Detailed view for Tb927.10.2560

Basic information

TDR Targets ID: 15274
Trypanosoma brucei, mitochondrial malate dehydrogenase
Source Database / ID:  TriTrypDB  GeneDB

pI: 8.1642 | Length (AA): 318 | MW (Da): 33188 | Paralog Number: 1

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

Druggability Group : DG4

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

PF00056   lactate/malate dehydrogenase, NAD binding domain
PF02866   lactate/malate dehydrogenase, alpha/beta C-terminal domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0016616   oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor  
GO:0030060   L-malate dehydrogenase activity  
GO:0016615   malate dehydrogenase activity  
GO:0016491   oxidoreductase activity  
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0055114   oxidation reduction  
GO:0044262   cellular carbohydrate metabolic process  
GO:0019752   carboxylic acid metabolic process  
GO:0008152   metabolic process  
GO:0006108   malate metabolic process  
GO:0006099   tricarboxylic acid cycle  
GO:0006096   glycolysis  
GO:0005975   carbohydrate metabolic process  

Structural information

Modbase 3D models:

No model available for this protein in Modbase.

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_127145)

Species Accession Gene Product
Arabidopsis thaliana AT3G15020   malate dehydrogenase 2
Arabidopsis thaliana AT3G47520   malate dehydrogenase
Arabidopsis thaliana AT5G09660   peroxisomal NAD-malate dehydrogenase 2
Arabidopsis thaliana AT1G53240   malate dehydrogenase 1
Arabidopsis thaliana AT2G22780   peroxisomal NAD-malate dehydrogenase
Brugia malayi Bm1_46465   Probable malate dehydrogenase, mitochondrial precursor
Candida albicans CaO19.7481   similar to all three S. cerevisiae malate dehydrogenases (YKL085W, YDL078C, YOL126C)
Candida albicans CaO19.12072   similar to S. cerevisiae MDH1 (YKL085W) mitochondrial malate dehydrogenase
Candida albicans CaO19.4602   similar to S. cerevisiae MDH1 (YKL085W) mitochondrial malate dehydrogenase
Candida albicans CaO19.12783   similar to S. cerevisiae MDH3 (YDL078C) peroxisomal malate dehydrogenase
Candida albicans CaO19.5323   similar to S. cerevisiae MDH3 (YDL078C) peroxisomal malate dehydrogenase
Caenorhabditis elegans CELE_F20H11.3   Protein MDH-2
Drosophila melanogaster Dmel_CG7998   Malate dehydrogenase 2
Escherichia coli b3236   malate dehydrogenase, NAD(P)-binding
Echinococcus granulosus EgrG_001185100   malate dehydrogenase
Echinococcus granulosus EgrG_001185000   malate dehydrogenase
Echinococcus multilocularis EmuJ_001185100   malate dehydrogenase
Echinococcus multilocularis EmuJ_001185000   malate dehydrogenase
Homo sapiens ENSG00000146701   malate dehydrogenase 2, NAD (mitochondrial)
Leishmania braziliensis LbrM.20.0010   mitochondrial malate dehydrogenase
Leishmania braziliensis LbrM.19.1020   glycosomal malate dehydrogenase
Leishmania braziliensis LbrM.20.0030   malate dehydrogenase
Leishmania donovani LdBPK_340170.1   mitochondrial malate dehydrogenase
Leishmania donovani LdBPK_340150.1   malate dehydrogenase
Leishmania donovani LdBPK_190710.1   glycosomal malate dehydrogenase
Leishmania infantum LinJ.34.0150   malate dehydrogenase
Leishmania infantum LinJ.34.0170   mitochondrial malate dehydrogenase
Leishmania infantum LinJ.19.0710   glycosomal malate dehydrogenase
Leishmania major LmjF.34.0140   malate dehydrogenase
Leishmania major LmjF.34.0160   mitochondrial malate dehydrogenase
Leishmania major LmjF.19.0710   glycosomal malate dehydrogenase
Leishmania mexicana LmxM.33.0160   malate dehydrogenase, putative
Leishmania mexicana LmxM.19.0710   glycosomal malate dehydrogenase
Leishmania mexicana LmxM.33.0140   malate dehydrogenase
Loa Loa (eye worm) LOAG_02046   malate dehydrogenase
Mus musculus ENSMUSG00000019179   malate dehydrogenase 2, NAD (mitochondrial)
Oryza sativa 4326249   Os01g0649100
Oryza sativa 4339682   Os05g0574400
Oryza sativa 4345657   Os08g0434300
Oryza sativa 4334274   Os03g0773800
Oryza sativa 4352871   Os12g0632700
Oryza sativa 4327423   Os01g0829800
Oryza sativa 4343993   Os07g0630800
Saccharomyces cerevisiae YKL085W   malate dehydrogenase MDH1
Schistosoma japonicum Sjp_0024400   ko:K00026 malate dehydrogenase [EC1.1.1.37B], putative
Schistosoma mansoni Smp_047370   malate dehydrogenase
Schmidtea mediterranea mk4.000346.13   Probable malate dehydrogenase, mitochondrial
Schmidtea mediterranea mk4.000255.00   Probable malate dehydrogenase, mitochondrial
Schmidtea mediterranea mk4.003219.02   Probable malate dehydrogenase, mitochondrial
Schmidtea mediterranea mk4.003441.01  
Trypanosoma brucei gambiense Tbg972.10.18820   glycosomal malate dehydrogenase, putative
Trypanosoma brucei gambiense Tbg972.10.3190   mitochondrial malate dehydrogenase, putative
Trypanosoma brucei Tb927.10.15410   glycosomal malate dehydrogenase
Trypanosoma brucei Tb927.10.2560   mitochondrial malate dehydrogenase
Trypanosoma congolense TcIL3000_10_2190   mitochondrial malate dehydrogenase
Trypanosoma congolense TcIL3000_10_13190   glycosomal malate dehydrogenase, putative
Trypanosoma cruzi TcCLB.506503.69   glycosomal malate dehydrogenase, putative
Trypanosoma cruzi TcCLB.506195.110   malate dehydrogenase, putative
Trypanosoma cruzi TcCLB.507883.109   mitochondrial malate dehydrogenase, putative
Trypanosoma cruzi TcCLB.511293.69   glycosomal malate dehydrogenase, putative

