Detailed view for Rv1305

Basic information

TDR Targets ID: 5700
Mycobacterium tuberculosis, Probable ATP synthase C chain AtpE (lipid-binding protein) (dicyclohexylcarbodiimide-binding protein)

Source Database / ID:  Tuberculist 

pI: 4.5441 | Length (AA): 81 | MW (Da): 8055 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 2

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

PF00137   ATP synthase subunit C

Gene Ontology

Mouse over links to read term descriptions.
GO:0033177   proton-transporting two-sector ATPase complex, proton-transporting domain  
GO:0045263   proton-transporting ATP synthase complex, coupling factor F(o)  
GO:0015078   hydrogen ion transmembrane transporter activity  
GO:0015991   ATP hydrolysis coupled proton transport  
GO:0015986   ATP synthesis coupled proton transport  

Metabolic Pathways

Structural information

Modbase 3D models:

There are 2 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
1 79 4v1g (A) 3 83 92.00 0 0.99 1.91911 0.39
5 36 5ft0 (A) 91 124 53.00 0 0.96 0.737362 2.09

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
Lower 0-20% 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_126818)

Species Accession Gene Product
Arabidopsis thaliana ArthMp094   ATPase subunit 9
Arabidopsis thaliana ArthCp009   ATPase III subunit
Arabidopsis thaliana AT2G07671   ATP synthase subunit C family protein
Babesia bovis BBOV_III004620   ATP synthase subunit C family protein
Brugia malayi Bm1_47320   ATP synthase lipid-binding protein, mitochondrial precursor
Candida albicans CaalfMp05   ATPase subunit 9
Caenorhabditis elegans CELE_Y82E9BR.3   Protein Y82E9BR.3
Dictyostelium discoideum DidioMp16   ATPase subunit 9
Drosophila melanogaster Dmel_CG1746   CG1746 gene product from transcript CG1746-RA
Escherichia coli b3737   F0 sector of membrane-bound ATP synthase, subunit c
Echinococcus granulosus EgrG_001064800   mitochondrial ATP synthase subunit 9
Echinococcus multilocularis EmuJ_001064800   mitochondrial ATP synthase subunit 9
Homo sapiens ENSG00000159199   ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9)
Homo sapiens ENSG00000135390   ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C2 (subunit 9)
Homo sapiens 518   ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C3 (subunit 9)
Leishmania braziliensis LbrM.21.0820   ATPase subunit 9, putative
Leishmania braziliensis LbrM.26.0480   ATPase subunit 9, putative
Leishmania donovani LdBPK_210820.1   ATPase subunit 9, putative
Leishmania donovani LdBPK_260450.1   ATPase subunit 9, putative
Leishmania donovani LdBPK_240640.1   ATPase subunit 9, putative
Leishmania infantum LinJ.21.0820   ATPase subunit 9, putative
Leishmania infantum LinJ.24.0640   ATPase subunit 9, putative
Leishmania major LmjF.24.0630   ATPase subunit 9, putative
Leishmania major LmjF.21.0740   ATPase subunit 9, putative
Leishmania major LmjF.26.0460   ATPase subunit 9, putative
Leishmania mexicana LmxM.21.0740   ATPase subunit 9, putative
Leishmania mexicana LmxM.26.0460   ATPase subunit 9, putative
Mycobacterium leprae ML1140   PROBABLE ATP SYNTHASE C CHAIN ATPE (LIPID-BINDING PROTEIN) (DICYCLOHEXYLCARBODIIMIDE-BINDING PROTEIN)
Mus musculus ENSMUSG00000018770   ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C3 (subunit 9)
Mus musculus ENSMUSG00000062683   ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C2 (subunit 9)
Mus musculus 11951   ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C1 (subunit 9)
Mycobacterium tuberculosis Rv1305   Probable ATP synthase C chain AtpE (lipid-binding protein) (dicyclohexylcarbodiimide-binding protein)
Mycobacterium ulcerans MUL_3959   F0F1 ATP synthase subunit C
Neospora caninum NCLIV_065850   ATP synthase lipid-binding protein, putative
Oryza sativa 6450130   ATP synthase F0 subunit 9
Oryza sativa 3131392   ATPase III subunit
Plasmodium berghei PBANKA_0803500   ATP synthase subunit C, putative
Plasmodium falciparum PF3D7_0705900   ATP synthase subunit C, putative
Plasmodium knowlesi PKNH_0104400   ATPase subunit 9, putative
Plasmodium vivax PVX_087835   ATP synthase lipid-binding protein, mitochondrial precursor, putative
Plasmodium yoelii PY03813   ATPase subunit 9, putative
Saccharomyces cerevisiae Q0130   F0 ATP synthase subunit C
Schistosoma japonicum Sjp_0205580   ko:K02128 F-type H+-transporting ATPase subunit c, putative
Schistosoma mansoni Smp_000880.1   ATP synthase lipid-binding protein-like protein
Schistosoma mansoni Smp_000880.2   ATP synthase lipid-binding protein-like protein
Schmidtea mediterranea mk4.000902.01   ATP synthase lipid-binding protein, mitochondrial
Schmidtea mediterranea mk4.009442.00   ATP synthase lipid-binding protein, mitochondrial
Trypanosoma brucei gambiense Tbg972.7.1470   ATPase subunit 9, putative
Trypanosoma brucei gambiense Tbg972.10.1860   ATPase subunit 9, putative
Trypanosoma brucei gambiense Tbg972.11.5960   ATPase subunit 9, putative
Trypanosoma brucei Tb927.11.5280   Mitochondrial ATP synthase subunit c-1
Trypanosoma brucei Tb927.10.1570   Mitochondrial ATP synthase subunit c-2
Trypanosoma brucei Tb927.8.595   hypothetical protein
Trypanosoma brucei Tb927.7.1470   Mitochondrial ATP synthase subunit c-3
Trypanosoma congolense TcIL3000_7_970   ATPase subunit 9, putative
Trypanosoma cruzi TcCLB.507517.60   ATPase subunit 9, putative
Trypanosoma cruzi TcCLB.503579.70   ATPase subunit 9, putative
Trypanosoma cruzi TcCLB.506977.70   ATPase subunit 9, putative
Trypanosoma cruzi TcCLB.504125.40   ATPase subunit 9, putative
Trypanosoma cruzi TcCLB.504131.180   ATPase subunit 9, putative
Toxoplasma gondii TGME49_249720   ATP synthase F0 subunit 9, putative
Theileria parva TP02_0804   ATP synthase F0, subunit C, putative
Wolbachia endosymbiont of Brugia malayi Wbm0459   ATP synthase F0F1 subunit C

