Detailed view for PF3D7_1148000

Basic information

TDR Targets ID: 1953
Plasmodium falciparum, serine/threonine protein kinase, putative
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.3228 | Length (AA): 1429 | MW (Da): 170705 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | 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:0051304   chromosome separation  
GO:0007093   mitotic cell cycle checkpoint  
GO:0004712   protein serine/threonine/tyrosine kinase activity  
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 14 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
980 1428 1omw (A) 34 458 24.00 0 1 0.5 0.11
1150 1427 2acx (A) 183 452 30.00 0.00000000044 1 0.6 -1.19
689 1206 2vkh (A) 3 516 25.00 0.22 0.79 0.269591 0.97
1066 1428 4yhj (A) 94 454 25.00 0 1 0.399624 0.66
1138 1429 2rku (A) 38 311 32.00 0 1 0.514939 0.11
1146 1423 2bdw (A) 5 271 25.00 0 1 0.449142 -0.03
1281 1355 4ix3 (A) 314 410 45.00 0.29 0.21 0.0405843 1.38
253 365 3na7 (A) 63 174 26.00 0.48 0.02 0.379143 -1.37
440 634 4uos (A) 2 180 34.00 0.081 1 0.305546 -0.14
508 697 4qts (A) 33 215 37.00 0.6 0.29 -0.0769602 2.24
1044 1424 2acx (A) 90 452 24.00 0.0000000047 1 0.204081 0.81
1135 1426 2rku (A) 38 311 32.00 0 1 0.514669 0.11
1196 1424 2i6l (B) 59 320 33.00 0.00014 1 0.315389 -0.1
1278 1352 4ix3 (A) 314 410 45.00 0.29 0.21 0.0403947 1.38

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 early schizont, early trophozoite, late trophozoite, Oocyst, Male Gametocyte. PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, gametocyte, sporozoite, late ring, late schizont, Female Gametocyte. Otto TD PlasmoDB Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, Ring, Sporozoite. Otto TD Zanghi G
Show/Hide expression data references
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.

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

PF3D7_1148000 has one or more orthologs with essentiality data
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 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.7220 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.8.7220 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.7220 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
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • 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
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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 1 Compounds References
Homo sapiens tousled-like kinase 2 Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Rattus norvegicus Mitogen-activated protein kinase 1 358 aa 29.8% 299 aa Compounds References
Rattus norvegicus MAP kinase p38 alpha 360 aa 25.3% 308 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 31.1% 241 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0098 0.3242 0.2614
0.0081 1 0.5
0.0042 0.5 0.5
0.0023 0.5 0.5
0.0004 0.5 0.5
0.0012 0.5 0.5
0.0032 0.5 0.5
0.0032 0.5 0.5
0.0064 0.3377 0
0.0012 0.5 0.5
0.0016 0.5 0.5
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 1
0.0007 0.5 0.5
0.0088 0.4477 0.5
0.0081 0.5 0.5
0.0033 0.5 0.5
0.0022 0.5 0.5
0.0059 1 1
0.0036 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
0.0008 0.5 0.5
0.0063 0.7244 0.7244
0.0056 1 0.5
0.0039 0.5 0.5
0.0091 1 0.5
0.0063 1 1
0.0037 1 0.5
0.0026 0.5 0.5
0.0018 0.5 0.5
0.0066 0.3101 0
0.0011 1 0.5
0.0039 0.5 0.5
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 1
0.0067 0.5 0.5
0.0062 0.6935 0

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier PF3D7_1148000 (Plasmodium falciparum), serine/threonine protein kinase, putative
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