Detailed view for Tb927.10.4000

Basic information

TDR Targets ID: 16286
Trypanosoma brucei, methylglutaconyl-CoA hydratase, mitochondrial precursor, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.7608 | Length (AA): 277 | MW (Da): 29196 | Paralog Number: 0

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

Druggability Group : DG2

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

PF00378   Enoyl-CoA hydratase/isomerase

Gene Ontology

Mouse over links to read term descriptions.
GO:0003824   catalytic activity  
GO:0008152   metabolic process  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in 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
4 277 3g64 (A) 2 275 26.00 0.000000048 1 1.28507 0.17
21 277 3kqf (A) 7 262 44.00 0.000000097 1 1.4917 -0.51
23 277 1hzd (A) 82 339 41.00 0 1 1.44278 -0.44
23 249 2a7k (A) 3 228 24.00 0 1 1.21379 -0.75

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. Siegel TN
Upregulation Percent Ranking Stage Dataset
Lower 20-40% 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_128987)

Species Accession Gene Product
Arabidopsis thaliana AT4G16800   ATP-dependent caseinolytic (Clp) protease/crotonase family protein
Caenorhabditis elegans CELE_F56B3.5   Protein ECH-5
Dictyostelium discoideum DDB_G0289471   enoyl-CoA hydratase/isomerase domain-containing protein
Drosophila melanogaster Dmel_CG8778   CG8778 gene product from transcript CG8778-RA
Homo sapiens ENSG00000148090   AU RNA binding protein/enoyl-CoA hydratase
Homo sapiens ENSG00000121310   enoyl CoA hydratase domain containing 2
Leishmania braziliensis LbrM.34.0400   enoyl-CoA hydratase/isomerase family protein, conserved
Leishmania donovani LdBPK_350360.1   enoyl-CoA hydratase/isomerase family protein, conserved
Leishmania infantum LinJ.35.0360   enoyl-CoA hydratase/isomerase family protein, conserved
Leishmania major LmjF.35.0360   enoyl-CoA hydratase/isomerase family protein, conserved
Leishmania mexicana LmxM.34.0360   enoyl-CoA hydratase/isomerase family protein, conserved
Mus musculus ENSMUSG00000028601   enoyl Coenzyme A hydratase domain containing 2
Mus musculus ENSMUSG00000021460   AU RNA binding protein/enoyl-coenzyme A hydratase
Neospora caninum NCLIV_022740   enoyl-CoA hydratase/isomerase family protein, putative
Oryza sativa 4330183   Os02g0654000
Oryza sativa 4330184   Os02g0654100
Schmidtea mediterranea mk4.005506.00  
Trypanosoma brucei gambiense Tbg972.10.5000   methylglutaconyl-CoA hydratase, mitochondrial precursor, putative
Trypanosoma brucei Tb927.10.4000   methylglutaconyl-CoA hydratase, mitochondrial precursor, putative
Trypanosoma congolense TcIL3000_10_3330   methylglutaconyl-CoA hydratase, mitochondrial precursor, putative
Trypanosoma cruzi TcCLB.510997.40   enoyl-CoA hydratase/isomerase family protein, putative
Trypanosoma cruzi TcCLB.506959.40   enoyl-CoA hydratase/isomerase family protein, putative
Toxoplasma gondii TGME49_202140   enoyl-CoA hydratase/isomerase family protein

Essentiality

Tb927.10.4000 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.4000 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.4000 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.4000 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.4000 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
TGME49_202140 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection

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 3 days). References: 21363968
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 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): 0.2

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

1 literature reference was 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 Tb927.10.4000 (Trypanosoma brucei), methylglutaconyl-CoA hydratase, mitochondrial precursor, putative
Title for this comment
Comment