Detailed view for Tb927.6.3550

Basic information

TDR Targets ID: 15782
Trypanosoma brucei, phospholipid-translocating P-type ATPase (flippase), putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.742 | Length (AA): 1196 | MW (Da): 132562 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 7

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

PF00122   E1-E2 ATPase
PF13246   Cation transport ATPase (P-type)
PF16209   Phospholipid-translocating ATPase N-terminal
PF16212   Phospholipid-translocating P-type ATPase C-terminal

Gene Ontology

Mouse over links to read term descriptions.
GO:0016021   integral to membrane  
GO:0016020   membrane  
GO:0005524   ATP binding  
GO:0004012   phospholipid-translocating ATPase activity  
GO:0000287   magnesium ion binding  
GO:0000166   nucleotide binding  
GO:0015914   phospholipid transport  
GO:0006754   ATP biosynthetic process  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in 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
391 887 4hqj (A) 349 739 30.00 0.0000003 1 0.336052 1.31
660 707 4bbj (A) 546 593 40.00 0.021 0.92 0.514634 0.09
833 892 2rbk (A) 181 241 35.00 0.091 0.3 0.297667 0.44
856 894 3fvv (A) 181 220 18.00 0 0.17 0.233209 -0.41

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 60-80% percentile Bloodstream Form. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Procyclic. 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_138687)

Species Accession Gene Product
Arabidopsis thaliana AT5G44240   aminophospholipid ATPase 2
Leishmania braziliensis LbrM.30.2210   phospholipid-translocating P-type ATPase (flippase), putative
Leishmania donovani LdBPK_302270.1   phospholipid-translocating P-type ATPase (flippase), putative
Leishmania infantum LinJ.30.2270   phospholipid-translocating P-type ATPase (flippase), putative
Leishmania major LmjF.30.2260   phospholipid-translocating P-type ATPase (flippase), putative
Leishmania mexicana LmxM.29.2260   phospholipid-translocating P-type ATPase (flippase), putative
Oryza sativa 4350436   Os11g0446500
Trypanosoma brucei gambiense Tbg972.6.3310   phospholipid-translocating P-type ATPase (flippase), putative
Trypanosoma brucei Tb927.6.3550   phospholipid-translocating P-type ATPase (flippase), putative
Trypanosoma congolense TcIL3000_6_3130   phospholipid-translocating P-type ATPase (flippase), putative
Trypanosoma cruzi TcCLB.511511.60   phospholipid-translocating P-type ATPase (flippase), putative
Trypanosoma cruzi TcCLB.506941.60   phospholipid-translocating P-type ATPase (flippase), putative
Trichomonas vaginalis TVAG_282980   phospholipid-transporting ATPase, putative
Trichomonas vaginalis TVAG_028590   phospholipid-transporting ATPase, putative

Essentiality

Tb927.6.3550 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.6.3550 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.6.3550 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.6.3550 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.6.3550 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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.
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

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) 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 procyclic forms . 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 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

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
Non orthologous druggable targets
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model
No druggable targets predicted through repurposing network model

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.

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Gene identifier Tb927.6.3550 (Trypanosoma brucei), phospholipid-translocating P-type ATPase (flippase), putative
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