Detailed view for Tb927.10.9440

Basic information

TDR Targets ID: 16762
Trypanosoma brucei, NADH dehydrogenase

Source Database / ID:  TriTrypDB  GeneDB

pI: 9.5691 | Length (AA): 491 | MW (Da): 54351 | Paralog Number: 0

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

Druggability Group : DG4

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

PF07992   Pyridine nucleotide-disulphide oxidoreductase

Gene Ontology

Mouse over links to read term descriptions.
GO:0016491   oxidoreductase activity  
GO:0055114   oxidation reduction  

Metabolic Pathways

Structural information

Modbase 3D models:

There are 5 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
2 37 1ps9 (A) 365 400 22.00 0.62 0.02 0.14252 1.22
9 433 5jwc (A) 39 532 26.00 0 1 0.97898 -0.04
9 432 4g6h (A) 52 509 28.00 0 1 1.09494 0.08
183 364 1ebd (A) 180 345 36.00 0.000000076 1 0.450772 1.03
183 360 2ywl (A) 5 175 22.00 0 0.99 0.595925 -0.25

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 Procyclic, 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_126960)

Species Accession Gene Product
Arabidopsis thaliana AT1G07180   internal alternative NAD(P)H-ubiquinone oxidoreductase A1
Arabidopsis thaliana AT2G20800   NAD(P)H dehydrogenase B4
Arabidopsis thaliana AT4G21490   NAD(P)H dehydrogenase B3
Arabidopsis thaliana AT2G29990   alternative NAD(P)H dehydrogenase 2
Arabidopsis thaliana AT4G28220   NAD(P)H dehydrogenase B1
Arabidopsis thaliana AT4G05020   NAD(P)H dehydrogenase B2
Babesia bovis BBOV_I004980   NADH dehydrogenase, putative
Candida albicans CaO19.13136   one of two genes similar to S. cerevisiae mitochondrial nonproton-pumping NADH dehydrogenases NDE1 (YMR145C), NDE2 (YDL085W) and
Candida albicans CaO19.5713   one of two genes similar to S. cerevisiae mitochondrial nonproton-pumping NADH dehydrogenases NDE1 (YMR145C), NDE2 (YDL085W) and
Candida albicans CaO19.339   one of two genes similar to S. cerevisiae mitochondrial nonproton-pumping NADH dehydrogenases NDE1 (YMR145C), NDE2 (YDL085W) and
Candida albicans CaO19.7972   one of two genes similar to S. cerevisiae mitochondrial nonproton-pumping NADH dehydrogenases NDE1 (YMR145C), NDE2 (YDL085W) and
Cryptosporidium hominis Chro.70218   NADH dehydrogenase
Cryptosporidium parvum cgd7_1900   mitochondrial NADH dehydrogenase
Dictyostelium discoideum DDB_G0270104   hypothetical protein
Dictyostelium discoideum DDB_G0295661   pyridine nucleotide-disulphide oxidoreductase, NAD-binding region domain-containing protein
Dictyostelium discoideum DDB_G0271532   pyridine nucleotide-disulphide oxidoreductase, NAD-binding region domain-containing protein
Dictyostelium discoideum DDB_G0290197   calcium-binding EF-hand domain-containing protein
Escherichia coli b1109   respiratory NADH dehydrogenase 2/cupric reductase
Leishmania braziliensis LbrM.35.5640   NADH dehydrogenase, putative
Leishmania donovani LdBPK_365620.1   NADH dehydrogenase, putative
Leishmania infantum LinJ.36.5620   NADH dehydrogenase, putative
Leishmania major LmjF.36.5380   NADH dehydrogenase, putative
Leishmania mexicana LmxM.36.5380   NADH dehydrogenase, putative
Mycobacterium leprae ML2061   PROBABLE NADH DEHYDROGENASE NDH
Mycobacterium tuberculosis Rv1854c   Probable NADH dehydrogenase Ndh
Mycobacterium tuberculosis Rv0392c   Probable membrane NADH dehydrogenase NdhA
Mycobacterium ulcerans MUL_3025   NADH dehydrogenase Ndh
Neospora caninum NCLIV_041240   NADH dehydrogenase (EC 1.6.99.3), related
Neospora caninum NCLIV_003560   mitochondrial alternative NADH dehydrogenase 1, putative
Oryza sativa 4343616   Os07g0564500
Oryza sativa 4341876   Os06g0684000
Oryza sativa 4327426   Os01g0830100
Oryza sativa 9266372   Os08g0141400
Oryza sativa 4338442   Os05g0331200
Plasmodium berghei PBANKA_0816000   type II NADH:ubiquinone oxidoreductase
Plasmodium falciparum PF3D7_0915000   type II NADH:ubiquinone oxidoreductase
Plasmodium knowlesi PKNH_0713000   type II NADH:ubiquinone oxidoreductase, putative
Plasmodium vivax PVX_099180   type II NADH:ubiquinone oxidoreductase, putative
Plasmodium yoelii PY03419   NADH dehydrogenase
Saccharomyces cerevisiae YMR145C   NADH-ubiquinone reductase (H(+)-translocating) NDE1
Saccharomyces cerevisiae YML120C   NADH-ubiquinone reductase (H(+)-translocating) NDI1
Saccharomyces cerevisiae YDL085W   NADH-ubiquinone reductase (H(+)-translocating) NDE2
Trypanosoma brucei gambiense Tbg972.10.11540   NADH dehydrogenase, putative
Trypanosoma brucei Tb927.10.9440   NADH dehydrogenase
Trypanosoma congolense TcIL3000_10_8200   NADH dehydrogenase, putative
Trypanosoma cruzi TcCLB.506839.70   NADH dehydrogenase, putative
Trypanosoma cruzi TcCLB.508717.20   NADH dehydrogenase, putative
Toxoplasma gondii TGME49_209150   non-proton pumping type-II NADH dehydrogenase I
Toxoplasma gondii TGME49_288830   NADH dehydrogenase (NDH2-II)
Theileria parva TP03_0539   NADH dehydrogenase (ubiquinone), putative

Essentiality

Tb927.10.9440 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu395 Mycobacterium tuberculosis non-essential nmpdr
Tb927.10.9440 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.10.9440 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.9440 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.9440 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
PBANKA_0816000 Plasmodium berghei Dispensable plasmo
TGME49_288830 Toxoplasma gondii Essentiality uncertain sidik
TGME49_209150 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • 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
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
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) 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 procyclic forms . 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

No validation data for this target

Associated compounds / Druggability

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
Plasmodium falciparum type II NADH:ubiquinone oxidoreductase Compounds References
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

  • Assay for Cytochrome C Reductase (1.6.99.3 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

Reagent availability

No reagent availability information for this target.

Bibliographic References

33 literature references were 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 Tb927.10.9440 (Trypanosoma brucei), NADH dehydrogenase
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