Detailed view for Tb927.8.7220

Basic information

TDR Targets ID: 17922
Trypanosoma brucei, tousled-like kinase II
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.1143 | Length (AA): 650 | MW (Da): 73422 | Paralog Number: 1

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 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
94 291 5nnv (A) 269 893 31.00 0.0009 0.36 0.166711 1.5
101 283 5cwp (A) 48 229 15.00 0 0.02 0.409747 -0.9
110 295 3edu (A) 1691 1880 16.00 0 0.23 0.27192 0.03
186 642 3v5w (A) 75 510 17.00 0 1 0.711038 0.69
308 605 2v7o (A) 10 284 30.00 0 1 0.805274 -0.45
312 594 3hyh (A) 55 307 37.00 0 1 0.59511 0.38
312 608 2acx (A) 186 464 24.00 0 1 0.706717 -0.48

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_128190)

Species Accession Gene Product
Arabidopsis thaliana AT5G20930   serine/threonine-protein kinase TOUSLED
Babesia bovis BBOV_III008760   protein kinase domain containing protein
Brugia malayi Bm1_45930   Serine/threonine-protein kinase C07A9.3
Caenorhabditis elegans CELE_C07A9.3   Protein TLK-1, isoform B
Cryptosporidium hominis Chro.80144   ENSANGP00000017360
Cryptosporidium hominis Chro.80146   hypothetical protein
Cryptosporidium parvum cgd8_1230   proteine kinase
Drosophila melanogaster Dmel_CG34412   Tousled-like kinase
Echinococcus granulosus EgrG_000784600   serine:threonine protein kinase tousled
Echinococcus multilocularis EmuJ_000784600   serine:threonine protein kinase tousled
Homo sapiens ENSG00000198586   tousled-like kinase 1
Homo sapiens ENSG00000146872   tousled-like kinase 2
Homo sapiens 101928451   serine/threonine-protein kinase tousled-like 2-like
Leishmania braziliensis LbrM.31.3220   protein kinase, putative
Leishmania donovani LdBPK_312960.1   protein kinase, putative
Leishmania infantum LinJ.31.2960   protein kinase, putative
Leishmania major LmjF.31.2860   protein kinase, putative
Leishmania mexicana LmxM.30.2860   protein kinase, putative
Loa Loa (eye worm) LOAG_04311   TLK protein kinase
Mus musculus ENSMUSG00000020694   tousled-like kinase 2 (Arabidopsis)
Mus musculus ENSMUSG00000041997   tousled-like kinase 1
Neospora caninum NCLIV_049660   MGC53542 protein, related
Oryza sativa 4334117   Os03g0749800
Plasmodium berghei PBANKA_0901100   serine/threonine protein kinase, putative
Plasmodium falciparum PF3D7_1148000   serine/threonine protein kinase, putative
Plasmodium knowlesi PKNH_0945900   serine/threonine protein kinase, putative
Plasmodium vivax PVX_092985   serine/threonine protein kinase, putative
Plasmodium yoelii PY05975   pKU-alpha protein kinase, putative
Plasmodium yoelii PY04928   hypothetical protein
Schistosoma japonicum Sjp_0201380   expressed protein
Schistosoma japonicum Sjp_0201370   expressed protein
Schistosoma mansoni Smp_141580   protein kinase
Schmidtea mediterranea mk4.000668.05   Serine/threonine-protein kinase tousled-like 1
Trypanosoma brucei gambiense Tbg972.4.5370   protein kinase, putative
Trypanosoma brucei gambiense Tbg972.8.7480   protein kinase, putative
Trypanosoma brucei Tb927.8.7220   tousled-like kinase II
Trypanosoma brucei Tb927.4.5180   tousled-like kinase I
Trypanosoma congolense TcIL3000_8_7300   protein kinase, putative
Trypanosoma congolense TcIL3000_0_18290   tousled-like kinase I
Trypanosoma congolense TcIL3000_0_46960   tousled-like kinase I
Trypanosoma cruzi TcCLB.506419.20   tousled-like kinase II, putative
Trypanosoma cruzi TcCLB.510597.9   tousled-like kinase II, putative
Toxoplasma gondii TGME49_234970   Tyrosine kinase-like (TKL) protein
Theileria parva TP04_0778   hypothetical protein, conserved
Theileria parva TP04_0777   hypothetical protein
Trichomonas vaginalis TVAG_394290   CAMK family protein kinase

Essentiality

Tb927.8.7220 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.4.5180 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.4.5180 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.4.5180 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.4.5180 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Tb927.8.7220 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.7220 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.8.7220 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.7220 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_C07A9.3 Caenorhabditis elegans embryonic lethal wormbase
CELE_C07A9.3 Caenorhabditis elegans sterile wormbase
PBANKA_0901100 Plasmodium berghei Essential plasmo
TGME49_234970 Toxoplasma gondii Probably essential sidik
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
  • 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.
  • 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.
  • 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
  • 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 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) 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) 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 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 tousled-like kinase 2 Compounds References
Homo sapiens tousled-like kinase 1 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 31.2% 186 aa Compounds References
Patiria pectinifera Cdc2 300 aa 26.6% 316 aa Compounds References
Rattus norvegicus Jak1 protein 210 aa 24.9% 201 aa Compounds References
Rattus norvegicus Mitogen-activated protein kinase 1 358 aa 25.2% 313 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 24.3% 309 aa Compounds References
Xenopus laevis Aurora kinase B-B 368 aa 30.3% 297 aa Compounds References
Xenopus laevis Aurora kinase B-A 361 aa 29.4% 299 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 24.9% 309 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 25.1% 311 aa Compounds References
Rattus norvegicus Serine/threonine-protein kinase pim-3 326 aa 26.6% 286 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

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

User comments

No user comments are available for this gene. Log in to add comments, or register.

Enter your comment

User ()
Gene identifier Tb927.8.7220 (Trypanosoma brucei), tousled-like kinase II
Title for this comment
Comment