Disease relevance of KARS

• The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly [1].
• Evidence exists that Gag alone is sufficient for the incorporation of LysRS into virions [1].
• Both regions have been implicated in homodimerization of capsid and LysRS, respectively [1].
• Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant [2].
• Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1 [3].

High impact information on KARS

• The sequencing of euryarchaeal genomes has suggested that the essential protein lysyl-transfer RNA (tRNA) synthetase (LysRS) is absent from such organisms [4].
• The predicted amino acid sequence of M. maripaludis LysRS is similar to open reading frames of unassigned function in both Methanobacterium thermoautotrophicum and Methanococcus jannaschii but is unrelated to canonical LysRS proteins reported in eubacteria, eukaryotes, and the crenarchaeote Sulfolobus solfataricus [4].
• The presence of amino acid motifs characteristic of the Rossmann dinucleotide-binding domain identifies M. maripaludis LysRS as a class I aminoacyl-tRNA synthetase, in contrast to the known examples of this enzyme, which are class II synthetases [4].
• Serum and IgG from four patients also inhibited leucyl-tRNA synthetase activity, and serum and IgG from two inhibited lysyl-tRNA synthetase [5].
• Among them, we found that lysyl-tRNA synthetase (KRS) was secreted from intact human cells, and its secretion was induced by TNF-alpha [6].

Biological context of KARS

• In the presence of Vpr, LysRS-mediated amino-acylation of tRNA(Lys) is inhibited [7].
• Since tRNA(Lys) is the primer for reverse transcription of the HIV-1 genome, this suggests that the interaction between Vpr and LysRS may influence the initiation of HIV-1 reverse transcription [7].
• Point mutations that disrupt the homodimerization of LysRS and Gag in vitro do not affect their interaction [8].
• The isolated N-domain of LysRS also displayed weak affinity for tRNA, suggesting that the catalytic and N-domains of LysRS act synergistically to provide a high affinity binding site for tRNA [9].
• Using a novel bioluminescence resonance energy transfer assay to directly measure HIV-1 protease activity in vivo also indicates that the overexpression of LysRS in the cell reduces viral protease activity [10].

Anatomical context of KARS

• LysRS is found (i). in the nucleus, (ii). in a cytoplasmic high-molecular-weight aminoacyl-tRNA synthetase complex (HMW aaRS complex), (iii). in mitochondria, and (iv). associated with plasma membrane [11].
• Exogenous mutant LysRS species unable to either enter the nucleus or bind to the cell membrane are still incorporated into virions [11].
• Translation and Transcription: the Dual Functionality of LysRS in Mast Cells [12].
• Our results provide new insights into tRNA(Lys) channeling in eukaryotic cells and shed new light on the possible requirement of native LysRS for triggering tRNA(3)Lys packaging into human immunodeficiency virus, type 1 viral particles [9].

Associations of KARS with chemical compounds

• Even though eukaryotic lysine tRNAs also encode G73, the motif 2 loop sequence of lysyl-tRNA synthetase differs at multiple positions from that of the aspartate enzyme [2].
• In confirmation of this idea, we found that newly synthesized LysRS is associated with Gag after a 10-min pulse with [(35)S]cysteine/methionine [11].
• Using data recently obtained from the emerging genome projects, our analysis points to the extant forms of lysyl-tRNA synthetase being preceded in evolution by the establishment of the identity of lysine tRNA [13].
• Here we describe the systematic substitution of the 13 lysine or arginine residues located within the general RNA-binding domain of hamster LysRS made of 70 residues [14].
• Gag alone is sufficient for packaging of LysRS, and these two proteins have been shown to interact in vitro using glutathione S-transferase pull-down assays [8].

Other interactions of KARS

• Significant sequence similarities between KARS and ADAT1 are apparent within their substrate interaction domains [15].
• In addition to its contribution to the translation process, LysRS also takes part in the regulation of MITF and USF2 target genes [12].
• This same organization is conserved at the human Rap1-KARS locus [16].
• By using the yeast two-hybrid system, Lys-tRNA synthetase (LysRS) was identified as a Vpr-interacting protein [7].
• Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24 [17].

Analytical, diagnostic and therapeutic context of KARS

• Gel chromatography studies further support the formation of a Gag/LysRS heterodimer [8].
• Functional dissection of the eukaryotic-specific tRNA-interacting factor of lysyl-tRNA synthetase [14].
• OBJECTIVES: To determine the seroprevalence of diphtheria in 767 children aged 0-6 years and to identify the relationship between diphtheria seroprevalence and several sociodemographic characteristics of the study subjects in the Erzurum, Erzincan and Kars cities situated in Eastern Turkey [18].

References