Detailed view for Tb927.8.5630

Basic information

TDR Targets ID: 12142
Trypanosoma brucei, dihydroorotase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.8974 | Length (AA): 390 | MW (Da): 42979 | 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

PF01979   Amidohydrolase family

Gene Ontology

Mouse over links to read term descriptions.
GO:0016812   hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides  
GO:0016810   hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds  
GO:0005575   cellular_component  
GO:0016787   hydrolase activity  
GO:0019856   pyrimidine base biosynthetic process  

Metabolic Pathways

Pyrimidine metabolism (KEGG)
Global map (KEGG)

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
2 390 4bjh (A) 50 410 27.00 0 1 1.22954 -0.02
4 389 4c6e (A) 1462 1783 40.00 0 1 1.30104 -0.18
7 387 4yiw (A) 53 408 35.00 0 1 1.26722 -0.07
7 389 3hm7 (A) 57 424 29.00 0 1 1.22835 -0.33

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, 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_127802)

Species Accession Gene Product
Arabidopsis thaliana AT4G04955   allantoinase
Candida albicans CaO19.12909   Allantoinase
Candida albicans CaO19.5454   Allantoinase
Dictyostelium discoideum DDB_G0270162   hypothetical protein
Dictyostelium discoideum DDB_G0282199   hypothetical protein
Drosophila melanogaster Dmel_CG6106   CG6106 gene product from transcript CG6106-RB
Escherichia coli b0512   allantoinase
Leishmania braziliensis LbrM.16.0590   dihydroorotase, putative
Leishmania donovani LdBPK_160580.1   dihydroorotase, putative
Leishmania infantum LinJ.16.0580   dihydroorotase, putative
Leishmania major LmjF.16.0580   dihydroorotase, putative
Leishmania mexicana LmxM.16.0580   dihydroorotase, putative
Mycobacterium leprae ML0533   Probable dihydroorotase PyrC (DHOase)
Mycobacterium tuberculosis Rv1381   Probable dihydroorotase PyrC (DHOase)
Mycobacterium ulcerans MUL_1781   dihydroorotase
Oryza sativa 4337428   Os04g0680400
Saccharomyces cerevisiae YIR027C   allantoinase
Trypanosoma brucei gambiense Tbg972.8.5630   dihydroorotase, putative
Trypanosoma brucei Tb927.8.5630   dihydroorotase, putative
Trypanosoma congolense TcIL3000_8_5400   dihydroorotase, putative
Trypanosoma cruzi TcCLB.508373.20   dihydroorotase, putative
Trypanosoma cruzi TcCLB.506747.20   dihydroorotase, putative
Trypanosoma cruzi TcCLB.507059.70   dihydroorotase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0446   dihydroorotase, PyrC

Essentiality

Tb927.8.5630 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.5630 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.8.5630 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.8.5630 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.5630 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b0512 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • 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
  • 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
  • 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.
  • 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

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) 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): 0.3

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
No druggable targets predicted through repurposing network model

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

3 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 Tb927.8.5630 (Trypanosoma brucei), dihydroorotase, putative
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