Detailed view for Rv0248c

Basic information

TDR Targets ID: 7253
Mycobacterium tuberculosis, Probable succinate dehydrogenase [iron-sulfur subunit] (succinic dehydrogenase)
Source Database / ID:  Tuberculist 

pI: 5.8063 | Length (AA): 646 | MW (Da): 70681 | Paralog Number: 2

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

PF00890   FAD binding domain
PF02910   Fumarate reductase flavoprotein C-term

Gene Ontology

Mouse over links to read term descriptions.
GO:0016491   oxidoreductase activity  
GO:0009055   electron carrier activity  
GO:0055114   oxidation reduction  

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
2 620 2wdq (A) 1 585 29.00 0 1 1.2354 0.02
2 592 2wdq (A) 1 566 36.00 0 1 1.27676 -0.24
4 38 3rha (A) 3 37 43.00 0.13 0.85 0.53638 -0.18
7 573 4ysx (A) 40 579 37.00 0 1 1.24251 -0.32
9 54 5u8u (A) 5 49 49.00 0.49 0.88 0.561007 0.61

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
Lower 20-40% percentile Dormant phase. murphy
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Dormant phase. hasan
Show/Hide expression data references
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.

Orthologs

Ortholog group members (OG5_126927)

Species Accession Gene Product
Arabidopsis thaliana AT2G18450   succinate dehydrogenase [ubiquinone] flavoprotein subunit 2
Arabidopsis thaliana AT5G66760   succinate dehydrogenase [ubiquinone] flavoprotein subunit 1
Babesia bovis BBOV_IV007210   succinate dehydrogenase alpha subunit, putative
Brugia malayi Bm1_17325   succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Brugia malayi Bm1_17330   succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Candida albicans CaO19.8070   succinate dehydrogenase
Candida albicans CaO19.440   succinate dehydrogenase
Candida albicans CaO19.10389   flavoprotein subunit of succinate dehydrogenase
Candida albicans CaO19.2871   flavoprotein subunit of succinate dehydrogenase
Caenorhabditis elegans CELE_C03G5.1   Protein SDHA-1
Caenorhabditis elegans CELE_C34B2.7   Protein SDHA-2
Chlamydia trachomatis CT_592   succinate dehydrogenase flavoprotein subunit
Dictyostelium discoideum DDB_G0280535   complex II, flavoprotein subunit
Drosophila melanogaster Dmel_CG17246   Succinate dehydrogenase A
Drosophila melanogaster Dmel_CG5718   CG5718 gene product from transcript CG5718-RA
Escherichia coli b0723   succinate dehydrogenase, flavoprotein subunit
Escherichia coli b4154   fumarate reductase (anaerobic) catalytic and NAD/flavoprotein subunit
Echinococcus granulosus EgrG_000422600   succinate dehydrogenase ubiquinone
Echinococcus multilocularis EmuJ_000422600   succinate dehydrogenase (ubiquinone)
Homo sapiens 101930534   succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial-like
Homo sapiens ENSG00000073578   succinate dehydrogenase complex, subunit A, flavoprotein (Fp)
Leishmania braziliensis LbrM.24.1690   succinate dehydrogenase flavoprotein, putative
Leishmania donovani LdBPK_241700.1   Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Leishmania infantum LinJ.24.1700   succinate dehydrogenase flavoprotein, putative
Leishmania major LmjF.24.1630   succinate dehydrogenase flavoprotein, putative
Leishmania mexicana LmxM.24.1630   succinate dehydrogenase flavoprotein, putative
Loa Loa (eye worm) LOAG_09746   succinate-ubiquinone oxidoreductase
Loa Loa (eye worm) LOAG_12615   succinate dehydrogenase flavoprotein subunit
Loa Loa (eye worm) LOAG_11674   hypothetical protein
Loa Loa (eye worm) LOAG_11671   succinate dehydrogenase flavoprotein subunit
Mycobacterium leprae ML0697c   Probable succinate dehydrogenase (flavoprotein subunit) SdhA (SUCCINIC DEHYDROGENASE) (FUMARATE REDUCTASE) (FUMARATE DEHYDROGENA
Mus musculus ENSMUSG00000021577   succinate dehydrogenase complex, subunit A, flavoprotein (Fp)
Mycobacterium tuberculosis Rv0248c   Probable succinate dehydrogenase [iron-sulfur subunit] (succinic dehydrogenase)
Mycobacterium tuberculosis Rv3318   Probable succinate dehydrogenase (flavoprotein subunit) SdhA (succinic dehydrogenase) (fumarate reductase) (fumarate dehydrogena
Mycobacterium tuberculosis Rv1552   Probable fumarate reductase [flavoprotein subunit] FrdA (fumarate dehydrogenase) (fumaric hydrogenase)
Mycobacterium ulcerans MUL_1172   succinate dehydrogenase flavoprotein subunit
Mycobacterium ulcerans MUL_1369   succinate dehydrogenase flavoprotein subunit
Neospora caninum NCLIV_068970   Succinate dehydrogenase flavoprotein subunit, related
Neospora caninum NCLIV_052500   hypothetical protein
Oryza sativa 4342350   Os07g0134800
Onchocerca volvulus OVOC2097   Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial homolog
Onchocerca volvulus OVOC2268   Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial homolog
Plasmodium berghei PBANKA_0518200   flavoprotein subunit of succinate dehydrogenase, putative
Plasmodium falciparum PF3D7_1034400   flavoprotein subunit of succinate dehydrogenase
Plasmodium knowlesi PKNH_0619600   flavoprotein subunit of succinate dehydrogenase, putative
Plasmodium vivax PVX_111005   flavoprotein subunit of succinate dehydrogenase, putative
Plasmodium yoelii PY05468   flavoprotein subunit of succinate dehydrogenase
Saccharomyces cerevisiae YJL045W   succinate dehydrogenase SDH1b
Saccharomyces cerevisiae YKL148C   succinate dehydrogenase flavoprotein subunit SDH1
Schistosoma japonicum Sjp_0300770   ko:K00239 succinate dehydrogenase flavoprotein subunit, putative
Schistosoma mansoni Smp_061230   succinate dehydrogenase
Schmidtea mediterranea mk4.000098.09   Succinate dehydrogenase
Schmidtea mediterranea mk4.046581.01   Succinate dehydrogenase
Trypanosoma brucei gambiense Tbg972.8.6750   succinate dehydrogenase flavoprotein, putative
Trypanosoma brucei Tb927.8.6580   Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Trypanosoma congolense TcIL3000_8_6450   Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Trypanosoma cruzi TcCLB.511909.40   Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Toxoplasma gondii TGME49_215590   flavoprotein subunit of succinate dehydrogenase
Theileria parva TP03_0230   succinate dehydrogenase flavoprotein subunit, putative
Wolbachia endosymbiont of Brugia malayi Wbm0448   succinate dehydrogenase flavoprotein subunit

