Detailed view for Tb927.8.5950

Basic information

TDR Targets ID: 10307
Trypanosoma brucei, mitogen-activated protein kinase kinase 4, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.5311 | Length (AA): 351 | MW (Da): 38694 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | 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:0005575   cellular_component  
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 5 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
1 333 4yhj (A) 118 450 27.00 0 1 1.18052 0.39
62 335 2rku (A) 41 308 27.00 0 1 1.14643 -0.45
65 350 3eqc (A) 59 379 35.00 0 1 1.22391 -0.55
65 272 2z7q (A) 56 262 44.00 0 1 0.857693 0.29
72 340 3bhh (A) 12 280 27.00 0 1 1.12518 -0.58

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 Procyclic, Bloodstream Form. Siegel TN
Show/Hide expression data references
  • Siegel TN Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites.

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

Tb927.8.5950 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.5950 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.5950 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.5950 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.5950 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) normal (PATO:0000461) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in bloodstream forms (stage 3 days). References: 21363968
cell proliferation (GO:0008283) increased (PATO:0000470) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: increased cell proliferation (significant gain of fitness) in bloodstream forms (stage 6 days). References: 21363968
cell proliferation (GO:0008283) normal (PATO:0000461) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in procyclic forms . References: 21363968
cell proliferation (GO:0008283) increased (PATO:0000470) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: increased cell proliferation (significant gain of fitness) in differentiation of procyclic to bloodstream forms . References: 21363968

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
Patiria pectinifera Cdc2 300 aa 24.7% 292 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 26.0% 288 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 26.7% 285 aa Compounds References
Rattus norvegicus Serine/threonine-protein kinase pim-3 326 aa 27.2% 302 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0022 0.5 0.5
0.0012 0.5 0.5
0.0093 0.8828 0
0.0018 0.5 0.5
0.0059 1 1
0.0081 1 0.5
0.0088 0.4477 0.5
0.0027 1 0.5
0.0016 0.5 0.5
0.0081 0.5 0.5
0.0059 1 1
0.0012 0.5 0.5
0.0067 0.5 0.5
0.0091 1 0.5
0.0098 0.3242 0.2614
0.0012 0.5 0.5
0.0016 0.5 0.5
0.0069 0.3067 1
0.0056 1 0.5
0.0026 0.5 0.5
0.0039 0.5 0.5
0.0029 0.5 0.5
0.0037 1 0.5
0.0008 0.5 0.5
0.0011 1 0.5
0.0066 0.3101 0
0.0033 0.5 0.5
0.0007 0.5 0.5
0.0063 0.7244 0.2543
0.0039 0.5 0.5
0.0092 1 0.5
0.0063 1 0.5
0.0007 0.5 0.5
0.0023 0.5 0.5
0.0007 0.5 0.5
0.0039 0.9485 0.5
0.0032 0.5 0.5
0.0033 1 0.5
0.0062 0.6935 0
0.0004 0.5 0.5
0.0003 0.5 0.5
0.0059 1 1
0.0036 0.5 0.5
0.0064 0.3377 0
0.0061 0.6883 0.5304
0.0032 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

27 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 Tb927.8.5950 (Trypanosoma brucei), mitogen-activated protein kinase kinase 4, putative
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