Leucyl-tRNA synthetase

Leucyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the LARS gene.[5][6]

LARS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2WFD
Identifiers
Aliases	LARS1, HSPC192, LEURS, LEUS, LFIS, LRS, PIG44, RNTLS, hr025Cl, ILFS1, Leucyl-tRNA synthetase, LARS, leucyl-tRNA synthetase 1
External IDs	OMIM: 151350 MGI: 1913808 HomoloGene: 7083 GeneCards: LARS1
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q32 Start 146,113,034 bp[1] End 146,182,650 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18|18 B3 Start 42,202,298 bp[2] End 42,262,194 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • aminoacyl-tRNA ligase activity • nucleotide binding • leucine-tRNA ligase activity • ligase activity • GO:0001948 protein binding • ATP binding • aminoacyl-tRNA editing activity • valine-tRNA ligase activity • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity • glutamine-tRNA ligase activity Cellular component • cytosol • nuclear body • cytoplasm • lysosome • endoplasmic reticulum • endomembrane system • aminoacyl-tRNA synthetase multienzyme complex Biological process • tRNA aminoacylation for protein translation • protein biosynthesis • leucyl-tRNA aminoacylation • valyl-tRNA aminoacylation • protein targeting to lysosome • regulation of cell size • negative regulation of autophagy • cellular response to amino acid starvation • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • cellular response to amino acid stimulus • cellular response to leucine • positive regulation of TORC1 signaling • cellular response to leucine starvation • glutaminyl-tRNA aminoacylation • aminoacyl-tRNA metabolism involved in translational fidelity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	51520	107045
Ensembl	ENSG00000133706	ENSMUSG00000024493
UniProt	Q9P2J5	Q8BMJ2
RefSeq (mRNA)	NM_020117 NM_001317964 NM_001317965 NM_016460	NM_134137
RefSeq (protein)	NP_001304893 NP_001304894 NP_057544 NP_064502	NP_598898
Location (UCSC)	Chr 5: 146.11 – 146.18 Mb	Chr 18: 42.2 – 42.26 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu). It is found in the cytoplasm as part of a multisynthetase complex and interacts with the arginine tRNA synthetase through its C-terminal domain. Alternatively spliced transcript variants of this gene have been found; however, their full-length nature is not known.[6]

Interactions

Leucyl-tRNA synthetase has been shown to interact with EEF1G.[7]

Inhibitors

• BC-LI-0186
• Tavaborole [8]

See also

• Leucine-tRNA ligase

References

1. GRCh38: Ensembl release 89: ENSG00000133706 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024493 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Giles RE, Shimizu N, Ruddle FH (Jan 1981). "Assignment of a human genetic locus to chromosome 5 which corrects the heat sensitive lesion associated with reduced leucyl-tRNA synthetase activity in ts025Cl Chinese hamster cells". Somatic Cell Genetics. 6 (5): 667–687. doi:10.1007/BF01538645. PMID 6933703. S2CID 11128003.
6. "Entrez Gene: LARS leucyl-tRNA synthetase".
7. Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (Feb 2002). "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochem. Biophys. Res. Commun. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID 11829477.
8. Markinson B, Ghannoum M, Winter T, Rycerz A, Rock F, Gupta AK. Examining the Benefits of the Boron-Based Mechanism of Action and Physicochemical Properties of Tavaborole in the Treatment of Onychomycosis. J Am Podiatr Med Assoc. 2018 Jan;108(1):12-19. doi:10.7547/16-154 PMID 29547036

Further reading

• Norcum MT (1991). "Structural analysis of the high molecular mass aminoacyl-tRNA synthetase complex. Effects of neutral salts and detergents". J. Biol. Chem. 266 (23): 15398–405. PMID 1651330.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M (1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". J. Mol. Biol. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID 9878398.
• Rho SB, Kim MJ, Lee JS, Seol W, Motegi H, Kim S, Shiba K (1999). "Genetic dissection of protein-protein interactions in multi-tRNA synthetase complex". Proc. Natl. Acad. Sci. U.S.A. 96 (8): 4488–93. doi:10.1073/pnas.96.8.4488. PMC 16359. PMID 10200289.
• Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
• Kang J, Kim T, Ko YG, Rho SB, Park SG, Kim MJ, Kwon HJ, Kim S (2000). "Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases". J. Biol. Chem. 275 (41): 31682–8. doi:10.1074/jbc.M909965199. PMID 10913161.
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
• Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (2002). "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochem. Biophys. Res. Commun. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID 11829477.
• Ling C, Yao YN, Zheng YG, Wei H, Wang L, Wu XF, Wang ED (2005). "The C-terminal appended domain of human cytosolic leucyl-tRNA synthetase is indispensable in its interaction with arginyl-tRNA synthetase in the multi-tRNA synthetase complex". J. Biol. Chem. 280 (41): 34755–63. doi:10.1074/jbc.M413511200. PMID 16055448.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• Maeso E, Rueda A, Jiménez S, Del Hoyo P, Martín R, Cabello A, Mendoza LM, Arenas J, Campos Y (2007). "A novel mutation in the mitochondrial DNA tRNA Leu (UUR) gene associated with late-onset ocular myopathy". Neuromuscul. Disord. 17 (5): 415–8. doi:10.1016/j.nmd.2007.01.015. PMID 17363246. S2CID 26750219.
• Lue SW, Kelley SO (2007). "A single residue in leucyl-tRNA synthetase affecting amino acid specificity and tRNA aminoacylation". Biochemistry. 46 (15): 4466–72. doi:10.1021/bi0618215. PMC 2518062. PMID 17378584.