Detailed view for Tb927.11.7010

Basic information

TDR Targets ID: 10818
Trypanosoma brucei, Calcium/calmodulin-dependent protein kinase kinase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.7764 | Length (AA): 691 | MW (Da): 75870 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 0

Druggability Group : DG4

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:0005575   cellular_component  
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  

Structural information

Modbase 3D models:

There are 6 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
34 458 3i6u (A) 110 485 26.00 0 1 0.527851 0.78
87 561 3nyn (A) 72 550 24.00 0 1 0.66021 0.48
166 482 2vd5 (A) 69 363 27.00 0 1 0.566555 -0.17
166 549 4tnd (A) 184 540 25.00 0 1 0.584516 0.32
177 416 4bbm (B) 8 208 43.00 0 1 0.492723 0.45
375 447 3kmu (A) 355 436 27.00 0.5 0.57 0.390044 -0.97

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 Procyclic, Bloodstream Form. Siegel TN
Show/Hide expression data references
  • Siegel TN Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites.

Orthologs

Ortholog group members (OG5_146532)

Species Accession Gene Product
Leishmania braziliensis LbrM.34.2270   protein kinase, putative
Leishmania donovani LdBPK_352370.1   protein kinase, putative
Leishmania infantum LinJ.35.2370   protein kinase, putative
Leishmania major LmjF.35.2320   protein kinase, putative
Leishmania mexicana LmxM.34.2320   protein kinase, putative
Trypanosoma brucei gambiense Tbg972.11.7940   protein kinase, putative
Trypanosoma brucei Tb927.11.7010   Calcium/calmodulin-dependent protein kinase kinase, putative
Trypanosoma congolense TcIL3000.11.7630   protein kinase, putative
Trypanosoma cruzi TcCLB.503613.10   Calcium/calmodulin-dependent protein kinase kinase, putative
Trypanosoma cruzi TcCLB.511165.80   Calcium/calmodulin-dependent protein kinase kinase, putative

Essentiality

Tb927.11.7010 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.4860 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb11.02.4860 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb11.02.4860 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.4860 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) decreased (PATO:0000468) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: decreased cell proliferation (significant loss of fitness) in bloodstream forms (stage 3 days). References: 21363968
cell proliferation (GO:0008283) normal (PATO:0000461) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in bloodstream forms (stage 6 days). References: 21363968
cell proliferation (GO:0008283) normal (PATO:0000461) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in differentiation of procyclic to bloodstream forms . References: 21363968

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): 0.7

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
Rattus norvegicus Serine/threonine-protein kinase pim-3 326 aa 22.9% 266 aa Compounds References
Bos taurus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 26.7% 292 aa Compounds References
Oryctolagus cuniculus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 25.7% 292 aa Compounds References
Rattus norvegicus MAP kinase p38 alpha 360 aa 24.8% 331 aa Compounds References
Rattus norvegicus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 26.4% 292 aa Compounds References
Oryctolagus cuniculus Cyclin-dependent kinase 4 189 aa 29.7% 185 aa Compounds References
Schizosaccharomyces pombe 972h- Casein kinase II subunit alpha 332 aa 22.8% 333 aa Compounds References
Xenopus laevis Aurora kinase B-B 368 aa 25.7% 335 aa Compounds References
Patiria pectinifera Cdc2 300 aa 26.5% 260 aa Compounds References
Rattus norvegicus Mitogen-activated protein kinase 1 358 aa 23.3% 343 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 26.2% 260 aa Compounds References
Rattus norvegicus Jak1 protein 210 aa 23.4% 197 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 26.9% 271 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 25.8% 326 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0059 1 1
0.0081 0.5 0.5
0.0004 0.5 0.5
0.0042 0.5 0.5
0.0039 0.5 0.5
0.0067 0.5 0.5
0.0081 1 0.5
0.0066 0.3101 0
0.0008 0.5 0.5
0.0022 0.5 0.5
0.0036 0.5 0.5
0.0039 0.9485 0.5
0.0033 1 0.5
0.0039 0.5 0.5
0.0063 0.7244 0.2543
0.0061 0.6883 0.5304
0.0003 0.5 0.5
0.0007 0.5 0.5
0.0092 1 0.5
0.0026 0.5 0.5
0.0091 1 0.5
0.0032 0.5 0.5
0.0027 1 0.5
0.0012 0.5 0.5
0.0069 0.3067 1
0.0016 0.5 0.5
0.0032 0.5 0.5
0.0059 1 1
0.0007 0.5 0.5
0.0033 0.5 0.5
0.0012 0.5 0.5
0.0007 0.5 0.5
0.0059 1 1
0.0064 0.3377 0
0.0023 0.5 0.5
0.0011 1 0.5
0.0093 0.8828 0
0.0029 0.5 0.5
0.0018 0.5 0.5
0.0037 1 0.5
0.0062 0.6935 0
0.0056 1 0.5
0.0088 0.4477 0.5
0.0063 1 0.5
0.0016 0.5 0.5
0.0012 0.5 0.5
0.0098 0.3242 0.2614

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

27 literature references were collected for this gene.

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Gene identifier Tb927.11.7010 (Trypanosoma brucei), Calcium/calmodulin-dependent protein kinase kinase, putative
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