gene encodes cytoplasmic aspartyl-tRNA synthetase. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing the specific aminoacylation of cognate tRNA in the initial step of ribosome-dependent protein biosynthesis. Mammalian synthetases differ from those of prokaryotes and lower eukaryotes in that they associate as multienzyme complexes (summary by Jacobo-Molina et al., 1989).CLONING
By screening a HeLa cell cDNA library with a rat Dars cDNA cloned by them, Jacobo-Molina et al. (1989) isolated a cDNA encoding DARS. The predicted DARS protein has 500 amino acids and a calculated molecular mass of 57,000 Da. The human DARS protein has 95% amino acid identity with rat Dars and shares unevenly distributed identity with yeast aspartyl-tRNA synthetase, with 69% identity at the C-terminal half and 46% identity at the N-terminal half. The authors discussed several potential functional domains in the DAR protein, including a region of conserved lysine residues which is also found in bacterial and yeast synthetases and is likely to be the binding site for the 3-prime end of tRNA, a nucleotide triphosphate-binding motif, an ATP-binding motif with strong similarity to that present in E. coli alanyl-tRNA synthetase, and a cyclic AMP-dependent protein kinase phosphorylation site. Jacobo-Molina et al. (1989) predicted a neutral amphiphilic helix at the N-terminal end of the DARS protein and stated that this structure does not occur in other known synthetases from bacteria, yeast, and higher organisms. Based on a curated set of publicly available data, Taft et al. (2013) found that Dars is diffusely localized in the cytoplasm and broadly expressed across tissue types, including the central nervous system. In mice, Dars showed specific expression in neurons of the hippocampus, the dentate gyrus, and the molecular layer of the cerebellum. DARS expression in the developing and adult human brain showed a similar pattern, with preferential immunostaining of neurons in the cerebellum, cerebral cortex, hippocampus, and lateral ventricle. In addition, staining of peripheral neurons was evident in the colon. 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 4 catalytic-null and 1 catalytic domain-retained splice variants for AspRS.MAPPING
Gross (2012) mapped the DARS gene to chromosome 2q21.3 based on an alignment of the DARS sequence (GenBank GENBANK BC000629) with the genomic sequence (GRCh37).MOLECULAR GENETICS
In 10 patients from 7 unrelated families of various origins with hypomyelination with brainstem and spinal cord involvement and spasticity (HBSL; 615281), Taft et al. (2013) identif ... 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 603084 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed