Detailed view for Tb927.3.4020

Basic information

TDR Targets ID: 15757
Trypanosoma brucei, phosphatidylinositol 4-kinase alpha, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.1917 | Length (AA): 2312 | MW (Da): 255502 | 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

PF00454   Phosphatidylinositol 3- and 4-kinase
PF00613   Phosphoinositide 3-kinase family, accessory domain (PIK domain)

Gene Ontology

Mouse over links to read term descriptions.
GO:0016301   kinase activity  
GO:0005488   binding  
GO:0004428   inositol or phosphatidylinositol kinase activity  
GO:0046854   phosphoinositide phosphorylation  
GO:0048015   phosphoinositide-mediated signaling  

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
1200 1423 4tql (A) 9 232 9.00 0.48 0.01 0.146886 -0.21
1475 2308 5dfz (C) 11 871 18.00 0 1 0.281727 1.47
1761 2297 4uwh (A) 295 872 24.00 0 1 0.377266 -0.47
1820 2291 5c4g (E) 141 781 27.00 0 1 0.391652 -0.24
2110 2168 2r5t (A) 173 242 44.00 0.46 0.64 0.252719 0.88

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. Siegel TN
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile 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_128362)

Species Accession Gene Product
Arabidopsis thaliana AT1G51040   phosphatidylinositol 4-kinase alpha 2
Arabidopsis thaliana AT1G49340   phosphatidylinositol 4-kinase alpha
Brugia malayi Bm1_45855   hypothetical protein
Brugia malayi Bm1_45860   phosphatidylinositol 4-kinase, catalytic, alpha polypeptide
Candida albicans CaO19.1814   Phosphatidylinositol-4-kinase.
Candida albicans CaO19.9377   Phosphatidylinositol-4-kinase.
Caenorhabditis elegans CELE_Y75B8A.24   Protein Y75B8A.24
Dictyostelium discoideum DDB_G0277537   phosphatidylinositol 4-kinase
Drosophila melanogaster Dmel_CG10260   Phosphatidylinositol 4-kinase III alpha
Echinococcus granulosus EgrG_000799800   phosphatidylinositol 4 kinase alpha
Entamoeba histolytica EHI_148700   phosphatidylinositol 4-kinase, putative
Echinococcus multilocularis EmuJ_000799800   phosphatidylinositol 4 kinase alpha
Homo sapiens ENSG00000241973   phosphatidylinositol 4-kinase, catalytic, alpha
Leishmania braziliensis LbrM.29.1540   phosphatidylinositol 4-kinase alpha, putative
Leishmania donovani LdBPK_291550.1   phosphatidylinositol-kinase domain protein, putative
Leishmania infantum LinJ.29.1550   phosphatidylinositol 4-kinase alpha, putative
Leishmania major LmjF.29.1450   phosphatidylinositol 4-kinase alpha, putative
Leishmania mexicana LmxM.08_29.1450   phosphatidylinositol-kinase domain protein, putative
Loa Loa (eye worm) LOAG_15974   hypothetical protein
Loa Loa (eye worm) LOAG_12597   phosphatidylinositol 4-kinase type 3 alpha isoform 1
Loa Loa (eye worm) LOAG_12125   hypothetical protein
Mus musculus ENSMUSG00000041720   phosphatidylinositol 4-kinase, catalytic, alpha polypeptide
Neospora caninum NCLIV_044900   hypothetical protein
Oryza sativa 4333883   Os03g0711200
Saccharomyces cerevisiae YLR305C   1-phosphatidylinositol 4-kinase STT4
Schistosoma japonicum Sjp_0123460   Phosphatidylinositol 4-kinase alpha, putative
Schistosoma japonicum Sjp_0082010   ko:K00888 phosphatidylinositol 4-kinase [EC2.7.1.67], putative
Schistosoma japonicum Sjp_0110720   expressed protein
Schistosoma japonicum Sjp_0131040   Phosphatidylinositol 4-kinase alpha, putative
Schistosoma japonicum Sjp_0129560   Phosphatidylinositol 4-kinase alpha, putative
Schistosoma mansoni Smp_053190   hypothetical protein
Schistosoma mansoni Smp_150660   phosphatidylinositol 4-kinase
Schmidtea mediterranea mk4.002463.00  
Trypanosoma brucei gambiense Tbg972.3.4410   phosphatidylinositol 4-kinase alpha, putative
Trypanosoma brucei Tb927.3.4020   phosphatidylinositol 4-kinase alpha, putative
Trypanosoma congolense TcIL3000_3_2660   phosphatidylinositol 4-kinase alpha, putative
Trypanosoma congolense TcIL3000_0_37620   phosphatidylinositol 4-kinase alpha, putative
Trypanosoma cruzi TcCLB.507531.19   phosphatidylinositol 4-kinase alpha, putative
Trypanosoma cruzi TcCLB.510003.30   phosphatidylinositol 4-kinase alpha, putative
Trypanosoma cruzi TcCLB.507533.10   phosphatidylinositol 4-kinase alpha, putative
Toxoplasma gondii TGME49_228690   phosphatidylinositol 3- and 4-kinase
Trichomonas vaginalis TVAG_161620   phosphatidylinositol 4-kinase, putative
Trichomonas vaginalis TVAG_236630   phosphatidylinositol kinase, putative

