Detailed view for PF3D7_1224000

Basic information

TDR Targets ID: 5283
Plasmodium falciparum, GTP cyclohydrolase I
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.8914 | Length (AA): 389 | MW (Da): 45877 | Paralog Number: 0

Signal peptide: N | 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

PF01227   GTP cyclohydrolase I

Gene Ontology

Mouse over links to read term descriptions.
GO:0005737   cytoplasm  
GO:0003934   GTP cyclohydrolase I activity  
GO:0046654   tetrahydrofolate biosynthetic process  
GO:0009396   folic acid and derivative biosynthetic process  
GO:0006730   one-carbon compound metabolic process  

Metabolic Pathways

Folate biosynthesis (KEGG)
Global map (KEGG)

Structural information

Modbase 3D models:

There are 6 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
174 381 1a8r (A) 1 214 27.00 0 1 0.88 -0.32
195 382 1is8 (A) 51 237 34.00 0 1 0.96 -0.74
45 130 2wps (A) 458 544 22.00 0.57 0 0.52088 -1.14
120 195 4dim (A) 327 400 38.00 0.32 0.1 0.569973 -0.14
151 387 1is8 (A) 48 241 31.00 0 1 0.578155 0.74
217 386 1wur (A) 50 216 37.00 0 1 0.797918 -0.46

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, early trophozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, sporozoite, early ring, early schizont, late ring, late trophozoite, Oocyst, Ring, Sporozoite, Male Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, late schizont, Female Gametocyte. Otto TD PlasmoDB 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.
  • 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
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.

Orthologs

Ortholog group members (OG5_127507)

Species Accession Gene Product
Arabidopsis thaliana AT3G07270   GTP cyclohydrolase I
Brugia malayi Bm1_50975   GTP cyclohydrolase I
Candida albicans CaO19.11439   GTP-cyclohydrolase I
Candida albicans CaO19.3957   GTP-cyclohydrolase I
Caenorhabditis elegans CELE_F32G8.6   Protein CAT-4
Dictyostelium discoideum DDB_G0288481   GTP cyclohydrolase I
Drosophila melanogaster Dmel_CG9441   Punch
Escherichia coli b2153   GTP cyclohydrolase I
Echinococcus granulosus EgrG_001065800   GTP cyclohydrolase I
Echinococcus multilocularis EmuJ_001065800   GTP cyclohydrolase I
Homo sapiens ENSG00000131979   GTP cyclohydrolase 1
Loa Loa (eye worm) LOAG_01526   GTP cyclohydrolase I
Mycobacterium leprae ML0223   Probable GTP cyclohydrolase I FolE (GTP-CH-I)
Mus musculus ENSMUSG00000037580   GTP cyclohydrolase 1
Mycobacterium tuberculosis Rv3609c   GTP cyclohydrolase I FolE (GTP-ch-I)
Mycobacterium ulcerans MUL_2233   GTP cyclohydrolase I FolE
Mycobacterium ulcerans MUL_4191   GTP cyclohydrolase I
Neospora caninum NCLIV_008130   GTP cyclohydrolase (EC 3.5.4.16), related
Oryza sativa 4337297   Os04g0662700
Plasmodium berghei PBANKA_1438900   GTP cyclohydrolase I, putative
Plasmodium falciparum PF3D7_1224000   GTP cyclohydrolase I
Plasmodium knowlesi PKNH_1443200   GTP cyclohydrolase I
Plasmodium vivax PVX_123830   GTP cyclohydrolase I, putative
Plasmodium yoelii PY03300   GTP cyclohydrolase I, putative
Saccharomyces cerevisiae YGR267C   GTP cyclohydrolase I
Schistosoma mansoni Smp_026920   GTP cyclohydrolase I
Schmidtea mediterranea mk4.002948.04   GTP cyclohydrolase 1
Toxoplasma gondii TGME49_253780   GTP cyclohydrolase I, putative

Essentiality

PF3D7_1224000 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu3671 Mycobacterium tuberculosis essential nmpdr
b2153 Escherichia coli essential goodall
YGR267C Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1438900 Plasmodium berghei Dispensable plasmo
TGME49_253780 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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.

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): 0.3

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

3 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_1224000 (Plasmodium falciparum), GTP cyclohydrolase I
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