Detailed view for PF3D7_1022800

Basic information

TDR Targets ID: 1295
Plasmodium falciparum, 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase

Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.0901 | Length (AA): 824 | MW (Da): 95226 | Paralog Number: 0

Signal peptide: Y | GPI Anchor: N | Predicted trans-membrane segments: 0

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

PF04551   GcpE protein

Gene Ontology

Mouse over links to read term descriptions.
GO:0020011   apicoplast  
GO:0019288   isopentenyl diphosphate biosynthetic process, mevalonate-independent pathway  
GO:0003674   molecular_function  
GO:0046429   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase activity  
GO:0005506   iron ion binding  
GO:0055114   oxidation reduction  
GO:0044237   cellular metabolic process  
GO:0016114   terpenoid biosynthetic process  
GO:0008299   isoprenoid biosynthetic process  

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
119 397 1tx2 (A) 2 274 13.00 0 0.91 0.17 -0.24
113 400 4mwa (A) 2 258 38.00 0 1 0.685015 -0.36
118 517 2y0f (B) 5 401 29.00 0 1 0.510137 0.45
410 594 4uos (A) 2 184 15.00 0.35 0.09 0.434015 -1.11
113 403 4mwa (A) 2 261 39.00 0 1 0.686184 -0.2
118 474 4s39 (A) 5 397 30.00 0 1 0.382979 0.06
435 626 4uos (A) 2 186 17.00 0.13 0.36 0.429893 -0.98

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 60-80% percentile intra-erythrocytic - 32 hs, Sporozoite. Otto TD Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, early schizont, late trophozoite, Oocyst, Ring, Male Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, early trophozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Female Gametocyte. 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.
  • 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
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.

Orthologs

Ortholog group members (OG5_130276)

Species Accession Gene Product
Arabidopsis thaliana AT5G60600   4-hydroxy-3-methylbut-2-enyl diphosphate synthase
Babesia bovis BBOV_II006930   gcpE protein
Chlamydia trachomatis CT_057   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase
Escherichia coli b2515   1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase
Mycobacterium leprae ML1581c   PROBABLE GCPE PROTEIN
Mycobacterium tuberculosis Rv2868c   Probable GcpE protein
Mycobacterium ulcerans MUL_2087   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase
Neospora caninum NCLIV_025400   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (EC 1.17.4.3), related
Oryza sativa 4329911   Os02g0603800
Plasmodium berghei PBANKA_0507000   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, putative
Plasmodium falciparum PF3D7_1022800   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase
Plasmodium knowlesi PKNH_0607100   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, putative
Plasmodium yoelii PY01664   GcpE
Toxoplasma gondii TGME49_262430   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase
Treponema pallidum TP0446   gcpE protein (gcpE)
Theileria parva TP02_0667   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0782   4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase

Essentiality

PF3D7_1022800 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b2515 Escherichia coli essential goodall
PBANKA_0507000 Plasmodium berghei Essential plasmo
TGME49_262430 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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

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
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

No literature references available for this target.

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Gene identifier PF3D7_1022800 (Plasmodium falciparum), 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase
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