Detailed view for PF3D7_0411900

Basic information

TDR Targets ID: 3893
Plasmodium falciparum, DNA polymerase alpha catalytic subunit A
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 8.4231 | Length (AA): 1912 | MW (Da): 225401 | Paralog Number: 0

Signal peptide: N | 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

PF00136   DNA polymerase family B

Gene Ontology

Mouse over links to read term descriptions.
GO:0005634   nucleus  
GO:0003887   DNA-directed DNA polymerase activity  
GO:0003677   DNA binding  
GO:0003676   nucleic acid binding  
GO:0000166   nucleotide binding  
GO:0006260   DNA replication  

Metabolic Pathways

Purine metabolism (KEGG)
Pyrimidine metabolism (KEGG)
Global map (KEGG)
DNA replication (KEGG)

Structural information

Modbase 3D models:

There are 17 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
660 891 1noy (A) 108 352 20.00 0 0.94 0.26 -0.03
714 1560 2gv9 (A) 431 1191 23.00 0 1 -0.09 1.06
1 180 4uos (A) 9 184 18.00 0.37 0.14 0.300742 -1.09
25 251 4tql (A) 10 235 17.00 0.052 0.09 0.287324 -0.76
366 1553 3iay (A) 95 980 22.00 0 1 0.359139 1.53
408 1551 4qcl (A) 359 1232 34.00 0 1 0.473526 1.24
1041 1542 4k8x (A) 349 744 33.00 0 1 0.323752 0.88
1588 1750 3flo (B) 1273 1451 25.00 0.000002 1 0.239851 -0.01
1666 1869 3n3m (A) 32 239 28.00 0.83 0.54 0.155895 0.64
1 180 4uos (A) 9 184 18.00 0.76 0.08 0.272687 -0.9
287 506 4wat (A) 210 460 33.00 0.34 0.42 0.10295 1.46
390 1550 4qcl (A) 342 1244 31.00 0 1 0.502274 1.19
407 1538 4qcl (A) 359 1232 34.00 0 1 0.494203 1.23
949 1293 4i9q (A) 273 627 29.00 0.0013 0.84 0.106775 1.2
1028 1432 4ahc (A) 349 734 32.00 0 1 0.23237 1.22
1575 1765 3flo (B) 1273 1451 22.00 0.0000017 0.8 0.166479 -0.06
1653 1856 3n3m (A) 32 239 28.00 0.86 0.29 0.127525 0.7

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 Sporozoite, Male Gametocyte. Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 32 hs, Oocyst. Otto TD Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, early schizont, Female Gametocyte. Otto TD PlasmoDB Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 24 hs, Ring. Otto TD Zanghi G
Show/Hide expression data references
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
  • 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

Orthologs

Ortholog group members (OG5_128177)

