Detailed view for Tb927.11.14870

Basic information

TDR Targets ID: 17469
Trypanosoma brucei, NAD+ synthase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.451 | Length (AA): 294 | MW (Da): 32916 | Paralog Number: 0

Signal peptide: N | 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

PF02540   NAD synthase

Gene Ontology

Mouse over links to read term descriptions.
GO:0003952   NAD+ synthase (glutamine-hydrolyzing) activity  
GO:0005524   ATP binding  
GO:0009435   NAD biosynthetic process  

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
7 293 4q16 (A) 8 273 24.00 0 1 1.21419 0.04
8 294 5huj (A) 9 276 19.00 0.00000029 1 1.09019 0.38
24 241 3fiu (A) 7 214 35.00 0 1 1.1028 -0.17
24 243 3fiu (A) 7 216 32.00 0 1 1.1067 -0.5

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_127076)

Species Accession Gene Product
Arabidopsis thaliana AT1G55090   glutamine-dependent NAD(+) synthetase
Candida albicans CaO19.1460   N terminal carbon-nitrogen hydrolase domain, C terminal NAD synthase domain
Candida albicans CaO19.9035   N terminal carbon-nitrogen hydrolase domain, C terminal NAD synthase domain
Caenorhabditis elegans CELE_C24F3.4   Protein QNS-1, isoform C
Dictyostelium discoideum DDB_G0285877   NAD+ synthase
Drosophila melanogaster Dmel_CG9940   CG9940 gene product from transcript CG9940-RB
Escherichia coli b1740   NAD synthetase, NH3/glutamine-dependent
Entamoeba histolytica EHI_134830   NAD synthetase, putative
Giardia lamblia GL50803_31530   NH3-dependent NAD+ synthetase
Homo sapiens ENSG00000172890   NAD synthetase 1
Leishmania braziliensis LbrM.32.1840   NAD synthase, putative
Leishmania donovani LdBPK_321750.1   NAD+ synthase, putative
Leishmania infantum LinJ.32.1750   NAD synthase, putative
Leishmania major LmjF.32.1670   NAD synthase, putative
Leishmania mexicana LmxM.31.1670   NAD synthase, putative
Mycobacterium leprae ML1463c   PROBABLE GLUTAMINE-DEPENDENT NAD(+) SYNTHETASE NADE (NAD(+) SYNTHASE [GLUTAMINE-HYDROLYSING])
Mus musculus ENSMUSG00000031090   NAD synthetase 1
Mycobacterium tuberculosis Rv2438c   Glutamine-dependent NAD(+) synthetase NadE (NAD(+) synthase [glutamine-hydrolysing])
Mycobacterium ulcerans MUL_3705   NAD synthetase
Neospora caninum NCLIV_036740   glutamine-dependent NAD( ) synthetase protein, putative
Oryza sativa 4342490   Os07g0167100
Plasmodium berghei PBANKA_0827500   glutamine-dependent NAD(+) synthetase, putative
Plasmodium falciparum PF3D7_0926700   glutamine-dependent NAD(+) synthetase, putative
Plasmodium knowlesi PKNH_0724800   glutamine-dependent NAD(+) synthetase, putative
Plasmodium vivax PVX_099765   glutamine-dependent NAD(+) synthetase, putative
Plasmodium yoelii PY00252   putative glutamine-dependent nad(+) synthetase
Saccharomyces cerevisiae YHR074W   glutamine-dependent NAD(+) synthetase
Schistosoma japonicum Sjp_0095200   ko:K01950 NAD+ synthase (glutamine-hydrolysing) [EC6.3.5.1], putative
Schistosoma mansoni Smp_162660   glutamine-dependent NAD(+) synthetase
Schistosoma mansoni Smp_075060   glutamine-dependent NAD(+) synthetase
Schmidtea mediterranea mk4.001756.00   Putative glutamine-dependent NAD() synthetase
Trypanosoma brucei gambiense Tbg972.11.16680   NAD synthase, putative
Trypanosoma brucei Tb927.11.14870   NAD+ synthase, putative
Trypanosoma congolense TcIL3000_0_36880   NAD+ synthase, putative
Trypanosoma cruzi TcCLB.506221.80   NAD+ synthase, putative
Trypanosoma cruzi TcCLB.427789.30   NAD+ synthase, putative
Toxoplasma gondii TGME49_269800   glutamine-dependent NAD(+) synthetase protein, putative
Treponema pallidum TP0780   NAD synthetase
Trichomonas vaginalis TVAG_188330   nh(3)-dependent NAD(+) synthetase, putative

Essentiality

Tb927.11.14870 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu2480 Mycobacterium tuberculosis essential nmpdr
Tb11.01.6500 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.01.6500 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb11.01.6500 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.01.6500 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b1740 Escherichia coli essential goodall
YHR074W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_0827500 Plasmodium berghei Slow plasmo
TGME49_269800 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • 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
  • 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.
  • 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
  • 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.
  • 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
  • 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) 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
Species Known druggable target Linked compounds Reference
Bacillus subtilis (strain 168) NH(3)-dependent NAD(+) synthetase Compounds References
Bacillus anthracis NH(3)-dependent NAD(+) synthetase 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
0.0137 0.4359 0.4359
0.0094 1 1
0.0184 0.4042 1
0.0205 1 1
0.0171 0.2953 0.5
0.0241 0.2774 1
0.0093 1 1
0.0099 0.2859 1
0.027 1 1

Assayability

Assay information

  • Assay for β-NAD Synthetase (6.3.5.1 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

Reagent availability

  • Tbru021844AAA;
  • Type Source Notes
    soluble recombinant protein Structural Genomics for Pathogenic Protozoa (SGPP) Tbru021844; Recombinant protein: full-length; Source: T brucei; NAD+ synthase, putative ;

Bibliographic References

1 literature reference was collected for this gene.

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Gene identifier Tb927.11.14870 (Trypanosoma brucei), NAD+ synthase, putative
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