Detailed view for Rv1878

Basic information

TDR Targets ID: 6150
Mycobacterium tuberculosis, Probable glutamine synthetase GlnA3 (glutamine synthase) (GS-I)
Source Database / ID:  Tuberculist 

pI: 4.8148 | Length (AA): 450 | MW (Da): 46720 | Paralog Number: 4

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

PF00120   Glutamine synthetase, catalytic domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0004356   glutamate-ammonia ligase activity  
GO:0003824   catalytic activity  
GO:0006807   nitrogen compound metabolic process  
GO:0006542   glutamine biosynthetic process  

Structural information

Modbase 3D models:

There are 3 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
7 450 1f52 (A) 2 468 20.00 0 1 1.09697 0.83
15 444 4hpp (A) 3 439 29.00 0 1 1.22446 0.22
104 256 4bax (A) 88 248 33.00 0.0000018 0.33 0.4832 0.77

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 Dormant phase, Dormant phase. hasan 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_127086)

Species Accession Gene Product
Arabidopsis thaliana AT3G53180   nodulin/glutamine synthase-like protein
Cryptosporidium hominis Chro.60524   glutamine synthetase
Cryptosporidium parvum cgd6_4570   glutamate synthetase, possible bacterial origin, beta-grasp+glutamate synthase catalytic domain
Dictyostelium discoideum DDB_G0295755   glutamine synthetase type I
Dictyostelium discoideum DDB_G0280191   amidohydrolase 2 family protein
Dictyostelium discoideum DDB_G0276835   glutamate-ammonia ligase
Escherichia coli b3870   glutamine synthetase
Escherichia coli b1297   glutamate--putrescine ligase
Homo sapiens ENSG00000146166   lengsin, lens protein with glutamine synthetase domain
Mycobacterium leprae ML1631c   PROBABLE GLUTAMINE SYNTHETASE GLNA2 (GLUTAMINE SYNTHASE) (GS-II)
Mycobacterium leprae ML0925   GLUTAMINE SYNTHETASE GLNA1 (GLUTAMINE SYNTHASE) (Glutamate--ammonia ligase 1) (GS-I)
Mus musculus ENSMUSG00000050217   lengsin, lens protein with glutamine synthetase domain
Mycobacterium tuberculosis Rv1879   Conserved hypothetical protein
Mycobacterium tuberculosis Rv2222c   Probable glutamine synthetase GlnA2 (glutamine synthase) (GS-II)
Mycobacterium tuberculosis Rv1878   Probable glutamine synthetase GlnA3 (glutamine synthase) (GS-I)
Mycobacterium tuberculosis Rv2220   Glutamine synthetase GlnA1 (glutamine synthase) (GS-I)
Mycobacterium tuberculosis Rv2860c   Probable glutamine synthetase GlnA4 (glutamine synthase) (GS-II)
Mycobacterium ulcerans MUL_2988   hypothetical protein
Mycobacterium ulcerans MUL_1335   glutamine synthetase
Mycobacterium ulcerans MUL_1340   glutamine synthetase GlnA1
Neospora caninum NCLIV_034160   Glutamine synthetase (EC 6.3.1.2), related
Oryza sativa 4348794   Os10g0456500
Plasmodium berghei PBANKA_0823500   glutamine synthetase, putative
Plasmodium falciparum PF3D7_0922600   glutamine synthetase, putative
Plasmodium knowlesi PKNH_0720600   glutamine synthetase, putative
Plasmodium vivax PVX_099540   glutamine synthetase, putative
Plasmodium yoelii PY04688   glutamine synthetase, putative
Schistosoma japonicum Sjp_0096930   Glutamine synthetase, putative
Schistosoma japonicum Sjp_0318030   expressed protein
Schistosoma japonicum Sjp_0217840   ko:K01915 glutamine synthetase [EC6.3.1.2], putative
Schistosoma mansoni Smp_133770   glutamine synthetase bacteria
Schistosoma mansoni Smp_021460   glutamine synthetase bacteria
Schmidtea mediterranea mk4.012966.02   Lengsin
Schmidtea mediterranea mk4.006404.02   Lengsin
Schmidtea mediterranea mk4.000871.05   Lengsin
Schmidtea mediterranea mk4.024807.00   Lengsin
Schmidtea mediterranea mk4.006224.04   Lengsin
Schmidtea mediterranea mk4.000871.04   Lengsin
Schmidtea mediterranea mk4.023608.00   Lengsin
Toxoplasma gondii TGME49_273490   glutamine synthetase, type I, putative
Wolbachia endosymbiont of Brugia malayi Wbm0275   glutamine synthetase

