Detailed view for PF3D7_0112200

Basic information

TDR Targets ID: 3240
Plasmodium falciparum, multidrug resistance-associated protein 1
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 8.9851 | Length (AA): 1822 | MW (Da): 214441 | Paralog Number: 1

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 11

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

PF00005   ABC transporter
PF00664   ABC transporter transmembrane region

Gene Ontology

Mouse over links to read term descriptions.
GO:0042626   ATPase activity, coupled to transmembrane movement of substances  
GO:0016021   integral to membrane  
GO:0017111   nucleoside-triphosphatase activity  
GO:0016887   ATPase activity  
GO:0005524   ATP binding  
GO:0000166   nucleotide binding  
GO:0055085   transmembrane transport  
GO:0006810   transport  

Metabolic Pathways

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

Structural information

Modbase 3D models:

There are 11 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
247 562 2fds (A) 2 324 15.00 0.000077 0.19 0.24 -0.87
654 892 1mv5 (A) 342 580 15.00 0 0.99 0.12 -0.03
1534 1821 2ghi (A) 10 254 27.00 0 1 0.35 -0.35
1556 1818 1g6h (A) 9 254 19.00 0 1 0.39 -1.11
135 308 4u5a (C) 47 239 18.00 0.82 0.08 0.242799 -0.3
247 1815 4q9h (A) 112 1263 16.00 0 1 0.297942 3.07
676 834 2cbz (A) 661 820 34.00 0.00000000082 0.9 0.385467 0.53
1533 1811 3b5x (A) 323 568 26.00 0.000095 0.61 0.219328 1.06
1554 1807 1g6h (A) 6 239 20.00 0 1 0.385207 -0.52
516 725 4p0d (A) 141 331 32.00 0.54 0.24 -0.017542 1.88
555 1815 4q9h (A) 294 1263 16.00 0 1 0.217197 2.77

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 - 24 hs. Otto TD
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs. Otto TD
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 16 hs, early schizont, early trophozoite, late schizont, late trophozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 8 hs, Ring. Otto TD Zanghi G
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.
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • 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.

Orthologs

Ortholog group members (OG5_144709)

Species Accession Gene Product
Cryptosporidium hominis Chro.20413   hypothetical protein
Cryptosporidium hominis Chro.30058   ATP-binding cassette protein 2
Cryptosporidium parvum cgd2_3870   putative ABC transporter with 2x AAA and 11+ transmembrane domains
Cryptosporidium parvum cgd3_410   putative ABC transporter, 12x transmembrane domains plus 2x AAA
Plasmodium berghei PBANKA_1443800   multidrug resistance-associated protein 2
Plasmodium falciparum PF3D7_0112200   multidrug resistance-associated protein 1
Plasmodium falciparum PF3D7_1229100   multidrug resistance-associated protein 2
Plasmodium knowlesi PKNH_1448500   multidrug resistance-associated protein 2, putative
Plasmodium vivax PVX_124085   multidrug resistance-associated protein 2, putative
Plasmodium yoelii PY05035   putative ABC transporter

Essentiality

PF3D7_0112200 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
PBANKA_1443800 Plasmodium berghei Slow plasmo
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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • 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.
  • 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
  • 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): 0.5

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

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0206 0.2586 0.2206
0.0038 0.2692 0.4673
0.0042 0.2624 0
0.0055 0.2884 0.2884
0.0074 0.2584 0
0.0032 0.2584 0.2433
0.0105 0.2581 0.0014
0.0053 0.2821 0
0.0086 0.2819 0
0.0113 0.283 0
0.0064 0.2606 0.2232
0.0074 0.2667 0.2495
0.0157 0.2814 0.5243
0.0119 0.2763 0
0.0177 0.2919 0.4309
0.0102 0.2778 0.2725
0.0117 0.2609 0
0.0178 0.289 0.5648
0.0097 0.2874 0
0.0125 0.2942 0
0.0057 0.2538 0.2443
0.011 0.2652 0.2652
0.01 0.2525 0
0.0103 0.2692 0
0.0101 0.297 0.297
0.0212 0.2836 0.1869
0.0101 0.3024 0
0.0086 0.2826 0
0.0038 0.2684 0
0.0107 0.2591 0
0.0053 0.2821 0
0.0029 0.2983 0.3702
0.0064 0.2602 0
0.0038 0.2684 0
0.01 0.2539 0
0.0054 0.2631 0
0.0096 0.2671 0
0.0107 0.2982 0.2976
0.0226 0.2607 0.1574
0.0126 0.3471 0.4107
0.0136 0.2913 0.2749
0.0177 0.2919 0.4309
0.0038 0.2692 0.4673
0.0088 0.2555 0.2555
0.0133 0.2801 0
0.0101 0.2856 0
0.0099 0.2891 0.278
0.0271 0.2507 0.2166
0.0089 0.2637 0
0.0055 0.2531 0
0.0085 0.2691 0
0.0063 0.3239 0.3239
0.0254 0.2524 0.176
0.0101 0.297 0.297
0.0226 0.2574 0.1564
0.0068 0.2634 0
0.0068 0.2504 0
0.0061 0.2824 0
0.0074 0.2596 0
0.0091 0.286 0
0.0204 0.2853 0.3044
0.0199 0.2537 0.2994
0.0122 0.2698 0.2698
0.0123 0.2787 0
0.0087 0.2619 0
0.0065 0.2748 0.269
0.0113 0.2726 0.2677
0.0129 0.2892 0.2712
0.0146 0.2695 0.2381
0.0086 0.2635 0.2346
0.0082 0.2995 0.5092
0.0137 0.2918 0.2678
0.0133 0.2951 0
0.0126 0.2956 0
0.005 0.2958 0
0.0065 0.2573 0
0.0161 0.2787 0.2722
0.0117 0.2749 0
0.013 0.28 0
0.0109 0.2892 0
0.003 0.2602 0.2457
0.0105 0.2629 0.2629
0.0029 0.2983 0.3702
0.009 0.2658 0
0.0117 0.2589 0.2781
0.0079 0.2588 0
0.0086 0.2639 0
0.0124 0.2765 0
0.0068 0.2634 0
0.0199 0.2537 0.2994
0.0077 0.2708 0
0.0029 0.2983 0.3702
0.0074 0.2621 0.2491
0.0029 0.2983 0.3702
0.0087 0.2825 0
0.0206 0.2785 0.2732
0.0088 0.2555 0.2555

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier PF3D7_0112200 (Plasmodium falciparum), multidrug resistance-associated protein 1
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