Detailed view for Tb927.4.2700

Basic information

TDR Targets ID: 19429
Trypanosoma brucei, Hydroxymethylglutaryl-CoA lyase, mitochondrial, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.3911 | Length (AA): 431 | MW (Da): 47272 | 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

PF00682   HMGL-like

Gene Ontology

Mouse over links to read term descriptions.
GO:0008150   biological_process  
GO:0005575   cellular_component  
GO:0005509   calcium ion binding  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  

Structural information

Modbase 3D models:

There are 5 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
5 320 2ftp (A) 1 292 31.00 0 1 1.11458 -0.57
9 415 5vyw (A) 523 890 15.00 0 1 1.00372 0.45
9 311 1ydn (A) 3 281 30.00 0 1 1.04642 -0.39
336 424 2y5i (A) 13 98 10.00 0 0.08 0.325797 -1.21
339 406 2opo (A) 17 80 39.00 0.046 0.07 0.282173 1.45

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 Bloodstream Form. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Procyclic. 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_128474)

Species Accession Gene Product
Arabidopsis thaliana AT2G26800   Hydroxymethylglutaryl-CoA lyase
Caenorhabditis elegans CELE_Y71G12B.10   Protein Y71G12B.10
Dictyostelium discoideum DDB_G0283813   hydroxymethylglutaryl-CoA lyase
Drosophila melanogaster Dmel_CG10399   CG10399 gene product from transcript CG10399-RB
Homo sapiens ENSG00000146151   3-hydroxymethyl-3-methylglutaryl-CoA lyase-like 1
Homo sapiens ENSG00000117305   3-hydroxymethyl-3-methylglutaryl-CoA lyase
Mus musculus ENSMUSG00000007908   3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase-like 1
Mus musculus ENSMUSG00000028672   3-hydroxy-3-methylglutaryl-Coenzyme A lyase
Mycobacterium ulcerans MUL_2447   hypothetical protein
Neospora caninum NCLIV_020790   Hydroxymethylglutaryl-CoA lyase (EC 4.1.3.4), related
Oryza sativa 4349718   Os11g0137200
Oryza sativa 4326266   Os01g0269000
Oryza sativa 4351434   Os12g0134000
Schistosoma mansoni Smp_185140   hydroxymethylglutaryl-CoA lyase mitochondrial precursor
Schmidtea mediterranea mk4.030480.00   3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic
Schmidtea mediterranea mk4.005979.00   3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic
Schmidtea mediterranea mk4.006656.00  
Trypanosoma brucei gambiense Tbg972.4.2670   hydroxymethylglutaryl-CoA lyase, putative,3- hydroxy-3-methylglutarate-CoA lyase, putative
Trypanosoma brucei Tb927.4.2700   Hydroxymethylglutaryl-CoA lyase, mitochondrial, putative
Trypanosoma congolense TcIL3000_4_2580   Hydroxymethylglutaryl-CoA lyase, mitochondrial, putative
Trypanosoma cruzi TcCLB.508029.10   Hydroxymethylglutaryl-CoA lyase, mitochondrial, putative
Trypanosoma cruzi TcCLB.506635.80   Hydroxymethylglutaryl-CoA lyase, mitochondrial, putative
Trypanosoma cruzi TcCLB.508027.129   Hydroxymethylglutaryl-CoA lyase, mitochondrial, putative
Toxoplasma gondii TGME49_204460   hydroxymethylglutaryl-CoA lyase, putative

Essentiality

Tb927.4.2700 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.4.2700 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.4.2700 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.4.2700 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.4.2700 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_Y71G12B.10 Caenorhabditis elegans embryonic lethal wormbase
TGME49_204460 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924

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 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

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.

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Gene identifier Tb927.4.2700 (Trypanosoma brucei), Hydroxymethylglutaryl-CoA lyase, mitochondrial, putative
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