Detailed view for Tb927.11.16790

Basic information

TDR Targets ID: 16891
Trypanosoma brucei, mitogen-activated protein kinase
Source Database / ID:  TriTrypDB  GeneDB

pI: 8.5638 | Length (AA): 657 | MW (Da): 72143 | 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  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models:

There are 2 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
1 407 3uzs (A) 188 576 19.00 0 1 0.517483 1.24
1 305 4bbm (A) 1 306 49.00 0 1 1.10523 -1.19

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
Mid 40-60% 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_128030)

Species Accession Gene Product
Brugia malayi Bm1_15925   serine/threonine-protein kinase
Caenorhabditis elegans CELE_Y42A5A.4   Protein Y42A5A.4, isoform A
Cryptosporidium hominis Chro.80358   serine/threonine protein kinase KKIALRE (EC 2.7.1.-)
Cryptosporidium parvum cgd8_3070   serine/threonine protein kinase KKIALRE
Drosophila melanogaster Dmel_CG7236   CG7236 gene product from transcript CG7236-RE
Echinococcus granulosus EgrG_001184700   cyclin dependent kinase 1
Echinococcus granulosus EgrG_000413300   cyclin dependent kinase 1
Echinococcus multilocularis EmuJ_001184700   cyclin dependent kinase 1
Echinococcus multilocularis EmuJ_000413300   cyclin dependent kinase 1
Giardia lamblia GL50803_96616   Kinase, CMGC CDKL
Homo sapiens ENSG00000205111   cyclin-dependent kinase-like 4
Homo sapiens ENSG00000100490   cyclin-dependent kinase-like 1 (CDC2-related kinase)
Homo sapiens 8999   cyclin-dependent kinase-like 2 (CDC2-related kinase)
Homo sapiens ENSG00000008086   cyclin-dependent kinase-like 5
Leishmania braziliensis LbrM.32.3540   mitogen-activated protein kinase, putative,kinase, putative
Leishmania donovani LdBPK_323450.1   mitogen-activated protein kinase, putative
Leishmania infantum LinJ.32.3450   mitogen-activated protein kinase, putative,kinase, putative
Leishmania major LmjF.32.3250   mitogen-activated protein kinase, putative,kinase, putative
Leishmania mexicana LmxM.31.3250   mitogen-activated protein kinase, putative,kinase, putative
Mus musculus ENSMUSG00000031292   cyclin-dependent kinase-like 5
Mus musculus ENSMUSG00000033966   cyclin-dependent kinase-like 4
Mus musculus ENSMUSG00000020990   cyclin-dependent kinase-like 1 (CDC2-related kinase)
Mus musculus ENSMUSG00000029403   cyclin-dependent kinase-like 2 (CDC2-related kinase)
Neospora caninum NCLIV_015030   cyclin-dependent kinase-like 5, putative
Onchocerca volvulus OVOC6227  
Schistosoma japonicum Sjp_0130070   Cyclin-dependent kinase-like 2, putative
Schistosoma japonicum Sjp_0121530   Cyclin-dependent kinase-like 2, putative
Schistosoma japonicum Sjp_0131230   Cyclin-dependent kinase-like 1, putative
Schistosoma japonicum Sjp_0091160   expressed protein
Schistosoma japonicum Sjp_0000210   ko:K08824 cyclin-dependent kinase-like, putative
Schistosoma japonicum Sjp_0083310   Cyclin-dependent kinase-like 2, putative
Schistosoma japonicum Sjp_0091150   Cyclin-dependent kinase-like 1, putative
Schistosoma mansoni Smp_157240   serine/threonine protein kinase
Schistosoma mansoni Smp_124130   serine/threonine protein kinase
Schistosoma mansoni Smp_163380   serine/threonine protein kinase
Schmidtea mediterranea mk4.001129.02   Cyclin-dependent kinase-like 1
Schmidtea mediterranea mk4.001129.09  
Schmidtea mediterranea mk4.004836.00   Cyclin-dependent kinase-like 1
Schmidtea mediterranea mk4.005480.01   Cyclin-dependent kinase-like 3
Schmidtea mediterranea mk4.006047.02   Cyclin-dependent kinase-like 1
Schmidtea mediterranea mk4.006699.02   Cyclin-dependent kinase-like 3
Schmidtea mediterranea mk4.006699.01   Cyclin-dependent kinase-like 3
Schmidtea mediterranea mk4.005480.00   Cyclin-dependent kinase-like 2
Trypanosoma brucei gambiense Tbg972.11.18950   protein kinase, putative
Trypanosoma brucei Tb927.11.16790   mitogen-activated protein kinase
Trypanosoma congolense TcIL3000.11.16750   mitogen-activated protein kinase
Trypanosoma cruzi TcCLB.511531.59   mitogen activated protein kinase, putative
Trypanosoma cruzi TcCLB.511025.30   mitogen-activated protein kinase, putative
Toxoplasma gondii TGME49_285160   cyclin-dependent kinase family 5 protein

Essentiality

Tb927.11.16790 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.01.8550 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.01.8550 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.01.8550 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb11.01.8550 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
TGME49_285160 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

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) decreased (PATO:0000468) 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: decreased cell proliferation (significant loss of fitness) in bloodstream forms (stage 6 days). References: 21363968
cell proliferation (GO:0008283) decreased (PATO:0000468) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: decreased cell proliferation (significant loss of fitness) in procyclic forms . 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 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): 0.5

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 cyclin-dependent kinase-like 2 (CDC2-related kinase) Compounds References
Homo sapiens cyclin-dependent kinase-like 5 Compounds References
Homo sapiens cyclin-dependent kinase-like 1 (CDC2-related kinase) Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Schizosaccharomyces pombe 972h- Casein kinase II subunit alpha 332 aa 28.1% 303 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 36.9% 293 aa Compounds References
Rattus norvegicus Mitogen-activated protein kinase 1 358 aa 33.6% 295 aa Compounds References
Oryctolagus cuniculus Cyclin-dependent kinase 4 189 aa 41.1% 168 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 37.8% 291 aa Compounds References
Xenopus laevis Aurora kinase B-B 368 aa 27.9% 301 aa Compounds References
Xenopus laevis Aurora kinase B-A 361 aa 27.9% 301 aa Compounds References
Rattus norvegicus MAP kinase p38 alpha 360 aa 34.2% 295 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 37.6% 290 aa Compounds References
Patiria pectinifera Cdc2 300 aa 37.6% 295 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

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

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Gene identifier Tb927.11.16790 (Trypanosoma brucei), mitogen-activated protein kinase
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