Detailed view for Rv0758

Basic information

TDR Targets ID: 6782
Mycobacterium tuberculosis, Possible two component system response sensor kinase membrane associated PhoR
Source Database / ID:  Tuberculist 

pI: 7.024 | Length (AA): 485 | MW (Da): 52016 | Paralog Number: 2

Signal peptide: Y | GPI Anchor: | Predicted trans-membrane segments: 2

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

PF00512   His Kinase A (phospho-acceptor) domain
PF00672   HAMP domain
PF02518   Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

Gene Ontology

Mouse over links to read term descriptions.
GO:0016772   transferase activity, transferring phosphorus-containing groups  
GO:0016021   integral to membrane  
GO:0016020   membrane  
GO:0005524   ATP binding  
GO:0004871   signal transducer activity  
GO:0004673   protein histidine kinase activity  
GO:0000155   two-component sensor activity  
GO:0016310   phosphorylation  
GO:0007165   signal transduction  
GO:0018106   peptidyl-histidine phosphorylation  

Metabolic Pathways

Two-component system (KEGG)

Structural information

Modbase 3D models:

There are 2 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
176 480 2q8g (A) 75 402 21.00 0.00000096 1 0.699266 0.42
238 310 5ukv (A) 238 310 96.00 0 1 1.30292 -1

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:

PDB tag
  • 5UKV:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5UKY:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase. murphy
Show/Hide expression data references
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.

Orthologs

Ortholog group members (OG5_128582)

Species Accession Gene Product
Escherichia coli b2078   sensory histidine kinase in two-component regulatory system with BaeR
Escherichia coli b0570   sensory histidine kinase in two-component regulatory system with CusR, senses copper ions
Escherichia coli b0400   sensory histidine kinase in two-component regulatory system with PhoB
Mycobacterium leprae ML2440c   PUTATIVE TWO COMPONENT SENSOR HISTIDINE KINASE SENX3
Mycobacterium leprae ML0774   probable two-component sensory transduction histidine kinase MtrB
Mycobacterium tuberculosis Rv3764c   Possible two component sensor kinase TcrY
Mycobacterium tuberculosis Rv0490   Putative two component sensor histidine kinase SenX3
Mycobacterium tuberculosis Rv0758   Possible two component system response sensor kinase membrane associated PhoR
Mycobacterium ulcerans MUL_4559   two component sensor histidine kinase SenX3
Mycobacterium ulcerans MUL_0464   two component system response phosphate sensor kinase, PhoR
Mycobacterium ulcerans MUL_1502   two component regulator - sensor kinase
Schmidtea mediterranea mk4.069327.01  
Schmidtea mediterranea mk4.050419.00  
Schmidtea mediterranea mk4.105972.01  
Schmidtea mediterranea mk4.035652.00  

Essentiality

Rv0758 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu773 this record Mycobacterium tuberculosis non-essential nmpdr
b0400 Escherichia coli non-essential goodall
b0570 Escherichia coli non-essential goodall
b2078 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170

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): 0.1

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
No additional associated druggable targets
Obtained from network model

Ranking Plot

No enough druggable targets predicted through repurposing network model to make a plot

Putative Drugs List

Compound Raw Global Species
0.0023 0.4737 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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 Rv0758 (Mycobacterium tuberculosis), Possible two component system response sensor kinase membrane associated PhoR
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