Detailed view for Tb927.10.1460

Basic information

TDR Targets ID: 14998
Trypanosoma brucei, NEK family Serine/threonine-protein kinase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.2857 | Length (AA): 846 | MW (Da): 93689 | 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: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 10 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
18 466 4fl2 (A) 121 618 23.00 0 1 0.576633 0.94
127 521 3i6u (A) 151 492 28.00 0 1 0.472803 1.14
148 517 4tnd (A) 121 450 28.00 0 1 0.521252 0.46
177 517 4yhj (A) 160 451 30.00 0 1 0.523973 0.39
178 427 1k9a (A) 171 387 30.00 0.00000000096 1 0.418308 0.21
179 587 3v5w (A) 161 546 26.00 0 1 0.517352 0.56
184 597 4rgj (A) 39 413 25.00 0 1 0.564262 0.55
216 427 3hyh (A) 59 252 41.00 0 1 0.431391 0.43
216 427 3ckx (A) 13 204 37.00 0 1 0.566391 0.08
218 524 5efq (A) 711 1007 24.00 0 1 0.623784 -0.21

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 Bloodstream Form. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Procyclic. 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_145725)

Species Accession Gene Product
Schmidtea mediterranea mk4.000976.03  
Trypanosoma brucei gambiense Tbg972.10.1680   protein kinase, putative
Trypanosoma brucei Tb927.10.1460   NEK family Serine/threonine-protein kinase, putative
Trypanosoma cruzi TcCLB.507743.9   tyrosine protein kinase, putative
Trypanosoma cruzi TcCLB.504133.30   tyrosine protein kinase, putative

Essentiality

Tb927.10.1460 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.1460 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.1460 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.1460 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.1460 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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) 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): 0.5

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
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 25.0% 324 aa Compounds References
Zea mays Casein kinase II alpha 332 aa 22.6% 328 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 25.0% 304 aa Compounds References
Schizosaccharomyces pombe 972h- Casein kinase II subunit alpha 332 aa 22.0% 304 aa Compounds References
Oryctolagus cuniculus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 25.2% 333 aa Compounds References
Bos taurus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 25.8% 333 aa Compounds References
Rattus norvegicus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 25.8% 306 aa Compounds References
Rattus norvegicus MAP kinase p38 alpha 360 aa 23.4% 338 aa Compounds References
Patiria pectinifera Cdc2 300 aa 28.1% 267 aa Compounds References
Oryctolagus cuniculus Cyclin-dependent kinase 4 189 aa 31.2% 199 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0092 1 0.5
0.0039 0.9485 0.5
0.0093 0.8828 0
0.0027 1 0.5
0.0061 0.6883 0.5304
0.0007 0.5 0.5
0.0088 0.4477 0.5
0.0098 0.3242 0.2614
0.0081 1 0.5
0.0042 0.5 0.5
0.0004 0.5 0.5
0.0023 0.5 0.5
0.0032 0.5 0.5
0.0012 0.5 0.5
0.0064 0.3377 0
0.0032 0.5 0.5
0.0016 0.5 0.5
0.0012 0.5 0.5
0.0029 0.5 0.5
0.0016 0.5 0.5
0.0069 0.3067 1
0.0063 0.7244 0.2543
0.0008 0.5 0.5
0.0056 1 0.5
0.0081 0.5 0.5
0.0033 0.5 0.5
0.0022 0.5 0.5
0.0012 0.5 0.5
0.0036 0.5 0.5
0.0059 1 1
0.0018 0.5 0.5
0.0066 0.3101 0
0.0011 1 0.5
0.0039 0.5 0.5
0.0039 0.5 0.5
0.0091 1 0.5
0.0063 1 0.5
0.0037 1 0.5
0.0026 0.5 0.5
0.0067 0.5 0.5
0.0062 0.6935 0
0.0059 1 1
0.0007 0.5 0.5
0.0007 0.5 0.5
0.0059 1 1
0.0003 0.5 0.5
0.0033 1 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 Tb927.10.1460 (Trypanosoma brucei), NEK family Serine/threonine-protein kinase, putative
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