Detailed view for PF3D7_1034900

Basic information

TDR Targets ID: 1414
Plasmodium falciparum, methionine--tRNA ligase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.6056 | Length (AA): 889 | MW (Da): 104168 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 0

Druggability Group : DG2

Targets have been classified into druggability groups (DG) according to their druggability score in network driven prioritizations. DGs range from 1 to 5; the higher the group number, the higher the chance of the target to be druggable

Pfam domains

PF09334   tRNA synthetases class I (M)

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0005737   cytoplasm  
GO:0005524   ATP binding  
GO:0004825   methionine-tRNA ligase activity  
GO:0004812   aminoacyl-tRNA ligase activity  
GO:0000166   nucleotide binding  
GO:0006431   methionyl-tRNA aminoacylation  
GO:0006418   tRNA aminoacylation for protein translation  
GO:0006412   translation  

Structural information

Modbase 3D models:

There are 10 models calculated for this protein. More info on these models, including the models themselves is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
35 885 1gax (A) 11 852 14.00 0 1 1 0.26
223 719 1a8h () 3 498 37.00 0 1 1.18 -1.72
2 31 2emx (A) 8 38 13.00 0.072 0.02 -0.166654 2.87
6 199 2hnl (A) 27 225 16.00 0.37 0.69 0.380623 -0.13
6 155 1axd (A) 2 168 19.00 0.00000000058 0.78 0.247129 0.6
222 721 2x1l (A) 2 512 37.00 0 1 1.10633 -1.13
222 762 1rqg (A) 1 593 20.00 0.000021 1 0.777949 0.11
223 662 2d5b (A) 3 442 41.00 0 1 0.997838 -0.42
223 711 4qre (A) 4 511 40.00 0 1 1.08396 -0.83
746 887 1ntg (A) 23 170 16.00 0.000013 0.9 0.29413 0.06

Help me make sense of these data.

Target Beg: first modeled residue
Target End: last modeled residue
Template: template structure used for modelling (PDB accession and chain)
Template Beg: first template residue in target-template alignment
Template End: last template residue in target-template alignment
Identity: sequence identity
Evalue: E value for target-template hit
Model Score: GA341 score (>0.7 for reliable model)
MPQS: ModPipe Quality Score (>1.1 for reliable model)
zDope: zDope Score (negative for reliable model)

A more detailed description of these scores is available at the Modbase Model Evaluation Help Pages, and in the papers referenced therein.

PDB Structures:

No structure availble in the PDB for this protein

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, gametocyte, merozoite, sporozoite, early ring, early schizont, early trophozoite, late ring, late schizont, late trophozoite, Oocyst, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile Female Gametocyte. Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Male Gametocyte. Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Sporozoite. Zanghi G
Show/Hide expression data references
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.

Orthologs

Ortholog group members (OG5_127468)

Species Accession Gene Product
Arabidopsis thaliana AT3G55400   methionyl-tRNA synthetase
Babesia bovis BBOV_I001970   methionyl-tRNA synthetase, putative
Brugia malayi Bm1_54415   methionyl-tRNA synthetase
Candida albicans CaO19.3950   mitochondrial tRNA methionyl-tRNA synthetase similar to S. cerevisiae MSM1 (YGR171C) mitochondrial methionyl-tRNA synthetase
Candida albicans CaO19.11432   mitochondrial tRNA methionyl-tRNA synthetase similar to S. cerevisiae MSM1 (YGR171C) mitochondrial methionyl-tRNA synthetase
Caenorhabditis elegans CELE_Y105E8A.20   Protein Y105E8A.20, isoform A
Cryptosporidium hominis Chro.80398   methionine -- tRNA ligase
Cryptosporidium parvum cgd8_3460   methionyl-tRNA synthetase of possible bacterial origin
Dictyostelium discoideum DDB_G0285759   methionine-tRNA ligase
Drosophila melanogaster Dmel_CG31322   Methionyl-tRNA synthetase
Echinococcus granulosus EgrG_000186800   methionine tRNA synthetase
Echinococcus multilocularis EmuJ_000186800   methionine tRNA synthetase
Giardia lamblia GL50803_22204   Methionyl-tRNA synthetase
Homo sapiens ENSG00000247626   methionyl-tRNA synthetase 2, mitochondrial
Leishmania braziliensis LbrM.21.0900   methionyl-tRNA synthetase, putative
Leishmania donovani LdBPK_210890.1   methionyl-tRNA synthetase, putative
Leishmania infantum LinJ.21.0890   methionyl-tRNA synthetase, putative
Leishmania major LmjF.21.0810   methionyl-tRNA synthetase, putative
Leishmania mexicana LmxM.21.0810   methionyl-tRNA synthetase, putative
Loa Loa (eye worm) LOAG_10885   tyrosyl-tRNA synthetase
Loa Loa (eye worm) LOAG_02240   methionyl-tRNA synthetase
Mycobacterium leprae ML0238c   Probable methionyl-tRNA synthase MetS
Mus musculus 212679   methionine-tRNA synthetase 2 (mitochondrial)
Mycobacterium tuberculosis Rv1007c   Methionyl-tRNA synthetase MetS (MetRS) (methionine--tRNA ligase)
Mycobacterium ulcerans MUL_4654   methionyl-tRNA synthetase
Neospora caninum NCLIV_041650   Methionine--tRNA ligase (EC 6.1.1.10), related
Oryza sativa 4332018   Os03g0209600
Onchocerca volvulus OVOC12840  
Plasmodium berghei PBANKA_0518700   methionine--tRNA ligase, putative
Plasmodium falciparum PF3D7_1034900   methionine--tRNA ligase
Plasmodium knowlesi PKNH_0620100   methionine--tRNA ligase, putative
Plasmodium vivax PVX_110980   methionine--tRNA ligase, putative
Plasmodium yoelii PY03894   methionyl-tRNA synthetase
Saccharomyces cerevisiae YGR171C   methionine--tRNA ligase MSM1
Schistosoma japonicum Sjp_0206550   ko:K01874 methionyl-tRNA synthetase [EC6.1.1.10], putative
Schistosoma mansoni Smp_005330   methionine-tRNA synthetase
Schmidtea mediterranea mk4.010622.00  
Schmidtea mediterranea mk4.019340.01  
Schmidtea mediterranea mk4.016299.00   MethionineALQ-tRNA ligase, mitochondrial
Schmidtea mediterranea mk4.031319.00   MethionineALQ-tRNA ligase, mitochondrial
Trypanosoma brucei gambiense Tbg972.10.1750   methionyl-tRNA synthetase, putative
Trypanosoma brucei Tb927.10.1500   methionyl-tRNA synthetase, putative
Trypanosoma congolense TcIL3000_10_1300   methionyl-tRNA synthetase, putative
Trypanosoma cruzi TcCLB.509247.50   methionyl-tRNA synthetase, putative
Toxoplasma gondii TGME49_289300   methionyl-tRNA synthetase
Theileria parva TP01_1212   methionyl-tRNA synthetase, putative
Theileria parva TP03_0137   methionyl-tRNA synthetase, putative
Trichomonas vaginalis TVAG_266630   methionine-tRNA synthetase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0196   methionyl-tRNA synthetase

