Detailed view for PF3D7_0505500

Basic information

TDR Targets ID: 4085
Plasmodium falciparum, DNA mismatch repair protein MSH6, putative

Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 6.3538 | Length (AA): 1350 | MW (Da): 156440 | 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

PF00488   MutS domain V
PF01624   MutS domain I
PF05190   MutS family domain IV
PF05192   MutS domain III

Gene Ontology

Mouse over links to read term descriptions.
GO:0030983   mismatched DNA binding  
GO:0005524   ATP binding  
GO:0006298   mismatch repair  

Metabolic Pathways

Structural information

Modbase 3D models:

There are 13 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
407 1308 1ewq (A) 15 759 32.00 0 1 0.83 -0.16
1278 1349 1qzm (A) 491 559 23.00 0.00000000025 0.03 0.25 -0.37
353 1317 2o8b (B) 362 1331 32.00 0 1 0.955615 0.14
411 1349 3thx (B) 226 1117 24.00 0 1 0.785556 0.78
536 1349 3thy (A) 92 915 25.00 0 1 0.821763 0.26
683 1342 3thx (A) 251 887 31.00 0 1 0.734789 0.37
12 194 2ap3 (A) 9 193 11.00 0.6 0 0.276856 -0.73
57 306 4lvn (A) 345 566 29.00 0.4 0.16 -0.0440148 1.28
364 1317 2o8b (B) 365 1331 31.00 0 1 0.935967 0.09
407 1308 1ewq (A) 15 759 32.00 0 1 0.771948 0.49
411 1349 3thx (B) 226 1117 24.00 0.00000031 1 0.738756 0.57
552 1349 3thy (A) 112 915 25.00 0 1 0.802411 0.17
756 1347 3thx (A) 313 912 28.00 0.00000001 1 0.553719 0.55

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 - 32 hs, gametocyte, sporozoite, early schizont, early trophozoite, late schizont, late trophozoite, Male Gametocyte. Otto TD PlasmoDB Lasonder E
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, merozoite, early ring, late ring, Oocyst, Sporozoite. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 8 hs, intra-erythrocytic - 24 hs, Ring, Female Gametocyte. Otto TD Zanghi G Lasonder E
Show/Hide expression data references
  • 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.
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.

Orthologs

Ortholog group members (OG5_126895)

Species Accession Gene Product
Arabidopsis thaliana AT4G02070   DNA mismatch repair protein MSH6
Arabidopsis thaliana AT3G24495   DNA mismatch repair protein Msh6-2
Babesia bovis BBOV_I004430   DNA repair protein, putative
Brugia malayi Bm1_41770   MutS domain III family protein
Candida albicans CaO19.4945   repair of insertion-deletion mispairs
Candida albicans CaO19.496   similar to S. cerevisiae MutS Homolog involved in Mitochondrial DNA mismatch repair
Candida albicans CaO19.12411   repair of insertion-deletion mispairs
Candida albicans CaO19.8126   similar to S. cerevisiae MutS Homolog involved in Mitochondrial DNA mismatch repair
Caenorhabditis elegans CELE_Y47G6A.11   Protein MSH-6
Cryptosporidium hominis Chro.80049   DNA repair protein
Cryptosporidium parvum cgd8_370   DNA repair protein
Chlamydia trachomatis CT_792   DNA mismatch repair protein MutS
Dictyostelium discoideum DDB_G0275999   DNA mismatch repair protein
Dictyostelium discoideum DDB_G0268614   DNA mismatch repair protein
Drosophila melanogaster Dmel_CG7003   CG7003 gene product from transcript CG7003-RA
Escherichia coli b2733   methyl-directed mismatch repair protein
Echinococcus granulosus EgrG_000822900   dna mismatch repair protein msh6
Entamoeba histolytica EHI_193340   mutS family protein
Echinococcus multilocularis EmuJ_000822900   dna mismatch repair protein msh6
Homo sapiens ENSG00000116062   mutS homolog 6
Leishmania braziliensis LbrM.35.2160   mismatch repair protein MSH8, putative
Leishmania donovani LdBPK_362050.1   DNA mismatch repair protein MSH6, putative
Leishmania infantum LinJ.36.2050   mismatch repair protein MSH8, putative
Leishmania major LmjF.36.1950   mismatch repair protein MSH8, putative
Leishmania mexicana LmxM.36.1950   mismatch repair protein MSH8, putative
Loa Loa (eye worm) LOAG_03556   hypothetical protein
Mus musculus ENSMUSG00000005370   mutS homolog 6 (E. coli)
Neospora caninum NCLIV_042630   DNA mismatch repair protein mutS, related
Oryza sativa 4347016   Os09g0407600
Oryza sativa 4325353   Os01g0180600
Plasmodium berghei PBANKA_1105100   DNA mismatch repair protein MSH6, putative
Plasmodium falciparum PF3D7_0505500   DNA mismatch repair protein MSH6, putative
Plasmodium knowlesi PKNH_1028100   DNA mismatch repair protein MSH6, putative
Plasmodium vivax PVX_097835   DNA mismatch repair protein MSH6, putative
Plasmodium yoelii PY02936   G/T mismatch binding protein-related
Saccharomyces cerevisiae YHR120W   mismatch repair ATPase MSH1
Saccharomyces cerevisiae YDR097C   mismatch repair ATPase MSH6
Schistosoma japonicum Sjp_0104370   ko:K08737 DNA mismatch repair protein MSH6, putative
Schistosoma japonicum Sjp_0058170   ko:K08737 DNA mismatch repair protein MSH6, putative
Schistosoma japonicum Sjp_0058180   DNA mismatch repair protein Msh6, putative
Schistosoma mansoni Smp_042670.1   hypothetical protein
Schistosoma mansoni Smp_042670.2   hypothetical protein
Schmidtea mediterranea mk4.038361.03  
Schmidtea mediterranea mk4.000110.01   Msh6
Schmidtea mediterranea mk4.000110.00  
Trypanosoma brucei gambiense Tbg972.10.7830   mismatch repair protein MSH8, putative,mismatch repair protein
Trypanosoma brucei Tb927.10.6410   DNA mismatch repair protein MSH6, putative
Trypanosoma cruzi TcCLB.510187.430   DNA mismatch repair protein MSH6, putative
Toxoplasma gondii TGME49_290640   DNA mismatch repair protein MSH6-1, putative
Treponema pallidum TP0328   DNA mismatch repair protein MutS
Theileria parva TP01_0185   DNA repair protein, putative
Trichomonas vaginalis TVAG_484110   mismatch repair protein Msh6 (mutS homolog)
Wolbachia endosymbiont of Brugia malayi Wbm0257   DNA mismatch repair protein MutS

Essentiality

PF3D7_0505500 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.6410 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.6410 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.6410 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.6410 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b2733 Escherichia coli non-essential goodall
PBANKA_1105100 Plasmodium berghei Essential plasmo
TGME49_290640 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

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
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

No literature references available for this target.

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Gene identifier PF3D7_0505500 (Plasmodium falciparum), DNA mismatch repair protein MSH6, putative
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