Detailed view for PF3D7_1133400

Basic information

TDR Targets ID: 1813
Plasmodium falciparum, apical membrane antigen 1
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 5.2283 | Length (AA): 622 | MW (Da): 72042 | Paralog Number: 0

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

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

PF02430   Apical membrane antigen 1

Gene Ontology

Mouse over links to read term descriptions.
GO:0030260   entry into host cell  
GO:0020007   apical complex  
GO:0016020   membrane  
GO:0009405   pathogenesis  

Metabolic Pathways

Malaria (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
100 532 1w8k (A) 45 474 62.00 0 1 1.18 0.24
108 438 1z40 (A) 108 438 99.99 0 1 1.62 -0.62
99 533 1w8k (A) 44 475 61.00 0 1 1.16016 0.34
104 438 4r19 (A) 104 438 99.99 0 1 1.67459 -0.86
99 533 1w8k (A) 44 475 61.00 0 1 1.21246 -0.12
104 438 4r19 (A) 104 438 94.00 0 1 1.62739 -0.97
108 438 4r1a (A) 108 438 99.99 0 1 1.40995 -0.26

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
  • 1HN6:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1W81:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1W8K:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1YXE:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1Z40:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2J4W:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2J5L:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2Q8A:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2Q8B:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2Z8V:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2Z8W:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3SRI:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3SRJ:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 3ZWZ:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4R19:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4R1A:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4R1B:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4R1C:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4Z09:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4Z0D:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4Z0E:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4Z0F:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5NQF:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, merozoite, sporozoite, early schizont, late schizont, Sporozoite. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 16 hs, intra-erythrocytic - 32 hs, early ring, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 24 hs, late ring, late trophozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Oocyst. Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Female Gametocyte, Male Gametocyte. Lasonder E
Show/Hide expression data references
  • 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.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB

Orthologs

Ortholog group members (OG5_147452)

Species Accession Gene Product
Babesia bovis BBOV_IV011230   apical membrane antigen 1
Neospora caninum NCLIV_064590   apical membrane antigen, putative
Plasmodium berghei PBANKA_0915000   apical membrane antigen 1
Plasmodium falciparum PF3D7_1133400   apical membrane antigen 1
Plasmodium knowlesi PKNH_0931500   apical membrane antigen 1
Plasmodium vivax PVX_092275   apical membrane antigen 1
Plasmodium yoelii PY01581   apical membrane antigen-1
Toxoplasma gondii TGME49_300130   apical membrane antigen 1 domain-containing protein
Theileria parva TP01_0650   apical membrane antigen 1, putative

Essentiality

PF3D7_1133400 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
TGME49_300130 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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

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

Known modulators for this target

Compound Source Reference
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
0.0283 0.3355 1
0.0283 0.3606 1
0.0055 0.3297 1

Assayability

Assay information

  • ChEMBL
  • Binding affinity to recombinant His-tagged Plasmodium falciparum 3D7 AMA1 assessed as inhibition of interaction with biotin-tagged RON2 peptide after 30 mins by AlphaScreen assay
  • ChEMBL
  • Competitive binding affinity to Plasmodium falciparum 3D7 AMA1 (104 to 442) at 80 uM after 200 milisecs by CPMG binding assay in presence of R1 peptide and absence of detergent
  • ChEMBL
  • Competitive binding affinity to Plasmodium falciparum 3D7 AMA1 (104 to 442) at 80 uM after 200 milisecs by CPMG binding assay in presence of RON2 peptide and absence of detergent
  • ChEMBL
  • Competitive binding affinity to Plasmodium falciparum 3D7 AMA1 (104 to 442) at 80 uM after 200 milisecs by CPMG binding assay in presence of R1 peptide and Tween 20
  • ChEMBL
  • Competitive binding affinity to Plasmodium falciparum 3D7 AMA1 (104 to 442) at 80 uM after 200 milisecs by CPMG binding assay in presence of RON2 peptide and Tween 20
  • ChEMBL
  • Binding affinity to Plasmodium falciparum 3D7 AMA1 (104 to 442) up to 200 uM by SPR analysis
  • ChEMBL
  • Binding affinity to Plasmodium falciparum 3D7 AMA1 (104 to 442) by SPR analysis
  • ChEMBL
  • Binding affinity to Plasmodium falciparum 3D7 AMA1 (108 to 434) expressed in Escherichia coli BL21(DE3) by SPR analysis
  • ChEMBL
  • Binding affinity to Plasmodium falciparum 3D7 AMA1 373W insertion mutant expressed in Escherichia coli BL21(DE3) by SPR analysis
  • ChEMBL
  • Binding affinity to Plasmodium falciparum 3D7 AMA1 F367W mutant expressed in Escherichia coli BL21(DE3) at 1 and 3 mM by SPR analysis
  • ChEMBL
  • Binding affinity to Plasmodium falciparum 3D7 5F-Trp-tagged AMA1 F367W mutant assessed as decrease in the W367 line width at 1 and 3 mM by 19F-NMR spectroscopy in presence of R1/RON2L
  • ChEMBL
  • Binding affinity to Plasmodium falciparum 3D7 5F-Trp-tagged AMA1 W110F mutant assessed as downfield shifts of W110 peak by 19F-NMR spectroscopy in presence of R1/RON2L
  • ChEMBL
  • Binding affinity to Plasmodium falciparum 3D7 5F-Trp-tagged AMA1 F367W mutant at 1 and 3 mM by 19F-NMR spectroscopy in presence of R1/RON2L
  • ChEMBL
  • Binding affinity to Plasmodium falciparum AMA1 at 200 uM by surface plasmon resonance method

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_1133400 (Plasmodium falciparum), apical membrane antigen 1
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