Essentiality

Rv1878 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1908 this record Mycobacterium tuberculosis non-essential nmpdr
mtu1909 Mycobacterium tuberculosis non-essential nmpdr
b1297 Escherichia coli non-essential goodall
b3870 Escherichia coli non-essential goodall
PBANKA_0823500 Plasmodium berghei Dispensable plasmo
TGME49_273490 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Mycobacterium avium 0   171278  
Annotator: crowther@u.washington.edu. Comment: 2007-12-21. References: 6144381
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium tuberculosis 0   527160   566641  
Annotator: crowther@u.washington.edu. Comment: 2007-12-21. References: 10224282
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium bovis 0  
Annotator: crowther@u.washington.edu. Comment: 2007-12-21. References: 10224282
growth (GO:0040007) normal (PATO:0000461) inferred from in vitro culture assay (ECO:0000182) Mycobacterium smegmatis 0  
Annotator: crowther@u.washington.edu. Comment: 2007-12-21. References: 10224282
growth (GO:0040007) normal (PATO:0000461) inferred from in vitro culture assay (ECO:0000182) Mycobacterium phlei 0  
Annotator: crowther@u.washington.edu. Comment: 2007-12-21. References: 10224282
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium avium 0  
Annotator: crowther@u.washington.edu. Comment: 2007-12-21. References: 10224282
growth (GO:0040007) decreased (PATO:0000468) inferred from animal model system (ECO:0000179) Mycobacterium tuberculosis 0  
Annotator: crowther@u.washington.edu. Comment: 2007-12-26. References: 12496196
weight loss (MP:0001263) decreased (PATO:0000468) host (GO:0018995) inferred from animal model system (ECO:0000179) Mycobacterium tuberculosis 0  
Annotator: crowther@u.washington.edu. Comment: 2007-12-26. References: 12496196
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Mycobacterium tuberculosis 8761   9552   19323   64869   171278  
Annotator: crowther@u.washington.edu. Comment: 2007-12-26. References: 12540549 16973920 7937767
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium tuberculosis 8761   9552   19323   64869  
Annotator: crowther@u.washington.edu. Comment: 2007-12-26. References: 12540549
growth (GO:0040007) normal (PATO:0000461) inferred from loss-of-function mutant phenotype (ECO:0000016) Mycobacterium tuberculosis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-26. References: 16262797
pathogenesis (GO:0009405) normal (PATO:0000461) inferred from animal model system (ECO:0000179) Mycobacterium tuberculosis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-26. References: 17057098

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

Compound Source Reference
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Mycobacterium tuberculosis Probable glutamine synthetase GlnA2 (glutamine synthase) (GS-II) Compounds References
Mycobacterium leprae PROBABLE GLUTAMINE SYNTHETASE GLNA2 (GLUTAMINE SYNTHASE) (GS-II) Compounds References
Escherichia coli glutamine synthetase 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
0.0116 0.283 0.4735
0.0713 0.4875 0.4467
0.0492 0.616 0.6926
0.0321 0.764 0.7628
0.0364 0.4812 0.6346
0.0707 0.7001 0.6999
0.0364 0.3596 0.5305
0.0395 0.4914 0.4914
0.05 0.6816 0.4681
0.0637 0.7674 0.7669
0.0492 0.616 0.6926
0.0492 0.616 0.6926
0.0394 0.4534 0.7026
0.0406 0.4779 0.7227
0.0479 0.6823 0.4705
0.0492 0.616 0.6926
0.0478 0.7025 0.4707
0.0265 0.5663 0.5565

Assayability

Assay information

  • Assay for Glutamine Synthetase (6.3.1.2 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

Reagent availability

No reagent availability information for this target.

Bibliographic References

41 literature references were collected for this gene.

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Gene identifier Rv1878 (Mycobacterium tuberculosis), Probable glutamine synthetase GlnA3 (glutamine synthase) (GS-I)
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