Detailed view for Tb927.9.10440

Basic information

TDR Targets ID: 18425
Trypanosoma brucei, DNA polymerase epsilon catalytic subunit, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.6952 | Length (AA): 2240 | MW (Da): 254337 | Paralog Number: 0

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

Druggability Group : DG3

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

PF00136   DNA polymerase family B
PF03104   DNA polymerase family B, exonuclease domain
PF08490   Domain of unknown function (DUF1744)

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0008622   epsilon DNA polymerase complex  
GO:0005634   nucleus  
GO:0003887   DNA-directed DNA polymerase activity  
GO:0003677   DNA binding  
GO:0003676   nucleic acid binding  
GO:0000166   nucleotide binding  
GO:0008270   zinc ion binding  
GO:0006281   DNA repair  
GO:0006261   DNA-dependent DNA replication  
GO:0006260   DNA replication  

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
9 1222 4m8o (A) 57 1186 51.00 0 1 1.01012 0.05

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 60-80% percentile Procyclic. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile 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_127942)

Species Accession Gene Product
Arabidopsis thaliana AT2G27120   DNA polymerase epsilon catalytic subunit B
Arabidopsis thaliana AT1G08260   DNA polymerase epsilon catalytic subunit A
Babesia bovis BBOV_III009080   DNA polymerase family B, exonuclease domain containing protein
Brugia malayi Bm1_41890   DNA polymerase family B, exonuclease domain containing protein
Candida albicans CaO19.9901   DNA polymerase II (epsilon) large subunit
Candida albicans CaO19.2365   DNA polymerase II (epsilon) large subunit
Caenorhabditis elegans CELE_F33H2.5   Protein F33H2.5
Cryptosporidium hominis Chro.80147   DNA polymerase epsilon catalytic subunit -related
Cryptosporidium parvum cgd8_1240   DNA polymerase epsilon catalytic subunit
Dictyostelium discoideum DDB_G0283189   hypothetical protein
Drosophila melanogaster Dmel_CG6768   DNA polymerase epsilon
Echinococcus granulosus EgrG_000500500   zinc transporter ZIP11
Echinococcus granulosus EgrG_000500400   dna polymerase epsilon catalytic subunit a
Echinococcus multilocularis EmuJ_000500400   dna polymerase epsilon catalytic subunit a
Echinococcus multilocularis EmuJ_000500500   zinc transporter ZIP11
Giardia lamblia GL50803_23064   DNA polymerase epsilon, catalytic subunit
Homo sapiens ENSG00000177084   polymerase (DNA directed), epsilon, catalytic subunit
Leishmania braziliensis LbrM.34.4340   DNA polymerase epsilon catalytic subunit, putative
Leishmania donovani LdBPK_354430.1   DNA polymerase epsilon catalytic subunit, putative
Leishmania infantum LinJ.35.4430   DNA polymerase epsilon catalytic subunit, putative
Leishmania major LmjF.35.4360   DNA polymerase epsilon catalytic subunit, putative
Leishmania mexicana LmxM.34.4360   DNA polymerase epsilon catalytic subunit, putative
Loa Loa (eye worm) LOAG_13456   DNA polymerase epsilon catalytic subunit
Loa Loa (eye worm) LOAG_05580   hypothetical protein
Loa Loa (eye worm) LOAG_08996   DNA polymerase epsilon catalytic subunit
Mus musculus ENSMUSG00000007080   polymerase (DNA directed), epsilon
Neospora caninum NCLIV_010380   DNA polymerase (EC 2.7.7.7), related
Oryza sativa 4329458   Os02g0511900
Onchocerca volvulus OVOC1597   DNA polymerase epsilon catalytic subunit A homolog
Plasmodium berghei PBANKA_1129100   DNA polymerase epsilon catalytic subunit A, putative
Plasmodium falciparum PF3D7_0630300   DNA polymerase epsilon catalytic subunit A, putative
Plasmodium knowlesi PKNH_1119200   DNA polymerase epsilon catalytic subunit A, putative
Plasmodium vivax PVX_114615   DNA polymerase epsilon, catalytic subunit a, putative
Plasmodium yoelii PY06086   Unknown protein
Plasmodium yoelii PY05353   DNA polymerase epsilon catalytic subunit-related
Saccharomyces cerevisiae YNL262W   Pol2p
Schistosoma japonicum Sjp_0086300   ko:K02324 DNA polymerase epsilon subunit 1, putative
Schistosoma japonicum Sjp_0027070   DNA polymerase epsilon catalytic subunit A, putative
Schistosoma mansoni Smp_146170   DNA polymerase epsilon catalytic subunit
Schmidtea mediterranea mk4.016866.02  
Schmidtea mediterranea mk4.016866.03   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.016866.04  
Schmidtea mediterranea mk4.000561.11  
Schmidtea mediterranea mk4.021430.00   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.021430.01  
Schmidtea mediterranea mk4.013086.01   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.020407.00  
Schmidtea mediterranea mk4.010099.00   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.001715.07  
Schmidtea mediterranea mk4.010670.02   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.017493.00  
Schmidtea mediterranea mk4.016932.00  
Schmidtea mediterranea mk4.000561.14  
Schmidtea mediterranea mk4.000561.15  
Schmidtea mediterranea mk4.000561.12   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.029523.01   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.043000.00   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.000546.24   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.000561.13   DNA polymerase epsilon catalytic subunit A
Schmidtea mediterranea mk4.000561.16   DNA polymerase epsilon catalytic subunit A
Trypanosoma brucei gambiense Tbg972.9.6060   DNA polymerase epsilon catalytic subunit, putative
Trypanosoma brucei Tb927.9.10440   DNA polymerase epsilon catalytic subunit, putative
Trypanosoma congolense TcIL3000_9_3980   DNA polymerase epsilon catalytic subunit, putative
Trypanosoma cruzi TcCLB.506147.180   DNA polymerase epsilon catalytic subunit, putative
Trypanosoma cruzi TcCLB.510733.60   DNA polymerase epsilon catalytic subunit, putative
Toxoplasma gondii TGME49_319860   DNA polymerase family B protein
Theileria parva TP04_0814   DNA polymerase epsilon, catalytic subunit A, putative
Theileria parva TP04_0813   DNA polymerase epsilon, catalytic subunit A, putative
Trichomonas vaginalis TVAG_453570   conserved hypothetical protein
Trichomonas vaginalis TVAG_197030   conserved hypothetical protein

