Detailed view for Rv2332

Basic information

TDR Targets ID: 6460
Mycobacterium tuberculosis, Probable [NAD] dependent malate oxidoreductase Mez (malic enzyme) (NAD-malic enzyme) (malate dehydrogenase (oxaloacetate decarbo
Source Database / ID:  Tuberculist 

pI: 4.9612 | Length (AA): 548 | MW (Da): 59423 | Paralog Number: 0

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

Druggability Group : DG2

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

PF00390   Malic enzyme, N-terminal domain
PF03949   Malic enzyme, NAD binding domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0004471   malate dehydrogenase (decarboxylating) activity  
GO:0051287   NAD binding  
GO:0005488   binding  
GO:0004470   malic enzyme activity  
GO:0003824   catalytic activity  
GO:0055114   oxidation reduction  
GO:0008152   metabolic process  
GO:0006108   malate metabolic process  

Metabolic Pathways

Pyruvate metabolism (KEGG)
Carbon metabolism (KEGG)
Two-component system (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
7 548 3wja (A) 23 560 37.00 0 1 1.48965 -0.89
8 548 1pj3 (A) 24 563 36.00 0 1 1.48183 -0.95
8 548 1gq2 (A) 24 563 37.00 0 1 1.51013 -0.83
8 548 1o0s (A) 38 575 38.00 0 1 1.49183 -0.81

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 Dormant phase, Dormant phase. hasan murphy
Show/Hide expression data references
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.

Orthologs

Ortholog group members (OG5_126753)

