Genome location: Pf3D7_13_v3:2,005,394..2,008,444(-)
Genome classification: Core
Product Description: lysine--tRNA ligase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 6.1.1.6 (Lysine--tRNA ligase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005829 | cytosol |
| Component | GO:0005634 | nucleus |
| Function | GO:0005524 | ATP binding |
| Function | GO:0004824 | lysine-tRNA ligase activity |
| Function | GO:0000049 | tRNA binding |
| Process | GO:0015966 | diadenosine tetraphosphate biosynthetic process |
| Process | GO:0006430 | lysyl-tRNA aminoacylation |
| Process | GO:0009410 | response to xenobiotic stimulus |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | expressed | N/A | N/A |
| Ring | expressed | 0.65 | 0.69 |
| Trophozoite | expressed | 1.00 | 0.49 |
| Schizont | expressed | 0.16 | 0.90 |
| Gametocyte | expressed | 0.46 | 0.74 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1350100
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.329 | MFS: -2.517 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IDJ8
"Best" AlphaFill ligand hit: MPO (3[n-morpholino]propane sulfonic acid, Local RMSD=0.05) with 5ZH2 (Global RMSD=0.77)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 6.1.1.6 | lysine-tRNA ligase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q15046 | Lysine--tRNA ligase | Homo sapiens | HOGENOM, OMA, OrthoDB | BDBM50242742BDBM50242742CHEMBL472840CHEMBL475882... |
| Q8IDJ8 | Lysine--tRNA ligase | HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CLADOSPORINCHEMBL4206602GNF-Pf-5378CHEMBL4211492... |
Ortholog Group (OrthoMCL): OG6_100559
Most Similar Human Ortholog: H3BPV7
TM-align score: 0.94 | RMSD: 1.09
Seq Identity: 0.57 | Length: 103 / 583
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000065427 | lysyl-tRNA synthetase 1 |
Protein Length: 583 | Molecular Weight (kDa): 67.591
UniProt ID(s): Q8IDJ8
PDB ID(s): 4H02, 4PG3, 6HCU, 6HCV, 6L3Y, 6L4Q
Isoelectric Point: 7.39
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR002313 | Lysine-tRNA ligase, class II |
| InterPro | IPR004364 | Aminoacyl-tRNA synthetase, class II (D/K/N) |
| InterPro | IPR004365 | OB-fold nucleic acid binding domain, AA-tRNA synthetase-type |
| InterPro | IPR012340 | Nucleic acid-binding, OB-fold |
| InterPro | IPR018149 | Lysyl-tRNA synthetase, class II, C-terminal |
| InterPro | IPR034762 | Bacterial/eukaryotic lysine-tRNA ligase, class II |
| PFam | PF00152 | Aminoacyl-tRNA synthetase, class II (D/K/N) |
| PFam | PF01336 | OB-fold nucleic acid binding domain, AA-tRNA synthetase-type |
| Superfamily | SSF50249 | Nucleic acid-binding, OB-fold |
| Superfamily | SSF55681 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 10 | 48 | 25 | 54 |
| disruptive | 3 | 25 | 17 | 52 |
| missense | 3 | 25 | 17 | 46 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 19 | 83 | 35 | 62 |
| disruptive | 4 | 73 | 36 | 123 |
| missense | 4 | 61 | 33 | 94 |
PlasmoDB Total SNPs: 142
Non-coding: 115 | Synonymous: 17 | Nonsynonymous: 10 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 23181666 | Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. | Oehring SC, Woodcroft BJ, ..., Voss TS | 10.1186/gb-2012-13-11-r108 |
| 23633587 | Structural analysis of malaria-parasite lysyl-tRNA synthetase provides a platformfor drug development. | Khan S, Garg A, ..., Sharma A | 10.1107/S0907444913001923 |
| 29326268 | Mapping the malaria parasite druggable genome by using in vitro evolution andchemogenomics. | Cowell AN, Istvan ES, ..., Winzeler EA | 10.1126/science.aan4472 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 30894487 | Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis. | Baragana B, Forte B, ..., Gilbert IH | 10.1073/pnas.1814685116 |
| 1628641 | The polyanion-binding domain of cytoplasmic Lys-tRNA synthetase fromSaccharomyces cerevisiae is not essential for cell viability | Martinez R, Mirande M | 10.1111/j.1432-1033.1992.tb17012.x |
| 36846776 | Retrospective analysis of Plasmodium vivax genomes from a pre-elimination Chinainland population in the 2010s | Liu Y, Zhang T, ..., Chen JH | 10.3389/fmicb.2023.1071689 |
| 2046655 | A PMR2 tandem repeat with a modified C-terminus is located downstream from theKRS1 gene encoding lysyl-tRNA synthetase in Saccharomyces cerevisiae | Martinez R, Latreille MT, Mirande M | 10.1007/BF00260720 |
| 1505029 | Autoregulation of the yeast lysyl-tRNA synthetase gene GCD5/KRS1 by translationaland transcriptional control mechanisms | Lanker S, Bushman JL, ..., Mueller PP | 10.1016/0092-8674(92)90433-d |
| 8952483 | Functional replacement of hamster lysyl-tRNA synthetase by the yeast enzymerequires cognate amino acid sequences for proper tRNA recognition | Agou F, Quevillon S, ..., Mirande M | 10.1021/bi9617926 |
| 17346711 | Dissecting yeast Hog1 MAP kinase pathway using a chemical genetic approach | Kim S, Shah K | 10.1016/j.febslet.2007.02.032 |
| 2903861 | The yeast lysyl-tRNA synthetase gene. Evidence for general amino acid control ofits expression and domain structure of the encoded protein | Mirande M, Waller JP | https://pubmed.ncbi.nlm.nih.gov/2903861/ |