Detailed view for Tb927.10.15490

Basic information

TDR Targets ID: 12834
Trypanosoma brucei, GDP-mannose 4,6 dehydratase
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.8101 | Length (AA): 362 | MW (Da): 40548 | Paralog Number: 0

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

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

PF16363   GDP-mannose 4,6 dehydratase

Gene Ontology

Mouse over links to read term descriptions.
GO:0008446   GDP-mannose 4,6-dehydratase activity  
GO:0005622   intracellular  
GO:0050662   coenzyme binding  
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0044237   cellular metabolic process  
GO:0019673   GDP-mannose metabolic process  
GO:0008152   metabolic process  

Structural information

Modbase 3D models:

There are 3 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
3 349 5in4 (A) 0 372 55.00 0 1 1.67046 -1.06
5 345 5uzh (A) 34 377 59.00 0 1 1.69089 -1.03
8 42 3dqp (A) 4 38 26.00 0 0.37 0.336285 0.32

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 Procyclic. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% 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_128711)

Species Accession Gene Product
Arabidopsis thaliana AT3G51160   GDP-mannose 4,6 dehydratase 2
Arabidopsis thaliana AT5G66280   GDP-mannose 4,6 dehydratase 1
Brugia malayi Bm1_36340   GDP-mannose 4,6-dehydratase
Caenorhabditis elegans CELE_C53B4.7   Protein BRE-1, isoform C
Caenorhabditis elegans CELE_F56H6.5   Protein GMD-2
Dictyostelium discoideum DDB_G0284553   GDP-mannose 4,6-dehydratase
Drosophila melanogaster Dmel_CG8890   GDP-mannose 4,6-dehydratase
Escherichia coli b2053   GDP-D-mannose dehydratase, NAD(P)-binding
Echinococcus granulosus EgrG_000690100   GDP mannose 46 dehydratase
Echinococcus granulosus EgrG_002034100   GDP mannose 4,6 dehydratase
Echinococcus multilocularis EmuJ_000690100   GDP mannose 4,6 dehydratase
Homo sapiens ENSG00000112699   GDP-mannose 4,6-dehydratase
Loa Loa (eye worm) LOAG_02555   GDP-mannose 4,6-dehydratase
Mus musculus ENSMUSG00000038372   GDP-mannose 4, 6-dehydratase
Mycobacterium tuberculosis Rv1511   GDP-D-mannose dehydratase GmdA (GDP-mannose 4,6 dehydratase) (GMD)
Neospora caninum NCLIV_015780   hypothetical protein
Oryza sativa 4340050   Os06g0137700
Plasmodium berghei PBANKA_1423700   GDP-mannose 4,6-dehydratase, putative
Plasmodium falciparum PF3D7_0813800   GDP-mannose 4,6-dehydratase
Plasmodium knowlesi PKNH_1426500   GDP-mannose 4,6-dehydratase, putative
Plasmodium vivax PVX_123080   GDP-mannose 4,6-dehydratase, putative
Plasmodium yoelii PY06463   GDP-mannose 4,6-dehydratase
Schistosoma japonicum Sjp_0074530   ko:K01711 GDPmannose 4,6-dehydratase [EC4.2.1.47], putative
Schistosoma japonicum Sjp_0123530   GDP-mannose 4,6 dehydratase, putative
Schistosoma mansoni Smp_153490   GDP-mannose 46-dehydratase
Schmidtea mediterranea mk4.000212.01   GDP-mannose 4,6 dehydratase
Trypanosoma brucei gambiense Tbg972.10.18930   GDP-mannose 4,6 dehydratase, putative
Trypanosoma brucei Tb927.10.15490   GDP-mannose 4,6 dehydratase
Trypanosoma congolense TcIL3000_10_13280   GDP-mannose 4,6 dehydratase, putative
Trypanosoma cruzi TcCLB.508897.10   GDP-mannose 4,6 dehydratase, putative
Trypanosoma cruzi TcCLB.510027.10   GDP-mannose 4,6 dehydratase, putative
Toxoplasma gondii TGME49_238940   GDP mannose 4,6-dehydratase, putative

Essentiality

Tb927.10.15490 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.15490 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.15490 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.15490 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.10.15490 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b2053 Escherichia coli non-essential goodall
CELE_F56H6.5 Caenorhabditis elegans larval arrest wormbase
CELE_F56H6.5 Caenorhabditis elegans larval lethal wormbase
PBANKA_1423700 Plasmodium berghei Dispensable plasmo
TGME49_238940 Toxoplasma gondii Essentiality uncertain sidik
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.
  • 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
  • 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.
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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

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): 0.3

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 Tb927.10.15490 (Trypanosoma brucei), GDP-mannose 4,6 dehydratase
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