Detailed view for PF3D7_0709000

Basic information

TDR Targets ID: 537
Plasmodium falciparum, chloroquine resistance transporter
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 8.6597 | Length (AA): 424 | MW (Da): 48675 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 10

Druggability Group : DG1

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

PF08627   CRT-like, chloroquine-resistance transporter-like

Gene Ontology

Mouse over links to read term descriptions.
GO:0042493   response to drug  
GO:0016020   membrane  
GO:0015238   drug transporter activity  
GO:0006855   multidrug transport  

Metabolic Pathways

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

Structural information

Modbase 3D models:

There are 7 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
122 373 1xme (A) 16 285 10.00 0.000047 0.02 0.74 -1.36
61 288 1s5l (D) 35 281 11.00 0.00053 0.01 0.350936 1.82
92 291 4hyj (A) 9 234 9.00 0.29 0.02 0.450898 -0.23
147 254 3lnm (D) 160 303 33.00 0.29 0.03 0.188917 1.98
58 292 4j72 (A) 17 280 12.00 0.26 0.01 0.637845 -0.2
59 317 2z73 (A) 39 321 10.00 0.55 0.01 0.521449 0.73
147 254 3lnm (D) 160 303 32.00 0.75 0.02 0.189817 1.86

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 - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, merozoite, sporozoite, early ring, early trophozoite, late ring, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile early schizont, late schizont, late trophozoite. PlasmoDB
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile gametocyte, Sporozoite, Male Gametocyte. PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Oocyst, Female Gametocyte. 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.
  • 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_133154)

Species Accession Gene Product
Arabidopsis thaliana AT4G24460   CRT (chloroquine-resistance transporter)-like transporter 2
Arabidopsis thaliana AT5G12170   CRT (chloroquine-resistance transporter)-like transporter 3
Arabidopsis thaliana AT5G19380   CRT (chloroquine-resistance transporter)-like transporter 1
Babesia bovis BBOV_III003790   conserved hypothetical protein
Cryptosporidium hominis Chro.60564   transporter
Cryptosporidium parvum cgd6_4890   transporter protein with conserved Zn ribbon C11C7CxxC
Dictyostelium discoideum DDB_G0277321   chloroquine resistance transporter-like protein
Dictyostelium discoideum DDB_G0270204   chloroquine resistance transporter-like protein
Dictyostelium discoideum DDB_G0276943   chloroquine resistance transporter-like protein
Neospora caninum NCLIV_057130   hypothetical protein, conserved
Oryza sativa 4325409   Os01g0955700
Oryza sativa 4352325   Os12g0511300
Plasmodium berghei PBANKA_1219500   chloroquine resistance transporter, putative
Plasmodium falciparum PF3D7_0709000   chloroquine resistance transporter
Plasmodium knowlesi PKNH_0107600   chloroquine resistance transporter, putative
Plasmodium vivax PVX_087980   chloroquine resistance transporter, putative
Plasmodium yoelii PY05061   putative transporter protein CG10
Toxoplasma gondii TGME49_313930   transmembrane protein
Theileria parva TP02_0224   hypothetical protein

Essentiality

PF3D7_0709000 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_1219500 Plasmodium berghei Essential plasmo
TGME49_313930 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource

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 1402   6701   503934   567171  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 15240840 15944738

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
ChEMBL23 References
Curated by TDRTargets References
Curated by TDRTargets References
ChEMBL23 References

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

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0267 0.3073 1
0.0177 0.3356 1
0.0277 0.7725 1
0.0157 0.7967 1

Assayability

Assay information

  • ChEMBL
  • Inhibition of chloroquine-resistant Plasmodium falciparum Dd2 chloroquine resistance transporter expressed in xenopus laevis oocytes assessed as inhibition of [3H]chloroquine uptake after 1 to 2 hrs
  • ChEMBL
  • Inhibition of chloroquine-resistant Plasmodium falciparum Dd2 CRT expressed in Xenopus laevis oocyte assessed as inhibition of [3H]chloroquine uptake at 100 uM measured from 1 to 2 hrs
  • ChEMBL
  • Inhibition of chloroquine-resistant Plasmodium falciparum Dd2 CRT expressed in Xenopus laevis oocyte assessed as inhibition of [3H]chloroquine uptake measured from 1 to 2 hrs
  • ChEMBL
  • Inhibition of chloroquine-resistant Plasmodium falciparum Dd2 CRT expressed in Xenopus laevis oocytes assessed as reduction in [3H]-chloroquine uptake after 1.5 to 2 hrs
  • ChEMBL
  • Inhibition of chloroquine-resistant Plasmodium falciparum Dd2 CRT expressed in Xenopus laevis oocytes plasma membrane assessed as reduction of [3H]-chloroquine transportation after 1 to 2 hrs

Reagent availability

No reagent availability information for this target.

Bibliographic References

2 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_0709000 (Plasmodium falciparum), chloroquine resistance transporter
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