Essentiality

Tb927.10.2560 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.2560 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.10.2560 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.2560 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.2560 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Tb927.10.15410 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.10.15410 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.15410 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.10.15410 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b3236 Escherichia coli non-essential goodall
CELE_F20H11.3 Caenorhabditis elegans embryonic lethal wormbase
CELE_F20H11.3 Caenorhabditis elegans larval arrest wormbase
CELE_F20H11.3 Caenorhabditis elegans slow growth wormbase
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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
  • 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.
  • 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.
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930

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 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 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): 0.5

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
Sus scrofa Malate dehydrogenase mitochondrial Compounds References
Homo sapiens malate dehydrogenase 2, NAD (mitochondrial) Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Plasmodium falciparum malate dehydrogenase 313 aa 26.8% 328 aa Compounds References
Plasmodium falciparum L-lactate dehydrogenase 316 aa 27.5% 284 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0295 0.8 0.7271
0.0344 0.4177 0.9788
0.0178 0.4584 0.7271
0.0086 0.6708 0.7271
0.0707 0.3602 0.7271
0.0086 0.6708 0.7271
0.0232 0.3813 1
0.0284 0.2867 0.2867
0.0102 0.4642 0.7271
0.0695 0.8464 0.9147
0.1384 0.5001 0.7271
0.0086 0.6708 0.7271
0.0119 0.5799 1
0.0295 0.8 0.7271
0.0316 0.3553 1
0.0521 0.6708 0.7271
0.0403 0.5942 0.7271
0.0463 0.6708 0.7271
0.12 0.4871 0.7271
0.1054 0.6934 0.9288
0.0057 0.2973 0.7271
0.0218 0.3195 0.3195
0.0464 0.8098 0.7271
0.0146 1 1
0.0086 0.6708 0.7271
0.0086 0.6708 0.7271
0.1331 0.6685 0.7271
0.0086 0.6708 0.7271
0.0812 0.5417 0.9485
0.084 0.4837 0.9238
0.0493 0.7794 0.91
0.0109 0.3162 1
0.0384 0.7522 0.7271
0.0608 0.8113 0.9157
0.0894 0.5328 0.7271
0.0086 0.6708 0.7271
0.0481 0.345 0.9206
0.0196 0.2947 0.5
0.0134 0.3565 1
0.0153 0.5832 1
0.0326 0.4074 0.9767
0.014 0.2529 0.5
0.0086 0.6708 0.7271
0.0659 0.4878 0.7271
0.0817719 0.414151 1
0.0086 0.6708 0.7271
0.0246 0.3856 1
0.0143 0.3059 0.2984
0.0086 0.6708 0.7271
0.0814413 0.456373 1
0.0108 0.2582 0.5218
0.0125 0.2988 0.3323
0.0109 0.3633 0.5
0.0043 0.4199 0.3964
0.0762 0.3878 0.7271
0.0043 0.2775 1
0.0086 0.6708 0.7271
0.0218 0.3195 0.3195
0.0266 0.3127 0.7271
0.0307 0.3846 1
