Detailed view for PF3D7_1411400

Basic information

TDR Targets ID: 2445
Plasmodium falciparum, plastid replication-repair enzyme
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.2801 | Length (AA): 2016 | MW (Da): 235818 | Paralog Number: 0

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

Druggability Group : DG2

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

PF00476   DNA polymerase family A
PF01612   3'-5' exonuclease
PF13481   AAA domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0020011   apicoplast  
GO:0006139   nucleobase, nucleoside, nucleotide and nucleic acid metabolic process  
GO:0005622   intracellular  
GO:0005739   mitochondrion  
GO:0005524   ATP binding  
GO:0003887   DNA-directed DNA polymerase activity  
GO:0003678   DNA helicase activity  
GO:0003677   DNA binding  
GO:0003676   nucleic acid binding  
GO:0008408   3'-5' exonuclease activity  
GO:0006261   DNA-dependent DNA replication  
GO:0006260   DNA replication  

Structural information

Modbase 3D models:

There are 26 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
335 463 1q57 (A) 113 244 35.00 0.0000045 0.79 0.42 -0.58
674 928 1cr0 (A) 271 543 21.00 0 0.96 0.27 -0.3
691 931 2cvh (A) 1 220 14.00 0 0.16 0.1 -0.67
1192 2016 1bgx (T) 31 831 20.00 0 1 0.37 0.62
1434 1614 2fby (A) 42 227 24.00 0 1 0.34 -1.3
335 463 1nui (A) 113 244 35.00 0.000048 0.72 0.367388 -0.12
503 1593 3ffz (A) 46 1200 23.00 0.0039 1 0.445571 1.85
674 923 1e0j (A) 271 538 26.00 0.0042 1 0.380408 -0.07
949 1209 4u0r (A) 178 497 13.00 0.35 0.02 0.214464 -0.24
1038 1337 4o87 (A) 23 311 28.00 0.28 0.96 0.17521 0.99
1241 1658 2vkh (A) 45 441 26.00 0.49 0.76 0.0947413 1.88
1266 2015 1bgx (T) 107 830 18.00 0 1 0.406224 1.27
1454 1615 2fby (A) 66 228 28.00 0.71 0.99 0.345757 0.23
1470 2012 1dpi (A) 355 924 31.00 0 1 0.293745 1.75
1512 1618 3saf (A) 352 455 31.00 0.098 0.95 0.328475 0.79
1596 2016 4bwj (A) 398 832 29.00 0 1 0.485829 -0.08
133 497 2au3 (A) 5 365 19.00 0.000011 1 0.215412 0.89
328 459 1nui (A) 110 244 34.00 0.000047 0.89 0.365606 -0.18
670 919 1e0j (A) 271 538 26.00 0.0044 1 0.381454 -0.07
1091 1384 2fds (A) 24 321 14.00 0.23 0.09 0.291123 -0.43
1390 1618 5c0y (A) 160 384 21.00 0.21 1 0.331017 0.33
1435 2008 2kfn (A) 324 924 28.00 0 1 0.532288 0.26
1450 1611 2fby (A) 66 228 28.00 0.74 0.99 0.346717 0.23
1466 2008 1dpi (A) 355 924 31.00 0 1 0.295081 1.75
1506 2010 4f3o (A) 355 874 26.00 0 1 0.469994 0.14
1508 1614 3saf (A) 352 455 31.00 0.1 0.95 0.329381 0.79

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
  • 5DKT:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5DKU:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile late trophozoite. PlasmoDB
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile early schizont, Oocyst. PlasmoDB Zanghi G
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, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, Ring, Female Gametocyte, Male Gametocyte. Otto TD Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Sporozoite. Zanghi G
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.
  • 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
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.

Orthologs

Ortholog group members (OG5_127218)

