Detailed view for PF3D7_1472900

Basic information

TDR Targets ID: 3027
Plasmodium falciparum, dihydroorotase, putative
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.3808 | Length (AA): 358 | MW (Da): 41718 | Paralog Number: 0

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

Druggability Group : DG1

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

No Pfam domain information for this protein.

Gene Ontology

Mouse over links to read term descriptions.
GO:0016812   hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides  
GO:0005575   cellular_component  
GO:0004151   dihydroorotase activity  
GO:0019856   pyrimidine base biosynthetic process  
GO:0006207   'de novo' pyrimidine base biosynthetic process  

Metabolic Pathways

Pyrimidine metabolism (KEGG)
Global map (KEGG)

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
2 357 1k1d (A) 46 433 15.00 0 1 1.07 -0.65
10 353 1j79 (A) 12 346 28.00 0 1 1.37 -1.14
2 357 1xrt (A) 49 414 20.00 0.00000001 1 0.991013 0.47
11 352 3jze (A) 14 346 29.00 0 1 1.31301 -0.44
12 354 3pnu (A) 8 335 32.00 0 1 1.2498 0.02

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

Orthologs

Ortholog group members (OG5_130129)

Species Accession Gene Product
Arabidopsis thaliana AT4G22930   dihydroorotase
Babesia bovis BBOV_III009670   dihydroorotase, putative
Candida albicans CaO19.1977   Dihydrooratase: used in pyrimidine biosynthesis.
Candida albicans CaO19.9533   Dihydrooratase: used in pyrimidine biosynthesis.
Escherichia coli b1062   dihydro-orotase
Neospora caninum NCLIV_000550   dihydroorotase protein, putative
Oryza sativa 4325542   Os01g0747500
Plasmodium berghei PBANKA_1336100   dihydroorotase, putative
Plasmodium falciparum PF3D7_1472900   dihydroorotase, putative
Plasmodium knowlesi PKNH_1208100   dihydroorotase, putative
Plasmodium vivax PVX_116830   dihydroorotase, putative
Plasmodium yoelii PY04293   hypothetical protein
Saccharomyces cerevisiae YLR420W   dihydroorotase
Toxoplasma gondii TGME49_293610   dihydroorotase
Theileria parva TP04_0882   dihydroorotase, putative

Essentiality

PF3D7_1472900 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b1062 Escherichia coli non-essential goodall
TGME49_293610 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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.
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924

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 336374   565769  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 7909690 9425362 9598156

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

Known modulators for this target

Compound Source Reference
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Non orthologous druggable targets
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
0.0423 0.5407 1
0.0249 0.2832 1
0.0228 0.3106 1

Assayability

Assay information

  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium berghei ( 2 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    PF3D7_1472900 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Plasmodium berghei ( 2 )

Bibliographic References

10 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_1472900 (Plasmodium falciparum), dihydroorotase, putative
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