Essentiality

Tb927.9.10440 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb09.211.1820 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb09.211.1820 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb09.211.1820 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb09.211.1820 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F33H2.5 Caenorhabditis elegans embryonic lethal wormbase
CELE_F33H2.5 Caenorhabditis elegans sterile wormbase
YNL262W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1129100 Plasmodium berghei Essential plasmo
TGME49_319860 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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
  • 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.
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) decreased (PATO:0000468) 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: decreased cell proliferation (significant loss of fitness) in bloodstream forms (stage 6 days). 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): 0.1

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Non orthologous druggable targets
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
0.0023 1 0.5
0.0334 0.266 0.266
0.0147 0.2972 0.2972
0.0147 0.2972 0.2972
0.0473 0.2924 0.2924
0.0521 0.296 0.296
0.0051 0.2561 0
0.0473 0.2924 0.2924
0.0148 0.335 0.3207
0.0662 0.254 0
0.0856 0.3223 0.3219
0.0334 0.266 0.266
0.0818 0.3027 0.3027
0.0129 0.2522 0.3138
0.0473 0.2924 0.2924
0.0294 0.3069 0.3069
0.021 0.3148 0.3072
0.057 0.2753 0.3329
0.0856 0.3223 0.3219
0.0202 0.2808 0
0.0341 0.2867 0.2867
0.08 0.2545 0
0.0129 0.2965 0.3207
0.0818 0.3027 0.3027
0.0856 0.3223 0.3219
0.0856 0.3223 0.3219

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.

User comments

No user comments are available for this gene. Log in to add comments, or register.

Enter your comment

User ()
Gene identifier Tb927.9.10440 (Trypanosoma brucei), DNA polymerase epsilon catalytic subunit, putative
Title for this comment
Comment