Detailed view for Tb927.3.4860

Basic information

TDR Targets ID: 13899
Trypanosoma brucei, mitogen-activated protein kinase kinase 1
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.3175 | Length (AA): 372 | MW (Da): 42148 | 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:0004672   protein kinase activity  
GO:0005524   ATP binding  
GO:0004713   protein tyrosine kinase activity  
GO:0004674   protein serine/threonine 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
18 367 5ckw (B) 7 365 20.00 0 1 0.92846 0.63
54 370 4lgd (A) 18 449 32.00 0 1 1.24065 -0.58
62 320 2rku (A) 53 307 29.00 0 1 1.08374 -0.67
68 318 3fme (A) 59 314 39.00 0 1 1.00283 -0.03
221 314 4feq (A) 665 774 26.00 0 0.96 0.617288 -0.82

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
Lower 20-40% 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_149772)

Species Accession Gene Product
Leishmania braziliensis LbrM.29.2290   mitogen activated protein kinase, putative
Leishmania donovani LdBPK_292430.1   mitogen-activated protein kinase kinase 1
Leishmania infantum LinJ.29.2430   mitogen activated protein kinase, putative
Leishmania major LmjF.29.2320   mitogen activated protein kinase, putative
Leishmania mexicana LmxM.08_29.2320   mitogen activated protein kinase, putative
Schistosoma japonicum Sjp_0112530   Dual specificity mitogen-activated protein kinase kinase 6, putative
Schistosoma mansoni Smp_073490   protein kinase
Trypanosoma brucei gambiense Tbg972.3.5450   protein kinase, putative
Trypanosoma brucei Tb927.3.4860   mitogen-activated protein kinase kinase 1
Trypanosoma congolense TcIL3000_0_42570   mitogen-activated protein kinase kinase 1
Trypanosoma cruzi TcCLB.508153.140   mitogen-activated protein kinase kinase 1

Essentiality

Tb927.3.4860 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.3.4860 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.3.4860 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.3.4860 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.3.4860 this record 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
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.

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 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

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 28.9% 287 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 30.1% 286 aa Compounds References
Schizosaccharomyces pombe 972h- Casein kinase II subunit alpha 332 aa 20.6% 291 aa Compounds References
Rattus norvegicus Serine/threonine-protein kinase pim-3 326 aa 26.6% 293 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 27.9% 297 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0022 0.5 0.5
0.0036 0.5 0.5
0.0008 0.5 0.5
0.0081 1 0.5
0.0066 0.3101 0
0.0004 0.5 0.5
0.0081 0.5 0.5
0.0059 1 1
0.0042 0.5 0.5
0.0067 0.5 0.5
0.0039 0.5 0.5
0.0033 1 0.5
0.0039 0.9485 0.5
0.0092 1 0.5
0.0007 0.5 0.5
0.0003 0.5 0.5
0.0061 0.6883 0.5304
0.0039 0.5 0.5
0.0063 0.7244 0.2543
0.0012 0.5 0.5
0.0027 1 0.5
0.0069 0.3067 1
0.0032 0.5 0.5
0.0026 0.5 0.5
0.0091 1 0.5
0.0012 0.5 0.5
0.0007 0.5 0.5
0.0064 0.3377 0
0.0059 1 1
0.0007 0.5 0.5
0.0033 0.5 0.5
0.0059 1 1
0.0032 0.5 0.5
0.0016 0.5 0.5
0.0062 0.6935 0
0.0093 0.8828 0
0.0029 0.5 0.5
0.0037 1 0.5
0.0018 0.5 0.5
0.0023 0.5 0.5
0.0011 1 0.5
0.0016 0.5 0.5
0.0063 1 0.5
0.0056 1 0.5
0.0088 0.4477 0.5
0.0098 0.3242 0.2614
0.0012 0.5 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

1 literature reference was collected for this gene.

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Gene identifier Tb927.3.4860 (Trypanosoma brucei), mitogen-activated protein kinase kinase 1
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