Species Accession Gene Product
Arabidopsis thaliana AT5G11670   NADP-dependent malic enzyme 2
Arabidopsis thaliana AT4G00570   NAD-dependent malic enzyme 2
Arabidopsis thaliana AT5G25880   NADP-dependent malic enzyme 3
Arabidopsis thaliana AT2G13560   NAD-dependent malic enzyme 1
Arabidopsis thaliana AT1G79750   NADP-malic enzyme 4
Arabidopsis thaliana AT2G19900   NADP-dependent malic enzyme 1
Brugia malayi Bm1_53540   NAD-dependent malic enzyme, mitochondrial precursor, putative
Brugia malayi Bm1_53260   NAD-dependent malic enzyme, mitochondrial precursor, putative
Candida albicans CaO19.3419   Mitochondrial malic enzyme
Candida albicans CaO19.10923   Mitochondrial malic enzyme
Caenorhabditis elegans CELE_Y48B6A.12   Protein MEN-1
Cryptosporidium hominis Chro.50314   malic enzyme
Cryptosporidium parvum cgd5_750   Mdh; malate dehydrogenase (oxaloacetate-decarboxylating)(NADP+)
Dictyostelium discoideum DDB_G0272524   NADP malic enzyme
Drosophila melanogaster Dmel_CG5889   Malic enzyme b
Drosophila melanogaster Dmel_CG10120   Malic enzyme
Escherichia coli b1479   malate dehydrogenase, (decarboxylating, NAD-requiring) (malic enzyme)
Echinococcus granulosus EgrG_001145700   NADP dependent malic enzyme
Echinococcus granulosus EgrG_000695200   NADP dependent malic enzyme
Echinococcus granulosus EgrG_000645800   NADP dependent malic enzyme
Echinococcus multilocularis EmuJ_001145700   NADP dependent malic enzyme
Echinococcus multilocularis EmuJ_000695200   NADP dependent malic enzyme
Echinococcus multilocularis EmuJ_000645800   NADP dependent malic enzyme
Giardia lamblia GL50803_14285   Malic enzyme
Homo sapiens ENSG00000151376   malic enzyme 3, NADP(+)-dependent, mitochondrial
Homo sapiens 4200   malic enzyme 2, NAD(+)-dependent, mitochondrial
Homo sapiens ENSG00000065833   malic enzyme 1, NADP(+)-dependent, cytosolic
Leishmania braziliensis LbrM.24.0790   malic enzyme, putative
Leishmania braziliensis LbrM.24.0780   malic enzyme
Leishmania donovani LdBPK_240790.1   malic enzyme, putative
Leishmania donovani LdBPK_240780.1   malic enzyme
Leishmania infantum LinJ.24.0780   malic enzyme
Leishmania infantum LinJ.24.0790   malic enzyme, putative
Leishmania major LmjF.24.0770   malic enzyme, putative
Leishmania mexicana LmxM.24.0761   malic enzyme
Leishmania mexicana LmxM.24.0770   malic enzyme, putative
Loa Loa (eye worm) LOAG_12660   NADP-malic enzyme
Mus musculus ENSMUSG00000030621   malic enzyme 3, NADP(+)-dependent, mitochondrial
Mus musculus ENSMUSG00000032418   malic enzyme 1, NADP(+)-dependent, cytosolic
Mus musculus ENSMUSG00000024556   malic enzyme 2, NAD(+)-dependent, mitochondrial
Mycobacterium tuberculosis Rv2332   Probable [NAD] dependent malate oxidoreductase Mez (malic enzyme) (NAD-malic enzyme) (malate dehydrogenase (oxaloacetate decarbo
Mycobacterium ulcerans MUL_1467   malate dehydrogenase
Oryza sativa 4349051   Os10g0503500
Oryza sativa 4338007   Os05g0186300
Oryza sativa 4326769   Os01g0188400
Oryza sativa 4343294   Os07g0496200
Oryza sativa 4324717   Os01g0723400
Oryza sativa 4326552   Os01g0743500
Onchocerca volvulus OVOC10386   Malic enzyme homolog
Onchocerca volvulus OVOC7455   Malic enzyme homolog
Onchocerca volvulus OVOC10388   Malic enzyme homolog
Onchocerca volvulus OVOC10389   Malic enzyme homolog
Saccharomyces cerevisiae YKL029C   malate dehydrogenase (oxaloacetate-decarboxylating)
Schistosoma japonicum Sjp_0109300   NADP-dependent malic enzyme, putative
Schistosoma japonicum Sjp_0111360   NAD-dependent malic enzyme, mitochondrial precursor, putative
Schistosoma japonicum Sjp_0301040   NADP-dependent malic enzyme, putative
Schistosoma japonicum Sjp_0073800   NADP-dependent malic enzyme, putative
Schistosoma mansoni Smp_128360   malic enzyme
Schmidtea mediterranea mk4.023715.00  
Schmidtea mediterranea mk4.013697.01   NAD-dependent malic enzyme, mitochondrial
Schmidtea mediterranea mk4.000163.01   NAD-dependent malic enzyme, mitochondrial
Schmidtea mediterranea mk4.003593.00  
Schmidtea mediterranea mk4.023715.01   Malic enzyme
Schmidtea mediterranea mk4.045088.00  
Schmidtea mediterranea mk4.000717.02   NAD-dependent malic enzyme, mitochondrial
Schmidtea mediterranea mk4.013697.00  
Schmidtea mediterranea mk4.006800.00   NAD-dependent malic enzyme, mitochondrial
Schmidtea mediterranea mk4.013697.02   Malic enzyme
Schmidtea mediterranea mk4.000163.02   NAD-dependent malic enzyme, mitochondrial
Trypanosoma brucei gambiense Tbg972.11.6150   malic enzyme, putative
Trypanosoma brucei gambiense Tbg972.11.6140   malic enzyme, putative
Trypanosoma brucei Tb927.11.5450   malic enzyme
Trypanosoma brucei Tb927.11.5440   NADP-dependent malic enzyme, cytosolic
Trypanosoma congolense TcIL3000.11.5680   malic enzyme
Trypanosoma congolense TcIL3000.11.5690   malic enzyme
Trypanosoma cruzi TcCLB.505183.30   malic enzyme, putative
Trypanosoma cruzi TcCLB.508647.280   malic enzyme
Trypanosoma cruzi TcCLB.505183.20   malic enzyme
Trypanosoma cruzi TcCLB.508647.270   malic enzyme, putative
Trichomonas vaginalis TVAG_183790   malic enzyme, putative
Trichomonas vaginalis TVAG_340290   malic enzyme, putative
Trichomonas vaginalis TVAG_267870   malic enzyme, putative
Trichomonas vaginalis TVAG_238830   malic enzyme, putative
Trichomonas vaginalis TVAG_416100   malic enzyme, putative
Trichomonas vaginalis TVAG_068130   malic enzyme, putative
Trichomonas vaginalis TVAG_412220   malic enzyme, putative

Essentiality

Rv2332 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu2373 this record Mycobacterium tuberculosis non-essential nmpdr
Tb11.02.3120 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.3120 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb11.02.3120 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.3120 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
Tb11.02.3130 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb11.02.3130 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.02.3130 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb11.02.3130 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b1479 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource

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

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
Homo sapiens malic enzyme 1, NADP(+)-dependent, cytosolic Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model

Ranking Plot

No enough druggable targets predicted through repurposing network model to make a plot

Putative Drugs List

Compound Raw Global Species
0.0014 1 0.5

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.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

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Gene identifier Rv2332 (Mycobacterium tuberculosis), Probable [NAD] dependent malate oxidoreductase Mez (malic enzyme) (NAD-malic enzyme) (malate dehydrogenase (oxaloacetate decarbo
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