Detailed view for TcCLB.506801.120

Basic information

TDR Targets ID: 31988
Trypanosoma cruzi, Calcium/calmodulin-dependent protein kinase kinase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.5238 | Length (AA): 1034 | MW (Da): 114491 | 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
PF13855   Leucine rich repeat

Gene Ontology

Mouse over links to read term descriptions.
GO:0008270   zinc ion binding  
GO:0005524   ATP binding  
GO:0005515   protein 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 17 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
189 555 2acx (A) 60 449 27.00 0 1 0.56 0.25
267 623 1omw (A) 162 552 25.00 0 1 0.59 0
293 555 1mq4 (A) 130 384 29.00 0 1 0.69 -1.11
665 800 1xku (A) 172 307 26.00 0.000017 1 0.42 -0.56
798 875 1ktm (A) 973 1044 14.00 0.000000079 0 0.14 -0.17
187 602 3pfq (A) 101 655 20.00 0 1 0.251421 1.13
226 264 5tdc (A) 98 140 36.00 0.94 0.37 0.252718 0.63
226 729 3pvu (A) 103 663 20.00 0 0.73 0.494527 0.98
255 595 4wih (A) 3 347 23.00 0 1 0.515887 -0.04
265 579 4aw2 (A) 45 393 27.00 0 1 0.489742 0.07
289 750 5iso (A) 9 550 20.00 0 1 0.585909 0.63
667 797 1ook (G) 80 206 28.00 0.02 1 0.529692 -1.02
669 798 2o6r (A) 56 193 29.00 0.033 0.86 0.396725 -0.34
688 933 4u09 (A) 110 380 22.00 0 0.96 0.353011 0.13
691 912 4qxf (A) 60 267 26.00 0.0000000015 1 0.3708 0.26
705 932 4u08 (A) 88 318 20.00 0 0.74 0.366603 -0.1
714 805 4nkh (A) 279 356 38.00 0.002 0.99 0.395975 -0.17

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 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_139200)

Species Accession Gene Product
Leishmania braziliensis LbrM.24.1790   protein kinase, putative,calcium/calmodulin-dependent protein kinase, putative
Leishmania donovani LdBPK_241800.1   protein kinase, putative
Leishmania infantum LinJ.24.1800   protein kinase, putative,calcium/calmodulin-dependent protein kinase, putative
Leishmania major LmjF.24.1730   protein kinase, putative,calcium/calmodulin-dependent protein kinase, putative
Leishmania mexicana LmxM.24.1730   protein kinase, putative,calcium/calmodulin-dependent protein kinase, putative
Trypanosoma brucei gambiense Tbg972.8.6580   protein kinase, putative
Trypanosoma brucei Tb927.8.6490   Basal body protein
Trypanosoma congolense TcIL3000_8_6320   protein kinase, putative
Trypanosoma cruzi TcCLB.511907.240   Calcium/calmodulin-dependent protein kinase kinase, putative
Trypanosoma cruzi TcCLB.506801.120   Calcium/calmodulin-dependent protein kinase kinase, putative

Essentiality

TcCLB.506801.120 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.6490 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.6490 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.6490 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.6490 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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
  • 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
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
Rattus norvegicus Mitogen-activated protein kinase 8 411 aa 21.8% 349 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 26.5% 298 aa Compounds References
Bos taurus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 25.1% 303 aa Compounds References
Oryctolagus cuniculus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 24.5% 314 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 24.3% 288 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 25.3% 297 aa Compounds References
Rattus norvegicus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 24.6% 309 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

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

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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Gene identifier TcCLB.506801.120 (Trypanosoma cruzi), Calcium/calmodulin-dependent protein kinase kinase, putative
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