Detailed view for TcCLB.509715.70

Basic information

TDR Targets ID: 48295
Trypanosoma cruzi, folylpolyglutamate synthase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.8635 | Length (AA): 487 | MW (Da): 53932 | Paralog Number: 1

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

Druggability Group : DG4

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

PF08245   Mur ligase middle domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0016874   ligase activity  
GO:0005524   ATP binding  
GO:0004326   tetrahydrofolylpolyglutamate synthase activity  
GO:0009396   folic acid and derivative biosynthetic process  
GO:0009058   biosynthetic process  

Metabolic Pathways

Folate biosynthesis (KEGG)
Global map (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
4 479 1e8c (A) 50 487 17.00 0 1 0.86 0.06
8 474 1w78 (A) 9 419 27.00 0 1 1.22 -0.92
54 213 2gc5 (A) 40 193 40.00 0 1 0.91 -1.34
5 474 1w78 (A) 6 419 25.00 0.00000012 1 1.14309 0.15
10 204 2gc5 (A) 1 184 31.00 0.015 1 0.748411 -0.25
34 417 3nrs (A) 32 409 33.00 0 1 1.0441 0.27
34 308 1w78 (A) 32 294 39.00 0 1 0.860282 -0.03

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

No expression data available for this gene

Orthologs

Ortholog group members (OG5_126889)

Species Accession Gene Product
Arabidopsis thaliana AT5G41480   dihydrofolate synthetase
Arabidopsis thaliana AT5G05980   folylpolyglutamate synthase 1
Arabidopsis thaliana AT3G55630   folylpolyglutamate synthase 3
Brugia malayi Bm1_32935   FolC bifunctional protein
Candida albicans CaO19.6908   similar to S. cerevisiae YMR113W
Candida albicans CaO19_6908   hypothetical protein
Candida albicans CaO19.4516   similar to S. cerevisiae MET7 (YOR241W) folylpolyglutamate synthetase involved in folate coenzyme metabolism
Candida albicans CaO19.11991   similar to S. cerevisiae MET7 (YOR241W) folylpolyglutamate synthetase involved in folate coenzyme metabolism
Caenorhabditis elegans CELE_F25B5.6   Protein F25B5.6, isoform C
Dictyostelium discoideum DDB_G0292632   folylpolyglutamate synthase
Drosophila melanogaster Dmel_CG2543   CG2543 gene product from transcript CG2543-RA
Escherichia coli b2315   bifunctional folylpolyglutamate synthase/dihydrofolate synthase
Echinococcus granulosus EgrG_002002400   folylpolyglutamate synthase, mitochondrial
Echinococcus granulosus EgrG_000654300   folylpolyglutamate synthase mitochondrial
Echinococcus multilocularis EmuJ_000654300   folylpolyglutamate synthase, mitochondrial
Echinococcus multilocularis EmuJ_000654700   folylpolyglutamate synthase, mitochondrial
Homo sapiens ENSG00000136877   folylpolyglutamate synthase
Leishmania braziliensis LbrM.35.2820   folylpolyglutamate synthetase
Leishmania donovani LdBPK_362740.1   folylpolyglutamate synthetase
Leishmania infantum LinJ.36.2740   folylpolyglutamate synthetase
Leishmania major LmjF.36.2610   folylpolyglutamate synthetase
Leishmania mexicana LmxM.36.2610   folylpolyglutamate synthetase
Loa Loa (eye worm) LOAG_04585   FolC protein
Mycobacterium leprae ML1471c   PROBABLE FOLYLPOLYGLUTAMATE SYNTHASE PROTEIN FOLC (FOLYLPOLY-GAMMA-GLUTAMATE SYNTHETASE) (FPGS)
Mus musculus ENSMUSG00000009566   folylpolyglutamyl synthetase
Mycobacterium tuberculosis Rv2447c   Probable folylpolyglutamate synthase protein FolC (folylpoly-gamma-glutamate synthetase) (FPGS)
Mycobacterium ulcerans MUL_3718   folylpolyglutamate synthase protein FolC
Neospora caninum NCLIV_035540   hypothetical protein
Oryza sativa 4349049   Os10g0503200
Oryza sativa 4331360   Os03g0111100
Oryza sativa 9266309   Os12g0623700
Onchocerca volvulus OVOC2981   Putative folylpolyglutamate synthase
Plasmodium berghei PBANKA_1340000   dihydrofolate synthase/folylpolyglutamate synthase, putative
Plasmodium falciparum PF3D7_1324800   dihydrofolate synthase/folylpolyglutamate synthase
Plasmodium knowlesi PKNH_1204000   dihydrofolate synthase/folylpolyglutamate synthase, putative
Plasmodium vivax PVX_116635   dihydrofolate synthase/folylpolyglutamate synthase, putative
Plasmodium yoelii PY03886   dihydrofolate synthase/folylpolyglutamate synthase
Saccharomyces cerevisiae YMR113W   dihydrofolate synthase
Saccharomyces cerevisiae YOR241W   tetrahydrofolate synthase
Schistosoma japonicum Sjp_0028870   ko:K01930 folylpolyglutamate synthase [EC6.3.2.17], putative
Schistosoma japonicum Sjp_0312200   Folylpolyglutamate synthase, mitochondrial precursor, putative
Schistosoma japonicum Sjp_0111720   ko:K01930 folylpolyglutamate synthase [EC6.3.2.17], putative
Schistosoma mansoni Smp_162030   folylpolyglutamate synthase
Schmidtea mediterranea mk4.001618.05   Putative folylpolyglutamate synthase
Trypanosoma brucei gambiense Tbg972.10.9210   folylpolyglutamate-dihydrofolate synthetase, putative
Trypanosoma brucei Tb927.10.7520   folylpolyglutamate synthase, putative
Trypanosoma cruzi TcCLB.509715.70   folylpolyglutamate synthase, putative
Trypanosoma cruzi TcCLB.510105.80   folylpolyglutamate synthetase
Toxoplasma gondii TGME49_271350   bifunctional protein FolC subfamily protein
Treponema pallidum TP0340   folylpolyglutamate synthetase (folC)
Theileria parva TP01_0440   dihydrofolate synthase/folylpolyglutamate synthase, putative
Trichomonas vaginalis TVAG_229870   dihydrofolate synthase/folylpolyglutamate synthase, putative

