Detailed view for Tb927.10.3650

Basic information

TDR Targets ID: 13903
Trypanosoma brucei, NADH-dependent fumarate reductase
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.8373 | Length (AA): 1232 | MW (Da): 133528 | Paralog Number: 3

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

PF00175   Oxidoreductase NAD-binding domain
PF00890   FAD binding domain
PF00970   Oxidoreductase FAD-binding domain
PF02424   ApbE family

Gene Ontology

Mouse over links to read term descriptions.
GO:0017013   protein amino acid flavinylation  
GO:0016491   oxidoreductase activity  
GO:0009055   electron carrier activity  
GO:0000104   succinate dehydrogenase activity  
GO:0055114   oxidation reduction  
GO:0009228   thiamin biosynthetic process  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models:

There are 13 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
109 346 5mgy (B) 33 271 21.00 0 1 0.350782 0.3
123 448 3pnd (A) 44 331 24.00 0 1 0.37561 0.43
154 416 5mgy (H) 75 305 31.00 0 1 0.325874 0.99
361 914 1y0p (A) 14 524 28.00 0.0016 1 0.668275 0.59
438 963 1y0p (A) 91 565 35.00 0 1 0.778948 -0.38
453 522 3kve (A) 7 82 39.00 0.034 0.62 0.333218 0.87
469 510 4iv9 (A) 34 76 48.00 0.81 0.6 0.491491 0.54
471 965 5glg (A) 32 500 40.00 0 1 0.851186 -0.48
473 511 1q1r (A) 4 44 31.00 0 0.13 0.246656 0.31
476 1010 3cir (A) 7 458 26.00 0 1 0.346253 1.22
952 1224 1tvc (A) 4 242 23.00 0 1 0.267591 0.98
968 1223 2eix (A) 39 279 33.00 0 1 0.591792 -0.51
990 1224 1qx4 (A) 50 299 30.00 0 1 0.583747 -0.75

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, 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_128620)

Species Accession Gene Product
Brugia malayi Bm1_04850   Hypothetical FAD-dependent oxidoreductase YEL047C, putative
Candida albicans CaO19.12472   potential fumarate reductase
Candida albicans CaO19.6882   similar to S. cerevisiae cytoplasmic (YEL047C) and mitochondrial (OSM1, YJR051W) soluble fumarate reductases required for anaero
Candida albicans CaO19.14171   similar to S. cerevisiae cytoplasmic (YEL047C) and mitochondrial (OSM1, YJR051W) soluble fumarate reductases required for anaero
Candida albicans CaO19.5005   potential fumarate reductase
Caenorhabditis elegans CELE_F48E8.3   Protein F48E8.3
Leishmania braziliensis LbrM.34.1110   NADH-dependent fumarate reductase, putative
Leishmania braziliensis LbrM.34.1100   NADH-dependent fumarate reductase, putative
Leishmania braziliensis LbrM.34.0820   NADH-dependent fumarate reductase-like protein
Leishmania braziliensis LbrM.34.1090   NADH-dependent fumarate reductase, putative
Leishmania donovani LdBPK_350850.1   NADH-dependent fumarate reductase-like protein
Leishmania donovani LdBPK_351200.1   NADH-dependent fumarate reductase, putative
Leishmania donovani LdBPK_070910.1   flavoprotein subunit-like protein
Leishmania donovani LdBPK_351190.1   NADH-dependent fumarate reductase, putative
Leishmania infantum LinJ.35.1190   NADH-dependent fumarate reductase, putative
Leishmania infantum LinJ.35.1200   NADH-dependent fumarate reductase, putative
Leishmania infantum LinJ.07.0910   flavoprotein subunit-like protein
Leishmania infantum LinJ.35.0850   NADH-dependent fumarate reductase-like protein
Leishmania major LmjF.35.0830   NADH-dependent fumarate reductase-like protein
Leishmania major LmjF.35.1190   NADH-dependent fumarate reductase, putative
Leishmania major LmjF.35.1180   NADH-dependent fumarate reductase, putative
Leishmania major LmjF.07.0800   flavoprotein subunit-like protein
Leishmania mexicana LmxM.34.0830   NADH-dependent fumarate reductase-like protein
Leishmania mexicana LmxM.34.1180   NADH-dependent fumarate reductase, putative
Leishmania mexicana LmxM.07.0800   flavoprotein subunit-like protein
Leishmania mexicana LmxM.34.1190   NADH-dependent fumarate reductase, putative
Loa Loa (eye worm) LOAG_01110   hypothetical protein
Loa Loa (eye worm) LOAG_01107   hypothetical protein
Onchocerca volvulus OVOC2551  
Saccharomyces cerevisiae YJR051W   Osm1p
Saccharomyces cerevisiae YEL047C   Frd1p
Trypanosoma brucei gambiense Tbg972.5.6520   NADH-dependent fumarate reductase, putative
Trypanosoma brucei gambiense Tbg972.10.4540   NADH-dependent fumarate reductase, putative
Trypanosoma brucei gambiense Tbg972.5.1290   NADH-dependent fumarate reductase
Trypanosoma brucei Tb11.v5.0613   NADH-dependent fumarate reductase, putative
Trypanosoma brucei Tb927.10.3650   NADH-dependent fumarate reductase
Trypanosoma brucei Tb927.5.930   NADH-dependent fumarate reductase
Trypanosoma brucei Tb927.5.940   NADH-dependent fumarate reductase, putative
Trypanosoma congolense TcIL3000_5_640   NADH-dependent fumarate reductase
Trypanosoma congolense TcIL3000_5_630   NADH-dependent fumarate reductase
Trypanosoma congolense TcIL3000_10_2980   NADH-dependent fumarate reductase
Trypanosoma congolense TcIL3000_0_22370   NADH-dependent fumarate reductase
Trypanosoma congolense TcIL3000_0_22360   NADH-dependent fumarate reductase
Trypanosoma cruzi TcCLB.510215.10   NADH-dependent fumarate reductase, putative
Trypanosoma cruzi TcCLB.508535.10   NADH-dependent fumarate reductase, putative
Trypanosoma cruzi TcCLB.503849.80   NADH-dependent fumarate reductase, putative
Trypanosoma cruzi TcCLB.510213.110   NADH-dependent fumarate reductase, putative
Trypanosoma cruzi TcCLB.503849.60   NADH-dependent fumarate reductase, putative

Essentiality

Tb927.10.3650 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.5.930 Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.5.930 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.5.930 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.5.930 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
Tb927.10.3650 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.3650 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.3650 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.3650 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Tb927.5.940 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.5.940 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.5.940 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.5.940 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) increased (PATO:0000470) 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: increased cell proliferation (significant 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): 0.5

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
Species Target Length Identity Alignment span Linked Drugs Reference
Plasmodium falciparum flavoprotein subunit of succinate dehydrogenase 631 aa 26.4% 535 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0032 0.5 0.5
0.0032 0.5 0.5
0.0032 0.5 0.5
0.0032 0.5 0.5

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 Tb927.10.3650 (Trypanosoma brucei), NADH-dependent fumarate reductase
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