Detailed view for Rv2614c

Basic information

TDR Targets ID: 9968
Mycobacterium tuberculosis, Probable threonyl-tRNA synthetase ThrS (threonine-tRNA synthetase)(ThrRS) (threonine-tRNA ligase)
Source Database / ID:  Tuberculist 

pI: 5.3524 | Length (AA): 692 | MW (Da): 77122 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | 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

PF00587   tRNA synthetase class II core domain (G, H, P, S and T)
PF03129   Anticodon binding domain
PF07973   Threonyl and Alanyl tRNA synthetase second additional domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005737   cytoplasm  
GO:0000166   nucleotide binding  
GO:0005524   ATP binding  
GO:0004829   threonine-tRNA ligase activity  
GO:0004812   aminoacyl-tRNA ligase activity  
GO:0043039   tRNA aminoacylation  
GO:0006435   threonyl-tRNA aminoacylation  
GO:0006418   tRNA aminoacylation for protein translation  
GO:0006412   translation  

Structural information

Modbase 3D models:

There are 4 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
11 677 1nyr (A) 4 643 38.00 0 1 1.34377 0.18
13 677 1qf6 (A) 4 636 37.00 0 1 1.35088 -0.02
268 678 4hwt (A) 354 750 39.00 0 1 1.08533 -0.66
579 678 1v95 (A) 7 110 14.00 0 0.8 0.423909 -1.13

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
Mid 40-60% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Dormant phase. murphy
Show/Hide expression data references
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.

Orthologs

Ortholog group members (OG5_126764)

Species Accession Gene Product
Arabidopsis thaliana AT5G26830   threonyl-tRNA synthetase
Arabidopsis thaliana AT2G04842   putative threonyl-tRNA synthetase / threonine--tRNA ligase
Babesia bovis BBOV_IV008180   threonyl-tRNA synthetase, putative
Brugia malayi Bm1_09350   threonyl-tRNA synthetase, cytoplasmic
Candida albicans CaO19.5685   similar to S. cerevisiae THS1 (YIL078W) cytoplasmic threonyl-tRNA synthetase
Caenorhabditis elegans CELE_C47D12.6   Protein TARS-1, isoform A
Cryptosporidium hominis Chro.70201   threonyl-tRNA synthetase
Cryptosporidium parvum cgd7_1710   threonyl-tRNA synthetase (RNA binding domain TGS+HxxxH+tRNA synthetase)
Chlamydia trachomatis CT_581   threonine--tRNA ligase
Dictyostelium discoideum DDB_G0274545   threonine-tRNA ligase
Dictyostelium discoideum DDB_G0288267   threonine-tRNA ligase
Drosophila melanogaster Dmel_CG5353   Threonyl-tRNA synthetase
Escherichia coli b1719   threonyl-tRNA synthetase
Echinococcus granulosus EgrG_000375800   Threonyl tRNA synthetase C
Entamoeba histolytica EHI_103730   threonyl-tRNA synthetase, putative
Echinococcus multilocularis EmuJ_000375800   Threonyl tRNA synthetase, C
Giardia lamblia GL50803_13998   Threonyl-tRNA synthetase
Homo sapiens ENSG00000185418   threonyl-tRNA synthetase-like 2
Homo sapiens ENSG00000143374   threonyl-tRNA synthetase 2, mitochondrial (putative)
Homo sapiens ENSG00000113407   threonyl-tRNA synthetase
Leishmania braziliensis LbrM.34.1330   threonyl-tRNA synthetase, putative
Leishmania donovani LdBPK_351420.1   threonyl-tRNA synthetase, putative
Leishmania infantum LinJ.35.1420   threonyl-tRNA synthetase, putative
Leishmania major LmjF.35.1410   threonyl-tRNA synthetase, putative
Leishmania mexicana LmxM.34.1410   threonyl-tRNA synthetase, putative
Loa Loa (eye worm) LOAG_05654   threonyl-tRNA synthetase
Mycobacterium leprae ML0456c   Probable threonyl-tRNA synthetase ThrS (threonine-tRNA synthetase) (ThrRS) (Threonine-tRNA ligase)
Mus musculus ENSMUSG00000030515   threonyl-tRNA synthetase-like 2
Mus musculus ENSMUSG00000022241   threonyl-tRNA synthetase
Mus musculus ENSMUSG00000028107   threonyl-tRNA synthetase 2, mitochondrial (putative)
Mycobacterium tuberculosis Rv2614c   Probable threonyl-tRNA synthetase ThrS (threonine-tRNA synthetase)(ThrRS) (threonine-tRNA ligase)
Mycobacterium ulcerans MUL_3256   threonyl-tRNA synthetase
Neospora caninum NCLIV_060420   hypothetical protein
Oryza sativa 4329580   Os02g0538000
Oryza sativa 4345200   Os08g0295300
Plasmodium berghei PBANKA_0922300   threonine--tRNA ligase, putative
Plasmodium falciparum PF3D7_1126000   threonine--tRNA ligase
Plasmodium knowlesi PKNH_0923900   threonine--tRNA ligase, putative
Plasmodium vivax PVX_091920   threonine--tRNA ligase, putative
Plasmodium yoelii PY06957   threonyl-tRNA synthetase, putative
Saccharomyces cerevisiae YIL078W   threonine--tRNA ligase THS1
Schistosoma japonicum Sjp_0208050   ko:K01868 threonyl-tRNA synthetase [EC6.1.1.3], putative
Schistosoma mansoni Smp_123990   threonyl-tRNA synthetase
Schmidtea mediterranea mk4.012914.01  
Schmidtea mediterranea mk4.016731.00   ThreonineALQ-tRNA ligase, mitochondrial
Schmidtea mediterranea mk4.012914.02   ThreonineALQ-tRNA ligase, cytoplasmic
Schmidtea mediterranea mk4.015477.01   ThreonineALQ-tRNA ligase, cytoplasmic
Schmidtea mediterranea mk4.070403.00  
Schmidtea mediterranea mk4.000044.10   ThreonineALQ-tRNA ligase, cytoplasmic
Schmidtea mediterranea mk4.055923.00  
Schmidtea mediterranea mk4.015477.00   Threonyl-tRNA synthetase
Trypanosoma brucei gambiense Tbg972.5.1490   threonyl-tRNA synthetase, putative
Trypanosoma brucei Tb927.5.1090   threonyl-tRNA synthetase, putative
Trypanosoma congolense TcIL3000_5_860   threonyl-tRNA synthetase, putative
Trypanosoma cruzi TcCLB.511181.80   threonyl-tRNA synthetase, putative
Trypanosoma cruzi TcCLB.508299.80   threonyl-tRNA synthetase, putative
Toxoplasma gondii TGME49_300260   threonyl-tRNA synthetase family protein
Treponema pallidum TP0837   threonyl-tRNA synthetase
Theileria parva TP01_0957   threonyl-tRNA synthetase, putative
Trichomonas vaginalis TVAG_208470   threonyl-tRNA synthetase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0472   threonyl-tRNA synthetase

