Detailed view for Rv0422c

Basic information

TDR Targets ID: 9958
Mycobacterium tuberculosis, Probable phosphomethylpyrimidine kinase ThiD (HMP-phosphate kinase) (HMP-P kinase)
Source Database / ID:  Tuberculist 

pI: 5.5085 | Length (AA): 265 | MW (Da): 27511 | 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

PF08543   Phosphomethylpyrimidine kinase

Gene Ontology

Mouse over links to read term descriptions.
GO:0008972   phosphomethylpyrimidine kinase activity  
GO:0009228   thiamin biosynthetic process  

Metabolic Pathways

Thiamine metabolism (KEGG)
Global map (KEGG)

Structural information

Modbase 3D models:

There are 4 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
1 264 1jxh (A) 1 265 38.00 0 1 1.40133 -0.37
2 258 4c5l (A) 2 258 35.00 0 1 1.40291 -0.67
3 260 1ub0 (A) 1 256 45.00 0.0000000000067 1 1.50468 -0.5
4 246 4jjp (A) 6 245 37.00 0 1 1.36008 -0.48

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, Dormant phase. hasan 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_128612)

Species Accession Gene Product
Arabidopsis thaliana AT1G22940   thiamine biosynthetic bifunctional enzyme TH1
Candida albicans CaO19.889   thiamine biosynthesis
Candida albicans CaO19.8508   thiamine biosynthesis
Escherichia coli b2103   bifunctional hydroxy-methylpyrimidine kinase/hydroxy-phosphomethylpyrimidine kinase
Mycobacterium leprae ML0295   Probable phosphomethylpyrimidine kinase ThiD
Mycobacterium tuberculosis Rv0422c   Probable phosphomethylpyrimidine kinase ThiD (HMP-phosphate kinase) (HMP-P kinase)
Mycobacterium ulcerans MUL_3599   phosphomethylpyrimidine kinase
Plasmodium falciparum PF3D7_0520500   phosphomethylpyrimidine kinase, putative
Plasmodium knowlesi PKNH_1012600   phosphomethylpyrimidine kinase, putative
Plasmodium vivax PVX_080220   phosphomethylpyrimidine kinase, putative
Saccharomyces cerevisiae YPL258C   bifunctional hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase
Saccharomyces cerevisiae YOL055C   trifunctional hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase/thiaminase
Saccharomyces cerevisiae YPR121W   putative phosphomethylpyrimidine kinase
Schmidtea mediterranea mk4.050116.03  
Treponema pallidum TP0115   phosphomethypyrimidine kinase (thiD)

Essentiality

Rv0422c has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu425 this record Mycobacterium tuberculosis essential nmpdr
b2103 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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

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.

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User comments

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Gene identifier Rv0422c (Mycobacterium tuberculosis), Probable phosphomethylpyrimidine kinase ThiD (HMP-phosphate kinase) (HMP-P kinase)
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