Detailed view for PF3D7_1023200

Basic information

TDR Targets ID: 1299
Plasmodium falciparum, orotidine 5'-phosphate decarboxylase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.562 | Length (AA): 323 | MW (Da): 37824 | Paralog Number: 1

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

PF00215   Orotidine 5'-phosphate decarboxylase / HUMPS family

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0004590   orotidine-5'-phosphate decarboxylase activity  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  
GO:0006221   pyrimidine nucleotide 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 3 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
1 323 2f84 (A) 1 323 99.99 0 1 2.26 -3.15
1 321 3n3m (A) 1 321 99.99 0 1 2.33611 -2.53
1 321 3n3m (A) 1 321 99.99 0 1 2.33951 -2.57

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:

PDB tag
  • 2AQW:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2F84:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2FDS:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2FFC:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2GUU:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2Q8L:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2Q8Z:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2QAF:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2ZA1:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2ZA2:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2ZA3:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2ZCG:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3BAR:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3BPW:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3MWA:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3N2M:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3N34:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3N3M:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3S9Y:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3VI2:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile intra-erythrocytic - 24 hs, Ring, Male Gametocyte. Otto TD Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 40 hs, sporozoite, early ring, early schizont, early trophozoite, late ring, late trophozoite, Oocyst. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 48 hs. Otto TD
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile gametocyte, Sporozoite, Female Gametocyte. PlasmoDB Zanghi G Lasonder E
Show/Hide expression data references
  • 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.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB

Orthologs

Ortholog group members (OG5_126793)

Species Accession Gene Product
Arabidopsis thaliana AT3G54470   bi-functional orotate phosphoribosyltransferase/orotidine-5'-phosphate decarboxylase
Babesia bovis BBOV_IV011760   orotidine 5'-phosphate decarboxylase, putative
Babesia bovis BBOV_IV000530   orotate phosphoribosyltransferase
Brugia malayi Bm1_23045   orotate phosphoribosyltransferase family protein
Candida albicans CaO19.1716   orotidine-5'-monophosphate decarboxylase
Candida albicans CaO19.9284   orotidine-5'-monophosphate decarboxylase
Candida albicans CaO19.10087   likely Phosphoribosyl transferase similar to S. cerevisiae URA5 (YML106W) orotate phosphoribosyltransferase I involved in pyrimi
Candida albicans CaO19.2555   likely Phosphoribosyl transferase similar to S. cerevisiae URA5 (YML106W) orotate phosphoribosyltransferase I involved in pyrimi
Caenorhabditis elegans CELE_T07C4.1   Protein UMPS-1
Caenorhabditis elegans CELE_R12E2.11   Protein R12E2.11
Dictyostelium discoideum DDB_G0280041   UMP synthase
Drosophila melanogaster Dmel_CG3593   rudimentary-like
Escherichia coli b3642   orotate phosphoribosyltransferase
Echinococcus granulosus EgrG_000392000   uridine 5' monophosphate synthase
Echinococcus multilocularis EmuJ_000392000   uridine 5' monophosphate synthase
Homo sapiens 7372   uridine monophosphate synthetase
Leishmania braziliensis LbrM.16.0570   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative,OMPDCase-OPRTase, putative
Leishmania donovani LdBPK_160560.1   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative
Leishmania infantum LinJ.16.0560   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative,OMPDCase-OPRTase, putative
Leishmania major LmjF.16.0550   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative,OMPDCase-OPRTase, putative
Leishmania mexicana LmxM.16.0550   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative,OMPDCase-OPRTase, putative
Loa Loa (eye worm) LOAG_01247   orotate phosphoribosyltransferase
Mycobacterium leprae ML0537   Probable orotidine 5'-phosphate decarboxylase PyrF (OMP decarboxylase) (OMPDCase) (OMPdecase)
Mycobacterium leprae ML2487c   PROBABLE OROTATE PHOSPHORIBOSYLTRANSFERASE PYRE (OPRT) (OPRTASE)
Mus musculus ENSMUSG00000022814   uridine monophosphate synthetase
Mycobacterium tuberculosis Rv0382c   Probable orotate phosphoribosyltransferase PyrE (OPRT) (oprtase)
Mycobacterium tuberculosis Rv1385   Probable orotidine 5'-phosphate decarboxylase PyrF (OMP decarboxylase) (ompdecase)
Mycobacterium ulcerans MUL_1785   orotidine 5'-phosphate decarboxylase
Mycobacterium ulcerans MUL_0123   orotate phosphoribosyltransferase
Neospora caninum NCLIV_027130   orotate phosphoribosyltransferase, putative
Neospora caninum NCLIV_027100   orotidine-monophosphate-decarboxylase, putative
Oryza sativa 4325739   Os01g0951200
Oryza sativa 4325740   Os01g0951400
Plasmodium berghei PBANKA_0507400   orotidine 5'-phosphate decarboxylase, putative
Plasmodium berghei PBANKA_1112400   orotate phosphoribosyltransferase, putative
Plasmodium falciparum PF3D7_1023200   orotidine 5'-phosphate decarboxylase
Plasmodium falciparum PF3D7_0512700   orotate phosphoribosyltransferase
Plasmodium knowlesi PKNH_0607700   orotidine 5'-phosphate decarboxylase, putative
Plasmodium knowlesi PKNH_1020400   orotate phosphoribosyltransferase, putative
Plasmodium vivax PVX_080605   orotate phosphoribosyltransferase, putative
Plasmodium vivax PVX_111555   orotidine 5'-phosphate decarboxylase, putative
Plasmodium yoelii PY04605   URA5
Plasmodium yoelii PY01515   putative orotidine-monophosphate-decarboxylase
Saccharomyces cerevisiae YML106W   orotate phosphoribosyltransferase URA5
Saccharomyces cerevisiae YEL021W   orotidine-5'-phosphate decarboxylase
Saccharomyces cerevisiae YMR271C   orotate phosphoribosyltransferase URA10
Schistosoma japonicum Sjp_0090850   ko:K00762 orotate phosphoribosyltransferase [EC2.4.2.10], putative
Schistosoma mansoni Smp_050540   orotidine 5'-phosphate decarboxylase
Schmidtea mediterranea mk4.010664.00   Orotidine 5'-phosphate decarboxylase
Schmidtea mediterranea mk4.010018.00   Uridine 5'-monophosphate synthase
Schmidtea mediterranea mk4.020292.01   Uridine 5'-monophosphate synthase
Trypanosoma brucei gambiense Tbg972.5.5300   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative,OMPDCase-OPRTase, putative
Trypanosoma brucei Tb927.5.3810   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative
Trypanosoma congolense TcIL3000_5_4260   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative
Trypanosoma cruzi TcCLB.507059.60   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative
Trypanosoma cruzi TcCLB.509899.110   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative
Trypanosoma cruzi TcCLB.508373.29   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase, putative
Toxoplasma gondii TGME49_259690   orotidine-5-phosphate decarboxylase/orotate phosphoribosyltransferase
Toxoplasma gondii TGME49_259660   orotate phosphoribosyltransferase
Theileria parva TP01_0073   orotate phosphoribosyltransferase, putative
Theileria parva TP01_1133   orotidine 5-phosphate decarboxylase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0790   orotate phosphoribosyltransferase

