Detailed view for Rv1493

Basic information

TDR Targets ID: 6557
Mycobacterium tuberculosis, Probable methylmalonyl-CoA mutase large subunit MutB (MCM)
Source Database / ID:  Tuberculist 

pI: 5.6852 | Length (AA): 750 | MW (Da): 80604 | Paralog Number: 0

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

PF01642   Methylmalonyl-CoA mutase
PF02310   B12 binding domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0046872   metal ion binding  
GO:0031419   cobalamin binding  
GO:0016866   intramolecular transferase activity  
GO:0016853   isomerase activity  
GO:0004494   methylmalonyl-CoA mutase activity  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  

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
6 747 1req (A) 2 728 69.00 0 1 1.82333 -0.77
614 744 4r3u (C) 3 133 37.00 0.00000052 1 0.762667 -1.31
615 744 2yxb (A) 19 148 45.00 0 1 0.847933 -1.59

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
  • 1SE5:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% 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_130968)

Species Accession Gene Product
Caenorhabditis elegans CELE_ZK1058.1   Protein MMCM-1
Dictyostelium discoideum DDB_G0287563   hypothetical protein
Escherichia coli b2917   methylmalonyl-CoA mutase
Homo sapiens ENSG00000146085   methylmalonyl CoA mutase
Leishmania braziliensis LbrM.27.0310   methylmalonyl-coenzyme a mutase, putative
Leishmania donovani LdBPK_270310.1   methylmalonyl-coenzyme a mutase, putative
Leishmania infantum LinJ.27.0310   methylmalonyl-coenzyme a mutase, putative
Leishmania major LmjF.27.0300   methylmalonyl-coenzyme a mutase, putative
Leishmania mexicana LmxM.27.0300   methylmalonyl-coenzyme a mutase, putative
Mycobacterium leprae ML1799c   PROBABLE METHYLMALONYL-CoA MUTASE LARGE SUBUNIT MUTB (MCM)
Mus musculus ENSMUSG00000023921   methylmalonyl-Coenzyme A mutase
Mycobacterium tuberculosis Rv1493   Probable methylmalonyl-CoA mutase large subunit MutB (MCM)
Mycobacterium ulcerans MUL_1506   methylmalonyl-CoA mutase
Mycobacterium ulcerans MUL_0367   methylmalonyl-CoA mutase beta subunit, McmA2a
Schmidtea mediterranea mk4.003044.04  
Schmidtea mediterranea mk4.026261.00  
Schmidtea mediterranea mk4.003044.03  
Schmidtea mediterranea mk4.047032.01   Probable methylmalonyl-CoA mutase, mitochondrial
Schmidtea mediterranea mk4.003044.01  

Essentiality

Rv1493 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1518 this record Mycobacterium tuberculosis non-essential nmpdr
b2917 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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): 0.2

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

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.

User comments

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Gene identifier Rv1493 (Mycobacterium tuberculosis), Probable methylmalonyl-CoA mutase large subunit MutB (MCM)
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