Detailed view for TcCLB.510773.20

Basic information

TDR Targets ID: 50090
Trypanosoma cruzi, Vacuolar proton pyrophosphatase 1, putative

Source Database / ID:  TriTrypDB  GeneDB

pI: 4.6854 | Length (AA): 814 | MW (Da): 85338 | Paralog Number: 1

Signal peptide: Y | GPI Anchor: N | Predicted trans-membrane segments: 16

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

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

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
171 600 1ots (A) 31 450 14.00 0.000031 0.06 0.53 -0.65
67 813 4a01 (A) 3 766 55.00 0 1 1.64759 -1.39

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 epimastigote. Smircich P
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile metacyclic. Smircich P
Show/Hide expression data references
  • Smircich P Ribosome profiling reveals translation control as a key mechanism generating differential gene expression in Trypanosoma cruzi.

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

TcCLB.510773.20 has one or more orthologs with essentiality data
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 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.4.4380 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.4.4380 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.4.4380 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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
  • 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.
  • 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.
  • 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

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): 0.7


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
Trypanosoma brucei Pyrophosphate-energized vacuolar membrane proton pump 1 Compounds References
Trypanosoma brucei gambiense vacuolar-type proton translocating pyrophosphatase 1, putative Compounds References
Trypanosoma brucei Pyrophosphate-energized vacuolar membrane proton pump 2, 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
0.0542081 0.5 0.5
0.0367 0.5 0.5
0.045852 0.521349 0.50818
0.0963983 1 1
0.1461 1 1
0.0354 0.6847 0.6847
0.0345 1 1
0.1016 1 1
0.0675 0.6663 1
0.0315 0.7359 0.5
0.1129 1 1
0.0405 1 1
0.0707 0.5166 1
0.0743 0.786 0.7854
0.3452 0.4899 0.4896
0.0345 0.2793 1
0.0675 0.6663 1
0.0387 1 0.5
0.0379 0.4681 0.5372
0.1096 1 1
0.0405 1 0.5
0.0345 0.2793 1
0.0361 0.5372 0.5372
0.0405 0.4988 1
0.0362 0.3073 0.3072
0.0675 0.6663 1
0.0163 0.276 0
0.0354 0.6876 0.6876
0.0718 1 1
0.0675 0.6663 1
0.0405 0.6792 1
0.0707 0.5166 1
0.0675 0.6663 1
0.0324 1 1
0.0405 0.4362 1
0.0542081 0.5 0.5
0.0405 0.4988 1
0.4827 1 1
0.0495 0.2944 0.2676
0.0675 0.6663 1
0.0405 0.4988 1
0.0265 0.2859 0.2925
0.0324 0.3747 1
0.0389 1 1
0.0542081 1 1
0.0325 0.3708 0.5745
0.0405 1 0.5
0.0718 1 1
0.0683 0.5 0.5
0.0325 0.3708 0.5745
0.0345 0.2793 1
0.0707 0.5166 1
0.0347 0.6436 0.6142
0.0396 0.5372 0.5372
0.0235 0.2694 0.2692
0.0163 0.276 0
0.2375 1 1
0.0375 0.9514 1
0.4827 1 1
0.0693 1 1
0.0343 0.2754 0.2752
0.0387 1 1
0.0405 1 1
0.1156 1 1
0.0324 1 1
0.0706 1 1
0.0405 1 1
0.0375 0.9514 1
0.0405 0.5 0.5
0.2375 1 1
0.0683 0.5 0.5
0.0542081 1 1
0.0362 0.3358 0.4564
0.033 1 1
0.3109 1 1
0.0328 0.4341 1
0.1071 1 1
0.0542081 0.5 0.5
0.0707 0.5166 1
0.0405 0.5892 1
0.0743 0.786 0.7854
0.0358 0.3502 0.3477
0.0379 0.4681 0.5372
0.0342 0.6369 0.551
0.0707 0.5166 1
0.0705 1 1
0.0345 0.3996 1
0.0363 0.2783 0
0.0707 0.5166 1
0.1461 1 1
0.0387 1 1
0.0324 1 1
0.0274 1 1
0.1714 1 1
0.1129 1 1
0.0693 1 1
0.0392 0.7667 0.7667
0.0761 0.8284 0.8282
0.0364 0.7142 0.7097
0.0694 1 1
0.0315 0.7359 0.5
0.0705 1 1
0.0542081 1 1

Assayability

Assay information

  • Assay for Inorganic Pyrophosphatase (3.6.1.1 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

Reagent availability

  • Reagent:
  • Target Type Source Notes
    TcCLB.510773.20 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Trypanosoma cruzi ( 1 )

Bibliographic References

8 literature references were collected for this gene.

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Gene identifier TcCLB.510773.20 (Trypanosoma cruzi), Vacuolar proton pyrophosphatase 1, putative
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