Essentiality

PF3D7_1023200 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.5.3810 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.5.3810 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.5.3810 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.5.3810 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b3642 Escherichia coli non-essential goodall
CELE_T07C4.1 Caenorhabditis elegans slow growth wormbase
CELE_T07C4.1 Caenorhabditis elegans sterile wormbase
CELE_R12E2.11 Caenorhabditis elegans embryonic lethal wormbase
PBANKA_0507400 Plasmodium berghei Slow plasmo
TGME49_259690 Toxoplasma gondii Essentiality uncertain sidik
TGME49_259660 Toxoplasma gondii Essentiality uncertain sidik
TGME49_259690 Toxoplasma gondii Probably essential sidik
TGME49_259660 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
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium falciparum 535216  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 7909690
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium falciparum 417035   535216   558217   558218   558219  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 15683248 3515174 7909690

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
ChEMBL23 References
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 uridine monophosphate synthetase Compounds References
Plasmodium falciparum orotate phosphoribosyltransferase Compounds References
Saccharomyces cerevisiae orotidine-5'-phosphate decarboxylase Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Methanobacterium thermoautotrophicum Orotidine 5'-phosphate decarboxylase 228 aa 19.8% 192 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0334 0.2766 1
0.012 0.4246 0.5721
0.0061 0.2931 1
0.0111 0.7106 0.7396
0.0355 0.2739 1
0.0334 0.265 1
0.0164 0.8652 1
0.0137 0.5643 1
0.0191 0.8652 1
0.0088 0.748 1
0.0217 0.8652 1
0.0186 0.8652 1
0.0114 0.3775 0.6686
0.0112 0.6804 0.7057
0.0115 0.5969 0.5719
0.0113 0.2592 1
0.0137 0.5643 1
0.0186 0.8652 1
0.0112 0.2799 0.6303
0.0148805 1 1
0.0113 0.2553 1
0.0334 0.265 1
0.0222 0.8812 1
0.0115 1 1
0.0137 0.386 0.7728
0.0315 0.2768 1
0.0315 0.2768 1
0.0121 0.4193 0.576
0.0355 0.2765 1
0.0224 0.8652 1
0.0334 0.2768 1
0.0115 0.6986 0.7266

Assayability

Assay information

  • Assay for Orotidine-5'-Monophosphate Decarboxylase (4.1.1.23 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • Inhibition of Plasmodium falciparum ODCase at 25 degreeC by competitive binding assay ChEMBL
  • Inhibition of Plasmodium falciparum ODCase at 25 degreeC by competitive binding assay
  • Affinity for Plasmodium falciparum ODCase at 25 degreeC by UV-based assay ChEMBL
  • Affinity for Plasmodium falciparum ODCase at 25 degreeC by UV-based assay
  • Inhibition of Plasmodium falciparum ODCase ChEMBL
  • Inhibition of Plasmodium falciparum ODCase
  • ChEMBL
  • Inhibition of Plasmodium falciparum uridine 5'-monophosphate synthase after overnight incubation at room temperature by VP-ITC microcalorimetry
  • ChEMBL
  • Inhibition of Plasmodium falciparum uridine 5'-monophosphate synthase at 0.5 to 5 mM after overnight incubation at room temperature by VP-ITC microcalorimetry
  • ChEMBL
  • Inhibition of Plasmodium falciparum ODCase by isothermal titration calorimetry
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 2 )

Reagent availability

  • Pviv000304AAA;
  • Type Source Notes
    soluble recombinant protein Structural Genomics for Pathogenic Protozoa (SGPP) Pviv000304; Recombinant protein: full-length; Source: P vivax; orotidine-monophosphate-decarboxylase, putative homolog ; Identifier: Pv111555
  • Reagent:
  • Target Type Source Notes
    PF3D7_1023200 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Plasmodium falciparum ( 1 )

Bibliographic References

17 literature references were collected for this gene.

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Gene identifier PF3D7_1023200 (Plasmodium falciparum), orotidine 5'-phosphate decarboxylase
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