Species Accession Gene Product
Babesia bovis BBOV_IV005810   DNA polymerase I, putative
Brugia malayi Bm1_47460   DNA polymerase I family protein
Caenorhabditis elegans CELE_F46G11.1   Protein F46G11.1
Chlamydia trachomatis CT_493   DNA polymerase I
Dictyostelium discoideum DDB_G0288209   T7-like mitochondrial DNA helicase
Dictyostelium discoideum DDB_G0282679   hypothetical protein
Dictyostelium discoideum DDB_G0274421   hypothetical protein
Dictyostelium discoideum DDB_G0277751   hypothetical protein
Drosophila melanogaster Dmel_CG5924   mitochondrial DNA helicase
Escherichia coli b3863   fused DNA polymerase I 5'->3' polymerase/3'->5' exonuclease/5'->3' exonuclease
Echinococcus granulosus EgrG_000742600   twinkle protein mitochondrial
Entamoeba histolytica EHI_073640   DNA-directed DNA polymerase, putative
Echinococcus multilocularis EmuJ_000742600   twinkle protein, mitochondrial
Homo sapiens ENSG00000130997   polymerase (DNA directed) nu
Homo sapiens ENSG00000107815   chromosome 10 open reading frame 2
Leishmania braziliensis LbrM.20.1290   mitochondrial DNA polymerase I protein A, putative
Leishmania donovani LdBPK_341370.1   mitochondrial DNA polymerase I protein A, putative
Leishmania infantum LinJ.34.1370   mitochondrial DNA polymerase I protein A, putative
Leishmania major LmjF.34.1260   mitochondrial DNA polymerase I protein A, putative
Leishmania mexicana LmxM.33.1260   mitochondrial DNA polymerase I protein A, putative
Loa Loa (eye worm) LOAG_05495   twinkle helicase
Loa Loa (eye worm) LOAG_04394   hypothetical protein
Mycobacterium leprae ML1381c   PROBABLE DNA POLYMERASE I POLA
Mus musculus ENSMUSG00000045102   DNA polymerase N
Mus musculus ENSMUSG00000025209   progressive external ophthalmoplegia 1 (human)
Mycobacterium tuberculosis Rv1629   Probable DNA polymerase I PolA
Mycobacterium ulcerans MUL_1611   DNA polymerase I
Neospora caninum NCLIV_012190   hypothetical protein
Neospora caninum NCLIV_025690   hypothetical protein
Onchocerca volvulus OVOC2210   Twinkle protein, mitochondrial homolog
Plasmodium berghei PBANKA_1031100   plastid replication-repair enzyme, putative
Plasmodium falciparum PF3D7_1411400   plastid replication-repair enzyme
Plasmodium knowlesi PKNH_1346900   plastid replication-repair enzyme, putative
Plasmodium vivax PVX_085880   plastid replication-repair enzyme, putative
Plasmodium yoelii PY00163   POM1
Schistosoma japonicum Sjp_0309860   Twinkle protein, mitochondrial precursor, putative
Schistosoma japonicum Sjp_0081820   ko:K02349 DNA polymerase theta subunit, putative
Schistosoma mansoni Smp_055500   DNA polymerase I
Schistosoma mansoni Smp_146360   hypothetical protein
Schistosoma mansoni Smp_177240   hypothetical protein
Schmidtea mediterranea mk4.000175.09  
Schmidtea mediterranea mk4.022779.01  
Schmidtea mediterranea mk4.030480.01   DNA polymerase nu
Schmidtea mediterranea mk4.022779.00  
Trypanosoma brucei gambiense Tbg972.4.2950   mitochondrial DNA polymerase I protein A, putative
Trypanosoma brucei Tb927.4.2950   mitochondrial DNA polymerase I protein A, putative
Trypanosoma brucei Tb11.v5.0971   mitochondrial DNA polymerase I protein A, putative
Trypanosoma congolense TcIL3000_0_38580   mitochondrial DNA polymerase I protein A, putative
Trypanosoma cruzi TcCLB.506435.30   mitochondrial DNA polymerase I protein A, putative
Trypanosoma cruzi TcCLB.506265.30   mitochondrial DNA polymerase I protein A, putative
Toxoplasma gondii TGME49_237830   DNA polymerase I domain-containing protein
Toxoplasma gondii TGME49_261850   helicase, putative
Treponema pallidum TP0105   DNA polymerase I (polA)
Theileria parva TP01_0386   hypothetical protein
Trichomonas vaginalis TVAG_045980   DNA polymerase I, putative
Wolbachia endosymbiont of Brugia malayi Wbm0725   DNA polymerase I

Essentiality

PF3D7_1411400 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.4.2950 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.4.2950 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.4.2950 Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb927.4.2950 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b3863 Escherichia coli non-essential goodall
PBANKA_1031100 Plasmodium berghei Essential plasmo
TGME49_237830 Toxoplasma gondii Probably essential sidik
TGME49_261850 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
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • 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
  • 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

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
Thermus thermophilus DNA polymerase I, thermostable Compounds References
Thermus aquaticus Taq polymerase 1 Compounds References
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

15 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_1411400 (Plasmodium falciparum), plastid replication-repair enzyme
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