Detailed view for PKNH_0509600

Basic information

TDR Targets ID: 529152
Plasmodium knowlesi, bifunctional dihydrofolate reductase-thymidylate synthase, putative
Source Database / ID: 

pI: 7.1988 | Length (AA): 626 | MW (Da): 72053 | Paralog Number: 0

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

Druggability Group : DG

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

PF00186   Dihydrofolate reductase
PF00303   Thymidylate synthase

Gene Ontology

Mouse over links to read term descriptions.
GO:0004799   thymidylate synthase activity  
GO:0004146   dihydrofolate reductase activity  
GO:0006730   one-carbon compound metabolic process  
GO:0006231   dTMP biosynthetic process  
GO:0055114   oxidation reduction  
GO:0046654   tetrahydrofolate biosynthetic process  

Structural information

Modbase 3D models:

There are 3 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
1 626 3qg2 (A) 2 608 78.00 0 1 1.7609 -0.38
2 238 2bl9 (A) 2 238 88.00 0 1 1.37049 -1.09
339 626 2aaz (A) 16 317 56.00 0 1 1.20506 -1.32

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_127385)

Species Accession Gene Product
Arabidopsis thaliana AT4G34570   bifunctional dihydrofolate reductase - thymidylate synthase
Arabidopsis thaliana AT2G16370   bifunctional dihydrofolate reductase-thymidylate synthase 1
Babesia bovis BBOV_II000780   dihydrofolate reductase/thymidilate synthase
Brugia malayi Bm1_33465   thymidylate synthase
Candida albicans CaO19.3549   Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C)
Candida albicans CaO19.11033   Thymidylate synthase capable of functional substitution for S. cerevisiae CDC21 (YOR074C)
Caenorhabditis elegans CELE_Y110A7A.4   Protein Y110A7A.4
Cryptosporidium hominis Chro.40506   chain A, crystal structure of Dhfr
Cryptosporidium parvum cgd4_4460   dihydrofolate reductase-thymidylate synthase
Drosophila melanogaster Dmel_CG3181   CG3181 gene product from transcript CG3181-RA
Escherichia coli b2827   thymidylate synthetase
Echinococcus granulosus EgrG_000260100   thymidylate synthase
Echinococcus multilocularis EmuJ_000260100   thymidylate synthase
Homo sapiens ENSG00000176890   thymidylate synthetase
Leishmania braziliensis LbrM.06.0830   dihydrofolate reductase-thymidylate synthase
Leishmania donovani LdBPK_060890.1   dihydrofolate reductase-thymidylate synthase
Leishmania infantum LinJ.06.0890   dihydrofolate reductase-thymidylate synthase
Leishmania major LmjF.06.0860   dihydrofolate reductase-thymidylate synthase
Leishmania mexicana LmxM.06.0860   dihydrofolate reductase-thymidylate synthase
Loa Loa (eye worm) LOAG_05742   thymidylate synthase
Mycobacterium leprae ML1519c   PROBABLE THYMIDYLATE SYNTHASE THYA (TS) (TSASE)
Mus musculus ENSMUSG00000025747   thymidylate synthase
Mycobacterium tuberculosis Rv2764c   Probable thymidylate synthase ThyA (ts) (TSASE)
Mycobacterium ulcerans MUL_2178   thymidylate synthase
Neospora caninum NCLIV_065390   Bifunctional dihydrofolate reductase-thymidylate synthase, related
Oryza sativa 4350527   Os11g0484400
Oryza sativa 9271078   Os12g0446900
Onchocerca volvulus OVOC2868  
Plasmodium berghei PBANKA_0719300   bifunctional dihydrofolate reductase-thymidylate synthase, putative
Plasmodium falciparum PF3D7_0417200   bifunctional dihydrofolate reductase-thymidylate synthase
Plasmodium knowlesi PKNH_0509600   bifunctional dihydrofolate reductase-thymidylate synthase, putative
Plasmodium vivax PVX_089950   bifunctional dihydrofolate reductase-thymidylate synthase, putative
Plasmodium yoelii PY04370   thymidylate synthase, putative
Saccharomyces cerevisiae YOR074C   thymidylate synthase
Schistosoma japonicum Sjp_0097190   hypothetical protein
Schistosoma japonicum Sjp_0303630   ko:K00560 thymidylate synthase [EC2.1.1.45], putative
Schistosoma mansoni Smp_135460   bifunctional dihydrofolate reductase-thymidylate synthase
Schmidtea mediterranea mk4.001483.01   Thymidylate synthase
Trypanosoma brucei gambiense Tbg972.7.6360   dihydrofolate reductase-thymidylate synthase
Trypanosoma brucei Tb927.7.5480   dihydrofolate reductase-thymidylate synthase
Trypanosoma cruzi TcCLB.509153.90   dihydrofolate reductase-thymidylate synthase
Toxoplasma gondii TGME49_249180   bifunctional dihydrofolate reductase-thymidylate synthase
Theileria parva TP04_0504   dihydrofolate reductase-thymidylate synthase, putative

Essentiality

PKNH_0509600 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.7.5480 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.7.5480 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.7.5480 Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb927.7.5480 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b2827 Escherichia coli essential goodall
CELE_Y110A7A.4 Caenorhabditis elegans embryonic lethal wormbase
YOR074C Saccharomyces cerevisiae inviable yeastgenome
Show/Hide essentiality data references
  • 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
  • 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.
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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

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
Species Known druggable target Linked compounds Reference
Cryptococcus neoformans var. neoformans B-3501A Thymidylate synthase Compounds References
Trypanosoma brucei dihydrofolate reductase-thymidylate synthase Compounds References
Cryptosporidium parvum dihydrofolate reductase-thymidylate synthase Compounds References
Plasmodium berghei bifunctional dihydrofolate reductase-thymidylate synthase, putative Compounds References
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase Compounds References
Toxoplasma gondii bifunctional dihydrofolate reductase-thymidylate synthase Compounds References
Rattus norvegicus Thymidylate synthase Compounds References
Escherichia coli thymidylate synthetase Compounds References
Mycobacterium tuberculosis Probable thymidylate synthase ThyA (ts) (TSASE) Compounds References
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase Compounds References
Bos taurus Thymidylate synthase Compounds References
Mus musculus thymidylate synthase Compounds References
Leishmania major dihydrofolate reductase-thymidylate synthase Compounds References
Homo sapiens thymidylate synthetase Compounds References
Lactobacillus casei Thymidylate synthase Compounds References
Enterococcus faecalis (strain ATCC 700802 / V583) Thymidylate synthase Compounds References
Pneumocystis carinii Thymidylate synthase Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Bos taurus Dihydrofolate reductase 187 aa 30.1% 209 aa Compounds References
Gallus gallus Dihydrofolate reductase 189 aa 28.7% 209 aa Compounds References
Escherichia coli Thymidylate synthase (EC 2.1.1.45) (TS) (TSase) 367 aa 25.6% 352 aa Compounds References
Rattus norvegicus Dihydrofolate reductase 187 aa 29.2% 209 aa Compounds References
Pneumocystis carinii Dihydrofolate reductase 206 aa 29.2% 226 aa Compounds References
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.

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

User comments

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Gene identifier PKNH_0509600 (Plasmodium knowlesi), bifunctional dihydrofolate reductase-thymidylate synthase, putative
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