Detailed view for PF3D7_1117800

Basic information

TDR Targets ID: 1653
Plasmodium falciparum, DNA mismatch repair protein MLH
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 6.3905 | Length (AA): 1016 | MW (Da): 118307 | 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

PF01119   DNA mismatch repair protein, C-terminal domain
PF13589   Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
PF16413   DNA mismatch repair protein Mlh1 C-terminus

Gene Ontology

Mouse over links to read term descriptions.
GO:0032300   mismatch repair complex  
GO:0016887   ATPase activity  
GO:0005524   ATP binding  
GO:0030983   mismatched DNA binding  
GO:0006298   mismatch repair  

Metabolic Pathways

Mismatch repair (KEGG)

Structural information

Modbase 3D models:

There are 6 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
50 246 1b63 (A) 3 199 38.00 0 1 0.72 -0.94
64 240 1h7s (A) 29 206 36.00 0 1 0.6 -0.98
50 494 4p7a (A) 8 298 50.00 0 1 0.318292 1.14
57 235 3h4l (A) 42 220 37.00 0 1 0.596481 -0.66
681 1011 3rbn (A) 10 284 26.00 0 1 0.222987 0.07
711 1016 4e4w (A) 511 769 32.00 0.000000018 0.97 0.334481 0.58

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 60-80% percentile intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 48 hs, sporozoite, early ring, early trophozoite, late ring, late schizont, Ring, Male Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 40 hs, gametocyte, early schizont, late trophozoite, Oocyst. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Sporozoite, Female Gametocyte. Zanghi G Lasonder E
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.
  • 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

Orthologs

Ortholog group members (OG5_127201)

Species Accession Gene Product
Arabidopsis thaliana AT4G09140   DNA mismatch repair protein MLH1
Babesia bovis BBOV_IV010910   DNA mismatch repair protein, putative
Brugia malayi Bm1_19980   DNA mismatch repair protein MutL containing protein
Candida albicans CaO19.11638   mismatch repair protein
Candida albicans CaO19.4162   mismatch repair protein
Caenorhabditis elegans CELE_T28A8.7   Protein MLH-1
Cryptosporidium hominis Chro.50122   hypothetical protein
Cryptosporidium parvum cgd5_2560   MutL family ATpase
Chlamydia trachomatis CT_575   DNA mismatch repair protein MutL
Dictyostelium discoideum DDB_G0287393   MutL DNA mismatch repair protein
Drosophila melanogaster Dmel_CG11482   CG11482 gene product from transcript CG11482-RB
Escherichia coli b4170   methyl-directed mismatch repair protein
Echinococcus granulosus EgrG_000761100   DNA mismatch repair protein Mlh1
Entamoeba histolytica EHI_129950   DNA mismatch repair protein MLH1, putative
Echinococcus multilocularis EmuJ_000761100   DNA mismatch repair protein Mlh1
Giardia lamblia GL50803_16149   Mlh1-like protein
Homo sapiens ENSG00000076242   mutL homolog 1
Leishmania braziliensis LbrM.24.1460   mismatch repair protein, putative
Leishmania donovani LdBPK_241460.1   mismatch repair protein, putative
Leishmania infantum LinJ.24.1460   mismatch repair protein, putative
Leishmania major LmjF.24.1420   mismatch repair protein, putative
Leishmania mexicana LmxM.24.1420   mismatch repair protein, putative
Loa Loa (eye worm) LOAG_07794   hypothetical protein
Mus musculus ENSMUSG00000032498   mutL homolog 1 (E. coli)
Neospora caninum NCLIV_039530   DNA mismatch repair protein, putative
Oryza sativa 4325393   Os01g0958900
Plasmodium berghei PBANKA_0930200   DNA mismatch repair protein MLH, putative
Plasmodium falciparum PF3D7_1117800   DNA mismatch repair protein MLH
Plasmodium knowlesi PKNH_0915500   DNA mismatch repair protein MLH, putative
Plasmodium vivax PVX_091525   DNA mismatch repair protein MLH, putative
Plasmodium yoelii PY05214   hMLH1 gene product-related
Saccharomyces cerevisiae YMR167W   mismatch repair ATPase MLH1
Schistosoma japonicum Sjp_0066040   ko:K08734 DNA mismatch repair protein MLH1, putative
Schistosoma japonicum Sjp_0106760   ko:K08734 DNA mismatch repair protein MLH1, putative
Schistosoma japonicum Sjp_0123060   IPR002099,DNA mismatch repair protein;IPR011186,DNA mismatch repair protein Mlh1;IPR013507,DNA mismatch repair protein, C-termin
Schistosoma mansoni Smp_009550   DNA mismatch repair protein MLH1
Schmidtea mediterranea mk4.004482.04  
Schmidtea mediterranea mk4.021716.00   Mlh1
Schmidtea mediterranea mk4.004482.05   DNA mismatch repair protein Mlh1
Trypanosoma brucei gambiense Tbg972.8.7030   mismatch repair protein MLH1, putative
Trypanosoma brucei Tb927.8.6840   mismatch repair protein MLH1
Trypanosoma congolense TcIL3000_8_6750   mismatch repair protein MLH1, putative
Trypanosoma cruzi TcCLB.507991.60   mismatch repair protein MLH1, putative
Trypanosoma cruzi TcCLB.504035.140   mismatch repair protein MLH1, putative
Toxoplasma gondii TGME49_266390   DNA mismatch repair protein, C-terminal domain-containing protein
Treponema pallidum TP0303   DNA mismatch repair protein (mutL)
Theileria parva TP01_0756   DNA mismatch repair protein MLH1, putative
Trichomonas vaginalis TVAG_226330   mismatch repair protein Mlh1B (mutL homolog)
Trichomonas vaginalis TVAG_364540   mismatch repair protein Mlh1C (mutL homolog)
Trichomonas vaginalis TVAG_302400   mismatch repair protein Mlh1A (mutL homolog)
Wolbachia endosymbiont of Brugia malayi Wbm0396   DNA mismatch repair protein

Essentiality

PF3D7_1117800 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.6840 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.6840 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.6840 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.6840 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b4170 Escherichia coli non-essential goodall
CELE_T28A8.7 Caenorhabditis elegans embryonic lethal wormbase
CELE_T28A8.7 Caenorhabditis elegans sterile wormbase
PBANKA_0930200 Plasmodium berghei Essential plasmo
TGME49_266390 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.

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_1117800 (Plasmodium falciparum), DNA mismatch repair protein MLH
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