Essentiality

Tb927.3.4020 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.3.4020 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.3.4020 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.3.4020 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.3.4020 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_Y75B8A.24 Caenorhabditis elegans slow growth wormbase
YLR305C Saccharomyces cerevisiae inviable yeastgenome
TGME49_228690 Toxoplasma gondii Essentiality uncertain sidik
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.
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

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) 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): 0.6

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 phosphatidylinositol 4-kinase, catalytic, alpha Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0059 0.7645 1
0.0366 0.3303 1
0.0225 0.476 1
0.0108 0.9372 1
0.0402 0.298 1
0.0531 0.259 0
0.014 1 1
0.025 0.9005 1
0.0114 0.4 1
0.0402 0.3862 1
0.0061 0.7645 1
0.0366 0.3159 0.3026
0.026 0.9565 1
0.0374 0.3634 1
0.0389 0.3835 0.4122
0.032 0.3292 0.8231
0.0097 1 1
0.0097 1 1
0.005 1 1
0.026 0.9565 1
0.033 0.2741 0.2133
0.0531 0.259 0
0.0233 0.3765 1
0.0108 0.9372 1
0.0519 0.26 0
0.0369 0.2846 0.2846
0.0113 0.4043 1
0.0367 0.3303 1
0.00880618 1 1
0.0411 0.3846 1
0.0113 0.6506 1
0.0629 0.3415 0
0.0467 0.2566 1
0.0108 0.3853 1
0.0113 0.6506 1
0.0274 0.4524 1
0.004 0.306 1
0.0173 0.2922 1
0.0113 0.3377 1
0.0244 0.2613 1
0.0057 0.2682 0.7715
0.0392 0.3907 1
0.0359 0.3044 0.2925
0.0175 0.6243 1
0.0139 0.5531 1
0.0377 0.2896 0.2845
0.0392 0.3902 1
0.0108 0.9372 1
0.0113 0.3889 1
0.0286 0.2825 1
0.0402 0.3912 1
0.0147 1 1
0.0287 0.4741 1
0.0395 0.3689 1
0.0255 0.8262 1
0.0113 0.3377 1
0.0387 0.3623 0.9591
0.033 0.2741 0.2133
0.033 0.2741 0.2133
0.0326 0.3926 0.8538
0.0376 0.3509 0.3495
0.0403 0.3906 1
0.0246 0.2856 1
0.0501 0.2572 0
0.0389 0.3911 1
0.037 0.3354 1
0.0409 0.3863 1
0.014 1 1
0.0287 0.4741 1
0.00496371 0.444341 0.444341
0.0061 0.7645 1
0.0111 0.4221 1
0.0384 0.3847 0.7387
0.0187 0.2919 0.8832
0.0462 0.2914 0.8083
0.0108 0.3923 1
0.0396 0.3723 1
0.0391 0.3905 1
0.0106 0.3827 1
0.026 0.9565 1
0.0376 0.3112 1
0.0399 0.3872 1
0.0332 0.357 1
0.0511 0.2553 0
0.0109 0.3856 1
0.038 0.2877 0.2877
0.0409 0.3853 1
0.0259 0.2538 0.2399
0.0497 0.2948 0
0.0097 0.3564 1
0.0204 0.2521 1
0.0227 0.2662 1
0.0399 0.3838 1
0.0237 0.2756 0.1152
0.0359 0.3171 1
0.0615 0.2637 1
0.038 0.3897 1
0.0284 0.2827 1
0.0061 0.7645 1
0.0615 0.2637 1
0.0108 0.9372 1
0.0061 0.7645 1
0.005 1 1
0.0098 1 1
0.0089 1 1
0.0348 0.3609 1
0.0531 0.259 0
0.0396 0.3934 1
0.0356 0.3381 1
0.066 0.2535 1
0.0061 0.7645 1
0.0389 0.318 0.3169
0.0615 0.2637 1
0.0439 0.2687 0
0.0559 0.2529 0
0.0184 0.2721 0.867
0.0199 0.3677 0.9691
0.0615 0.2637 1
0.036 0.309 1
0.0353 0.3603 1
0.0392 0.3907 1
0.0392 0.3897 1
0.0108 0.9372 1
0.0115 0.3977 1
0.0153 0.5868 1
0.0388 0.3845 1
0.0401 0.3836 1
0.0178 0.3809 1
0.0402 0.298 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

4 literature references were collected for this gene.

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Gene identifier Tb927.3.4020 (Trypanosoma brucei), phosphatidylinositol 4-kinase alpha, putative
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