Detailed view for Rv3457c

Basic information

TDR Targets ID: 7068
Mycobacterium tuberculosis, Probable DNA-directed RNA polymerase (alpha chain) RpoA (transcriptase alpha chain) (RNA polymerase alpha subunit) (DNA-directed

Source Database / ID:  Tuberculist 

pI: 4.3794 | Length (AA): 347 | MW (Da): 37706 | Paralog Number: 0

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

Druggability Group : DG1

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

PF01000   RNA polymerase Rpb3/RpoA insert domain
PF01193   RNA polymerase Rpb3/Rpb11 dimerisation domain
PF03118   Bacterial RNA polymerase, alpha chain C terminal domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0006351   transcription, DNA-dependent  
GO:0046983   protein dimerization activity  
GO:0003899   DNA-directed RNA polymerase activity  
GO:0003677   DNA binding  
GO:0006350   transcription  

Metabolic Pathways

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
1 233 5tw1 (B) 1 233 91.00 0 1 1.69657 -0.25
3 319 5uaq (A) 7 325 43.00 0 1 1.36824 0.19
251 303 5tw1 (T) 251 303 99.99 0 1 1.39184 -1.49

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:

  • 5UH5:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UH6:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UH8:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UH9:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UHA:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UHB:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UHC:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UHD:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UHE:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UHF:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 5UHG:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6BZO:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6C04:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6C05:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6C06:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6EDT:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6EE8:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6EEC:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6FBV:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6M7J:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase, Dormant phase. hasan murphy
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_130460)

Species Accession Gene Product
Arabidopsis thaliana ArthCp055   RNA polymerase alpha chain
Babesia bovis BBOV_III011410   hypothetical protein
Chlamydia trachomatis CT_507   DNA-directed RNA polymerase subunit alpha
Escherichia coli b3295   RNA polymerase, alpha subunit
Mycobacterium leprae ML1957c   PROBABLE DNA-DIRECTED RNA POLYMERASE (ALPHA CHAIN) RPOA (TRANSCRIPTASE ALPHA CHAIN) (RNA POLYMERASE ALPHA SUBUNIT) (DNA-DIRECTED
Mycobacterium tuberculosis Rv3457c   Probable DNA-directed RNA polymerase (alpha chain) RpoA (transcriptase alpha chain) (RNA polymerase alpha subunit) (DNA-directed
Mycobacterium ulcerans MUL_0848   DNA-directed RNA polymerase subunit alpha
Neospora caninum NCLIV_065720   DNA-directed RNA polymerase alpha chain, putative
Oryza sativa 3131431   RNA polymerase alpha chain
Plasmodium berghei PBANKA_1406100   DNA-directed RNA polymerase alpha chain, putative
Plasmodium falciparum PF3D7_1307600   DNA-directed RNA polymerase alpha chain, putative
Plasmodium knowlesi PKNH_1407900   DNA-directed RNA polymerase alpha chain, putative
Plasmodium vivax PVX_122210   DNA-directed RNA polymerase alpha chain, putative
Plasmodium yoelii PY00033   DNA-directed RNA polymerase alpha chain
Toxoplasma gondii TGME49_249560   DNA-directed RNA polymerase alpha chain rpoA
Treponema pallidum TP0212   DNA-directed RNA polymerase subunit alpha
Theileria parva TP03_0199   DNA-directed RNA polymerase, alpha subunit, putative
Theileria parva TP03_0198   hypothetical protein
Wolbachia endosymbiont of Brugia malayi Wbm0318   DNA-directed RNA polymerase subunit alpha

Essentiality

Rv3457c has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu3518 this record Mycobacterium tuberculosis essential nmpdr
b3295 Escherichia coli essential goodall
PBANKA_1406100 Plasmodium berghei Essential plasmo
TGME49_249560 Toxoplasma gondii Probably essential 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
  • 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.
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource

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

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
Bacteria Bacterial DNA-directed RNA polymerase 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
0.0013 0.3777 0.5
0.01 0.3256 0.5

Assayability

Assay information

  • Assay for Ribonucleic Acid Polymerase (2.7.7.6 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

Reagent availability

No reagent availability information for this target.

Bibliographic References

219 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.

User comments

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Gene identifier Rv3457c (Mycobacterium tuberculosis), Probable DNA-directed RNA polymerase (alpha chain) RpoA (transcriptase alpha chain) (RNA polymerase alpha subunit) (DNA-directed
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