Detailed view for Tb927.4.4380

Basic information

TDR Targets ID: 15476
Trypanosoma brucei, Pyrophosphate-energized vacuolar membrane proton pump 1
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.0463 | Length (AA): 826 | MW (Da): 85936 | Paralog Number: 1

Signal peptide: Y | GPI Anchor: | Predicted trans-membrane segments: 14

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

PF03030   Inorganic H+ pyrophosphatase

Gene Ontology

Mouse over links to read term descriptions.
GO:1902600   GO:proton transmembrane transport  

GO:0016020   membrane  
GO:0009678   hydrogen-translocating pyrophosphatase activity  
GO:0004427   inorganic diphosphatase activity  
GO:0015992   proton transport  

Metabolic Pathways

Oxidative phosphorylation (KEGG)

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_128905)

Species Accession Gene Product
Arabidopsis thaliana AT1G15690   Pyrophosphate-energized vacuolar membrane proton pump 1
Arabidopsis thaliana AT1G16780   2
Arabidopsis thaliana AT1G78920   pyrophosphate-energized membrane proton pump 2
Leishmania braziliensis LbrM.31.1450   vacuolar-type proton translocating pyrophosphatase 1, putative
Leishmania donovani LdBPK_311240.1   Pyrophosphate-energized vacuolar membrane proton pump 1, putative
Leishmania infantum LinJ.31.1240   vacuolar-type proton translocating pyrophosphatase 1, putative
Leishmania major LmjF.31.1220   vacuolar-type proton translocating pyrophosphatase 1, putative
Leishmania mexicana LmxM.30.1220   vacuolar-type proton translocating pyrophosphatase 1, putative
Neospora caninum NCLIV_064810   hypothetical protein
Oryza sativa 4340298   Os06g0178900
Oryza sativa 4328526   Os02g0184200
Oryza sativa 4331044   Os02g0802500
Oryza sativa 4337864   Os05g0156900
Oryza sativa 4329579   Os02g0537900
Oryza sativa 4326846   Os01g0337500
Oryza sativa 4341645   Os06g0644200
Plasmodium berghei PBANKA_1449800   inorganic pyrophosphatase, putative
Plasmodium berghei PBANKA_1320500   V-type H(+)-translocating pyrophosphatase, putative
Plasmodium falciparum PF3D7_1235200   V-type K+-independent H+-translocating inorganic pyrophosphatase
Plasmodium falciparum PF3D7_1456800   V-type H(+)-translocating pyrophosphatase, putative
Plasmodium knowlesi PKNH_1454900   vacuolar-type H+-translocating inorganic pyrophosphatase, putative
Plasmodium knowlesi PKNH_1225000   V-type H(+)-translocating pyrophosphatase, putative
Plasmodium vivax PVX_117625   V-type H(+)-translocating pyrophosphatase, putative
Plasmodium vivax PVX_100710   vacuolar-type H+ pumping pyrophosphatase, putative
Plasmodium yoelii PY06858   V-type H(+)-translocating pyrophosphatase
Plasmodium yoelii PY00513   vacuolar-type H+ pumping pyrophosphatase-related
Trypanosoma brucei gambiense Tbg972.4.4470   vacuolar-type proton translocating pyrophosphatase 1, putative
Trypanosoma brucei gambiense Tbg972.8.8300   vacuolar-type proton translocating pyrophosphatase 1
Trypanosoma brucei Tb927.8.7980   Pyrophosphate-energized vacuolar membrane proton pump 2, putative
Trypanosoma brucei Tb927.4.4380   Pyrophosphate-energized vacuolar membrane proton pump 1
Trypanosoma congolense TcIL3000_0_60300   vacuolar-type proton translocating pyrophosphatase 1
Trypanosoma cruzi TcCLB.511385.30   vacuolar-type proton translocating pyrophosphatase 1
Trypanosoma cruzi TcCLB.510773.20   Vacuolar proton pyrophosphatase 1, putative
Toxoplasma gondii TGME49_248670   V-type H(+)-translocating pyrophosphatase VP1

Essentiality

Tb927.4.4380 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.7980 Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.7980 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.7980 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.7980 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Tb927.4.4380 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.4.4380 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.4.4380 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.4.4380 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
PBANKA_1320500 Plasmodium berghei Slow plasmo
PBANKA_1449800 Plasmodium berghei Dispensable plasmo
TGME49_248670 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.
  • 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
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • 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.

