Detailed view for PF3D7_1236800

Basic information

TDR Targets ID: 5409
Plasmodium falciparum, protein-S-isoprenylcysteine O-methyltransferase, putative
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.8284 | Length (AA): 509 | MW (Da): 62431 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 6

Druggability Group : DG4

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

PF04140   Isoprenylcysteine carboxyl methyltransferase (ICMT) family

Gene Ontology

Mouse over links to read term descriptions.
GO:0020011   apicoplast  
GO:0016021   integral to membrane  
GO:0005783   endoplasmic reticulum  
GO:0004671   protein-S-isoprenylcysteine O-methyltransferase activity  
GO:0016458   gene silencing  
GO:0006481   C-terminal protein amino acid methylation  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models:

There are 4 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
115 347 1yo8 (A) 962 1171 6.00 0 0 0.23 -0.01
421 498 4a2n (B) 109 186 37.00 0.00063 0.17 0.348342 1.3
197 319 1w33 (A) 121 241 21.00 0.85 0.03 0.43185 -0.33
421 498 4a2n (B) 109 186 36.00 0.0004 0.28 0.349142 1.31

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 - 40 hs, intra-erythrocytic - 48 hs. Otto TD
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 32 hs, Female Gametocyte. Otto TD Lasonder E
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, early schizont, late schizont, Sporozoite. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, Oocyst, Male Gametocyte. Otto TD Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Ring. Zanghi G
Show/Hide expression data references
  • 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
  • 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_127842)

Species Accession Gene Product
Arabidopsis thaliana AT5G08335   S-isoprenylcysteine O-methyltransferase B
Arabidopsis thaliana AT5G23320   protein-S-isoprenylcysteine O-methyltransferase A
Brugia malayi Bm1_06675   protein-S isoprenylcysteine O-methyltransferase, putative
Candida albicans CaO19.7766   one of two adjacent potential Isoprenylcysteine carboxyl methyltransferase genes similar to S. cerevisiae STE14 (YDR410C) involv
Candida albicans CaO19.120   one of two adjacent potential Isoprenylcysteine carboxyl methyltransferase genes similar to S. cerevisiae STE14 (YDR410C) involv
Candida albicans CaO19.7767   one of two adjacent potential Isoprenylcysteine carboxyl methyltransferase genes similar to S. cerevisiae STE14 (YDR410C) involv
Caenorhabditis elegans CELE_M01E11.1   Protein M01E11.1
Caenorhabditis elegans CELE_F21F3.3   Protein F21F3.3
Dictyostelium discoideum DDB_G0272799   prenylcysteine methyltransferase
Dictyostelium discoideum DDB_G0273995   prenylcysteine methyltransferase
Drosophila melanogaster Dmel_CG11268   isoprenylcysteine carboxylmethyltransferase
Echinococcus granulosus EgrG_000894500   protein S isoprenylcysteine O methyltransferase
Entamoeba histolytica EHI_006100   prenyl cysteine carboxyl methyltransferase, putative
Entamoeba histolytica EHI_045150   prenyl cysteine carboxyl methyltransferase, putative
Echinococcus multilocularis EmuJ_000894500  
Giardia lamblia GL50803_17013   Isoprenylcysteine carboxyl methyltransferase
Homo sapiens ENSG00000116237   isoprenylcysteine carboxyl methyltransferase
Leishmania braziliensis LbrM.34.2940   prenyl protein specific carboxyl methyltransferase, putative
Leishmania donovani LdBPK_353080.1   prenyl protein specific carboxyl methyltransferase, putative
Leishmania infantum LinJ.35.3080   prenyl protein specific carboxyl methyltransferase, putative
Leishmania major LmjF.35.3030   prenyl protein specific carboxyl methyltransferase, putative
Leishmania mexicana LmxM.34.3030   prenyl protein specific carboxyl methyltransferase, putative
Loa Loa (eye worm) LOAG_09538   protein-S isoprenylcysteine O-methyltransferase
Mus musculus ENSMUSG00000039662   isoprenylcysteine carboxyl methyltransferase
Oryza sativa 4336894   Os04g0602900
Plasmodium berghei PBANKA_1451400   protein-S-isoprenylcysteine O-methyltransferase, putative
Plasmodium falciparum PF3D7_1236800   protein-S-isoprenylcysteine O-methyltransferase, putative
Plasmodium knowlesi PKNH_1456500   protein-S-isoprenylcysteine O-methyltransferase, putative
Plasmodium vivax PVX_100790   protein-S-isoprenylcysteine O-methyltransferase, putative
Plasmodium yoelii PY05541   hypothetical protein
Saccharomyces cerevisiae YDR410C   Ste14p
Schistosoma japonicum Sjp_0303920   ko:K00587 protein-S-isoprenylcysteine O-methyltransferase [EC2.1.1.100], putative
Schistosoma mansoni Smp_080130.1   protein-s-isoprenylcysteine o-methyltransferase
Schmidtea mediterranea mk4.000181.04  
Trypanosoma brucei gambiense Tbg972.9.7750   prenyl protein specific carboxyl methyltransferase
Trypanosoma brucei Tb927.9.12690   prenyl protein specific carboxyl methyltransferase
Trypanosoma cruzi TcCLB.510743.40   prenyl protein specific carboxyl methyltransferase, putative
Trypanosoma cruzi TcCLB.510659.264   prenyl protein specific carboxyl methyltransferase, putative
Toxoplasma gondii TGME49_306470   isoprenylcysteine carboxyl methyltransferase (icmt) family protein
Trichomonas vaginalis TVAG_470080   protein-S isoprenylcysteine O-methyltransferase, putative
Trichomonas vaginalis TVAG_459020   protein-S isoprenylcysteine O-methyltransferase, putative
Trichomonas vaginalis TVAG_476130   protein-S isoprenylcysteine O-methyltransferase, putative