Essentiality

PF3D7_1034900 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu1023 Mycobacterium tuberculosis essential nmpdr
Tb927.10.1500 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.1500 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.1500 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.1500 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_Y105E8A.20 Caenorhabditis elegans embryonic lethal wormbase
TGME49_289300 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • plasmo Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes. Bushell, Ellen, et al. "Functional profiling of a Plasmodium genome reveals an abundance of essential genes." Cell 170.2 (2017): 260-272.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • sidik A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes. Sidik, Saima M., et al. "A genome-wide CRISPR screen in toxoplasma identifies essential apicomplexan genes." Cell 166.6 (2016): 1423-1435.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • goodall The Essential Genome of Escherichia coli K-12 (Transposon directed high-throughput mutagenesis) Goodall, Emily CA, et al. "The essential genome of Escherichia coli K-12." mBio 9.1 (2018): e02096-17.

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

In TDR Targets, information about phenotypes that are caused by drugs, or by genetic manipulation of cells (e.g. gene knockouts or knockdowns) is manually curated from the literature. These descriptions help to describe the potential of the target for drug development. If no information is available for this gene or if the information is incomplete, this may mean that i) the papers containing this information either appeared after the curation effort for this organism was carried out or they were inadvertently missed by curators; or that ii) the curation effort for this organism has not yet started.

In any case, if you have information about papers containing relevant validation data for this target, please contact us.

Annotated validation

No validation data for this target

Associated compounds / Druggability

Druggability index (range: 0 to 1): 0.7

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Staphylococcus aureus subsp. aureus MW2 Methionyl-tRNA synthetase Compounds References
Trypanosoma brucei methionyl-tRNA synthetase, putative Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0395 0.4382 1
0.0406 0.2744 1
0.0066 0.3372 1
0.006 0.3565 0.7103
0.0066 0.3397 1
0.0066 0.3754 1
0.0127 1 1
0.0033 0.511 0.5
0.0107 0.2638 1
0.0062 1 0.5
0.0057 0.269 1
0.006 1 0.5
0.0066 1 0.5
0.0066 0.2954 1
0.0228 0.2578 1
0.0229 0.366 1
0.0066 1 0.5
0.04 0.3878 1
0.0066 0.5 0.5
0.0066 1 0.5
0.0043 0.4732 1
0.0054 0.6868 1
0.0066 0.2793 1
0.0561 0.2958 1
0.0066 0.8402 1
0.0066 0.4543 1
0.0059 0.3533 1
0.0057 0.269 1
0.0057 0.269 1
0.0062 1 0.5
0.0276 0.3174 1
0.0066 0.3754 1
0.0066 0.2527 1
0.0286 0.3697 1
0.0147 0.4261 1
0.0066 0.715 0.5
0.0066 0.4211 1
0.0066 1 0.5
0.0066 1 1
0.0123 0.3604 1
0.0066 0.3784 1
0.0063 0.3315 0.7203
0.0355 0.4047 1
0.0066 1 1
0.0066 1 1
0.0471 0.3286 1
0.0066 1 0.5
0.0066 0.3784 1
0.0066 0.3784 1
0.012 0.2932 1
0.0066 0.3455 1
0.0458 0.4264 1
0.0062 1 1
0.0453 0.3976 1
0.0033 0.4906 0.5
0.0264 0.3693 1
0.0053 0.4211 1
0.0154 0.4261 1
0.0066 0.8556 1
0.0063 0.3315 0.7203
0.0057 1 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier PF3D7_1034900 (Plasmodium falciparum), methionine--tRNA ligase
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