Detailed view for Rv0014c

Basic information

TDR Targets ID: 6795
Mycobacterium tuberculosis, Transmembrane serine/threonine-protein kinase B PknB (protein kinase B) (STPK B)

Source Database / ID: Tuberculist / Rv0014c 

pI: 5.0798 | Length (AA): 626 | MW (Da): 66510 | Paralog Number: 0

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

Pfam domains

PF00069   Protein kinase domain
PF03793   PASTA domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0008658   penicillin binding  
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 21 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
1 290 3f61 (A) 1 290 99.00 0 1 1.58836 -1.26
11 382 3nyn (A) 186 556 22.00 0 1 0.839249 0.17
112 293 6ewx (A) 1093 1307 24.00 0.000016 0.98 0.456735 -0.06
123 235 6fyi (A) 275 401 35.00 0.000055 0.61 0.362611 -0.32
124 233 3alo (A) 214 325 43.00 0.000000000054 0.46 0.491819 0.69
355 626 2kui (A) 355 626 99.99 0 1 1.5076 0.06
360 423 2mgv (A) 2 64 29.00 0 1 0.508436 -1.31
1 290 3f61 (A) 1 290 99.00 0 1 1.58836 -1.26
11 382 3nyn (A) 186 556 22.00 0 1 0.839249 0.17
112 293 6ewx (A) 1093 1307 24.00 0.000016 0.98 0.456735 -0.06
123 235 6fyi (A) 275 401 35.00 0.000055 0.61 0.362611 -0.32
124 233 3alo (A) 214 325 43.00 0.000000000054 0.46 0.491819 0.69
355 626 2kui (A) 355 626 99.99 0 1 1.5076 0.06
360 423 2mgv (A) 2 64 29.00 0 1 0.508436 -1.31
1 290 3f61 (A) 1 290 99.00 0 1 1.58836 -1.26
11 382 3nyn (A) 186 556 22.00 0 1 0.839249 0.17
112 293 6ewx (A) 1093 1307 24.00 0.000016 0.98 0.456735 -0.06
123 235 6fyi (A) 275 401 35.00 0.000055 0.61 0.362611 -0.32
124 233 3alo (A) 214 325 43.00 0.000000000054 0.46 0.491819 0.69
355 626 2kui (A) 355 626 99.99 0 1 1.5076 0.06
360 423 2mgv (A) 2 64 29.00 0 1 0.508436 -1.31

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:

  • 2FUM: Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone
  • Wehenkel, A., Alzari, P.M.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.89 X-RAY DIFFRACTION 7998 1196 2006-01-27 2006-08-01 2011-07-13
  • Ligand information
  • 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE c1cc(c2c(c1NCCNCCO)C(=O)c3c(ccc(c3C2=O)O)O)NCCNCCO non-polymer Search in DB
  • 3F69: Crystal structure of the Mycobacterium tuberculosis PknB mutant kinase domain in complex with KT5720
  • Alber, T., Mieczkowski, C.A., TB Structural Genomics Consortium (TBSGC)
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.80 X-RAY DIFFRACTION 4356 622 2008-11-05 2008-12-02 2017-10-25
  • Ligand information
  • SULFATE ION [O-]S(=O)(=O)[O-] non-polymer Search in DB
  • PHOSPHOTHREONINE C[C@H]([C@@H](C(=O)O)N)OP(=O)(O)O L-peptide linking Search in DB
  • hexyl (5S,6R,8R)-6-hydroxy-5-methyl-13-oxo-5,6,7,8-tetrahydro-13H-5,8-epoxy-4b,8a,14-triazadibenzo[b,h]cycloocta[1,2,3,4-jkl]cyclopenta[e]-as-indacene-6-carboxylate CCCCCCOC(=O)[C@]1(C[C@@H]2n3c4ccccc4c5c3c6c(c7ccccc7n6[C@]1(O2)C)c8c5C(=O)N=C8)O non-polymer Search in DB
  • 3OUV: SeMet Derivative of L512M mutant of PASTA domain 3 of Mycobacterium tuberculosis PknB
  • Prigozhin, D.M., Chen, T.Y., Alber, T.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.00 X-RAY DIFFRACTION 484 71 2010-09-15 2011-09-21 2016-12-14
  • Ligand information
  • SELENOMETHIONINE C[Se]CC[C@@H](C(=O)O)N L-peptide linking Search in DB
  • 4X3F: Crystal structure of the intracellular domain of the M. tuberculosis Ser/Thr kinase PknA
  • Wagner, T., Wehenkel, A., Alzari, P.M., Bellinzoni, M.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.90 X-RAY DIFFRACTION 6017 1011 2014-11-28 2015-01-21 2015-04-22
  • Ligand information
  • PHOSPHOSERINE C([C@@H](C(=O)O)N)OP(=O)(O)O L-peptide linking Search in DB
  • PHOSPHOTHREONINE C[C@H]([C@@H](C(=O)O)N)OP(=O)(O)O L-peptide linking Search in DB
  • 5E12: Crystal Structure of PASTA Domains 2, 3 and 4 of Mycobacterium tuberculosis Protein Kinase B
  • Prigozhin, D.M., TB Structural Genomics Consortium (TBSGC)
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.21 X-RAY DIFFRACTION 2911 408 2015-09-29 2016-09-14 2017-09-13
  • Ligand information
  • CITRATE ANION C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O non-polymer Search in DB
  • 5U94: Crystal structure of the Mycobacterium tuberculosis PASTA kinase PknB in complex with the potential theraputic kinase inhibitor GSK690693.
  • Wlodarchak, N., Satyshur, K., Striker, R.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.20 X-RAY DIFFRACTION 2091 285 2016-12-15 2017-12-20 2019-01-16
  • Ligand information
  • 4-{2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[(3S)-piperidin-3-ylmethoxy]-1H-imidazo[4,5-c]pyridin-4-yl}-2-methylbut-3-yn-2-ol CCn1c2c(cnc(c2nc1c3c(non3)N)C#CC(C)(C)O)OC[C@H]4CCCNC4 non-polymer Search in DB
  • GLYCEROL C(C(CO)O)O non-polymer Search in DB
  • MAGNESIUM ION [Mg+2] non-polymer Search in DB
  • 6B2P: Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis
  • Zuccola, H.J.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    3.01 X-RAY DIFFRACTION 1992 279 2017-09-20 2018-02-14 2018-02-14
  • Ligand information
  • 5-{5-chloro-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}thiophene-2-sulfonamide c1cc(sc1c2ncc(c(n2)Nc3cc([nH]n3)C4CC4)Cl)S(=O)(=O)N non-polymer Search in DB
  • 6B2Q: Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis
  • Zuccola, H.J.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.88 X-RAY DIFFRACTION 8162 1268 2017-09-20 2018-02-14 2018-02-14
  • Ligand information
  • 3-methyl-1-(2-methylpropyl)butyl 4-O-beta-L-gulopyranosyl-beta-D-glucopyranoside CC(C)CC(CC(C)C)O[C@H]1[C@@H]([C@H]([C@@H]([C@H](O1)CO)O[C@@H]2[C@H]([C@H]([C@@H]([C@@H](O2)CO)O)O)O)O)O D-saccharide Search in DB
  • 5-{5-chloro-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}thiophene-2-sulfonamide c1cc(sc1c2ncc(c(n2)Nc3cc([nH]n3)C4CC4)Cl)S(=O)(=O)N non-polymer Search in DB
  • PHOSPHOTHREONINE C[C@H]([C@@H](C(=O)O)N)OP(=O)(O)O L-peptide linking Search in DB

