Detailed view for Tb927.10.12370

Basic information

TDR Targets ID: 14927
Trypanosoma brucei, gamma-glutamylcysteine synthetase
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.4619 | Length (AA): 679 | MW (Da): 77468 | Paralog Number: 0

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

Druggability Group : DG4

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

PF03074   Glutamate-cysteine ligase

Gene Ontology

Mouse over links to read term descriptions.
GO:0004357   glutamate-cysteine ligase activity  
GO:0003824   catalytic activity  
GO:0006750   glutathione biosynthetic process  

Structural information

Modbase 3D models:

There are 2 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
2 669 3ig5 (A) 2 662 33.00 0 1 1.1667 -0.08
2 660 3ig5 (A) 2 650 34.00 0 1 1.13604 -0.22

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 Procyclic, Bloodstream Form. Siegel TN
Show/Hide expression data references
  • Siegel TN Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites.

Orthologs

Ortholog group members (OG5_128698)

Species Accession Gene Product
Babesia bovis BBOV_I002580   glutamate-cysteine ligase catalytic subunit, putative
Brugia malayi Bm1_09550   glutamate--cysteine ligase
Candida albicans CaO19.12526   similar to S. cerevisiae GSH1 (YJL101C)
Candida albicans CaO19.5059   similar to S. cerevisiae GSH1 (YJL101C)
Caenorhabditis elegans CELE_F37B12.2   Protein GCS-1
Dictyostelium discoideum DDB_G0284651   gamma glutamylcysteine synthetase
Drosophila melanogaster Dmel_CG2259   Glutamate-cysteine ligase catalytic subunit
Echinococcus granulosus EgrG_000800600   glutamate cysteine ligase catalytic subunit
Echinococcus multilocularis EmuJ_000800600   glutamate cysteine ligase, catalytic subunit
Giardia lamblia GL50803_16001   Glutamate-cysteine ligase
Homo sapiens ENSG00000001084   glutamate-cysteine ligase, catalytic subunit
Leishmania braziliensis LbrM.18.1700   gamma-glutamylcysteine synthetase, putative
Leishmania donovani LdBPK_181660.1   gamma-glutamylcysteine synthetase, putative
Leishmania infantum LinJ.18.1660   gamma-glutamylcysteine synthetase
Leishmania major LmjF.18.1660   gamma-glutamylcysteine synthetase, putative
Leishmania mexicana LmxM.18.1660   gamma-glutamylcysteine synthetase, putative
Loa Loa (eye worm) LOAG_06492   glutamate-cysteine ligase
Mus musculus ENSMUSG00000032350   glutamate-cysteine ligase, catalytic subunit
Neospora caninum NCLIV_032550   gamma-glutamylcysteine synthetase, putative
Plasmodium berghei PBANKA_0819800   gamma-glutamylcysteine synthetase
Plasmodium falciparum PF3D7_0918900   gamma-glutamylcysteine synthetase
Plasmodium knowlesi PKNH_0716900   gamma-glutamylcysteine synthetase, putative
Plasmodium vivax PVX_099360   gamma-glutamylcysteine synthetase, putative
Plasmodium yoelii PY01606   gamma-glutamylcysteine synthetase-related
Saccharomyces cerevisiae YJL101C   glutamate--cysteine ligase
Schistosoma japonicum Sjp_0005910   ko:K01919 glutamate--cysteine ligase [EC6.3.2.2], putative
Schistosoma mansoni Smp_013860   glutamate-cysteine ligase
Schmidtea mediterranea mk4.001058.05   Glutamate-cysteine ligase
Schmidtea mediterranea mk4.001058.04   GlutamateALQ-cysteine ligase
Trypanosoma brucei Tb927.10.12370   gamma-glutamylcysteine synthetase
Trypanosoma congolense TcIL3000_10_10590   gamma-glutamylcysteine synthetase, putative
Trypanosoma cruzi TcCLB.507787.100   gamma-glutamylcysteine synthetase, putative
Trypanosoma cruzi TcCLB.507625.99   gamma-glutamylcysteine synthetase, putative
Toxoplasma gondii TGME49_232590   glutamate-cysteine ligase, catalytic subunit domain-containing protein
Theileria parva TP03_0084   gamma-glutamylcysteine synthetase, putative

Essentiality

Tb927.10.12370 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.12370 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.12370 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.12370 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.12370 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F37B12.2 Caenorhabditis elegans larval lethal wormbase
TGME49_232590 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) single cell organism (CARO:0000064) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 12888552
cell proliferation (GO:0008283) normal (PATO:0000461) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in bloodstream forms (stage 3 days). References: 21363968
cell proliferation (GO:0008283) increased (PATO:0000470) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: increased cell proliferation (significant gain of fitness) in bloodstream forms (stage 6 days). References: 21363968
cell proliferation (GO:0008283) normal (PATO:0000461) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in differentiation of procyclic to bloodstream forms . References: 21363968

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
Plasmodium falciparum gamma-glutamylcysteine synthetase Compounds References
Homo sapiens glutamate-cysteine ligase, catalytic subunit 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
0.0353 0.4807 1
0.0216 0.9355 1
0.0443 0.478 1
0.0298 0.3684 1
0.0353 0.4799 1
0.00988336 0.336337 1
0.0109 0.3809 0.6784
0.00988336 0.336337 1
0.0215 0.9046 1
0.0214 0.8999 1

Assayability

Assay information

  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Trypanosoma brucei ( 5 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Tb927.10.12370 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Trypanosoma brucei ( 5 )

Bibliographic References

8 literature references were collected for this gene.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

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Gene identifier Tb927.10.12370 (Trypanosoma brucei), gamma-glutamylcysteine synthetase
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