Detailed view for TcCLB.504089.54

Basic information

TDR Targets ID: 39057
Trypanosoma cruzi, ULK family serine/threonine-protein kinase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.2345 | Length (AA): 1094 | MW (Da): 122265 | 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:0004674   protein serine/threonine kinase activity  
GO:0004672   protein kinase activity  
GO:0005524   ATP binding  
GO:0005488   binding  
GO:0004713   protein tyrosine 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 9 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
2 339 1kob (A) 51 375 27.00 0 1 0.4 -0.58
2 254 2bdw (A) 11 271 32.00 0 1 0.77 -1.65
867 1094 2c1m (A) 223 457 17.00 0.00000000053 1 0.54 -1.61
898 1094 1jdh (A) 154 353 18.00 0.000012 1 0.55 -1.72
2 34 4ix3 (A) 170 202 27.00 0 0.13 0.164365 0.97
13 200 4bbm (B) 8 202 40.00 0 0.92 0.555246 0.11
281 1020 3zkv (A) 149 920 11.00 0 1 0.694617 0.52
937 1045 1wa5 (B) 299 409 25.00 0.66 1 0.570034 -1.48
979 1072 5aei (A) 13 107 23.00 0 1 0.528123 -1.75

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
Mid 40-60% 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_130036)

Species Accession Gene Product
Arabidopsis thaliana AT1G50240   serine/threonine-protein kinase FUSED
Caenorhabditis elegans CELE_F32D8.1   Protein F32D8.1
Dictyostelium discoideum DDB_G0267962   ULK family protein kinase
Drosophila melanogaster Dmel_CG6551   fused
Echinococcus granulosus EgrG_001028900   serine:threonine protein kinase 36
Echinococcus multilocularis EmuJ_001028900   serine:threonine protein kinase 36
Giardia lamblia GL50803_17368   Kinase, ULK
Homo sapiens ENSG00000163482   serine/threonine kinase 36
Leishmania braziliensis LbrM.13.0260   mitogen-activated protein kinase kinase 2
Leishmania donovani LdBPK_130280.1   mitogen-activated protein kinase kinase 2
Leishmania infantum LinJ.13.0280   mitogen-activated protein kinase kinase 2
Leishmania major LmjF.13.0440   mitogen-activated protein kinase kinase 2
Leishmania mexicana LmxM.13.0440   mitogen-activated protein kinase kinase 2
Mus musculus ENSMUSG00000033276   serine/threonine kinase 36
Oryza sativa 4352122   Os12g0433500
Schistosoma japonicum Sjp_0026310   ko:K06228 fused,Serine/threonine protein kinase, putative
Schistosoma mansoni Smp_132260   serine/threonine protein kinase
Schmidtea mediterranea mk4.014854.00  
Schmidtea mediterranea mk4.020170.00   Fused-like protein
Schmidtea mediterranea mk4.020170.01   Serine/threonine-protein kinase 36
Schmidtea mediterranea mk4.009350.00  
Trypanosoma brucei gambiense Tbg972.11.5110   protein kinase, putative,serine/threonine protein kinase, putative
Trypanosoma brucei Tb927.11.4470   ULK family serine/threonine-protein kinase, putative
Trypanosoma congolense TcIL3000.11.4540   serine/threonine protein kinase, putative
Trypanosoma cruzi TcCLB.504089.54   ULK family serine/threonine-protein kinase, putative
Trypanosoma cruzi TcCLB.504001.6   ULK family serine/threonine-protein kinase, putative
Trichomonas vaginalis TVAG_196800   CAMK family protein kinase
Trichomonas vaginalis TVAG_368920   CAMK family protein kinase
Trichomonas vaginalis TVAG_462850   AGC family protein kinase

Essentiality

TcCLB.504089.54 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.2050 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb11.02.2050 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.02.2050 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.2050 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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.
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

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
Species Known druggable target Linked compounds Reference
Homo sapiens serine/threonine kinase 36 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 35.6% 163 aa Compounds References
Rattus norvegicus Mitogen-activated protein kinase 8 411 aa 24.9% 385 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 31.2% 237 aa Compounds References
Rattus norvegicus Serine/threonine-protein kinase pim-3 326 aa 27.5% 262 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0029 0.5 0.5
0.0037 1 0.5
0.0023 0.5 0.5
0.0056 1 0.5
0.0061 0.6883 0.5304
0.0033 1 0.5
0.0007 0.5 0.5
0.0027 1 0.5
0.0016 0.5 0.5
0.0003 0.5 0.5
0.0069 0.3067 1
0.0032 0.5 0.5
0.0039 0.9485 0.5
0.0012 0.5 0.5
0.0088 0.4477 0.5
0.0016 0.5 0.5
0.0093 0.8828 0
0.0042 0.5 0.5
0.0067 0.5 0.5
0.0007 0.5 0.5
0.0059 1 1
0.0039 0.5 0.5
0.0059 1 1
0.0033 0.5 0.5
0.0036 0.5 0.5
0.0092 1 0.5
0.0012 0.5 0.5
0.0081 1 0.5
0.0026 0.5 0.5
0.0091 1 0.5
0.0066 0.3101 0
0.0063 1 0.5
0.0063 0.7244 0.2543
0.0022 0.5 0.5
0.0039 0.5 0.5
0.0059 1 1
0.0064 0.3377 0
0.0018 0.5 0.5
0.0008 0.5 0.5
0.0011 1 0.5
0.0007 0.5 0.5
0.0032 0.5 0.5
0.0098 0.3242 0.3649
0.0012 0.5 0.5
0.0062 0.6935 0
0.0004 0.5 0.5
0.0081 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.504089.54 (Trypanosoma cruzi), ULK family serine/threonine-protein kinase, putative
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