Detailed view for TcCLB.511075.60

Basic information

TDR Targets ID: 35722
Trypanosoma cruzi, mitogen-activated protein kinase kinase 4, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.5642 | Length (AA): 352 | MW (Da): 39390 | 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: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 7 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
2 352 2acx (A) 94 469 18.00 0 1 0.79 0.42
5 335 2f2u (A) 27 356 25.00 0 1 1.26 -0.36
73 333 2bdw (A) 11 271 28.00 0 1 1.17 -1.03
2 334 3c4z (A) 104 453 24.00 0 1 1.20262 -0.06
63 352 4lgd (D) 15 294 33.00 0 1 1.24346 -0.49
72 335 2y7j (A) 21 293 24.00 0 1 1.0886 -0.88
178 273 2x7g (A) 204 595 45.00 0.0000054 0.89 0.440227 -0.35

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 80-100% percentile epimastigote, metacyclic. 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_144825)

Species Accession Gene Product
Brugia malayi Bm1_54585   Protein kinase domain containing protein
Echinococcus granulosus EgrG_000221400   dual specificity mitogen activated protein
Echinococcus multilocularis EmuJ_000221400   dual specificity mitogen activated protein
Leishmania braziliensis LbrM.24.2400   mitogen-activated protein kinase
Leishmania donovani LdBPK_242410.1   mitogen-activated protein kinase
Leishmania infantum LinJ.24.2410   mitogen-activated protein kinase
Leishmania major LmjF.24.2320   mitogen-activated protein kinase
Leishmania mexicana LmxM.24.2320   mitogen-activated protein kinase
Loa Loa (eye worm) LOAG_11954   STE/STE7/MEK4 protein kinase
Schistosoma japonicum Sjp_0034990   Dual specificity mitogen-activated protein kinase kinase 6, putative
Schistosoma japonicum Sjp_0084080   Dual specificity mitogen-activated protein kinase kinase 6, putative
Schistosoma mansoni Smp_073510   protein kinase
Schmidtea mediterranea mk4.015537.00  
Schmidtea mediterranea mk4.023281.00  
Trypanosoma brucei gambiense Tbg972.8.5950   protein kinase, putative
Trypanosoma brucei Tb927.8.5950   mitogen-activated protein kinase kinase 4, putative
Trypanosoma congolense TcIL3000_8_5700   protein kinase, putative
Trypanosoma cruzi TcCLB.440099.28   protein kinase, putative
Trypanosoma cruzi TcCLB.511075.60   mitogen-activated protein kinase kinase 4, putative

Essentiality

TcCLB.511075.60 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.5950 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.5950 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.5950 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.5950 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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.
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
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 26.8% 265 aa Compounds References
Patiria pectinifera Cdc2 300 aa 28.9% 280 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
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
0.0007 0.5 0.5
0.0012 0.5 0.5
0.0016 0.5 0.5
0.0033 1 0.5
0.0064 0.3377 0
0.0063 0.7244 0.2543
0.0022 0.5 0.5
0.0059 1 1
0.0093 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
0.0026 0.5 0.5
0.0061 0.6883 0.5304
0.0036 0.5 0.5
0.0039 0.5 0.5
0.0016 0.5 0.5
0.0067 0.5 0.5
0.0027 1 0.5
0.0066 0.3101 0
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
0.0029 0.5 0.5
0.0092 1 0.5
0.0011 1 0.5
0.0008 0.5 0.5
0.0007 0.5 0.5
0.0063 1 0.5
0.0033 0.5 0.5
0.0081 0.5 0.5
0.0091 1 0.5
0.0004 0.5 0.5
0.0069 0.3067 1
0.0059 1 1
0.0018 0.5 0.5
0.0042 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.511075.60 (Trypanosoma cruzi), mitogen-activated protein kinase kinase 4, putative
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