Detailed view for TcCLB.506493.70

Basic information

TDR Targets ID: 37733
Trypanosoma cruzi, STE/STE11 serine/threonine-protein kinase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.0598 | Length (AA): 1527 | MW (Da): 168496 | Paralog Number: 1

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 2

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
PF00211   Adenylate and Guanylate cyclase catalytic domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0035556   GO:intracellular signal transduction  

GO:0016849   phosphorus-oxygen lyase activity  
GO:0005524   ATP binding  
GO:0004713   protein tyrosine kinase activity  
GO:0004674   protein serine/threonine kinase activity  
GO:0004672   protein kinase activity  
GO:0009190   cyclic nucleotide biosynthetic process  
GO:0007242   intracellular signaling cascade  
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 10 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
736 837 1ybt (A) 292 389 20.00 0.0000011 0.94 0.24 -0.9
1210 1526 2f2u (A) 35 355 25.00 0 1 0.5 -0.32
1429 1525 2c30 (A) 565 658 30.00 0.0000069 0.89 0.5 -1.09
740 913 2w01 (A) 442 625 22.00 0.062 1 0.297749 0.27
745 911 1wc3 (A) 1016 1199 23.00 0 1 0.190165 0.44
771 883 4wp3 (A) 92 191 37.00 0.77 0.89 0.129801 1.24
1046 1164 4k0d (A) 37 155 16.00 0.98 0.01 0.353731 -1.34
1137 1517 2c0t (A) 119 484 25.00 0 1 0.373309 0.67
1261 1465 1csn (A) 9 218 26.00 0.00000000015 0.95 0.34795 0.43
1264 1521 5kbr (A) 270 517 39.00 0 1 0.437659 0.13

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_145063)

Species Accession Gene Product
Leishmania braziliensis LbrM.21.0180   protein kinase, putative,serine/threonine protein kinase, putative
Leishmania braziliensis LbrM.21.0190   protein kinase, putative,serine/threonine protein kinase, putative
Leishmania donovani LdBPK_210190.1   serine/threonine protein kinase, putative
Leishmania infantum LinJ.21.0190   protein kinase, putative,serine/threonine protein kinase, putative
Leishmania major LmjF.21.0130   protein kinase, putative,serine/threonine protein kinase, putative
Leishmania mexicana LmxM.21.0130   protein kinase, putative,serine/threonine protein kinase, putative
Trypanosoma brucei gambiense Tbg972.10.2310   protein kinase, putative,serine/threonine protein kinase, putative
Trypanosoma brucei Tb11.v5.0556   protein kinase, putative
Trypanosoma brucei Tb927.10.1910   STE/STE11 serine/threonine-protein kinase, putative
Trypanosoma congolense TcIL3000_10_1620   serine/threonine protein kinase, putative
Trypanosoma cruzi TcCLB.506493.70   STE/STE11 serine/threonine-protein kinase, putative
Trypanosoma cruzi TcCLB.510121.150   STE/STE11 serine/threonine-protein kinase, putative

Essentiality

TcCLB.506493.70 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.1910 Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.1910 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.1910 Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb927.10.1910 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • 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.

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
Xenopus laevis Aurora kinase B-A 361 aa 25.9% 321 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 25.3% 292 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 23.1% 299 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 26.0% 288 aa Compounds References
Rattus norvegicus Jak1 protein 210 aa 25.7% 202 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

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

No literature references available for this target.

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Gene identifier TcCLB.506493.70 (Trypanosoma cruzi), STE/STE11 serine/threonine-protein kinase, putative
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