Species Accession Gene Product
Arabidopsis thaliana AT5G67100   DNA polymerase alpha catalytic subunit
Babesia bovis BBOV_IV007060   DNA polymerase alpha subunit, putative
Brugia malayi Bm1_48460   DNA polymerase alpha catalytic subunit
Candida albicans CaO19.5873   likely DNA polymerase I alpha subunit p180
Candida albicans CaO19.13294   likely DNA polymerase I alpha subunit p180
Caenorhabditis elegans CELE_Y47D3A.29   Protein Y47D3A.29, isoform B
Cryptosporidium hominis Chro.30484   DNA polymerase alpha, DNAPol alpha
Cryptosporidium parvum cgd3_4290   DNA polymerase alpha catalytic subunit
Dictyostelium discoideum DDB_G0282191   DNA polymerase alpha catalytic subunit
Drosophila melanogaster Dmel_CG6349   DNA polymerase alpha 180kD
Echinococcus granulosus EgrG_000475300   DNA polymerase alpha catalytic subunit
Entamoeba histolytica EHI_151520   DNA polymerase alpha catalytic subunit, putative
Echinococcus multilocularis EmuJ_000475300   DNA polymerase alpha catalytic subunit
Giardia lamblia GL50803_27326   DNA polymerase alpha subunit A
Homo sapiens ENSG00000101868   polymerase (DNA directed), alpha 1, catalytic subunit
Leishmania braziliensis LbrM.16.1600   DNA polymerase I alpha catalytic subunit, putative
Leishmania donovani LdBPK_161640.1   DNA polymerase I alpha catalytic subunit, putative
Leishmania infantum LinJ.16.1640   DNA polymerase I alpha catalytic subunit, putative
Leishmania major LmjF.16.1540   DNA polymerase I alpha catalytic subunit, putative
Leishmania mexicana LmxM.16.1540   DNA polymerase I alpha catalytic subunit, putative
Loa Loa (eye worm) LOAG_01730   hypothetical protein
Mus musculus ENSMUSG00000006678   polymerase (DNA directed), alpha 1
Neospora caninum NCLIV_062650   DNA polymerase alpha catalytic subunit, putative
Oryza sativa 4325052   Os01g0868300
Onchocerca volvulus OVOC1050   DNA polymerase alpha catalytic subunit homolog
Plasmodium berghei PBANKA_0613200   DNA polymerase alpha catalytic subunit A, putative
Plasmodium falciparum PF3D7_0411900   DNA polymerase alpha catalytic subunit A
Plasmodium knowlesi PKNH_0310100   DNA polymerase alpha catalytic subunit A, putative
Plasmodium vivax PVX_000650   DNA polymerase alpha, putative
Plasmodium yoelii PY06115   DNA polymerase alpha-related
Saccharomyces cerevisiae YNL102W   DNA-directed DNA polymerase alpha catalytic subunit POL1
Schistosoma japonicum Sjp_0041180   ko:K02320 DNA polymerase alpha subunit A, putative
Schistosoma mansoni Smp_178260   DNA polymerase alpha catalytic subunit
Schmidtea mediterranea mk4.003330.10   DNA polymerase alpha catalytic subunit
Schmidtea mediterranea mk4.006149.00  
Schmidtea mediterranea mk4.000561.18  
Schmidtea mediterranea mk4.002208.05   DNA polymerase alpha catalytic subunit
Schmidtea mediterranea mk4.003330.09   DNA polymerase alpha catalytic subunit
Schmidtea mediterranea mk4.002208.06   DNA polymerase alpha catalytic subunit
Schmidtea mediterranea mk4.035062.00   DNA polymerase alpha catalytic subunit
Trypanosoma brucei gambiense Tbg972.8.4690   DNA polymerase alpha catalytic subunit,DNA polymerase I, putative
Trypanosoma brucei Tb927.8.4880   DNA polymerase alpha catalytic subunit
Trypanosoma congolense TcIL3000_0_02350   DNA polymerase alpha catalytic subunit
Trypanosoma cruzi TcCLB.508837.180   DNA polymerase I alpha catalytic subunit, putative
Toxoplasma gondii TGME49_217910   DNA polymerase (pol2) superfamily protein
Theileria parva TP03_0202   DNA polymerase alpha, putative
Trichomonas vaginalis TVAG_342390   DNA polymerase alpha catalytic subunit, putative
Trichomonas vaginalis TVAG_198840   DNA polymerase II, putative

Essentiality

PF3D7_0411900 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.4880 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.8.4880 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.8.4880 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.4880 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_Y47D3A.29 Caenorhabditis elegans embryonic lethal wormbase
YNL102W Saccharomyces cerevisiae inviable yeastgenome
TGME49_217910 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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.
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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): 0.8

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
Homo sapiens polymerase (DNA directed), alpha 1, catalytic subunit 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

  • Reagent:
  • Target Type Source Notes
    PF3D7_0411900 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Plasmodium falciparum ( 1 )

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_0411900 (Plasmodium falciparum), DNA polymerase alpha catalytic subunit A
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