Detailed view for PF3D7_1228300

Basic information

TDR Targets ID: 5326
Plasmodium falciparum, NIMA related kinase 1
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.8199 | Length (AA): 1057 | MW (Da): 124945 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 0

Druggability Group : DG3

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:0007067   mitosis  
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 18 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
12 305 1gz8 (A) 1 293 29.00 0 1 0.43 -0.64
12 483 1omw (A) 188 646 21.00 0 1 0.51 0.83
1 292 2j0j (A) 409 672 26.00 0 1 0.405254 0.22
10 306 2w5a (A) 3 279 40.00 0 1 0.669884 -0.24
11 315 4b9d (A) 0 275 34.00 0 1 0.604553 -0.35
15 569 4kik (B) 15 549 18.00 0.0000002 1 0.675971 0.34
62 290 1cm8 (A) 74 277 31.00 0.0000055 1 0.269651 0.61
100 287 2jii (A) 261 444 18.00 0.038 0.91 0.244862 0.15
398 583 4tql (A) 21 203 24.00 0.0086 0.23 0.50197 -1.99
413 507 1d7m (A) 256 343 39.00 0.91 0.02 0.422877 -1.47
474 874 4dv8 (A) 265 665 26.00 0.3 0.81 0.433376 0.51
825 1042 4u0r (A) 211 495 16.00 0.24 0 0.292144 -0.31
15 300 3c0g (B) 12 278 29.00 0 1 0.570601 -0.37
15 558 4kik (B) 15 541 18.00 0.00000014 1 0.632384 0.54
67 288 4ff8 (A) 563 768 25.00 0.000000023 0.99 0.00153206 0.8
425 585 4tql (A) 14 187 23.00 0.013 0.16 0.496326 -2.16
474 874 4dv8 (A) 265 665 26.00 0.18 0.85 0.441034 0.5
843 1017 4u5a (C) 47 238 20.00 1 0.01 0.398285 -0.83

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 80-100% percentile Oocyst, Male Gametocyte. Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile early schizont, late schizont, late trophozoite, Female Gametocyte. PlasmoDB Lasonder E
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 32 hs, gametocyte, merozoite, early trophozoite, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 24 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, Sporozoite. Otto TD Zanghi G
Show/Hide expression data references
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • 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.

Orthologs

Ortholog group members (OG5_129446)

Species Accession Gene Product
Babesia bovis BBOV_III010080   protein kinase domain containing protein
Candida albicans CaO19.5325   likely protein kinase similar to S. cerevisiae KIN3 (YAR018C)
Candida albicans CaO19.12785   likely protein kinase similar to S. cerevisiae KIN3 (YAR018C)
Cryptosporidium hominis Chro.10172   NEK2 protein
Cryptosporidium parvum cgd1_1490   NEK2 protein, putative
Dictyostelium discoideum DDB_G0270814   NEK family protein kinase
Drosophila melanogaster Dmel_CG17256   CG17256 gene product from transcript CG17256-RA
Giardia lamblia GL50803_5375   Kinase, NEK
Giardia lamblia GL50803_95593   Kinase, NEK
Giardia lamblia GL50803_11311   Kinase, NEK
Homo sapiens ENSG00000117650   NIMA-related kinase 2
Mus musculus ENSMUSG00000026622   NIMA (never in mitosis gene a)-related expressed kinase 2
Neospora caninum NCLIV_043340   MGC81305 protein, related
Plasmodium berghei PBANKA_1443000   NIMA related kinase 1, putative
Plasmodium falciparum PF3D7_1228300   NIMA related kinase 1
Plasmodium knowlesi PKNH_1447700   NIMA related kinase 1, putative
Plasmodium vivax PVX_124045   NIMA-related protein kinase (Pfnek-1), putative
Plasmodium yoelii PY04005   NIMA-related protein kinase
Saccharomyces cerevisiae YAR018C   Kin3p
Schmidtea mediterranea mk4.011291.01  
Toxoplasma gondii TGME49_292140   NIMA-related protein kinase NIMA1
Theileria parva TP02_0139   NIMA-related protein kinase, putative
Trichomonas vaginalis TVAG_025740   AGC family protein kinase
Trichomonas vaginalis TVAG_050700   STE family protein kinase

Essentiality

PF3D7_1228300 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_1443000 Plasmodium berghei Essential plasmo
TGME49_292140 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
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • 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
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium falciparum 590200  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 11322879 16513357
Plasmodium falciparum 13885   323911  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 11322879 16513357
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium falciparum 590200  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 11322879 16513357