Essentiality

Rv0248c has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.6580 Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.6580 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.6580 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.6580 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b0723 Escherichia coli non-essential goodall
b4154 Escherichia coli non-essential goodall
CELE_C03G5.1 Caenorhabditis elegans embryonic lethal wormbase
CELE_C03G5.1 Caenorhabditis elegans larval arrest wormbase
CELE_C03G5.1 Caenorhabditis elegans slow growth wormbase
CELE_C34B2.7 Caenorhabditis elegans embryonic lethal wormbase
CELE_C34B2.7 Caenorhabditis elegans larval arrest wormbase
CELE_C34B2.7 Caenorhabditis elegans slow growth wormbase
CELE_C34B2.7 Caenorhabditis elegans sterile wormbase
PBANKA_0518200 Plasmodium berghei Dispensable plasmo
TGME49_215590 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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.
  • 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
  • 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
  • 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
  • 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)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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
Species Known druggable target Linked compounds Reference
Plasmodium falciparum flavoprotein subunit of succinate dehydrogenase 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

  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Mycobacterium phlei ( 1 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Rv0248c purified protein BRENDA A protein with this EC number or name or sequence has been purified from Mycobacterium phlei ( 1 )

Bibliographic References

69 literature references were collected for this gene.

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Gene identifier Rv0248c (Mycobacterium tuberculosis), Probable succinate dehydrogenase [iron-sulfur subunit] (succinic dehydrogenase)
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