Detailed view for Tb927.7.7420

Basic information

TDR Targets ID: 12992
Trypanosoma brucei, ATP synthase F1, alpha subunit
Source Database / ID:  TriTrypDB  GeneDB

pI: 10.07 | Length (AA): 584 | MW (Da): 63503 | Paralog Number: 1

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

Druggability Group : DG3

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

PF00006   ATP synthase alpha/beta family, nucleotide-binding domain
PF00306   ATP synthase alpha/beta chain, C terminal domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0046933   hydrogen ion transporting ATP synthase activity, rotational mechanism  
GO:0045261   proton-transporting ATP synthase complex, catalytic core F(1)  
GO:0032559   adenyl ribonucleotide binding  
GO:0016469   proton-transporting two-sector ATPase complex  
GO:0005524   ATP binding  
GO:0046034   ATP metabolic process  
GO:0015992   proton transport  
GO:0015986   ATP synthesis coupled proton transport  

Metabolic Pathways

Oxidative phosphorylation (KEGG)
Global map (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
27 557 5dn6 (A) 3 510 44.00 0 1 1.36205 -0.13
43 497 2r9v (A) 17 458 52.00 0 1 1.35831 -0.47
50 557 2r9v (A) 26 501 47.00 0 1 1.37466 -0.25
92 497 4xd7 (B) 61 457 57.00 0 1 1.12381 0.44

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:

PDB tag
  • 6F5D:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Procyclic. Siegel TN
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile 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_127165)

Species Accession Gene Product
Arabidopsis thaliana ArthCp007   ATP synthase CF1 alpha chain
Arabidopsis thaliana AT2G07698   ATPase, F1 complex, alpha subunit protein
Arabidopsis thaliana ArthMp100   ATPase subunit 1
Babesia bovis BBOV_III002130   ATP synthase F1, alpha subunit family protein
Brugia malayi Bm1_47570   ATP synthase alpha chain, mitochondrial precursor, putative
Candida albicans CaO19.14144   C terminus of mitochondrial F1F0 H+ATPase
Candida albicans CaO19.6854   C terminus of mitochondrial F1F0 H+ATPase
Caenorhabditis elegans CELE_H28O16.1   Protein H28O16.1, isoform B
Cryptosporidium hominis Chro.60082   ATP synthase alpha chain
Cryptosporidium parvum cgd6_610   ATP synthase alpha chain
Dictyostelium discoideum DidioMp11   ATPase subunit 1
Drosophila melanogaster Dmel_CG3612   bellwether
Escherichia coli b3734   F1 sector of membrane-bound ATP synthase, alpha subunit
Echinococcus granulosus EgrG_000720500   ATP synthase subunit alpha mitochondrial
Echinococcus multilocularis EmuJ_000720500   ATP synthase subunit alpha, mitochondrial
Homo sapiens ENSG00000152234   ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1, cardiac muscle
Leishmania braziliensis LbrM.05.0520   ATPase alpha subunit
Leishmania donovani LdBPK_050510.1   ATP synthase F1, alpha subunit, putative
Leishmania infantum LinJ.05.0500   ATPase alpha subunit
Leishmania infantum LinJ.05.0510   ATPase alpha subunit
Leishmania major LmjF.05.0500   ATPase alpha subunit
Leishmania major LmjF.05.0510   ATPase alpha subunit
Leishmania mexicana LmxM.05.0510   ATPase alpha subunit, putative
Leishmania mexicana LmxM.05.0500   ATPase alpha subunit, putative
Leishmania mexicana LmxM.05.0510b  
Mycobacterium leprae ML1143   PROBABLE ATP SYNTHASE ALPHA CHAIN ATPA
Mus musculus ENSMUSG00000025428   ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1
Mycobacterium tuberculosis Rv1308   Probable ATP synthase alpha chain AtpA
Mycobacterium ulcerans MUL_3956   F0F1 ATP synthase subunit alpha
Neospora caninum NCLIV_020840   hypothetical protein
Oryza sativa 3131390   ATP synthase CF1 alpha chain
Oryza sativa 6450183   ATP synthase F0 subunit 1
Onchocerca volvulus OVOC1523   ATP synthase subunit alpha, mitochondrial homolog
Plasmodium berghei PBANKA_0313800   ATP synthase F1, alpha subunit, putative
Plasmodium falciparum PF3D7_0217100   ATP synthase F1, alpha subunit
Plasmodium knowlesi PKNH_0403800   ATP synthase F1, alpha subunit, putative
Plasmodium vivax PVX_002685   ATP synthase alpha chain, putative
Plasmodium yoelii PY05971   ATP synthase F1, alpha subunit
Saccharomyces cerevisiae YBL099W   F1F0 ATP synthase subunit alpha
Schistosoma japonicum Sjp_0089940   ko:K02132 F-type H+-transporting ATPase alpha chain, putative
Schistosoma mansoni Smp_002880.2   ATP synthase alpha subunit mitochondrial
Schmidtea mediterranea mk4.000367.04  
Schmidtea mediterranea mk4.010027.01   ATP synthase subunit alpha, mitochondrial
Schmidtea mediterranea mk4.000367.03   ATP synthase subunit alpha, mitochondrial
Trypanosoma brucei gambiense Tbg972.7.8720   ATP synthase alpha chain, mitochondrial precursor, putative
Trypanosoma brucei Tb927.7.7430   ATP synthase F1, alpha subunit
Trypanosoma brucei Tb927.7.7420   ATP synthase F1, alpha subunit
Trypanosoma congolense TcIL3000_7_6050   ATP synthase F1, alpha subunit, putative
Theileria parva TP03_0569   ATP synthase F1, alpha chain, putative
Wolbachia endosymbiont of Brugia malayi Wbm0314   ATP synthase F0F1 subunit alpha

Essentiality

Tb927.7.7420 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1330 Mycobacterium tuberculosis essential nmpdr
Tb927.7.7420 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.7.7420 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.7.7420 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.7.7420 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b3734 Escherichia coli non-essential goodall
CELE_H28O16.1 Caenorhabditis elegans embryonic lethal wormbase
CELE_H28O16.1 Caenorhabditis elegans larval arrest wormbase
CELE_H28O16.1 Caenorhabditis elegans slow growth wormbase
CELE_H28O16.1 Caenorhabditis elegans sterile wormbase
CELE_H28O16.1 Caenorhabditis elegans terminal arrest variable wormbase
PBANKA_0313800 Plasmodium berghei Slow plasmo
Show/Hide essentiality data references
  • 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.
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.

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 3 days). References: 21363968
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 6 days). 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

  • Validation: inhibited in cell-free system. As observed in: T. b. brucei.Evidence: inferred from specific protein inhibition
  • annotated by: ts4@sanger.ac.uk.
  • References: 8806783

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
Mycobacterium tuberculosis Probable ATP synthase alpha chain AtpA 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
0.0276 0.6229 1
0.0274 0.5201 1
0.0036 0.4109 1
0.0175 0.5458 1
0.004 0.2558 0.1702

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

1 literature reference was collected for this gene.

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

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Gene identifier Tb927.7.7420 (Trypanosoma brucei), ATP synthase F1, alpha subunit
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