Detailed view for Tb927.3.2960

Basic information

TDR Targets ID: 18430
Trypanosoma brucei, inosine-adenosine-guanosine-nucleosidehydrolase
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.0623 | Length (AA): 327 | MW (Da): 35848 | 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

PF01156   Inosine-uridine preferring nucleoside hydrolase

Gene Ontology

Mouse over links to read term descriptions.
GO:0005829   cytosol  
GO:0016810   hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds  
GO:0006166   purine ribonucleoside salvage  

Structural information

Modbase 3D models:

There is 1 model calculated for this protein. More info on this model, including the model itself is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
1 327 4i70 (A) 1 327 99.99 0 1 2.2589 -1.98

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:

PDB tag
  • 4I70:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4I71:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4I72:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4I73:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4I74:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4I75:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

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_144830)

Species Accession Gene Product
Leishmania braziliensis LbrM.29.2850   inosine-adenosine-guanosine-nucleoside hydrolase, putative
Leishmania donovani LdBPK_292910.1   inosine-adenosine-guanosine-nucleosidehydrolase, putative
Leishmania infantum LinJ.29.2910   inosine-adenosine-guanosine-nucleoside hydrolase, putative
Leishmania major LmjF.29.2800   inosine-adenosine-guanosine-nucleoside hydrolase, putative
Leishmania mexicana LmxM.08_29.2800  
Trypanosoma brucei gambiense Tbg972.3.3040   inosine-adenosine-guanosine-nucleosidehydrolase,IAG-nucleoside hydrolase
Trypanosoma brucei Tb927.3.2960   inosine-adenosine-guanosine-nucleosidehydrolase
Trypanosoma congolense TcIL3000_3_1870   inosine-adenosine-guanosine-nucleosidehydrolase, putative
Trypanosoma cruzi TcCLB.510315.10   inosine-adenosine-guanosine-nucleosidehydrolase, putative
Trypanosoma cruzi TcCLB.508153.640   inosine-adenosine-guanosine-nucleosidehydrolase, putative

Essentiality

Tb927.3.2960 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.3.2960 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.3.2960 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.3.2960 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.3.2960 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • 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.
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
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 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

  • Validation: inhibited in cell-free system. As observed in: T. b. brucei.Evidence: inferred from specific protein inhibition
  • annotated by: ts4@sanger.ac.uk.
  • References: 9132003

Associated compounds / Druggability

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
Trypanosoma brucei gambiense inosine-adenosine-guanosine-nucleosidehydrolase,IAG-nucleoside hydrolase Compounds References
Trypanosoma cruzi inosine-adenosine-guanosine-nucleosidehydrolase, putative Compounds References
Trypanosoma vivax IAG-nucleoside hydrolase Compounds References
Trypanosoma cruzi inosine-adenosine-guanosine-nucleosidehydrolase, 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
0.0424 0.3048 1
0.0554 0.6216 1
0.0514 1 1
0.0468 0.428 1
0.0573 1 1
0.0728 0.7423 1
0.0573 1 1
0.0462 1 1
0.0504 0.5902 0.5866
0.0864 1 1
0.0907 1 1
0.0424 0.3048 1
0.0405 0.2608 1
0.0514 1 1
0.1027 0.3155 1
0.0514 1 1
0.0573 1 1
0.1027 0.3155 1
0.0485 1 1
0.044 0.5 0.5
0.0825 1 1
0.0573 1 1
0.0433 0.5976 1
0.0465 0.3508 1
0.0504 0.5902 0.5866
0.0504 0.5902 0.5866
0.0504 0.5902 0.5866
0.0424 0.3048 1
0.0477 0.5 0.5
0.0504 0.5902 0.5866
0.1027 0.3155 1
0.0418 1 1

Assayability

Assay information

  • ChEMBL
  • Inhibition of Trypanosoma brucei brucei inosine-adenosine-guanosine nucleoside hydrolase expressed in Escherichia coli
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Trypanosoma brucei ( 1 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Tb927.3.2960 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Trypanosoma brucei ( 1 )

Bibliographic References

13 literature references were collected for this gene.

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Gene identifier Tb927.3.2960 (Trypanosoma brucei), inosine-adenosine-guanosine-nucleosidehydrolase
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