Genome location: Pf3D7_11_v3:1,013,901..1,017,911(-)
Genome classification: Core
Product Description: threonine--tRNA ligase
SignalP Peptide: MKKIIMVIFFLLSKICKNNA
# Transmembrane Domains: 0
EC Numbers: 6.1.1.3 (Threonine--tRNA ligase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005829 | cytosol |
| Component | GO:0005739 | mitochondrion |
| Component | GO:0005634 | nucleus |
| Function | GO:0005524 | ATP binding |
| Function | GO:0004812 | aminoacyl-tRNA ligase activity |
| Function | GO:0004829 | threonine-tRNA ligase activity |
| Process | GO:0042493 | response to drug |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0006418 | tRNA aminoacylation for protein translation |
| Process | GO:0006435 | threonyl-tRNA aminoacylation |
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 | 0.71 | 0.67 |
| Trophozoite | expressed | 0.96 | 0.50 |
| Schizont | expressed | 0.31 | 0.80 |
| Gametocyte | expressed | 0.55 | 0.70 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1126000
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: 0.119 | MFS: -2.949 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0922300)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IIA4
"Best" AlphaFill ligand hit: SSA (5'-o-(n-(l-seryl)-sulfamoyl)adenosine, Local RMSD=0.32) with 4EO4 (Global RMSD=1.35)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 6.1.1.3 | threonine-tRNA ligase | borrelidinthreonyl-AMPZINC27215482ZINC67910544ZINC72320615ZINC72320626ZINC35270978ZINC35458951hydrogen peroxideoperator mRNA domain 2tubercidin 5'-triphosphatePurineriboside 5'-triphosphate... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P26639 | Threonine--tRNA ligase 1, cytoplasmic | Homo sapiens | HOGENOM, OrthoDB | CHEMBL1163068CHEMBL2316960CHEMBL2311929CHEMBL2311928... |
| Q8ZDW5 | Threonine--tRNA ligase | Yersinia pestis | OMA, OrthoMCL | CHEMBL2311917CHEMBL2316961CHEMBL2316960CHEMBL2311929... |
Ortholog Group (OrthoMCL): OG6_100294
Most Similar Human Ortholog: H0YKB9
TM-align score: 0.92 | RMSD: 1.40
Seq Identity: 0.53 | Length: 148 / 1013
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000113407 | threonyl-tRNA synthetase 1 |
| ENSG00000143374 | threonyl-tRNA synthetase 2, mitochondrial |
| ENSG00000185418 | threonyl-tRNA synthetase 3 |
Protein Length: 1013 | Molecular Weight (kDa): 119.546
UniProt ID(s): Q8IIA4
PDB ID(s): None
Isoelectric Point: 9.05
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR002314 | Aminoacyl-tRNA synthetase, class II (G/ P/ S/T) |
| InterPro | IPR002320 | Threonine-tRNA ligase, class IIa |
| InterPro | IPR004154 | Anticodon-binding |
| InterPro | IPR012947 | Threonyl/alanyl tRNA synthetase, SAD |
| InterPro | IPR018163 | Threonyl/alanyl tRNA synthetase, class II-like, putative editing domain superfamily |
| InterPro | IPR033728 | Threonine-tRNA ligase catalytic core domain |
| PFam | PF00587 | Aminoacyl-tRNA synthetase, class II (G/ P/ S/T) |
| PFam | PF03129 | Anticodon-binding |
| PFam | PF07973 | Threonyl/alanyl tRNA synthetase, SAD |
| Superfamily | SSF52954 | Threonyl/alanyl tRNA synthetase, class II-like, putative editing domain superfamily |
| Superfamily | SSF55186 | |
| Superfamily | SSF55681 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 36 | 30 | 61 |
| disruptive | 48 | 118 | 57 | 124 |
| missense | 25 | 85 | 43 | 104 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 14 | 86 | 44 | 77 |
| disruptive | 76 | 231 | 90 | 200 |
| missense | 37 | 169 | 74 | 138 |
PlasmoDB Total SNPs: 180
Non-coding: 87 | Synonymous: 38 | Nonsynonymous: 55 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 22222968 | Dual targeting of aminoacyl-tRNA synthetases to the apicoplast and cytosol inPlasmodium falciparum. | Jackson KE, Pham JS, ..., Ralph SA | 10.1016/j.ijpara.2011.11.008 |
| 25489076 | Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo. | Novoa EM, Camacho N, ..., Ribas de Pouplana L | 10.1073/pnas.1405994111 |
| 30212465 | Integrative proteomics and bioinformatic prediction enable a high-confidenceapicoplast proteome in malaria parasites. | Boucher MJ, Ghosh S, ..., Yeh E | 10.1371/journal.pbio.2005895 |
| 37335076 | Synthesis and evaluation of an agrocin 84 toxic moiety (TM84) analogue as amalarial threonyl tRNA synthetase inhibitor | Buitrago JAR, Leitis G, ..., Jirgensons A | 10.1039/d3ob00670k |