Detailed view for Tb927.11.11680

Basic information

TDR Targets ID: 11519
Trypanosoma brucei, 2-oxoglutarate dehydrogenase E2 component, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 8.1469 | Length (AA): 383 | MW (Da): 41143 | 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

PF00198   2-oxoacid dehydrogenases acyltransferase (catalytic domain)
PF00364   Biotin-requiring enzyme

Gene Ontology

Mouse over links to read term descriptions.
GO:0016746   transferase activity, transferring acyl groups  
GO:0045252   oxoglutarate dehydrogenase complex  
GO:0008415   acyltransferase activity  
GO:0004149   dihydrolipoyllysine-residue succinyltransferase activity  
GO:0008152   metabolic process  
GO:0006099   tricarboxylic acid cycle  

Structural information

Modbase 3D models:

There are 6 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
26 102 1ghj (A) 2 78 45.00 0.00000000018 1 0.765844 -0.23
38 99 2d5d (A) 84 145 31.00 0 1 0.55838 -0.05
104 151 4ke2 (A) 148 195 25.00 0 0.2 0.481826 -1.05
140 380 1b5s (A) 185 425 36.00 0 1 1.10104 -0.3
154 382 1scz (A) 176 404 54.00 0 1 1.30771 -0.78
179 379 4n72 (A) 425 628 38.00 0 1 1.0736 -0.87

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_127362)

Species Accession Gene Product
Arabidopsis thaliana AT4G26910   Dihydrolipoamide succinyltransferase
Arabidopsis thaliana AT5G55070   dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex 1
Babesia bovis BBOV_IV004840   dihydrolipoamide succinyltransferase, putative
Brugia malayi Bm1_34630   dihydrolipoamide succinyltransferase
Brugia malayi Bm1_34625   Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial precursor, puta
Candida albicans CaO19.13545   Dihydrolipoamide S-succinyltransferase
Candida albicans CaO19.6126   Dihydrolipoamide S-succinyltransferase
Caenorhabditis elegans CELE_W02F12.5   Protein DLST-1
Chlamydia trachomatis CT_055   dihydrolipoamide succinyltransferase
Dictyostelium discoideum DDB_G0275029   2-oxoglutarate dehydrogenase E2 component
Drosophila melanogaster Dmel_CG5214   CG5214 gene product from transcript CG5214-RA
Escherichia coli b0727   dihydrolipoyltranssuccinase
Echinococcus granulosus EgrG_000851500   dihydrolipoyllysine residue succinyltransferase
Echinococcus multilocularis EmuJ_000851500   dihydrolipoyllysine residue succinyltransferase
Homo sapiens ENSG00000119689   dihydrolipoamide S-succinyltransferase (E2 component of 2-oxo-glutarate complex)
Leishmania braziliensis LbrM.28.2620   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Leishmania donovani LdBPK_282600.1   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Leishmania infantum LinJ.28.2600   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Leishmania major LmjF.28.2420   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Leishmania mexicana LmxM.28.2420   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Loa Loa (eye worm) LOAG_04620   hypothetical protein
Loa Loa (eye worm) LOAG_04619   hypothetical protein
Mycobacterium leprae ML0861c   Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex SucB
Mus musculus ENSMUSG00000004789   dihydrolipoamide S-succinyltransferase (E2 component of 2-oxo-glutarate complex)
Mycobacterium tuberculosis Rv2215   DlaT, dihydrolipoamide acyltransferase, E2 component of pyruvate dehydrogenase
Mycobacterium ulcerans MUL_3575   dihydrolipoamide acetyltransferase
Neospora caninum NCLIV_061040   hypothetical protein
Oryza sativa 4335689   Os04g0394200
Onchocerca volvulus OVOC4905  
Plasmodium berghei PBANKA_1419100   dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, putative
Plasmodium falciparum PF3D7_1320800   dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex
Plasmodium knowlesi PKNH_1421400   dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, putative
Plasmodium vivax PVX_122850   dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, putative
Plasmodium yoelii PY03521   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Saccharomyces cerevisiae YDR148C   alpha-ketoglutarate dehydrogenase KGD2
Schistosoma japonicum Sjp_0112430   ko:K00658 2-oxoglutarate dehydrogenase E2 component (dihydrolipoamide [EC2.3.1.61], putative
Schistosoma mansoni Smp_104330   dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase
Schmidtea mediterranea mk4.000008.00   Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial
Trypanosoma brucei gambiense Tbg972.11.13100   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Trypanosoma brucei Tb927.11.11680   2-oxoglutarate dehydrogenase E2 component, putative
Trypanosoma congolense TcIL3000.11.12290   2-oxoglutarate dehydrogenase E2 component, putative
Trypanosoma cruzi TcCLB.506025.60   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Trypanosoma cruzi TcCLB.503935.20   2-oxoglutarate dehydrogenase, E2 component, dihydrolipoamide succinyltransferase, putative
Toxoplasma gondii TGME49_219550   dihydrolipoyllysine-residue succinyltransferase component of oxoglutarate dehydrogenase
Theileria parva TP01_0262   dihydrolipoamide succinyltransferase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0108   dihydrolipoamide acyltransferase E2 component

Essentiality

Tb927.11.11680 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.01.3550 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb11.01.3550 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.01.3550 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb11.01.3550 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b0727 Escherichia coli essential goodall
CELE_W02F12.5 Caenorhabditis elegans embryonic lethal wormbase
CELE_W02F12.5 Caenorhabditis elegans larval arrest wormbase
CELE_W02F12.5 Caenorhabditis elegans slow growth wormbase
CELE_W02F12.5 Caenorhabditis elegans sterile wormbase
PBANKA_1419100 Plasmodium berghei Dispensable plasmo
TGME49_219550 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.

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): 0.2

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
Mycobacterium tuberculosis DlaT, dihydrolipoamide acyltransferase, E2 component of pyruvate dehydrogenase Compounds References
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.

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Gene identifier Tb927.11.11680 (Trypanosoma brucei), 2-oxoglutarate dehydrogenase E2 component, putative
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