Leucine--tRNA ligase, cytoplasmic (LARS)
The protein contains 1176 amino acids for an estimated molecular weight of 134466 Da.
Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two 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. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs. (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.
- 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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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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| Variant | Description |
|---|---|
| dbSNP:rs112954500 | |
| ILFS1 | |
| dbSNP:rs10988 |
Biological Process
Cellular response to amino acid starvation
Cellular response to amino acid stimulus
Cellular response to leucine
Cellular response to leucine starvation
Gene expression
Glutaminyl-tRNA aminoacylation
Leucyl-tRNA aminoacylation
Negative regulation of autophagy
Positive regulation of GTPase activity
Positive regulation of TOR signaling
Positive regulation of TORC1 signaling
Protein targeting to lysosome
Regulation of cell size
TRNA aminoacylation for protein translation
Valyl-tRNA aminoacylation
The reference OMIM entry for this protein is 151350
Leucyl-trna synthetase; lars
Lrs
Lars1
Leus
Rntls
DESCRIPTION
The LARS gene encodes a cytoplasmic amino-acyl tRNA synthetase enzyme (aaRS) called LeuRS. LeuRS is one of several known aaRS proteins that form a macromolecular multisynthetase complex that regulates transcription, translation, and various signalling pathways (summary by Casey et al., 2012).CLONING
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 6 catalytic-null splice variants for LeuRS.GENE FUNCTION
The aminoacyl-tRNA synthetases catalyze ligation of amino acids to their respective transfer RNAs. Han et al. (2012) showed that LRS senses intracellular leucine concentration and interacts directly with Rag GTPase (RRAGD; 608268). RRAGD then activates MTORC1 (601231), a key regulator of growth. When the authors modified the LRS protein to inhibit leucine binding, they observed a loss of amino acid regulation signaling to mTORC1.MAPPING
By study of hybrids of Chinese hamster and human cells, Giles et al. (1980) found evidence that a structural gene for leucyl-tRNA synthetase is on chromosome 5. Dana and Wasmuth (1982) did cytogenetic and biochemical analyses of spontaneous segregants from Chinese hamster-human interspecific hybrid cells that contained human chromosome 5 and expressed the 4 syntenic genes LEUS, HEXB (606873), EMTB (130620), and CHR (118840), the hybrid cells being subjected to selective conditions requiring them to retain the LEUS gene. From these analyses, Dana and Wasmuth (1982) concluded that the order is as listed above and that the specific locations are: LEUS, 5pter-5q1; HEXB, 5q13; EMTB, 5q23-5q35; CHR, 5q35. Gerken et al. (1986) stated that LARS is located in 5cen-q11 and that threonyl-tRNA synthetase (187790) is closely linked, at 5p13-cen.NOMENCLATURE
Following the system used for isoenzymes encoded by nuclear genes, in which 1 is used to designate the cytoplasmic or soluble form and 2 is used to designate the mitochondrial form (e.g., SOD1 (147450) and SOD2 (147460)), cytoplasmic LARS might be referred to as LARS1, and the mitochondrial form as LARS2 (604544).MOLECULAR GENETICS
In a 4-generation family of Irish Travellers segregating infantile liver failure (ILFS1; 615438), Casey et al. (2012) identified homozygosity for 2 missense mutations in the LARS gene. One (Y373C; 151350.0001) was a mutation at a conserved residue in the connective peptide-1 (CP1) domain. The other was predicted to be a rare nonpathogenic variant. ... 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 151350 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed