Detailed view for PF3D7_0507500

Basic information

TDR Targets ID: 4106
Plasmodium falciparum, subtilisin-like protease 1

Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 5.9178 | Length (AA): 688 | MW (Da): 77647 | Paralog Number: 0

Signal peptide: Y | 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

PF00082   Subtilase family

Gene Ontology

Mouse over links to read term descriptions.
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 10 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
176 662 1r6v (A) 9 446 17.00 0 1 0.52 0.4
333 663 1thm () 1 279 29.00 0 1 0.79 -1.18
2 159 4uos (A) 12 180 18.00 0.0012 0.14 0.421851 -1.02
38 668 4tr2 (A) 38 611 72.00 0 1 1.38665 0.13
137 217 4lvn (P) 137 217 99.99 0 1 1.38223 -1.72
334 669 4lvn (A) 334 669 99.99 0 1 1.75887 -1.78
2 152 4uos (A) 30 184 17.00 0.012 0.03 0.399677 -0.69
38 668 4tr2 (A) 38 611 72.00 0 1 1.39315 0.08
137 217 4lvn (P) 137 217 99.99 0 1 1.38473 -1.73
334 669 4lvn (A) 334 669 99.99 0 1 1.76137 -1.79

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:

  • 4LVN:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 4LVO:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile intra-erythrocytic - 8 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, merozoite, sporozoite, early schizont, late schizont. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 0 hs, early ring, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, gametocyte, early trophozoite, late trophozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 32 hs. Otto TD
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Oocyst, Sporozoite, Female Gametocyte, Male Gametocyte. Zanghi G Lasonder E
Show/Hide expression data references
  • 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
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.

Orthologs

Ortholog group members (OG5_138369)

Species Accession Gene Product
Babesia bovis BBOV_II006080   subtilisin-like protein, putative
Cryptosporidium hominis Chro.60558   subtilisin-like serine protease
Neospora caninum NCLIV_021050   hypothetical protein
Plasmodium berghei PBANKA_1107100   subtilisin-like protease 1
Plasmodium falciparum PF3D7_0507500   subtilisin-like protease 1
Plasmodium knowlesi PKNH_1026100   subtilisin-like protease 1, putative
Plasmodium vivax PVX_097935   subtilisin-like protease 1
Plasmodium yoelii PY04329   PfSUB-1
Toxoplasma gondii TGME49_204050   subtilisin SUB1

Essentiality

PF3D7_0507500 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_1107100 Plasmodium berghei Essential plasmo
TGME49_204050 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • 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.
  • 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
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.

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 berghei No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: Drug: Subtilase propeptides. . References: 12764150 15225303
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: Subtilase propeptides. . References: 12764150 15225303
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: Subtilase propeptides. . References: 12764150 15225303

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

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Plasmodium falciparum Subtilisin-like serine protease Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Bacillus licheniformis Subtilisin 379 aa 28.5% 305 aa Compounds References
Bacillus lentus Subtilisin 269 aa 27.3% 308 aa Compounds References

Obtained from network model

Ranking Plot


Putative Drugs List


Compound Raw Global Species
0.1103 0.4672 0.6141
0.1091 0.4884 1
0.0702 0.3853 1
0.0296 0.3496 1
0.0909 0.3944 0.7406
0.0898 0.2979 0.557
0.0174 0.2658 0.255
0.0176 0.547 0.5
0.0176 0.931 0.5
0.1186 0.9668 1
0.1126 0.5005 1
0.0714 0.3051 1
0.1163 0.4476 1
0.1085 0.2824 1
0.1123 0.2932 1
0.0907 0.6704 1
0.1122 0.9168 1
0.0711 0.3742 0.471
0.019 0.296 1
0.1382 0.9549 0.9536
0.1089 0.4242 1
0.1166 0.7172 1
0.0898 0.2979 0.557
0.0924 0.3432 1
0.0215 0.6277 1
0.0185 0.4091 1
0.0533 0.7836 1
0.1335 0.262 1
0.1376 0.3552 1
0.0911 0.4721 0.5078
0.132 0.8828 0.8823
0.0711 0.375 0.4716
0.0898 0.2979 0.557
0.0898 0.2979 0.557
0.0173 0.589 0.5
0.0716 0.5422 1
0.0911 0.4721 0.5078
0.0176 0.547 0.5
0.0212 0.5143 0.5
0.1379 0.8403 1
0.1122 0.9168 1
0.0538 0.3231 0.5407
0.1176 0.3014 1
0.1382 0.9549 0.9536
0.0911 0.4721 0.5078
0.0732 0.2694 0.823
0.0895 0.3909 1
0.1077 0.5568 1
0.0895 0.3909 1
0.0176 0.3564 1
0.1372 0.2703 1
0.0178 0.5699 1
0.0189 0.2722 1
0.1091 0.4884 1
0.0898 0.2979 0.557
0.1103 0.4672 0.6141
0.1382 0.9549 0.9536
0.0932 0.3425 0.9381
0.0217 0.4718 1
0.0911 0.4721 0.5078

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

8 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_0507500 (Plasmodium falciparum), subtilisin-like protease 1
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