Detailed view for TGME49_263430

Basic information

TDR Targets ID: 263471
Toxoplasma gondii, 3-hydroxyisobutyrate dehydrogenase
Source Database / ID:  ToxoDB 

pI: 7.4147 | Length (AA): 320 | MW (Da): 34160 | Paralog Number: 1

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

Druggability Group : DG5

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

PF03446   NAD binding domain of 6-phosphogluconate dehydrogenase
PF14833   NAD-binding of NADP-dependent 3-hydroxyisobutyrate dehydrogenase

Gene Ontology

Mouse over links to read term descriptions.
GO:0004616   phosphogluconate dehydrogenase (decarboxylating) activity  
GO:0051287   NAD binding  
GO:0050662   coenzyme binding  
GO:0016491   oxidoreductase activity  
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0055114   oxidation reduction  
GO:0008152   metabolic process  
GO:0006098   pentose-phosphate shunt  

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
24 310 4dll (A) 29 313 35.00 0 1 1.41507 -0.98
25 306 3ws7 (A) 0 280 42.00 0.000000037 1 1.47655 -1.07
27 311 3doj (A) 1 285 31.00 0.000000000006 1 1.39593 -1.17
28 319 2cvz (A) 3 289 28.00 0.0000043 1 1.2668 -0.16

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 VEG Tachyzoite, ME49 Tachyzoite. Gregory
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile ME49 Bradyzoite. Sibley/Greg
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile ME49 merozoite. Hehl AB
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile ME49 Oocyst. Fritz HM
Show/Hide expression data references
  • Gregory ToxoDB
  • Sibley/Greg ToxoDB
  • Hehl AB Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-overlapping gene families to attach, invade, and replicate within feline enterocytes.
  • Fritz HM Transcriptomic analysis of toxoplasma development reveals many novel functions and structures specific to sporozoites and oocysts.

Orthologs

Ortholog group members (OG5_126809)

Species Accession Gene Product
Arabidopsis thaliana AT4G29120   6-phosphogluconate dehydrogenase family protein
Arabidopsis thaliana AT3G25530   gamma-hydroxybutyrate dehydrogenase
Arabidopsis thaliana AT4G20930   probable 3-hydroxyisobutyrate dehydrogenase
Arabidopsis thaliana AT1G17650   glyoxylate reductase 2
Candida albicans CaO19.5565   match to NAD binding domain of 6-phosphogluconate dehydrogenase (pentose-phosphate shunt pathway)
Candida albicans CaO19.13011   match to NAD binding domain of 6-phosphogluconate dehydrogenase (pentose-phosphate shunt pathway)
Caenorhabditis elegans CELE_B0250.5   Protein B0250.5
Dictyostelium discoideum DDB_G0292566   3-hydroxyisobutyrate dehydrogenase
Drosophila melanogaster Dmel_CG15093   CG15093 gene product from transcript CG15093-RB
Drosophila melanogaster Dmel_CG4747   CG4747 gene product from transcript CG4747-RB
Escherichia coli b3125   tartronate semialdehyde reductase
Escherichia coli b3882   gamma-hydroxybutyrate dehydrogenase, NADH-dependent
Escherichia coli b0509   tartronate semialdehyde reductase, NADH-dependent
Escherichia coli b2736   putative dehydrogenase
Homo sapiens ENSG00000106049   3-hydroxyisobutyrate dehydrogenase
Homo sapiens ENSG00000140632   glyoxylate reductase 1 homolog (Arabidopsis)
Leishmania braziliensis LbrM.30.0180   2-hydroxy-3-oxopropionate reductase, putative
Leishmania donovani LdBPK_300170.1   2-hydroxy-3-oxopropionate reductase, putative
Leishmania infantum LinJ.30.0170   2-hydroxy-3-oxopropionate reductase, putative
Leishmania major LmjF.30.0180   2-hydroxy-3-oxopropionate reductase, putative
Leishmania mexicana LmxM.29.0180   2-hydroxy-3-oxopropionate reductase, putative
Mus musculus ENSMUSG00000022536   glyoxylate reductase 1 homolog (Arabidopsis)
Mus musculus ENSMUSG00000029776   3-hydroxyisobutyrate dehydrogenase
Mycobacterium tuberculosis Rv0751c   Probable 3-hydroxyisobutyrate dehydrogenase MmsB (hibadh)
Mycobacterium tuberculosis Rv0770   Probable dehydrogenase/reductase
Mycobacterium ulcerans MUL_0835   3-hydroxyisobutyrate dehydrogenase
Neospora caninum NCLIV_034890   3-hydroxyisobutyrate dehydrogenase, putative
Neospora caninum NCLIV_024500   NAD binding domain of 6-phosphogluconate dehydrogenase, putative
Oryza sativa 4329690   Os02g0562700
Oryza sativa 9270569   Os02g0248100
Oryza sativa 4326545   Os01g0742300
Oryza sativa 4326312   Os01g0574600
Oryza sativa 9268115   Os06g0677400
Schmidtea mediterranea mk4.006913.00   3-hydroxyisobutyrate dehydrogenase, mitochondrial
Schmidtea mediterranea mk4.064011.04  
Trypanosoma brucei gambiense Tbg972.6.1240   2-hydroxy-3-oxopropionate reductase, putative
Trypanosoma brucei Tb927.6.1570   2-hydroxy-3-oxopropionate reductase, putative
Trypanosoma congolense TcIL3000_0_01600   NAD binding domain of 6-phosphogluconate dehydrogenase/NAD-binding of NADP-dependent 3-hydroxyisobutyrate dehydrogenase, putativ
Trypanosoma congolense TcIL3000_0_16560   2-hydroxy-3-oxopropionate reductase, putative
Trypanosoma congolense TcIL3000_6_1070   2-hydroxy-3-oxopropionate reductase, putative
Trypanosoma cruzi TcCLB.505807.180   2-hydroxy-3-oxopropionate reductase, putative
Trypanosoma cruzi TcCLB.507017.40   2-hydroxy-3-oxopropionate reductase, putative
Toxoplasma gondii TGME49_263430   3-hydroxyisobutyrate dehydrogenase
Toxoplasma gondii TGME49_272410   phosphogluconate dehydrogenase (decarboxylating), NAD binding domain-containing protein

Essentiality

TGME49_263430 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu765 Mycobacterium tuberculosis non-essential nmpdr
mtu785 Mycobacterium tuberculosis non-essential nmpdr
Tb927.6.1570 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.6.1570 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.6.1570 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.6.1570 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b0509 Escherichia coli non-essential goodall
b2736 Escherichia coli non-essential goodall
b3125 Escherichia coli non-essential goodall
b3882 Escherichia coli non-essential goodall
TGME49_272410 Toxoplasma gondii Probably non-essential sidik
TGME49_263430 this record 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
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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

No literature references available for this target.

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Gene identifier TGME49_263430 (Toxoplasma gondii), 3-hydroxyisobutyrate dehydrogenase
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