Detailed view for TcCLB.506775.190

Basic information

TDR Targets ID: 42124
Trypanosoma cruzi, Calcium/calmodulin-dependent protein kinase kinase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.785 | Length (AA): 640 | MW (Da): 71221 | Paralog Number: 1

Signal peptide: N | GPI Anchor: N | 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: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 13 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
64 510 1qcf (A) 89 531 19.00 0 1 0.62 0.36
141 558 2etr (A) 12 404 20.00 0 1 0.63 0.24
426 507 1yoj (A) 445 531 23.00 0.0000065 0.59 0.45 -1.23
81 506 2fo0 (A) 92 524 19.00 0 1 0.575025 0.7
160 529 4lqq (A) 303 707 25.00 0 1 0.395525 1.62
179 544 3war (A) 3 329 25.00 0 1 0.601275 0.5
209 527 2a2a (A) 4 289 29.00 0 1 0.577838 0.1
213 373 3cok (A) 6 154 23.00 0 0.94 0.444663 0.35
216 532 4neu (A) 15 313 32.00 0 1 0.643013 0.44
217 529 3w32 (A) 711 1008 22.00 0 1 0.606462 -0.18
219 639 4e3c (A) 16 480 21.00 0 1 0.531213 1.06
327 373 4o1p (A) 451 501 45.00 0.017 0.72 0.408138 0.89
403 497 2j0k (A) 565 679 22.00 0 0.59 0.428537 -0.69

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
Upper 60-80% percentile metacyclic. Smircich P
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile epimastigote. Smircich P
Show/Hide expression data references
  • Smircich P Ribosome profiling reveals translation control as a key mechanism generating differential gene expression in Trypanosoma cruzi.

Orthologs

Ortholog group members (OG5_142576)

Species Accession Gene Product
Leishmania braziliensis LbrM.19.0070   protein kinase
Leishmania donovani LdBPK_110250.1   serine/threonine protein kinase, putative
Leishmania infantum LinJ.11.0250   protein kinase, putative,serine/threonine protein kinase, putative
Leishmania major LmjF.11.0250   protein kinase, putative,serine/threonine protein kinase, putative
Leishmania mexicana LmxM.11.0250   protein kinase, putative,serine/threonine protein kinase, putative
Trypanosoma brucei gambiense Tbg972.11.7920   protein kinase, putative,serine/threonine protein kinase, putative
Trypanosoma brucei Tb927.11.6990   Calcium/calmodulin-dependent protein kinase kinase, putative
Trypanosoma congolense TcIL3000.11.7610   serine/threonine protein kinase, putative
Trypanosoma cruzi TcCLB.511165.100   Calcium/calmodulin-dependent protein kinase kinase, putative
Trypanosoma cruzi TcCLB.506775.190   Calcium/calmodulin-dependent protein kinase kinase, putative

Essentiality

TcCLB.506775.190 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.4830 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb11.02.4830 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.02.4830 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.4830 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • 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

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): 0.7

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 25.8% 314 aa Compounds References
Patiria pectinifera Cdc2 300 aa 27.3% 242 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 25.0% 256 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 27.9% 258 aa Compounds References
Schizosaccharomyces pombe 972h- Casein kinase II subunit alpha 332 aa 23.4% 278 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0033 1 0.5
0.0016 0.5 0.5
0.0012 0.5 0.5
0.0007 0.5 0.5
0.0037 1 0.5
0.0039 0.5 0.5
0.0032 0.5 0.5
0.0003 0.5 0.5
0.0012 0.5 0.5
0.0012 0.5 0.5
0.0056 1 0.5
0.0088 0.4477 0.5
0.0081 1 0.5
0.0032 0.5 0.5
0.0093 0.8828 0
0.0022 0.5 0.5
0.0059 1 1
0.0063 0.7244 0.2543
0.0064 0.3377 0
0.0029 0.5 0.5
0.0092 1 0.5
0.0011 1 0.5
0.0008 0.5 0.5
0.0039 0.9485 0.5
0.0098 0.3242 0.3649
0.0007 0.5 0.5
0.0023 0.5 0.5
0.0059 1 1
0.0062 0.6935 0
0.0066 0.3101 0
0.0067 0.5 0.5
0.0016 0.5 0.5
0.0027 1 0.5
0.0036 0.5 0.5
0.0061 0.6883 0.5304
0.0039 0.5 0.5
0.0026 0.5 0.5
0.0018 0.5 0.5
0.0042 0.5 0.5
0.0059 1 1
0.0069 0.3067 1
0.0091 1 0.5
0.0081 0.5 0.5
0.0004 0.5 0.5
0.0033 0.5 0.5
0.0063 1 0.5
0.0007 0.5 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

21 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.

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Gene identifier TcCLB.506775.190 (Trypanosoma cruzi), Calcium/calmodulin-dependent protein kinase kinase, putative
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