Essentiality

Rv2614c has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu2659 this record Mycobacterium tuberculosis essential nmpdr
Tb927.5.1090 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.5.1090 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.5.1090 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.5.1090 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b1719 Escherichia coli essential goodall
CELE_C47D12.6 Caenorhabditis elegans embryonic lethal wormbase
CELE_C47D12.6 Caenorhabditis elegans larval arrest wormbase
CELE_C47D12.6 Caenorhabditis elegans larval lethal wormbase
CELE_C47D12.6 Caenorhabditis elegans slow growth wormbase
CELE_C47D12.6 Caenorhabditis elegans sterile wormbase
YIL078W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_0922300 Plasmodium berghei Essential plasmo
TGME49_300260 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • 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
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

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): 0.3

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
Homo sapiens threonyl-tRNA synthetase Compounds References
Phytophthora sojae Threonyl-tRNA synthase Compounds References
Yersinia pestis Threonine--tRNA ligase 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
0.0059 0.8494 0.5
0.0107 0.8494 0.5
0.0059 0.5904 0.5
0.0059 0.8494 0.5
0.0059 0.8494 0.5
0.0155 0.8641 1
0.0059 0.8494 0.5
0.0085 0.8494 0.5
0.0095 0.2557 0.3515
0.0076 0.8494 1
0.0057 0.8494 0.5
0.0213 0.5782 1
0.0059 0.8119 0.5
0.0059 0.8494 0.5
0.0192 0.2528 0.3455
0.0057 0.8494 0.5
0.0059 0.8372 0.5
0.0059 0.7054 0.5
0.0158 0.8434 0.5
0.0052 0.8494 0.5
0.0157 0.3873 1
0.0084 0.8494 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 Rv2614c (Mycobacterium tuberculosis), Probable threonyl-tRNA synthetase ThrS (threonine-tRNA synthetase)(ThrRS) (threonine-tRNA ligase)
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