Expression

Upregulation Percent Ranking Shows this level of upregulation in
This gene ranks in the lower 0-20% group of genes. Dormant phase, Dormant phase.
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_146588)

Species Accession Gene Product
Mycobacterium leprae ML0016c   Probable transmembrane serine/threonine-protein kinase B PknB (protein kinase B) (STPK B)
Mycobacterium tuberculosis Rv0014c this record   Transmembrane serine/threonine-protein kinase B PknB (protein kinase B) (STPK B)
Mycobacterium ulcerans MUL_0018   serine/threonine-protein kinase B PknB
Trypanosoma cruzi TcCLB.511301.90   NEK family Serine/threonine-protein kinase, putative
Trypanosoma cruzi TcCLB.507211.20   NEK family Serine/threonine-protein kinase, putative
Trypanosoma cruzi TcCLB.508621.10   NEK family Serine/threonine-protein kinase, putative
Trypanosoma cruzi TcCLB.511351.30   NEK family Serine/threonine-protein kinase, putative

Essentiality

Rv0014c has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu14 this record Mycobacterium tuberculosis essential nmpdr
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • 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
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium smegmatis 4649   161165   576113   576114   590790  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 11750829 16674948 16980473
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium bovis 161165  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 11750829
catalytic activity (GO:0003824) decreased (PATO:0000468) inferred from specific protein inhibition (ECO:0000020) Mycobacterium tuberculosis 161165  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 11750829
growth (GO:0040007) decreased (PATO:0000468) inferred from loss-of-function mutant phenotype (ECO:0000016) Mycobacterium smegmatis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16436437
barrier septum formation (GO:0000917) abnormal (PATO:0000460) inferred from visible phenotype (ECO:0000176) Mycobacterium smegmatis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16436437
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Mycobacterium tuberculosis 0   4649   34576   55244   132331   568050   574748   574749   576113   576114   590790  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16674948 16980473
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium tuberculosis 4649   576113   576114   590790  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16674948 16980473
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium aurum 4649   576113   576114   590790  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16674948 16980473
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) inferred from loss-of-function mutant phenotype (ECO:0000016) Mycobacterium tuberculosis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16980473
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) inferred from loss-of-function mutant phenotype (ECO:0000016) Mycobacterium smegmatis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16980473
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Mycobacterium aurum 0   590790  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16980473
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Mycobacterium smegmatis 0   590790  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16980473
catalytic activity (GO:0003824) normal (PATO:0000461) in vitro (MI:0492) inferred from enzyme assay (ECO:0000005) Mycobacterium tuberculosis 161165  
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 16980473

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 log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.

Annotated validation

No validation data for this target

Associated compounds / Druggability

Druggability index (range: 0 to 1): 0.7


Known modulators for this target

132 chemical compounds are associated with this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Mycobacterium leprae Probable transmembrane serine/threonine-protein kinase B PknB (protein kinase B) (STPK B) Compounds References
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 32.3% 161 aa Compounds References

Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis PKNB at 10 uM
  • ChEMBL
  • Binding constant for PKNB(M.tuberculosis) kinase domain
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis GST-fused PknB expressed in Escherichia coli assessed as GarA substrate phosphorylation after 30 mins
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis PKNB assessed as residual activity at 10 uM relative to control
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis PknB

Reagent availability

No reagent availability information for this target.

Bibliographic References

80 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

No user comments are available for this gene. Log in to add comments, or register.

Enter your comment

User ()
Gene identifier Rv0014c (Mycobacterium tuberculosis), Transmembrane serine/threonine-protein kinase B PknB (protein kinase B) (STPK B)
Title for this comment
Comment