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): 0.7

Known modulators for this target

Compound Source Reference
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Homo sapiens NIMA-related kinase 2 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 30.8% 247 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 29.8% 245 aa Compounds References
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 31.1% 244 aa Compounds References
Rattus norvegicus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 26.2% 298 aa Compounds References
Rattus norvegicus Serine/threonine-protein kinase pim-3 326 aa 24.6% 305 aa Compounds References
Oryctolagus cuniculus Cyclin-dependent kinase 4 189 aa 28.4% 190 aa Compounds References
Patiria pectinifera Cdc2 300 aa 27.6% 254 aa Compounds References
Schizosaccharomyces pombe 972h- Casein kinase II subunit alpha 332 aa 23.0% 274 aa Compounds References
Bos taurus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 26.5% 298 aa Compounds References
Oryctolagus cuniculus cAMP-dependent protein kinase alpha-catalytic subunit 351 aa 28.1% 292 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.1149 1 0.5
0.0323 1 1
0.0078 0.2718 1
0.0888 0.6211 0.6208
0.0189 0.3784 1
0.1275 1 1
0.0003 0.5 0.5
0.0061 0.6883 1
0.0023 0.5 0.5
0.0356 1 1
0.0448 0.623 1
0.0098 0.3242 0.2614
0.0125 0.4077 1
0.0818 1 1
0.0682 1 0.5
0.0039 0.5 0.5
0.0663 0.7904 1
0.0125 1 0.5
0.0063 0.7244 0.7244
0.0436 1 0.5
0.0012 0.5 0.5
0.0125 0.3676 1
0.0057863 0.320697 0.413437
0.0888 0.6211 0.6208
0.1105 1 1
0.0448 0.623 1
0.0037 1 0.5
0.0367 1 0.5
0.1333 0.2571 1
0.0365 1 0.5
0.0447 0.8521 0.5
0.1257 1 0.5
0.0027 1 0.5
0.169477 1 1
0.0128 0.4046 0.6284
0.0067 0.5 0.5
0.0125 1 0.5
0.0128 0.4046 0.6284
0.0125 1 0.5
0.0105 0.357 1
0.1081 0.3282 1
0.0029 0.5 0.5
0.0346 0.8811 0.8974
0.0004 0.5 0.5
0.0125 1 0.5
0.0105 0.357 1
0.0125 1 0.5
0.0325 0.3444 1
0.0039 0.9485 0.5
0.0437 0.5115 1
0.0665 1 0.5
0.0125 1 1
0.0283 0.2908 1
0.0759 1 1
0.0033 0.5 0.5
0.0904 1 1
0.013 0.2609 1
0.0091 1 0.5
0.0039 0.5 0.5
0.0008 0.5 0.5
0.0126 0.5909 1
0.0064 0.3377 0
0.0125 1 1
0.0733 0.4435 1
0.1173 1 0.5
0.1333 0.2571 1
0.0124 1 0.5
0.0107 0.2918 0.8822
0.0088 0.4477 0.5
0.0007 0.5 0.5
0.0124 0.6271 1
0.0213 1 1
0.0032 0.5 0.5
0.0125 1 0.5
0.0452 0.4154 1
0.0016 0.5 0.5
0.0032 0.5 0.5
0.0066 0.3101 0
0.1285 1 0.5
0.0016 0.5 0.5
0.0124 0.3418 1
0.1404 0.5578 1
0.0007 0.5 0.5
0.0437 0.5115 1
0.0993 0.485 1
0.0603 0.3274 1
0.034 0.8586 1
0.0117 0.3724 1
0.0081 1 0.5
0.0692 1 1
0.0106 0.3718 1
0.0126 0.324 1
0.0069 0.3067 1
0.1242 1 1
0.0482 0.5397 1
0.0033 1 1
0.0012 0.5 0.5
0.0103 0.278 1
0.0042 0.5 0.5
0.0124 0.7261 1
0.0109 0.3558 0.5
0.0213 1 1
0.0102 0.3506 1
0.0357 0.4342 1
0.0059 1 1
0.0104 0.3181 1
0.0036 0.5 0.5
0.0011 1 0.5
0.0127 0.4224 0.3779
0.0356 0.9563 1
0.0603 0.3274 1
0.0093 0.8828 0
0.0007 0.5 0.5
0.0026 0.5 0.5
0.1289 1 0.5
0.169477 1 1
0.1506 0.2974 1
0.0743 1 1
0.0103 0.278 1
0.1046 1 1
0.1203 1 0.5
0.0363 0.4277 0.5
0.0124 1 0.5
0.0124 0.4183 1
0.0235 0.4902 0.5
0.1081 1 1
0.0125 1 0.5
0.0665 0.6772 1
0.0105 0.357 1
0.0056 1 0.5
0.0875 1 1
0.0129 0.4581 1
0.0059 1 1
0.0124 1 1
0.0059 1 1
0.0326 1 0.5
0.0322 0.9739 1
0.0223 0.371 1
0.0062 0.6935 0
0.0012 0.5 0.5
0.0128 0.4046 0.6284
0.0648 1 0.5
0.0124 0.8903 0.5
0.0092 1 0.5
0.0063 1 1
0.0022 0.5 0.5
0.0678 0.6446 1
0.1263 1 1
0.0124 0.32 1
0.0081 0.5 0.5
0.1218 1 0.5
0.1168 1 1
0.1218 1 0.5
0.0125 1 0.5
0.0018 0.5 0.5
0.0356 0.9563 1
0.0108 0.3702 0.5
0.1213 1 1
0.0559 0.3993 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

57 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.

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Gene identifier PF3D7_1228300 (Plasmodium falciparum), NIMA related kinase 1
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