Detailed view for Tb927.8.6110

Basic information

TDR Targets ID: 13311
Trypanosoma brucei, 3-hydroxy-3-methylglutaryl-CoA synthase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.4053 | Length (AA): 499 | MW (Da): 54670 | Paralog Number: 0

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

Druggability Group : DG1

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

PF01154   Hydroxymethylglutaryl-coenzyme A synthase N terminal
PF08540   Hydroxymethylglutaryl-coenzyme A synthase C terminal

Gene Ontology

Mouse over links to read term descriptions.
GO:0004421   hydroxymethylglutaryl-CoA synthase activity  
GO:0003824   catalytic activity  
GO:0008299   isoprenoid biosynthetic process  
GO:0008152   metabolic process  

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
34 527 2wya (A) 49 505 18.00 0 1 1.03174 0.52
37 526 2f82 (A) 3 449 23.00 0 1 1.05518 0.41
84 484 3leh (A) 49 348 37.00 0 0.81 0.570934 1.62
367 457 3a5r (A) 288 381 14.00 0.75 0.05 0.282923 -0.06

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_127526)

Species Accession Gene Product
Arabidopsis thaliana AT4G11820   Hydroxymethylglutaryl-CoA synthase
Candida albicans CaO19.7312   3-hydroxy-3-methylglutaryl coenzyme A synthase
Caenorhabditis elegans CELE_F25B4.6   Protein HMGS-1
Dictyostelium discoideum DDB_G0288461   hydroxymethylglutaryl-CoA synthase
Dictyostelium discoideum DDB_G0274871   hypothetical protein
Drosophila melanogaster Dmel_CG4311   HMG Coenzyme A synthase
Echinococcus granulosus EgrG_000283100   hydroxymethylglutaryl coenzyme A synthase
Echinococcus multilocularis EmuJ_000283100   hydroxymethylglutaryl coenzyme A synthase
Giardia lamblia GL50803_13962   Hydroxymethylglutaryl-CoA synthase
Homo sapiens ENSG00000134240   3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)
Homo sapiens ENSG00000112972   3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble)
Leishmania braziliensis LbrM.24.2190   hypothetical protein, conserved
Leishmania donovani LdBPK_242200.1   3-hydroxy-3-methylglutaryl-CoA synthase, putative
Leishmania infantum LinJ.24.2200   hypothetical protein, conserved
Leishmania major LmjF.24.2110   hypothetical protein, conserved
Leishmania mexicana LmxM.24.2110   hypothetical protein, conserved
Loa Loa (eye worm) LOAG_12671   cytosolic 3-hydroxy-3-methylglutaryl-CoA synthase
Mus musculus ENSMUSG00000093930   3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1
Mus musculus ENSMUSG00000027875   3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2
Oryza sativa 4346215   Os08g0544900
Oryza sativa 4331418   Os03g0118800
Oryza sativa 4347614   Os09g0521400
Saccharomyces cerevisiae YML126C   hydroxymethylglutaryl-CoA synthase
Schistosoma mansoni Smp_195010   hydroxymethylglutaryl-CoA synthase
Schmidtea mediterranea mk4.002981.04   Hydroxymethylglutaryl-CoA synthase
Schmidtea mediterranea mk4.002981.02   HMG-CoA synthase
Trypanosoma brucei gambiense Tbg972.8.6150   hypothetical protein, conserved
Trypanosoma brucei Tb927.8.6110   3-hydroxy-3-methylglutaryl-CoA synthase, putative
Trypanosoma congolense TcIL3000_8_5930   3-hydroxy-3-methylglutaryl-CoA synthase, putative
Trypanosoma cruzi TcCLB.511903.40   3-hydroxy-3-methylglutaryl-CoA synthase, putative
Trichomonas vaginalis TVAG_438940   hydroxymethylglutaryl-CoA synthase, putative
Trichomonas vaginalis TVAG_304570   hydroxymethylglutaryl-CoA synthase, putative

Essentiality

Tb927.8.6110 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.6110 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.6110 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.8.6110 this record Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb927.8.6110 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F25B4.6 Caenorhabditis elegans embryonic lethal wormbase
CELE_F25B4.6 Caenorhabditis elegans larval arrest wormbase
CELE_F25B4.6 Caenorhabditis elegans larval lethal wormbase
CELE_F25B4.6 Caenorhabditis elegans slow growth wormbase
CELE_F25B4.6 Caenorhabditis elegans sterile wormbase
YML126C Saccharomyces cerevisiae inviable yeastgenome
Show/Hide essentiality data references
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • 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
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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) 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 3 days). References: 21363968
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) 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): 0.6

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
Rattus norvegicus HMG-CoA synthase 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.

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Gene identifier Tb927.8.6110 (Trypanosoma brucei), 3-hydroxy-3-methylglutaryl-CoA synthase, putative
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