Lysine--tRNA ligase (KARS)
The protein contains 597 amino acids for an estimated molecular weight of 68048 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 (PubMed:9278442, PubMed:18029264, PubMed:18272479). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:5338216, PubMed:14975237, PubMed:19524539, PubMed:23159739).', '(Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. (updated: Jan. 31, 2018)
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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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, is annotated as membranous in UniProt.
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Biological Process
Activation of MAPK activity
Basophil activation involved in immune response
Diadenosine tetraphosphate biosynthetic process
ERK1 and ERK2 cascade
Gene expression
Lysyl-tRNA aminoacylation
Negative regulation of cell population proliferation
Positive regulation of cytokine production involved in immune response
Positive regulation of cytokine production involved in inflammatory response
Positive regulation of cytokine secretion involved in immune response
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of inflammatory response to antigenic stimulus
Positive regulation of macrophage activation
Positive regulation of macrophage chemotaxis
Positive regulation of metallopeptidase activity
Positive regulation of p38MAPK cascade
Positive regulation of transcription, DNA-templated
Response to X-ray
TRNA aminoacylation for protein translation
TRNA processing
Tumor necrosis factor-mediated signaling pathway
Viral process
The reference OMIM entry for this protein is 601421
Lysyl-trna synthetase; kars
Krs
DESCRIPTION
The KARS gene encodes lysyl-tRNA synthetase, which catalyzes the aminoacylation of tRNA-lys in the cytoplasm and mitochondria. Protein synthesis is initiated by the attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (ARSs). At least 6 of 20 human ARSs, including KARS, had been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis (Targoff et al. (1993)).CLONING
Tolkunova et al. (2000) identified 2 full-length sequences for KARS and determined that they represent cytoplasmic and mitochondrial isoforms. The 625-amino acid mitochondrial enzyme and the 597-amino acid cytoplasmic enzyme are identical over the last 576 amino acids, but the mitochondrial enzyme has a different 49-amino acid N terminus containing a mitochondrial targeting sequence. Transfection of both fluorescence-tagged isoforms into an osteosarcoma cell line showed that the cytoplasmic isoform produced a diffuse, cellwide fluorescence, while the mitochondrial isoform resulted in a punctate pattern that colocalized with mitochondrial markers. Ribonuclease protection analysis indicated that the mRNA encoding the cytoplasmic isoform makes up approximately 70%, and the mitochondrial isoform approximately 30%, of mature KARS transcripts. Using massively parallel sequencing and RT-PCR experiments, Santos-Cortez et al. (2013) demonstrated that KARS is expressed in hair cells of zebrafish, chickens, and mice, as well as in maculae of zebrafish and mice. Immunolabeling experiments using mouse vestibular tissue revealed broad distribution of KARS in hair cells and supporting cells, and organ of Corti sections showed KARS localization to inner and outer hair cells, Dieter cells, and basilar membrane. In addition, the tectorial membrane showed a strong affinity for KARS antibody, and KARS labeling was strongest within the spiral ligament, particularly in the area containing type II and type IV fibrocytes. KARS was also strongly localized to the outer and inner sulcus cells and spiral limbus epithelium. 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 3 catalytic-null splice variants for cytoplasmic LysRS.GENE STRUCTURE
Tolkunova et al. (2000) determined that the KARS gene contains 15 exons and spans about 20 kb. The cytoplasmic and mitochondrial KARS isoforms result from alternative splicing of the first 3 exons. Tolkunova et al. (2000) found that the initiation codons for KARS and RAP1 (605061) are separated by 243 bp. This region lacks a conventional TATA sequence but contains several SP1 (189906)-binding domains oriented in both directions.MAPPING
Nichols et al. (1996) used ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 601421 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed