Detailed view for PF3D7_1127100

Basic information

TDR Targets ID: 1751
Plasmodium falciparum, deoxyuridine 5'-triphosphate nucleotidohydrolase

Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 6.9703 | Length (AA): 173 | MW (Da): 19573 | 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

PF00692   dUTPase

Gene Ontology

Mouse over links to read term descriptions.
GO:0006399   tRNA metabolic process  
GO:0005575   cellular_component  
GO:0016787   hydrolase activity  
GO:0004170   dUTP diphosphatase activity  
GO:0046080   dUTP metabolic process  
GO:0006260   DNA replication  

Metabolic Pathways

Structural information

Modbase 3D models:

There are 2 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
1 159 1vyq (A) 1 159 99.99 0 1 1.99 -0.9
1 167 3t64 (A) 1 167 99.99 0 1 2.04612 -0.78

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:

  • 1VYQ:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 2Y8C:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 3T60:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 3T64:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 3T6Y:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 3T70:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, gametocyte, merozoite, sporozoite, early schizont, early trophozoite, late schizont, late trophozoite, Oocyst, Male Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 16 hs, early ring, late ring. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 8 hs, Ring, Sporozoite. Otto TD Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Female Gametocyte. Lasonder E
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
  • 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.
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.

Orthologs

Ortholog group members (OG5_126992)

Species Accession Gene Product
Arabidopsis thaliana AT3G46940   deoxyuridine 5'-triphosphate nucleotidohydrolase
Babesia bovis BBOV_IV005770   deoxyuridine 5'-triphosphate nucleotidohydrolase, putative
Brugia malayi Bm1_03525   dUTP diphosphatase
Candida albicans CaO19.3322   dUTP pyrophosphatase gene isolated by genetic complementation in S. cerevisiae.
Candida albicans CaO19.10832   dUTP pyrophosphatase gene isolated by genetic complementation in S. cerevisiae.
Caenorhabditis elegans CELE_K07A1.2   Protein DUT-1
Cryptosporidium hominis Chro.70577   deoxyuridine 5-triphosphate nucleotidohydrolase
Cryptosporidium parvum cgd7_5170   deoxyuridinetriphosphatase, possible bacterial origin
Chlamydia trachomatis CT_292   deoxyuridine 5'-triphosphate nucleotidohydrolase
Dictyostelium discoideum DDB_G0293374   dUTP diphosphatase
Drosophila melanogaster Dmel_CG4584   Deoxyuridine triphosphatase
Echinococcus granulosus EgrG_000119100   dUTP pyrophosphatase
Entamoeba histolytica EHI_026890   deoxyuridine 5-triphosphate nucleotidohydrolase, mitochondrial precursor, putative
Entamoeba histolytica EHI_034560   deoxyuridine 5-triphosphate nucleotidohydrolase domain containing protein
Entamoeba histolytica EHI_144170   hypothetical protein
Entamoeba histolytica EHI_072960   hypothetical protein
Entamoeba histolytica EHI_059310   deoxyuridine 5-triphosphate nucleotidohydrolase domain containing protein
Entamoeba histolytica EHI_137470   deoxyuridine 5-triphosphate nucleotidohydrolase, mitochondrial precursor, putative
Entamoeba histolytica EHI_126430   hypothetical protein
Entamoeba histolytica EHI_018140   hypothetical protein
Entamoeba histolytica EHI_193660   deoxyuridine 5-triphosphate nucleotidohydrolase domain containing protein
Entamoeba histolytica EHI_116940   deoxyuridine 5-triphosphate nucleotidohydrolase domain containing protein
Echinococcus multilocularis EmuJ_000119100   dUTP pyrophosphatase
Homo sapiens ENSG00000128951   deoxyuridine triphosphatase
Loa Loa (eye worm) LOAG_13155   dUTP diphosphatase
Mus musculus ENSMUSG00000027203   deoxyuridine triphosphatase
Neospora caninum NCLIV_032950   deoxyuridine 5-triphosphate nucleotidohydrolase, putative
Oryza sativa 4333679   Os03g0669100
Plasmodium berghei PBANKA_0921300   deoxyuridine 5'-triphosphate nucleotidohydrolase, putative
Plasmodium falciparum PF3D7_1127100   deoxyuridine 5'-triphosphate nucleotidohydrolase
Plasmodium knowlesi PKNH_0925100   deoxyuridine 5'-triphosphate nucleotidohydrolase, putative
Plasmodium vivax PVX_091970   deoxyuridine 5'-triphosphate nucleotidohydrolase, putative
Plasmodium yoelii PY05536   putative deoxyuridine 5'-triphosphate nucleotidohydrolase
Saccharomyces cerevisiae YBR252W   bifunctional dITP/dUTP diphosphatase
Schistosoma japonicum Sjp_0204430   ko:K01520 dUTP pyrophosphatase [EC3.6.1.23], putative
Schistosoma mansoni Smp_079240   deoxyuridine 5'-triphosphate nucleotidohydrolase
Toxoplasma gondii TGME49_233140   deoxyuridine 5'-triphosphate nucleotidohydrolase, putative
Treponema pallidum TP0885   deoxyuridine 5'-triphosphate nucleotidohydrolase (dut)
Theileria parva TP01_0381   deoxyuridine 5'-triphosphate nucleotidohydrolase, putative
Trichomonas vaginalis TVAG_379830   deoxyuridine 5'-triphosphate nucleotidohydrolase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0355   dUTPase

Essentiality

PF3D7_1127100 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
CELE_K07A1.2 Caenorhabditis elegans embryonic lethal wormbase
CELE_K07A1.2 Caenorhabditis elegans larval arrest wormbase
CELE_K07A1.2 Caenorhabditis elegans sterile wormbase
YBR252W Saccharomyces cerevisiae inviable yeastgenome
TGME49_233140 Toxoplasma gondii Probably essential 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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.
  • 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.
  • 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
  • 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
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium falciparum 567114  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 15698576 16161998 16821778

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

Compound Source Reference
ChEMBL23 References
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Curated by TDRTargets References
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Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Homo sapiens deoxyuridine triphosphatase 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
0.0331 1 0.5
0.0948 1 0.5
0.0538 0.5453 1
0.0091 1 0.5
0.0315 0.315 1
0.0697 1 1
0.0091 1 0.5
0.0073 0.292 0.5
0.0091 1 0.5
0.347 0.6203 1
0.122 1 0.5
0.0401 0.4564 1
0.0083 1 1
0.0226 1 1
0.3552 1 1
0.0091 0.2583 0.5
0.0314 0.4446 1
0.078 0.9348 1
0.0091 1 0.5
0.0343 0.3753 1
0.0091 1 0.5
0.0147 1 0.5
0.214 0.3062 1
0.0091 1 0.5
0.0149 0.6749 1
0.0174 0.5326 1
0.1793 1 1
0.0782 0.7845 1
0.1025 0.7391 1
0.095 1 0.5
0.0331 0.2657 1
0.0091 1 0.5
0.0401 0.4564 1
0.0091 1 0.5
0.0643 0.5291 1
0.0146 0.4739 0.5
0.0322 1 1
0.1228 1 1
0.0091 1 0.5
0.4001 1 1
0.3349 0.2685 0.8754
0.0091 1 0.5
0.0737 1 0.5
0.0091 1 0.5
0.1222 1 0.5
0.015 0.4025 0.5
0.0091 1 0.5
0.0313 0.4938 0.5007
0.0888 1 1
0.3709 1 0.5
0.3349 0.2685 0.8754
0.033 0.3259 1
0.1055 0.6215 0.5
0.4001 1 1
0.1188 1 1
0.1205 1 1
0.0161 0.3613 0.5
0.0504 1 1
0.1076 0.5 0.5
0.122 1 0.5
0.0091 0.6814 1
0.0157 0.2572 0.5
0.1085 1 0.5
0.0706 0.8946 1
0.0632 1 0.5
0.0091 1 0.5
0.0313 0.4938 0.5007
0.0746 0.4655 1
0.0091 1 0.5
0.0147 1 0.5
0.379 1 1
0.0319 0.7627 1
0.3551 1 1
0.0091 1 0.5
0.0091 1 0.5
0.0729 0.7883 1
0.1188 1 1
0.0184 0.8529 1
0.0091 1 0.5
0.0775 1 1
0.09 1 0.5
0.3649 1 1
0.0578 1 0.5
0.0596 0.7092 0.5
0.0091 1 0.5
0.3636 1 1
0.0073 0.292 0.5
0.068 0.7686 0.5
0.0335 0.6602 1
0.0331 0.2657 1
0.0257 0.2918 1
0.1004 1 1
0.0342 0.4194 0.5
0.0315 0.7871 0.5
0.0377 1 0.5
0.0494 1 0.5
0.0331 1 0.5
0.0091 1 0.5
0.3456 1 0.5
0.0165 0.4638 0.5
0.0091 1 0.5
0.0091 0.551 0.5
0.109 1 1
0.0313 0.4938 0.5007
0.3416 1 0.5
0.0557 0.2714 0.8105
0.214 0.3062 1
0.0326 1 0.5
0.015 0.2902 0.5
0.0091 1 0.5
0.1383 1 1
0.0164 0.537 1
0.0435 0.5406 1
0.0237 1 0.5
0.0091 0.2688 1
0.0471 0.6282 1
0.0091 0.3615 1
0.0309 1 1
0.0091 1 0.5
0.1774 1 1
0.0091 1 0.5
0.113 1 1
0.0332 1 0.5
0.0578 1 0.5
0.1854 1 1
0.0233 0.6297 0.5
0.1975 0.6013 1
0.1025 0.7385 1
0.0091 0.2776 0.5
0.1436 1 1
0.0494 1 0.5
0.0091 1 0.5
0.0091 1 0.5
0.0494 1 0.5
0.0343 0.3753 1
0.09 1 0.5
0.0406 1 0.5
0.0091 1 0.5
0.0706 0.8946 1
0.0606 1 1
0.3702 1 1
0.0781 0.335 1
0.3776 1 0.5
0.0091 0.2773 0.5
0.0706 0.8218 1
0.0173 0.461 1
0.0082 1 0.5
0.043 1 1
0.0091 1 0.5
0.0149 0.6749 1
0.1178 1 1
0.0331 1 0.5
0.0539 0.2971 1
0.0834 0.3714 1
0.0174 0.5817 0.5
0.0091 1 0.5
0.0074 0.2591 0.5
0.0864 1 1
0.0408 1 1
0.214 0.3062 1
0.1632 1 1
0.0091 1 0.5
0.0091 0.6572 0.5
0.1346 0.9009 1
0.3715 1 0.5
0.3349 0.2685 0.8754
0.0123608 0.253843 1
0.0091 1 0.5
0.0785 1 1
0.0076 0.3986 0.5
0.0526 0.529 0.5
0.1205 1 1
0.086 1 1
0.0091 1 0.5
0.0091 0.2674 0.5
0.0333 1 0.5
0.3649 1 1
0.379 1 0.5
0.0313 0.4938 0.5007
0.1211 1 1
0.0471 0.6282 1
0.1383 1 1
0.0401 0.4564 1
0.0824 1 1
0.0307 0.2973 0.5
0.0228 0.268 0.5
0.0705 0.7744 1
0.0404 0.3736 0.5
0.1753 1 0.5
0.1035 1 1
0.0123608 0.730229 1
0.0471 0.6282 1
0.0146 0.2998 0.5
0.0606 0.5189 1
0.1079 0.6619 1
0.0341 0.3318 0.5
0.0091 1 0.5
0.0803 1 0.5
0.0966 1 1
0.0091 1 0.5
0.1346 0.9009 1
0.0148 1 0.5
0.0815 1 0.5
0.0091 1 0.5
0.0796 0.394 1
0.0091 1 0.5
0.0224 0.4444 0.5
0.0302 1 0.5
0.0826 1 1
0.0091 0.2776 0.5
0.0176 0.3555 1
0.3349 0.2685 0.8754
0.214 0.3062 1
0.0538 0.5453 1
0.3297 1 1
0.0173 0.461 1
0.0091 1 0.5
0.3423 1 0.5
0.4001 1 1
0.0091 1 0.5
0.0774 1 0.5
0.0307 1 0.5
0.0478 1 0.5
0.0901 0.9168 1
0.0091 1 0.5
0.0304 1 1
0.0387 0.2708 0.5
0.0155 0.2744 0.5
0.3436 1 0.5
0.0108 0.8641 0.5
0.0805 1 0.5
0.0091 1 0.5
0.1025 0.7382 1
0.379 1 1
0.1157 0.5 0.5
0.0073 1 0.5
0.00778006 0.39647 0.5
0.0528 0.2784 0.8156
0.0966 1 1
0.3495 1 1

