Detailed view for Tb927.11.7210

Basic information

TDR Targets ID: 15211
Trypanosoma brucei, eukaryotic translation initiation factor 2-alpha kinase 1, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.8835 | Length (AA): 1236 | MW (Da): 137629 | 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:0005524   ATP binding  
GO:0005515   protein 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 8 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
18 148 2ebk (A) 2 127 17.00 0 0.84 0.163287 0.09
18 148 1ukx (A) 5 136 19.00 0 0.82 0.175287 -0.15
186 654 4fl2 (A) 88 622 15.00 0 1 0.36825 0.64
270 348 1x8b (A) 294 373 46.00 0.000000016 1 0.435816 0.84
273 694 2b9h (A) 11 351 26.00 0 1 -0.0467761 1.01
452 531 1csn (A) 91 159 35.00 0.035 0.99 0.323625 0.26
473 655 4x7q (B) 136 281 31.00 0.0013 1 0.331958 -0.48
718 854 2x5i (C) 29 179 28.00 0.56 0.05 -0.0712586 2.03

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_130490)

Species Accession Gene Product
Brugia malayi Bm1_33235   hypothetical protein
Dictyostelium discoideum DDB_G0283065   PEK family protein kinase
Echinococcus granulosus EgrG_000183600   eukaryotic translation initiation factor 2 alpha
Entamoeba histolytica EHI_035950   protein kinase domain containing protein
Entamoeba histolytica EHI_109700   protein kinase domain containing protein
Echinococcus multilocularis EmuJ_000183600   eukaryotic translation initiation factor 2 alpha
Homo sapiens ENSG00000086232   eukaryotic translation initiation factor 2-alpha kinase 1
Leishmania braziliensis LbrM.19.0260   protein kinase
Leishmania donovani LdBPK_110060.1   protein kinase, putative
Leishmania infantum LinJ.11.0060   protein kinase, putative
Leishmania major LmjF.11.0060   protein kinase, putative
Leishmania mexicana LmxM.11.0060   protein kinase, putative
Loa Loa (eye worm) LOAG_05819   PEK/HRI protein kinase
Mus musculus 15467   eukaryotic translation initiation factor 2 alpha kinase 1
Trypanosoma brucei gambiense Tbg972.11.8150   protein kinase, putative
Trypanosoma brucei Tb11.02.5050b   protein kinase, putative
Trypanosoma brucei Tb927.11.7210   eukaryotic translation initiation factor 2-alpha kinase 1, putative
Trypanosoma congolense TcIL3000.11.7780   protein kinase, putative
Trypanosoma congolense TcIL3000_0_47340   protein kinase, putative

Essentiality

Tb927.11.7210 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.5050 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.5050 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb11.02.5050 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.5050 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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.
  • 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
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84

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
Species Known druggable target Linked compounds Reference
Homo sapiens eukaryotic translation initiation factor 2-alpha kinase 1 Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Rattus norvegicus Cell division protein kinase 5 292 aa 25.2% 242 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.1039 0.3143 1
0.0059 1 1
0.1564 1 1
0.0101 0.4263 1
0.0098 0.3242 0.2614
0.0063 0.7244 0.2543
0.1887 1 1
0.0963 0.7114 1
0.1402 1 0.5
0.0165 0.2862 1
0.0069 0.3067 1
0.0039 0.5 0.5
0.0091 1 0.5
0.0039 0.9485 0.5
0.1887 1 1
0.01 0.2665 1
0.0169 0.3972 1
0.0036 0.5 0.5
0.0279 0.2659 1
0.0061 0.6883 0.5304
0.1589 1 0.5
0.1827 1 0.5
0.1514 1 1
0.01 0.5873 1
0.0032 0.5 0.5
0.0101 0.3584 1
0.0063 1 0.5
0.0064 0.3377 0
0.0004 0.5 0.5
0.1451 1 0.5
0.1039 0.3143 1
0.0066 0.3101 0
0.0003 0.5 0.5
0.1597 0.629 1
0.0033 1 0.5
0.1039 0.3143 1
0.0016 0.5 0.5
0.0027 1 0.5
0.0008 0.5 0.5
0.0101 0.4066 1
0.0088 0.4477 0.5
0.0042 0.5 0.5
0.198 1 0.5
0.0093 0.8828 0
0.0022 0.5 0.5
0.0062 0.6935 0
0.0011 1 0.5
0.1717 1 0.5
0.0037 1 0.5
0.0012 0.5 0.5
0.0336 0.3872 0.5
0.0039 0.5 0.5
0.0087 0.3819 1
0.1589 1 0.5
0.0336 0.3872 0.5
0.0059 1 1
0.0096 0.3956 1
0.0067 0.5 0.5
0.1699 1 0.5
0.0059 1 1
0.0016 0.5 0.5
0.1887 1 1
0.01 0.3579 0.5
0.0032 0.5 0.5
0.0081 0.5 0.5
0.0018 0.5 0.5
0.0081 1 0.5
0.0023 0.5 0.5
0.1597 0.629 1
0.0849 1 0.5
0.01 0.2711 1
0.0029 0.5 0.5
0.0012 0.5 0.5
0.0101 0.4127 1
0.01 0.3721 1
0.0007 0.5 0.5
0.0087 0.3819 1
0.0187 0.5422 1
0.1887 1 1
0.0056 1 0.5
0.0007 0.5 0.5
0.0012 0.5 0.5
0.0007 0.5 0.5
0.0033 0.5 0.5
0.0026 0.5 0.5
0.0092 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.

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Gene identifier Tb927.11.7210 (Trypanosoma brucei), eukaryotic translation initiation factor 2-alpha kinase 1, putative
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