0.0086 0.6708 0.7271
0.016 0.3265 1
0.0249 0.3023 0.3019
0.0215 0.256 0.4311
0.052 0.3631 0.7271
0.052 0.4217 0.7271
0.0105 0.3654 1
0.0086 0.6708 0.7271
0.0286 0.3074 0.7271
0.0232 0.3813 1
0.1786 0.5439 0.7271
0.0691 0.4632 0.7271
0.0215 0.2525 0.5
0.0173 0.6708 0.7271
0.0086 0.6708 0.7271
0.019 0.2905 0.3904
0.0086 0.6708 0.7271
0.0088 0.4001 0.3957
0.0086 0.6708 0.7271
0.0813 0.4171 0.7271
0.0134 0.2706 0.4299
0.0568 0.4006 0.7271
0.0108 0.4642 0.7271
0.0084 0.6708 0.7271
0.0086 0.6708 0.7271
0.0472 0.5783 0.9065
0.0814413 0.456373 1
0.1229 0.684 0.9314
0.0485 0.2988 0.7271
0.0218 0.3195 0.3195
0.0536 0.7433 0.7271
0.0547 0.3557 0.7271
0.0108 0.4642 0.7271
0.0182 0.2905 0.3904
0.019 0.2816 0.5
0.0251 0.2947 1
0.0086 0.6708 0.7271
0.0216 0.6708 0.7271
0.0232 0.3813 1
0.0702 0.6681 0.9315
0.0086 0.6708 0.7271
0.0251 0.318 0.7271
0.0816 0.5407 0.9487
0.0086 0.6708 0.7271
0.0086 1 1
0.0218 0.3195 0.3195
0.0329 0.4074 0.9767
0.0109 0.3162 1
0.0513 0.4229 0.9702
0.0178 0.3627 0.7271
0.0237 0.6708 0.7271
0.0481 0.345 0.9206
0.0215 0.3147 0.3147
0.0351 0.2974 0.7271
0.069 0.7144 0.7271
0.0764 0.7621 0.7271
0.0182 0.2905 0.3904
0.0155 0.3572 0.5118
0.0108 0.5876 0.7271
0.0086 0.6708 0.7271
0.0347 0.406 0.9781
0.0764 0.7621 0.7271
0.0105 0.371 0.7271
0.1054 0.6934 0.9288
0.0719 0.4023 0.7271
0.0613 0.4427 0.7271
0.0256 0.3172 0.7271
0.1229 0.684 0.9314
0.0234 0.3314 1
0.0292 0.3077 0.7271
0.0386 0.2911 0.7271
0.0256 0.2814 0.2814
0.0547 0.3557 0.7271
0.069 0.7144 0.7271
0.0419 0.5347 0.7271
0.0252 0.7163 0.7799
0.029 0.4098 0.9736
0.0086 0.6708 0.7271
0.0979 0.7361 0.9245
0.0271 0.2879 0.0311
0.0277 0.2695 0.0315
0.0035 0.7271 0.7271
0.0086 0.6708 0.7271
0.0108 0.4642 0.7271
0.0108 0.4642 0.7271
0.0378 0.2901 0.7271
0.0052 0.2847 1
0.0463 0.8166 0.7271
0.0086 0.6708 0.7271
0.0249 0.3023 0.3019
0.0384 0.7522 0.7271
0.0108 0.4642 0.7271
0.0376 0.2904 0.7271
0.0214 0.3373 0.042
0.1523 0.5375 0.7271
0.016 0.3341 0.5
0.0086 0.6708 0.7271
0.0513 0.4229 0.9702
0.0355 1 1
0.0592 0.6625 0.7271
0.0072 0.2592 0.5
0.1022 0.4753 0.7271
0.0379 1 1
0.0134 0.3565 1
0.0493 0.7794 0.91
0.0893 0.3925 0.7271
0.0086 0.6708 0.7271
0.0108 0.4642 0.7271
0.0108 0.4642 0.7271
0.0284 0.302 0.2986
0.0279 0.2963 0.4343
0.0387 0.7269 0.7271
0.0223 0.3042 0.5
0.084 0.4837 0.9238
0.0214 0.3373 0.042

Assayability

Assay information

  • Assay for Malic Dehydrogenase (1.1.1.37 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Trypanosoma brucei ( 1 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Tb927.10.2560 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Trypanosoma brucei ( 1 )

Bibliographic References

67 literature references were collected for this gene.

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Gene identifier Tb927.10.2560 (Trypanosoma brucei), mitochondrial malate dehydrogenase
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