Detailed view for Rv1746

Basic information

TDR Targets ID: 6798
Mycobacterium tuberculosis, Anchored-membrane serine/threonine-protein kinase PknF (protein kinase F) (STPK F)
Source Database / ID:  Tuberculist 

pI: 5.8237 | Length (AA): 476 | MW (Da): 50668 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 1

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

PF00069   Protein kinase domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005524   ATP binding  
GO:0004713   protein tyrosine kinase activity  
GO:0004674   protein serine/threonine kinase activity  
GO:0004672   protein kinase activity  
GO:0006468   protein amino acid phosphorylation  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in 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
3 281 5xka (A) 3 258 56.00 0 1 1.15703 -0.77
12 362 6c9d (A) 60 719 25.00 0.00000000002 1 0.915295 0.36
338 435 4dt5 (A) 36 137 39.00 0.51 0.31 0.363782 0.27
349 441 3fhv (A) 32 125 19.00 0 0.2 0.299478 -0.31

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
  • 1MRU:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1O6Y:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2FUM:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2H34:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3F61:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3F69:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3ORI:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3ORK:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3ORL:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3ORM:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3ORO:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3ORP:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3ORT:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5M06:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5M07:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5M08:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5M09:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5U94:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5XKA:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 6B2P:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 6B2Q:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Lower 0-20% 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_144303)

Species Accession Gene Product
Leishmania braziliensis LbrM.07.0160   protein kinase, putative
Leishmania donovani LdBPK_070320.1   protein kinase, putative
Leishmania infantum LinJ.07.0320   protein kinase, putative
Leishmania major LmjF.07.0160   protein kinase, putative
Leishmania mexicana LmxM.07.0160   protein kinase, putative
Mycobacterium tuberculosis Rv1746   Anchored-membrane serine/threonine-protein kinase PknF (protein kinase F) (STPK F)
Mycobacterium ulcerans MUL_2200   membrane-anchored serine/threonine-protein kinase
Mycobacterium ulcerans MUL_0482   serine/threonine-protein kinase PknF_2
Mycobacterium ulcerans MUP011   transmembrane serine/threonine-protein kinase PknQ
Mycobacterium ulcerans MUL_4471   anchored-membrane serine/threonine-protein kinase PknF
Trypanosoma brucei gambiense Tbg972.8.1280   serine/threonine-protein kinase, putative
Trypanosoma brucei Tb927.8.1670   Serine/threonine-protein kinase NEK14, putative
Trypanosoma congolense TcIL3000_8_1500   serine/threonine-protein kinase, putative
Trypanosoma cruzi TcCLB.505071.30   Serine/threonine-protein kinase NEK14, putative
Trypanosoma cruzi TcCLB.511395.90   Serine/threonine-protein kinase NEK14, putative

Essentiality

Rv1746 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1776 this record Mycobacterium tuberculosis non-essential nmpdr
Tb927.8.1670 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.1670 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.1670 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.1670 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • 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.
  • 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
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

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): 0.5

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
Species Target Length Identity Alignment span Linked Drugs Reference
Oryctolagus cuniculus Cyclin-dependent kinase 4 189 aa 26.5% 155 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 26.9% 242 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0063 0.7244 1
0.0059 1 0.5
0.0056 1 0.5
0.0033 1 1
0.0091 1 0.5
0.0022 0.5 0.5
0.0081 1 0.5
0.0064 0.3377 0.5
0.0032 0.5 0.5
0.0039 0.5 0.5
0.0027 1 0.5
0.0012 0.5 0.5
0.0093 0.8828 0.5
0.0063 1 1
0.0016 0.5 0.5
0.0032 0.5 0.5
0.0012 0.5 0.5
0.0098 0.3242 0.3676
0.0059 1 0.5
0.0039 0.9485 1
0.0039 0.5 0.5
0.0008 0.5 0.5
0.0059 1 0.5
0.0007 0.5 0.5
0.0067 0.5 0.5
0.0036 0.5 0.5
0.0062 0.6935 0.5
0.0061 0.6883 0.6563
0.0007 0.5 0.5
0.0033 0.5 0.5
0.0012 0.5 0.5
0.0081 0.5 0.5
0.0003 0.5 0.5
0.0011 1 0.5
0.0018 0.5 0.5
0.0004 0.5 0.5
0.0092 1 0.5
0.0026 0.5 0.5
0.0066 0.3101 0.5
0.0042 0.5 0.5
0.0007 0.5 0.5
0.0029 0.5 0.5
0.0069 0.3067 1
0.0088 0.4477 1
0.0016 0.5 0.5
0.0023 0.5 0.5
0.0037 1 0.5

Assayability

Assay information

  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis PknF

Reagent availability

No reagent availability information for this target.

Bibliographic References

79 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 Rv1746 (Mycobacterium tuberculosis), Anchored-membrane serine/threonine-protein kinase PknF (protein kinase F) (STPK F)
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