Essentiality

Rv1305 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1327 this record Mycobacterium tuberculosis essential nmpdr
Tb927.10.1570 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.10.1570 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.1570 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.10.1570 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
Tb927.7.1470 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.7.1470 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.7.1470 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.7.1470 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Tb11.02.2950 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.2950 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.02.2950 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.2950 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b3737 Escherichia coli non-essential goodall
CELE_Y82E9BR.3 Caenorhabditis elegans embryonic lethal wormbase
CELE_Y82E9BR.3 Caenorhabditis elegans larval arrest wormbase
TGME49_249720 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Mycobacterium phlei 30897   149780   279196   319620   542139  
Annotator: crowther@u.washington.edu. Comment: 2008-01-02. References: 6221756 6231050
acid sensitivity (PATO:0000106) increased sensitivity toward (PATO:0001549) inferred from in vitro culture assay (ECO:0000182) Mycobacterium smegmatis 279196  
Annotator: crowther@u.washington.edu. Comment: 2008-01-02. References: 11283297

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): 0.1


Known modulators for this target

Compound Source Reference
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
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Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Mycobacterium leprae PROBABLE ATP SYNTHASE C CHAIN ATPE (LIPID-BINDING PROTEIN) (DICYCLOHEXYLCARBODIIMIDE-BINDING PROTEIN) Compounds References
Mycobacterium smegmatis Putative uncharacterized protein atpE Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets

Obtained from network model

Ranking Plot


Putative Drugs List


Compound Raw Global Species
0.013 0.4153 1
0.0216 0.4488 0.7663
0.0106 0.2603 1
0.0233 0.2743 0.3171
0.0237 0.4484 0.7658
0.0224 0.4466 0.7558
0.0064 1 0.5
0.025 0.4482 0.7655
0.013 0.4153 1
0.0225 0.4438 0.7656
0.0213 0.4469 0.7664
0.0233 0.4484 0.7659
0.0108 0.2825 1
0.0129 0.4047 1

Assayability

Assay information

  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis ATP synthase
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis H37Rv ATP synthase assessed as reduction in total ATP content at 100 uM after 18 hrs by bead-vortexing settling method

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Rv1305 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Mycobacterium phlei ( 1 )

Bibliographic References

15 literature references were collected for this gene.

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Gene identifier Rv1305 (Mycobacterium tuberculosis), Probable ATP synthase C chain AtpE (lipid-binding protein) (dicyclohexylcarbodiimide-binding protein)
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