Detailed view for Tb927.11.9170

Basic information

TDR Targets ID: 19899
Trypanosoma brucei, DNA topoisomerase III, putative

Source Database / ID:  TriTrypDB  GeneDB

pI: 8.2049 | Length (AA): 841 | MW (Da): 93689 | 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

PF01131   DNA topoisomerase
PF01751   Toprim domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005694   chromosome  
GO:0003677   DNA binding  
GO:0003676   nucleic acid binding  
GO:0003917   DNA topoisomerase type I activity  
GO:0003916   DNA topoisomerase activity  
GO:0006304   DNA modification  
GO:0006268   DNA unwinding during replication  
GO:0006265   DNA topological change  
GO:0006259   DNA metabolic process  

Metabolic Pathways

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
2 605 4cgy (A) 33 639 35.00 0 1 1.20289 -0.73
2 602 5gvc (A) 1 612 51.00 0 1 1.38803 -0.9
584 670 1a6a (B) 29 121 33.00 0.83 0.06 0.0678483 1.75
810 840 1x6e (A) 32 63 10.00 0.66 0 0.170261 -0.96

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_129147)

Species Accession Gene Product
Arabidopsis thaliana AT2G32000   DNA topoisomerase, type IA, core
Babesia bovis BBOV_II000360   DNA topoisomerase, putative
Brugia malayi Bm1_24915   DNA topoisomerase III beta-1
Caenorhabditis elegans CELE_Y48C3A.14   Protein Y48C3A.14, isoform D
Cryptosporidium hominis Chro.60278   DNA topoisomerase III beta-1
Cryptosporidium parvum cgd6_2390   DNA topoisomerase III beta-1, putative
Drosophila melanogaster Dmel_CG3458   Topoisomerase 3beta
Echinococcus granulosus EgrG_000718300   DNA topoisomerase 3 beta 1
Entamoeba histolytica EHI_042880   DNA topoisomerase III, putative
Echinococcus multilocularis EmuJ_000718300   DNA topoisomerase 3 beta 1
Giardia lamblia GL50803_15190   DNA topoisomerase III
Homo sapiens ENSG00000100038   topoisomerase (DNA) III beta
Leishmania braziliensis LbrM.28.1950   DNA topoisomerase III, putative
Leishmania donovani LdBPK_281900.1   DNA topoisomerase III, putative
Leishmania infantum LinJ.28.1900   DNA topoisomerase III, putative
Leishmania major LmjF.28.1780   DNA topoisomerase III, putative
Leishmania mexicana LmxM.28.1780   DNA topoisomerase III, putative
Loa Loa (eye worm) LOAG_06591   DNA topoisomerase III beta-1
Mus musculus ENSMUSG00000022779   topoisomerase (DNA) III beta
Neospora caninum NCLIV_040590   DNA topoisomerase (EC 5.99.1.2), related
Oryza sativa 4347482   Os09g0500600
Onchocerca volvulus OVOC10269  
Schistosoma japonicum Sjp_0097620   expressed protein
Schistosoma japonicum Sjp_0045500   ko:K03165 DNA topoisomerase III, putative
Schistosoma mansoni Smp_169790   prokaryotic DNA topoisomerase
Schmidtea mediterranea mk4.000116.05   DNA topoisomerase 3-beta-1
Schmidtea mediterranea mk4.000116.04  
Trypanosoma brucei gambiense Tbg972.11.10250   DNA topoisomerase III, putative
Trypanosoma brucei Tb927.11.9170   DNA topoisomerase III, putative
Trypanosoma congolense TcIL3000.11.9530   DNA topoisomerase III, putative
Trypanosoma cruzi TcCLB.510901.100   DNA topoisomerase III, putative

Essentiality

Tb927.11.9170 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.01.0910 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.01.0910 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb11.01.0910 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.01.0910 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

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 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 procyclic forms . References: 21363968
cell proliferation (GO:0008283) decreased (PATO:0000468) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: decreased cell proliferation (significant loss 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
Bacillus subtilis (strain 168) DNA topoisomerase III 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
0.116 0.9986 1
0.0074 1 1
0.05 1 1
0.0626 0.7111 1
0.0953 0.861 1
0.0123 1 1
0.0621 0.723 1
0.1104 1 1
0.0695 0.793 1
0.034 1 1
0.0074 1 1
0.0711 0.5076 0.5743
0.0621 0.723 1
0.0763 0.859 1
0.1151 0.6468 0.6465
0.0683 0.4293 1
0.0145 1 1
0.0074 0.2525 1
0.0711 0.5076 0.5743
0.0626 0.7111 1
0.0711 0.5076 0.5743
0.0434 0.9969 1
0.1211 0.3401 1
0.0698 0.7726 0.8044
0.0763 0.859 1
0.0555 0.8683 1
0.0698 0.7726 0.8044
0.0621 0.723 1
0.0619 1 1
0.0183 0.7942 1
0.1121 0.6377 1
0.0711 0.5076 0.5743

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

22 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 Tb927.11.9170 (Trypanosoma brucei), DNA topoisomerase III, putative
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