Assayability

Assay information

  • Inhibitory constant against Plasmodium falciparum deoxyuridine 5'-triphosphate nucleotidohydrolase expressed in E. coli BL21 (DE3) cells ChEMBL
  • Inhibitory constant against Plasmodium falciparum deoxyuridine 5'-triphosphate nucleotidohydrolase expressed in Escherichia coli BL21 (DE3) cells
  • Selectivity index for Plasmodium falciparum deoxyuridine 5'-triphosphate nucleotidohydrolase defined as (Ki Human)/(Ki P. falciparum); na= not relevant ChEMBL
  • Selectivity index for Plasmodium falciparum deoxyuridine 5'-triphosphate nucleotidohydrolase defined as (Ki Human)/(Ki Plasmodium falciparum); na= not relevant
  • Inhibitory constant against Plasmodium falciparum deoxyuridine 5'-triphosphate nucleotidohydrolase expressed in E. coli BL21 (DE3) cells; nd = not determined ChEMBL
  • Inhibitory constant against Plasmodium falciparum deoxyuridine 5'-triphosphate nucleotidohydrolase expressed in Escherichia coli BL21 (DE3) cells; nd = not determined
  • Selectivity index for Plasmodium falciparum deoxyuridine 5'-triphosphate nucleotidohydrolase defined as (Ki Human)/(Ki P. falciparum) ChEMBL
  • Selectivity index for Plasmodium falciparum deoxyuridine 5'-triphosphate nucleotidohydrolase defined as (Ki Human)/(Ki Plasmodium falciparum)
  • Selectivity index, human dUTPase/Plasmodium falciparum dUTPase ChEMBL
  • Selectivity index, human dUTPase/Plasmodium falciparum dUTPase
  • Inhibition of Plasmodium falciparum dUTPase ChEMBL
  • Inhibition of Plasmodium falciparum dUTPase
  • ChEMBL
  • Inhibition of Plasmodium falciparum dUTPase
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 1 )

Reagent availability

  • Pviv001447AAA;
  • Type Source Notes
    soluble recombinant protein Structural Genomics for Pathogenic Protozoa (SGPP) Pviv001447; Recombinant protein: full-length; Source: P vivax; deoxyuridine 5'-triphosphate nucleotidohydrolase, putative homolog ; Identifier: Pv091970
  • Reagent:
  • Target Type Source Notes
    PF3D7_1127100 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Plasmodium falciparum ( 2 )

Bibliographic References

4 literature references were collected for this gene.

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Gene identifier PF3D7_1127100 (Plasmodium falciparum), deoxyuridine 5'-triphosphate nucleotidohydrolase
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