Detailed view for Rv2457c

Basic information

TDR Targets ID: 5756
Mycobacterium tuberculosis, Probable ATP-dependent CLP protease ATP-binding subunit ClpX

Source Database / ID:  Tuberculist 

pI: 4.7843 | Length (AA): 426 | MW (Da): 46783 | 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

PF06689   ClpX C4-type zinc finger
PF07724   AAA domain (Cdc48 subfamily)
PF10431   C-terminal, D2-small domain, of ClpB protein

Gene Ontology

Mouse over links to read term descriptions.
GO:0046983   protein dimerization activity  
GO:0017111   nucleoside-triphosphatase activity  
GO:0016887   ATPase activity  
GO:0008270   zinc ion binding  
GO:0005524   ATP binding  
GO:0000166   nucleotide binding  
GO:0051082   unfolded protein binding  
GO:0019538   protein metabolic process  
GO:0006457   protein folding  

Metabolic Pathways

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

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
8 50 2ds5 (A) 9 51 77.00 0 1 0.938139 0.27
58 412 1um8 (A) 76 437 52.00 0 1 1.35853 -0.61
61 412 3hws (A) 64 412 63.00 0 1 1.51349 -0.63
61 412 4i81 (C) 64 412 56.00 0 1 1.19679 0.11
320 405 1qzm (A) 496 577 18.00 0 1 0.549378 -1.35

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
Mid 40-60% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase. 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_128011)

Species Accession Gene Product
Arabidopsis thaliana AT5G53350   CLP protease regulatory subunit X
Arabidopsis thaliana AT5G49840   ATP-dependent Clp protease
Arabidopsis thaliana AT1G33360   ATP-dependent Clp protease
Brugia malayi Bm1_57610   ATP-dependent Clp protease, ATP-binding subunit, putative
Caenorhabditis elegans CELE_D2030.2   Protein D2030.2, isoform B
Chlamydia trachomatis CT_705   ATP-dependent Clp protease ATP-binding subunit ClpX
Drosophila melanogaster Dmel_CG4538   CG4538 gene product from transcript CG4538-RC
Escherichia coli b0438   ATPase and specificity subunit of ClpX-ClpP ATP-dependent serine protease
Echinococcus granulosus EgrG_001010800   ATP dependent Clp Protease ATP binding subunit
Echinococcus multilocularis EmuJ_001010800   ATP dependent Clp Protease ATP binding subunit
Homo sapiens 10845   caseinolytic mitochondrial matrix peptidase chaperone subunit
Loa Loa (eye worm) LOAG_03700   ATP-dependent Clp protease
Mycobacterium leprae ML1477c   PROBABLE ATP-DEPENDENT CLP PROTEASE ATP-BINDING SUBUNIT CLPX
Mus musculus ENSMUSG00000015357   caseinolytic mitochondrial matrix peptidase chaperone subunit
Mycobacterium tuberculosis Rv2457c   Probable ATP-dependent CLP protease ATP-binding subunit ClpX
Mycobacterium ulcerans MUL_3728   ATP-dependent protease ATP-binding subunit ClpX
Neospora caninum NCLIV_012090   ATP-dependent protease ATP-binding subunit, putative
Oryza sativa 4324891   Os01g0886600
Oryza sativa 4329696   Os02g0564400
Saccharomyces cerevisiae YBR227C   Mcx1p
Schistosoma japonicum Sjp_0057960   ko:K03544 ATP-dependent Clp protease ATP-binding subunit ClpX, putative
Schistosoma japonicum Sjp_0057950   ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial precursor, putative
Schistosoma mansoni Smp_063480   ATP-dependent clp protease ATP-binding subunit clpx
Schmidtea mediterranea mk4.000896.04  
Schmidtea mediterranea mk4.028359.00   Putative hsl and clp protease
Schmidtea mediterranea mk4.013929.01  
Schmidtea mediterranea mk4.008842.01  
Schmidtea mediterranea mk4.019730.00   Putative hsl and clp protease
Schmidtea mediterranea mk4.042617.00   ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial
Schmidtea mediterranea mk4.008842.03  
Treponema pallidum TP0508   ATP-dependent protease ATP-binding subunit ClpX
Wolbachia endosymbiont of Brugia malayi Wbm0552   ATP-dependent protease ATP-binding subunit ClpX

Essentiality

Rv2457c has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu2500 this record Mycobacterium tuberculosis essential nmpdr
b0438 Escherichia coli non-essential goodall
CELE_D2030.2 Caenorhabditis elegans larval arrest wormbase
CELE_D2030.2 Caenorhabditis elegans slow growth wormbase
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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

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): 0.2


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
No druggable targets predicted through repurposing network model

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.

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Gene identifier Rv2457c (Mycobacterium tuberculosis), Probable ATP-dependent CLP protease ATP-binding subunit ClpX
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