Detailed view for Tb927.8.3290

Basic information

TDR Targets ID: 18171
Trypanosoma brucei, DNA polymerase zeta catalytic subunit, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 8.3291 | Length (AA): 1958 | MW (Da): 216886 | 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

Gene Ontology

Mouse over links to read term descriptions.
GO:0019985   bypass DNA synthesis  
GO:0016035   zeta 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:0006281   DNA repair  
GO:0006260   DNA replication  

Metabolic Pathways

Global map (KEGG)
DNA replication (KEGG)

Structural information

Modbase 3D models:

There are 3 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
887 1952 5exr (C) 429 1455 16.00 0 1 0.488933 1.44
1127 1712 2xhb (A) 241 751 26.00 0 1 0.399185 0.61
1276 1503 1s5j (A) 481 670 32.00 0.0000018 1 0.104945 1.29

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
Mid 40-60% 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_128651)

Species Accession Gene Product
Arabidopsis thaliana AT1G67500   DNA polymerase zeta subunit
Arabidopsis thaliana AT1G55040   Zn-finger in Ran binding domain-containing protein
Babesia bovis BBOV_III010120   DNA polymerase family B family protein
Brugia malayi Bm1_09315   DNA polymerase family B containing protein
Candida albicans CaO19.7389   similar to N terminus of S. cerevisiae REV3 (YPL167C) DNA polymerase zeta subunit involved in DNA repair
Candida albicans CaO19.7390   similar to C terminus of S. cerevisiae REV3 (YPL167C) DNA polymerase zeta subunit involved in DNA repair
Caenorhabditis elegans CELE_Y37B11A.2   Protein Y37B11A.2
Dictyostelium discoideum DDB_G0271608   DNA polymerase zeta catalytic subunit
Drosophila melanogaster Dmel_CG1925   mutagen-sensitive 205
Echinococcus granulosus EgrG_000149300   DNA polymerase zeta catalytic subunit
Entamoeba histolytica EHI_068010   DNA polymerase zeta catalytic subunit, putative
Echinococcus multilocularis EmuJ_000149300   DNA polymerase zeta catalytic subunit
Homo sapiens ENSG00000009413   REV3-like, polymerase (DNA directed), zeta, catalytic subunit
Leishmania braziliensis LbrM.23.1450   DNA polymerase zeta catalytic subunit, putative
Leishmania donovani LdBPK_231590.1   DNA polymerase zeta catalytic subunit, putative
Leishmania infantum LinJ.23.1590   DNA polymerase zeta catalytic subunit, putative
Leishmania major LmjF.23.1330   DNA polymerase zeta catalytic subunit, putative
Leishmania mexicana LmxM.23.1330   DNA polymerase zeta catalytic subunit, putative
Loa Loa (eye worm) LOAG_13925   hypothetical protein
Loa Loa (eye worm) LOAG_14745   hypothetical protein
Loa Loa (eye worm) LOAG_11287   hypothetical protein
Loa Loa (eye worm) LOAG_12098   hypothetical protein
Mus musculus ENSMUSG00000019841   REV3-like, catalytic subunit of DNA polymerase zeta RAD54 like (S. cerevisiae)
Neospora caninum NCLIV_040490   DNA polymerase (EC 2.7.7.7), related
Oryza sativa 4342984   Os07g0404300
Onchocerca volvulus OVOC2477   DNA polymerase homolog
Saccharomyces cerevisiae YPL167C   Rev3p
Schistosoma japonicum Sjp_0210840   ko:K02350 DNA polymerase zeta subunit, putative
Schistosoma japonicum Sjp_0210830   expressed protein
Schistosoma mansoni Smp_125680   DNA polymerase zeta catalytic subunit
Schmidtea mediterranea mk4.001967.04  
Schmidtea mediterranea mk4.001967.03   DNA polymerase
Schmidtea mediterranea mk4.001967.02   DNA polymerase
Trypanosoma brucei gambiense Tbg972.8.3050   DNA polymerase zeta catalytic subunit, putative
Trypanosoma brucei Tb927.8.3290   DNA polymerase zeta catalytic subunit, putative
Trypanosoma congolense TcIL3000_8_3340   DNA polymerase zeta catalytic subunit, putative
Trypanosoma cruzi TcCLB.509769.130   DNA polymerase zeta catalytic subunit, putative
Toxoplasma gondii TGME49_264670   DNA polymerase family B protein
Trichomonas vaginalis TVAG_328140   DNA polymerase alpha catalytic subunit, putative

Essentiality

Tb927.8.3290 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.3290 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.3290 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.3290 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.3290 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
TGME49_264670 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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
  • 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.
  • 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.
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
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) increased (PATO:0000470) procyclic (PLO:0034) 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 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): 0.5

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

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Gene identifier Tb927.8.3290 (Trypanosoma brucei), DNA polymerase zeta catalytic subunit, putative
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