Detailed view for TcCLB.503405.10

Basic information

TDR Targets ID: 46784
Trypanosoma cruzi, glutamine synthetase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.9658 | Length (AA): 421 | MW (Da): 47716 | Paralog Number: 1

Signal peptide: Y | GPI Anchor: N | Predicted trans-membrane segments: 1

Druggability Group : DG5

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
PF03951   Glutamine synthetase, beta-Grasp 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 5 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
38 396 2d3a (A) 5 352 44.00 0 1 1.3 -0.75
39 421 2bvc (A) 4 417 16.00 0 1 0.89 0.16
23 400 2ojw (A) 0 364 44.00 0 1 1.40636 -0.36
44 396 2d3a (A) 12 352 45.00 0 1 1.38318 -0.72
48 410 3fky (A) 21 366 45.00 0 1 1.38973 -0.65

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 epimastigote, metacyclic. Smircich P
Show/Hide expression data references
  • Smircich P Ribosome profiling reveals translation control as a key mechanism generating differential gene expression in Trypanosoma cruzi.

Orthologs

Ortholog group members (OG5_127569)

Species Accession Gene Product
Arabidopsis thaliana AT1G48470   5
Arabidopsis thaliana AT5G37600   glutamine synthetase 1
Arabidopsis thaliana AT3G17820   glutamine synthetase cytosolic isozyme 1-3
Arabidopsis thaliana AT5G16570   4
Arabidopsis thaliana AT5G35630   glutamine synthetase 2
Brugia malayi Bm1_53470   glutamine synthetase
Candida albicans CaO19.646   likely glutamine synthetase similar to S. cerevisiae GLN1 (YPR035W)
Candida albicans CaO19.8260   likely glutamine synthetase similar to S. cerevisiae GLN1 (YPR035W)
Caenorhabditis elegans CELE_Y105C5B.28   Protein GLN-3, isoform C
Drosophila melanogaster Dmel_CG2718   Glutamine synthetase 1
Drosophila melanogaster Dmel_CG1743   Glutamine synthetase 2
Echinococcus granulosus EgrG_000959900   glutamine synthetase
Echinococcus multilocularis EmuJ_000959900   glutamine synthetase
Homo sapiens ENSG00000135821   glutamate-ammonia ligase
Leishmania braziliensis LbrM.06.0350   glutamine synthetase, putative
Leishmania donovani LdBPK_060370.1   glutamine synthetase, putative
Leishmania infantum LinJ.06.0370   glutamine synthetase, putative
Leishmania major LmjF.06.0370   glutamine synthetase, putative
Leishmania mexicana LmxM.06.0370   glutamine synthetase, putative
Mus musculus ENSMUSG00000026473   glutamate-ammonia ligase (glutamine synthetase)
Oryza sativa 4333896   Os03g0712800
Oryza sativa 4337272   Os04g0659100
Oryza sativa 4330649   Os02g0735200
Oryza sativa 4332108   Os03g0223400
Saccharomyces cerevisiae YPR035W   glutamate--ammonia ligase
Schistosoma japonicum Sjp_0041380   ko:K01915 glutamine synthetase [EC6.3.1.2], putative
Schistosoma mansoni Smp_091460   glutamine synthetase 1 2 (glutamate-amonia ligase) (gs)
Schmidtea mediterranea mk4.006595.00   Glutamine synthetase
Schmidtea mediterranea mk4.000905.09   Glutamine synthetase
Schmidtea mediterranea mk4.002580.02  
Schmidtea mediterranea mk4.002580.01   Glutamine synthetase
Schmidtea mediterranea mk4.000905.06   Glutamine synthetase
Schmidtea mediterranea mk4.000905.08  
Schmidtea mediterranea mk4.000905.04   Glutamine synthetase
Schmidtea mediterranea mk4.000876.02  
Trypanosoma brucei gambiense Tbg972.7.5700   glutamine synthetase, putative
Trypanosoma brucei Tb927.7.4970   glutamine synthetase, putative
Trypanosoma congolense TcIL3000_7_4160   glutamine synthetase, putative
Trypanosoma cruzi TcCLB.508175.370   glutamine synthetase, putative
Trypanosoma cruzi TcCLB.503405.10   glutamine synthetase, putative

Essentiality

TcCLB.503405.10 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.7.4970 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.7.4970 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.7.4970 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.7.4970 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
YPR035W Saccharomyces cerevisiae inviable yeastgenome
Show/Hide essentiality data references
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • 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
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.

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): 0.6

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 glutamate-ammonia ligase Compounds References
Zea mays Glutamine synthetase, chloroplastic Compounds References
Oryza sativa Os04g0659100 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
0.07 1 0.5
0.031 0.4026 1
0.0341 0.4386 0.5
0.011 1 1
0.0114893 1 0.5
0.0886 0.985 0.5
0.0223 0.339 0.5
0.0134 0.4807 0.5
0.0203 0.4696 1
0.0892 1 0.5
0.0773 0.9297 1
0.0908 1 0.5
0.0222 0.2678 0.5
0.0888 0.2935 1
0.0687 0.6339 0.5
0.0132 1 0.5
0.0897 1 0.5
0.0753 0.7504 0.5
0.0886 1 0.5
0.0351 0.4388 1
0.0682 1 0.5
0.0769 0.8428 1
0.0469 0.4684 0.4663
0.0358 0.4426 0.5
0.0888 0.2935 1
0.0339 0.884 0.5
0.0558 1 0.5
0.0239 0.8178 0.5
0.0888 0.2935 1
0.0714 1 1
0.0758 1 1
0.0675 1 0.5
0.0524 0.5087 1
0.0402 0.4773 1
0.0369 0.7175 0.7175
0.0244 0.4022 0.3529
0.0369 0.719 0.719
0.068 1 0.5
0.0341 1 0.5
0.0758 1 1
0.0351 0.4388 1
0.0342 0.3884 0.5
0.0726 0.9044 1
0.034 0.4739 0.5
0.0138341 0.354905 1
0.0587 1 0.5
0.0726 0.9044 1
0.0332 1 0.5
0.0888 0.2935 1
0.0676 0.5891 0.5
0.0534 0.327 0.5
0.0891 1 0.5
0.011 0.3551 0.5
0.0267 1 0.5
0.0133 1 0.5
0.0255 0.5742 0.5
0.0753 0.7504 0.5
0.0747 1 0.5
0.0235 1 1
0.0138 0.7067 0.5
0.0707 0.8941 1
0.0682 0.6163 0.5
0.0332 1 0.5
0.0756 1 0.5
0.0226 0.443 1
0.0883 1 0.5
0.0502 1 1
0.0276 0.3108 1
0.0268 0.29 1
0.0769 0.8139 1
0.0339 0.8742 0.5
0.0351 0.4388 1
0.0489 1 1
0.0276 0.6183 1
0.0351 0.4388 1
0.0713 0.8215 1

Assayability

Assay information

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

Reagent availability

  • Tcru000580AAA;
  • Type Source Notes
    soluble recombinant protein Structural Genomics for Pathogenic Protozoa (SGPP) Tcru000580; Recombinant protein: full-length; Source: T cruzi; Glutamine synthetase, catalytic domain, putative ;

Bibliographic References

2 literature references were collected for this gene.

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Gene identifier TcCLB.503405.10 (Trypanosoma cruzi), glutamine synthetase, putative
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