Detailed view for PF3D7_1323500

Basic information

TDR Targets ID: 2118
Plasmodium falciparum, plasmepsin V
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.5796 | Length (AA): 590 | MW (Da): 68480 | Paralog Number: 0

Signal peptide: Y | GPI Anchor: N | Predicted trans-membrane segments: 2

Druggability Group : DG4

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

PF00026   Eukaryotic aspartyl protease
PF14543   Xylanase inhibitor N-terminal

Gene Ontology

Mouse over links to read term descriptions.
GO:0020011   apicoplast  
GO:0016020   membrane  
GO:0004190   aspartic-type endopeptidase activity  
GO:0006508   proteolysis  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models:

There are 4 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
42 517 1miq (A) 84 326 19.00 0 1 0.56 0.72
444 516 1b5f (B) 249 325 23.00 0.000000022 0.27 0.27 -0.31
85 521 4zl4 (A) 47 469 72.00 0 1 1.52208 -0.91
85 521 4zl4 (A) 47 469 72.00 0 1 1.51368 -0.82

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 - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, Ring. Otto TD Zanghi G
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 0 hs, sporozoite, early ring, early schizont, early trophozoite, late ring, late schizont, late trophozoite, Oocyst, Sporozoite. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Female Gametocyte. Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Male Gametocyte. 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.
  • 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.

Orthologs

Ortholog group members (OG5_132039)

Species Accession Gene Product
Arabidopsis thaliana AT3G50050   aspartyl protease family protein
Arabidopsis thaliana AT5G43100   aspartyl protease family protein
Babesia bovis BBOV_III001640   aspartyl protease family protein
Cryptosporidium hominis Chro.10255   AT hook motif protein
Cryptosporidium hominis Chro.40249   hypothetical protein
Cryptosporidium parvum cgd4_2190   membrane associated aspartyl protease with a transmembrane domain at the C-terminus
Cryptosporidium parvum cgd1_2240   AT hook motif protein, putative
Neospora caninum NCLIV_017720   hypothetical protein
Oryza sativa 4343783   Os07g0592200
Plasmodium berghei PBANKA_1338700   plasmepsin V, putative
Plasmodium falciparum PF3D7_1323500   plasmepsin V
Plasmodium knowlesi PKNH_1205300   plasmepsin V, putative
Plasmodium vivax PVX_116695   plasmepsin V, putative
Plasmodium yoelii PY02085   aspartyl protease-like
Toxoplasma gondii TGME49_242720   aspartyl protease ASP5
Theileria parva TP03_0676   aspartyl protease, putative

Essentiality

PF3D7_1323500 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_1338700 Plasmodium berghei Essential plasmo
TGME49_242720 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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): 0.1

Known modulators for this target

Compound Source Reference
ChEMBL23 References
ChEMBL23 References
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ChEMBL23 References
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ChEMBL23 References
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ChEMBL23 References
ChEMBL23 References
ChEMBL23 References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Plasmodium vivax plasmepsin V, putative Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Rattus norvegicus Beta-secretase 2 514 aa 22.6% 439 aa Compounds References
Rattus norvegicus Beta-secretase 1 501 aa 18.9% 429 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.1117 0.4951 1
0.0288 0.8517 1
0.0402 0.9169 0.9169
0.107 0.7731 1
0.1037 0.4111 1
0.0203671 0.384809 0.5
0.1037 0.4066 1
0.1051 0.5611 1
0.0021 1 0.5
0.0307 0.3738 1
0.0021 0.443 0.5
0.0757 0.5862 1
0.0979 0.4359 1
0.1051 0.5279 1
0.0021 1 0.5
0.1038 0.7492 1
0.0145 0.3313 0.3261
0.0979 0.4359 1
0.0642 0.8517 1
0.0021 1 0.5
0.0106 0.5 0.5
0.0106 0.5 0.5
0.1037 0.4007 1
0.0274 0.9845 0.5
0.0303 0.5881 1
0.0145 0.3313 0.3261
0.1034 0.5409 1
0.0877 0.4391 1
0.0021 1 0.5
0.0139 0.8517 1
0.1152 0.4197 1
0.1205 0.4147 1
0.1205 0.4147 1
0.0688836 1 1
0.0021 1 0.5
0.0129 0.5379 1
0.0467 0.5265 0.5
0.0021 1 0.5
0.1045 0.408 1
0.1062 0.7717 1
0.0157 0.2708 0.5
0.132747 1 1
0.1008 0.5264 1
0.1037 0.4081 1
0.0137 0.8967 1
0.0692 0.2509 1
0.1035 0.5389 1
0.0157 0.2708 0.5
0.0675 0.8185 1
0.0969 0.2559 1
0.1038 0.7492 1
0.1037 0.3996 1
0.0168 0.7227 1
0.0145 0.3313 0.3261
0.0021 1 0.5
0.1013 0.5282 1
0.0021 1 0.5
0.0303 0.2928 1
0.0139 0.8517 1
0.1122 0.4109 1
0.1097 0.384 1
0.1117 0.4951 1
0.0392 0.3644 0.5
0.1042 0.4069 1
0.002 0.5 0.5
0.0877 0.4391 1
0.0157 0.6032 0.5
0.061 0.6241 1
0.0146 0.8517 1
0.0021 0.7491 0.5
0.0157 0.6032 0.5
0.1038 0.7492 1
0.0068 1 0.5
0.0802 0.8851 1
0.0157 0.4181 0.5
0.0021 1 0.5
0.0675 0.8185 1
0.1037 0.404 1
0.061 0.6241 1
0.0021 0.4249 0.5
0.1205 0.3527 1

Assayability

Assay information

  • ChEMBL
  • Inhibition of Plasmodium falciparum plasmepsin V assessed as cleavage of wtKAHRP fluorogenic substrate
  • ChEMBL
  • Inhibition of Plasmodium falciparum plasmepsin V assessed as cleavage of wtKAHRP fluorogenic substrate at 1 uM
  • ChEMBL
  • Inhibition of plasmepsin V in Plasmodium falciparum trophozoite expressing PfEMP3-GFP infected erythrocyte assessed as PEXEL processing at 20 uM by immunoblotting analysis
  • ChEMBL
  • Inhibition of PMV in trophozoite stage of Plasmodium flaciparum 3D7 expressing PfEMP3-GFP infected in human erythrocytes assessed as PEXEL processing of PfEMP3 at 1 to 20 uM after 5 hrs by Western blot method
  • ChEMBL
  • Inhibition of PMV in trophozoite stage of Plasmodium flaciparum 3D7 expressing PfEMP3-GFP infected in human erythrocytes assessed as PEXEL processing of PfEMP3 at 20 uM after 5 hrs by Western blot method

Reagent availability

No reagent availability information for this target.

Bibliographic References

140 literature references were collected for this gene.

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Gene identifier PF3D7_1323500 (Plasmodium falciparum), plasmepsin V
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