Essentiality

PF3D7_1236800 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb09.211.3640 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb09.211.3640 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb09.211.3640 Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb09.211.3640 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F21F3.3 Caenorhabditis elegans embryonic lethal wormbase
TGME49_306470 Toxoplasma gondii Probably non-essential 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • 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.

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
Saccharomyces cerevisiae Ste14p Compounds References
Homo sapiens isoprenylcysteine carboxyl methyltransferase Compounds References
Rattus norvegicus Isoprenylcysteine carboxyl methyltransferase Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0478 1 0.5
0.2322 1 0.5
0.0705 0.8685 1
0.4329 1 0.5
0.034 0.994 1
0.0358 1 1
0.0254 0.6046 1
0.193 1 0.5
0.3998 1 0.5
0.2859 0.418 1
0.0113 1 0.5
0.234 1 0.5
0.0388 0.52 1
0.1479 1 0.5
0.2377 0.4023 1
0.2614 0.3844 1
0.2864 1 0.5
0.2614 0.3844 1
0.0139 0.2796 1
0.1982 1 1
0.0112 0.2568 1
0.2728 1 1
0.1168 1 1
0.3284 0.8969 1
0.1047 0.9744 1
0.4355 0.637 1
0.0235 0.5294 1
0.1793 1 1
0.0382 1 0.5
0.0886 1 1
0.0711 1 0.5
0.0123 1 1
0.0234 0.5 0.5
0.0266 0.277 0.587
0.0252 0.3948 0.5
0.3294 1 1
0.0367 1 0.5
0.1957 1 1
0.1793 0.4921 1
0.048 1 0.5
0.2074 1 1
0.1793 0.4921 1
0.0241 1 1
0.35 1 0.5
0.0234 0.5501 1
0.1598 1 0.5
0.0224 0.7332 1
0.2859 1 0.5
0.1322 1 0.5
0.1924 1 0.5
0.0924 1 0.5
0.2426 0.7216 1
0.0352 1 0.5
0.0453 0.889 1
0.023 0.4252 1
0.0354 0.5 0.5
0.2545 1 0.5
0.0139 0.5 0.5
0.2614 0.3844 1
0.2689 1 0.5
0.0236 1 0.5
0.4355 0.637 1
0.3137 0.5144 0.7115
0.2426 0.7216 1
0.2614 0.3844 1
0.0139 0.5 0.5
0.0139 0.5 0.5
0.3002 0.4789 0.5
0.4355 0.637 1
0.0415 0.3515 0.9931
