Detailed view for PF3D7_1013500

Basic information

TDR Targets ID: 1208
Plasmodium falciparum, phosphoinositide-specific phospholipase C
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 8.4287 | Length (AA): 1385 | MW (Da): 164152 | 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

PF00387   Phosphatidylinositol-specific phospholipase C, Y domain
PF00388   Phosphatidylinositol-specific phospholipase C, X domain
PF12814   Meiotic cell cortex C-terminal pleckstrin homology

Gene Ontology

Mouse over links to read term descriptions.
GO:0035556   GO:intracellular signal transduction  

GO:0032065   cortical protein anchoring  
GO:0005938   cell cortex  
GO:0005575   cellular_component  
GO:0008081   phosphoric diester hydrolase activity  
GO:0005543   phospholipid binding  
GO:0005515   protein binding  
GO:0004629   phospholipase C activity  
GO:0004435   phosphoinositide phospholipase C activity  
GO:0007242   intracellular signaling cascade  
GO:0007165   signal transduction  
GO:0006644   phospholipid metabolic process  
GO:0006629   lipid metabolic process  

Structural information

Modbase 3D models:

There are 9 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
210 283 2ami (A) 1 76 8.00 0.000000000014 0.01 0.3 -1.97
1256 1351 1a25 (A) 172 264 16.00 0 0.08 0.2 -0.22
29 315 2fds (A) 21 294 28.00 0.73 0.55 0.16002 1.35
131 535 3er9 (B) 16 475 17.00 0.54 0.85 0.319919 0.91
284 351 2ami (A) 8 76 16.00 0.84 0.14 0.282597 -1.17
379 1383 2zkm (X) 79 799 23.00 0 0.95 0.182132 2.61
480 1230 1djx (B) 158 745 25.00 0 1 0.268738 2.46
578 1087 1djx (A) 252 609 39.00 0 1 0.040031 1.71
1247 1351 1wfj (A) 2 97 7.00 0.13 0 -0.108688 1.27

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 intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, early schizont, early trophozoite, late trophozoite, Sporozoite, Male Gametocyte. Otto TD PlasmoDB Zanghi G 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 - 24 hs, intra-erythrocytic - 32 hs, gametocyte, sporozoite, early ring, late schizont, Oocyst, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 20-40% 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
  • 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_131119)

Species Accession Gene Product
Homo sapiens ENSG00000149527   phospholipase C, eta 2
Homo sapiens ENSG00000114805   phospholipase C, eta 1
Loa Loa (eye worm) LOAG_06906   hypothetical protein
Mus musculus ENSMUSG00000036834   phospholipase C, eta 1
Mus musculus ENSMUSG00000029055   phospholipase C, eta 2
Onchocerca volvulus OVOC9507  
Plasmodium berghei PBANKA_1211900   phosphoinositide-specific phospholipase C
Plasmodium falciparum PF3D7_1013500   phosphoinositide-specific phospholipase C
Plasmodium knowlesi PKNH_0813300   phosphoinositide-specific phospholipase C, putative
Plasmodium vivax PVX_094895   phospholipase C-like, putative
Plasmodium yoelii PY04832   hypothetical protein
Plasmodium yoelii PY05133   hypothetical protein
Schistosoma mansoni Smp_177030   phospholipase C-like protein 2 plc-L2
Schistosoma mansoni Smp_177020   phospholipase C-like protein 1 plc-l
Toxoplasma gondii TGME49_248830   phosphoinositide phospholipase PIPLC

Essentiality

PF3D7_1013500 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_1211900 Plasmodium berghei Essential plasmo
TGME49_248830 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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.
  • 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.
  • 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
  • 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
  • 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.

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 0  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 11781362
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium falciparum 0  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 11781362

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): 0.3

Known modulators for this target

No chemical compounds associated to this gene

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
No druggable targets predicted through repurposing network model

Assayability

Assay information

  • Assay for Phospholipase C (3.1.4.3 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 1 )

Reagent availability

No reagent availability information for this target.

Bibliographic References

13 literature references were collected for this gene.

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Gene identifier PF3D7_1013500 (Plasmodium falciparum), phosphoinositide-specific phospholipase C
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