Essentiality

TcCLB.509715.70 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu2490 Mycobacterium tuberculosis essential nmpdr
Tb927.10.7520 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.7520 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.7520 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.7520 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b2315 Escherichia coli essential goodall
YMR113W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1340000 Plasmodium berghei Essential plasmo
TGME49_271350 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

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): 0.6

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Escherichia coli bifunctional folylpolyglutamate synthase/dihydrofolate synthase Compounds References
Homo sapiens folylpolyglutamate synthase Compounds References
Mus musculus folylpolyglutamyl synthetase Compounds References
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
0.0241 0.2857 0.5336
0.0206 0.3319 1
0.012 0.4097 0
0.012 0.2688 1
0.0108 1 1
0.0241 0.2857 0.5336
0.0116 0.5 0.5
0.0196 0.3175 0.4289
0.0241 0.2857 0.5336
0.0219 0.5997 1
0.012 0.5 0.5
0.0193 0.5997 1
0.012 0.2896 0.5
0.0219 0.5997 1
0.0195 0.6137 1
0.012 0.2597 0.5
0.0196 0.3175 0.4289
0.0226 0.2989 0.4712
0.0241 0.2857 0.5336
0.0316 0.4348 1
0.0216 0.3242 0.3689

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.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

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Gene identifier TcCLB.509715.70 (Trypanosoma cruzi), folylpolyglutamate synthase, putative
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