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

Compound Source Reference
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
Curated by TDRTargets References
Curated by TDRTargets References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Trypanosoma brucei Pyrophosphate-energized vacuolar membrane proton pump 2, putative Compounds References
Trypanosoma brucei gambiense vacuolar-type proton translocating pyrophosphatase 1, putative 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
0.2375 1 1
0.033 1 1
0.0675 0.6663 1
0.0542081 1 1
0.0345 1 1
0.0375 0.9514 1
0.0387 1 1
0.0707 0.5166 1
0.0325 0.3708 0.9871
0.0718 1 1
0.0706 1 1
0.0675 0.6663 1
0.0358 0.3502 0.3477
0.0343 0.2754 0.2752
0.0693 1 1
0.0694 1 1
0.1129 1 1
0.0345 0.2793 1
0.0405 1 0.5
0.1156 1 1
0.0542081 0.5 0.5
0.1016 1 1
0.0389 1 1
0.0705 1 1
0.0274 1 1
0.0324 0.3747 1
0.0362 0.3358 0.4564
0.1714 1 1
0.0363 0.2783 0
0.0963983 1 0.5
0.0315 0.7359 0.5
0.0345 0.2793 1
0.0542081 1 1
0.0405 0.4988 1
0.0405 1 1
0.0707 0.5166 1
0.0235 0.2694 0.2694
0.0675 0.6663 1
0.1461 1 1
0.0743 0.786 0.7854
0.0379 0.4681 0.5337
0.0362 0.3073 0.3072
0.0743 0.786 0.7854
0.0163 0.276 0
0.0324 1 1
0.0324 1 1
0.0675 0.6663 1
0.0379 0.4681 0.5337
0.0328 0.4341 1
0.1461 1 1
0.045852 0.521349 1
0.0675 0.6663 1
0.0405 1 1
0.0396 0.5372 0.5303
0.0405 0.4362 1
0.0345 0.2793 1
0.0693 1 1
0.2375 1 1
0.0325 0.3708 0.9871
0.0707 0.5166 1
0.0405 0.4988 1
0.0542081 0.5 0.5
0.0361 0.5372 0.5303
0.0718 1 1
0.1129 1 1
0.0387 1 1
0.0405 1 1
0.4827 1 1
0.0315 0.7359 0.5
0.1071 1 1
0.0683 0.5 0.5
0.0405 1 0.5
0.3452 0.4899 0.4896
0.0542081 1 1
0.0405 0.5 0.5
0.0163 0.276 0
0.0405 0.5892 1
0.0405 0.4988 1
0.0542081 0.5 0.5
0.0345 0.3996 1
0.0675 0.6663 1
0.0707 0.5166 1
0.0364 0.7142 0.7097
0.0347 0.6436 0.6142
0.0683 0.5 0.5
0.1096 1 1
0.0375 0.9514 1
0.0354 0.6847 0.6847
0.0265 0.2859 0.2925
0.0342 0.6369 0.551
0.0707 0.5166 1
0.3109 1 1
0.0761 0.8284 0.8282
0.0495 0.2944 0.2676
0.4827 1 1
0.0707 0.5166 1
0.0387 1 1
0.0324 1 1
0.0367 0.5 0.5
0.0354 0.6876 0.6876
0.0392 0.7667 0.7667
0.0705 1 1
0.0405 0.6792 1

Assayability

Assay information

  • Assay for Inorganic Pyrophosphatase (3.6.1.1 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • Inhibition of recombinant trypanosoma brucei soluble vacuolar pyrophosphatase expressed in escherichia coli ChEMBL
  • Inhibition of recombinant Trypanosoma brucei soluble vacuolar pyrophosphatase expressed in Escherichia coli
  • 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
    Tb927.4.4380 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Trypanosoma brucei ( 1 )

Bibliographic References

9 literature references were collected for this gene.

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Gene identifier Tb927.4.4380 (Trypanosoma brucei), Pyrophosphate-energized vacuolar membrane proton pump 1
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