Detailed view for PF3D7_1136900

Basic information

TDR Targets ID: 1849
Plasmodium falciparum, subtilisin-like protease 2
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 8.5437 | Length (AA): 1341 | MW (Da): 154800 | Paralog Number: 0

Signal peptide: Y | GPI Anchor: N | Predicted trans-membrane segments: 1

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

PF00082   Subtilase family

Gene Ontology

Mouse over links to read term descriptions.
GO:0020026   merozoite dense granule  
GO:0016021   integral to membrane  
GO:0016020   membrane  
GO:0004252   serine-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 20 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
577 1136 1r6v (A) 9 588 18.00 0 1 0.26 0.12
617 1020 1r6v (A) 31 446 25.00 0 1 0.6 -0.93
714 1118 1p8j (A) 109 503 21.00 0 1 0.49 -0.37
716 1019 1thm () 1 277 32.00 0 1 0.48 -1.58
19 199 4uos (A) 3 183 20.00 0.0085 0.09 0.454774 -1.69
32 230 4tql (A) 38 238 22.00 0.00033 0.36 0.391197 -0.75
39 269 4dvz (A) 572 797 29.00 0.037 0.07 0.12696 0.53
60 617 1epw (A) 729 1289 18.00 0.00000082 0.9 0.489907 0.98
261 1341 3s5h (A) 67 1189 21.00 0.017 1 0.696815 1.1
552 640 2lu1 (A) 26 114 99.99 0 1 1.12007 0.37
710 1023 3wiu (A) 71 397 29.00 0 1 0.521954 -0.86
739 1012 2b6n (A) 24 273 29.00 0 1 0.466125 -0.5
25 188 4u5a (C) 47 238 21.00 0.38 0.45 0.413533 -1.31
26 245 4tql (A) 10 235 17.00 0.00054 0.26 0.450169 -1.45
39 269 4dvz (A) 572 797 29.00 0.053 0.09 0.127447 0.53
41 441 3tnf (B) 217 577 23.00 0.63 0.86 0.307841 0.76
261 1345 3s5h (A) 67 1189 21.00 0.016 1 0.707391 1.09
556 644 2lu1 (A) 26 114 99.00 0 1 1.11887 0.27
719 1025 1dbi (A) 1 280 31.00 0 1 0.557853 -0.94
743 1016 2b6n (A) 24 273 29.00 0 1 0.469317 -0.5

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
  • 2LU1:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

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

Orthologs

Ortholog group members (OG5_149511)

Species Accession Gene Product
Plasmodium berghei PBANKA_0911700   subtilisin-like protease 2
Plasmodium falciparum PF3D7_1136900   subtilisin-like protease 2
Plasmodium knowlesi PKNH_0935100   subtilisin-like protease 2, putative
Plasmodium vivax PVX_092460   subtilisin-like protease 2, putative
Plasmodium yoelii PY01222   subtilisin-like protease 2

Essentiality

PF3D7_1136900 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_0911700 Plasmodium berghei Essential plasmo
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.
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

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) Plasmodium berghei No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 14678331
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) Plasmodium falciparum No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 15225303
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium berghei No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: Drug: Subtilisin 2 propeptides. . References: 10551362 15225303 16322767
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium falciparum No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: Drug: Subtilisin 2 propeptides. . References: 10551362 15225303 16322767
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium yoelii yoelii No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: Drug: Subtilisin 2 propeptides. . References: 10551362 15225303 16322767

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
Species Target Length Identity Alignment span Linked Drugs Reference
Bacillus lentus Subtilisin 269 aa 31.1% 283 aa Compounds References
Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

89 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_1136900 (Plasmodium falciparum), subtilisin-like protease 2
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