0.2063 1 1
0.2377 0.4023 1
0.2614 0.3844 1
0.1167 1 0.5
0.4355 0.637 1
0.0135 0.291 0
0.3284 0.8969 1
0.2027 1 1
0.0139 0.5 0.5
0.0247 0.5197 1
0.2614 0.3844 1
0.0258 0.2503 0.5
0.1168 1 1
0.2795 0.6601 1
0.2426 0.7216 1
0.2314 1 0.5
0.0357 1 0.5
0.0362 0.3676 1
0.4019 1 1
0.2614 0.3844 1
0.1188 0.5 0.5
0.0114 0.2554 1
0.3077 1 0.5
0.2693 1 0.5
0.0139 0.4136 1
0.0123 0.2757 1
0.1426 1 1
0.0112 1 0.5
0.0511 1 0.5
0.1079 1 0.5
0.3403 1 1
0.024 0.828 0.5
0.0139 0.2647 1
0.0948 1 0.5
0.187853 1 0.5
0.2426 1 0.5
0.0756 0.517 0.5
0.0139 0.5 0.5
0.3572 1 0.5
0.2213 0.2511 1
0.3354 0.5 0.5
0.2181 1 0.5
0.2825 1 1
0.3403 1 1
0.0123 1 1
0.0346 0.345 1
0.0254 0.2931 1
0.2859 0.418 1
0.1781 1 1
0.0246 0.6048 1
0.0225 1 1
0.4355 0.637 1
0.0574 0.3178 1
0.0235 1 0.5
0.0469 0.5 0.5
0.0139 0.9373 0
0.2614 0.3844 1
0.0139 1 0.5
0.0947 1 1
0.0139 1 0.5
0.0139 0.2528 1
0.1413 1 1
0.3137 0.5144 0.7115
0.2935 1 0.5
0.0113 0.3619 1
0.2608 1 1
0.0139 0.5 0.5
0.0133 1 0.5
0.4019 1 1
0.2859 0.418 1
0.092 0.659 1
0.0114 0.6001 0.0183
0.0244 1 1
0.4684 1 0.5
0.0116 1 1
0.0258 0.2503 0.5
0.0113 0.4716 1
0.0139 1 1
0.0139 0.5 0.5
0.0139 0.4212 0.5
0.0246 0.3099 0.5
0.2614 0.3844 1
0.1911 1 0.5
0.4019 1 1
0.1665 1 0.5
0.0139 0.5 0.5
0.4462 1 0.5
0.2477 0.5 0.5
0.0139 1 0.5
0.0246 0.6048 1
0.2138 1 0.5
0.0139 0.7377 1
0.4454 1 0.5
0.0239 0.5744 0.5
0.0574 0.3178 1
0.2614 0.3844 1
0.2314 1 0.5
0.0139 1 1
0.22 1 0.5
0.092 0.659 1
0.0232 0.5 0.5
0.0756 0.5193 1
0.0139 1 0.5
0.0266 0.277 0.587
0.0127 1 1
0.0139 0.4983 1
0.0139 0.34 1
0.2614 0.3844 1
0.2207 1 0.5
0.2614 0.3844 1
0.2795 0.6601 1
0.0139 0.9061 1
0.0139 0.2948 1
0.0378 0.5584 1
0.0246 0.6048 1
0.0139 0.3247 1
0.0139 1 1
0.0246 0.6048 1
0.2207 1 0.5
0.0232 1 0.5
0.2614 0.3844 1
0.2377 0.4023 1
0.2614 0.3844 1
0.0246 0.6048 1
0.2866 0.5 0.5
0.0139 1 0.5
0.1455 1 0.5
0.1802 1 0.5
0.0415 0.3515 0.9931
0.14225 1 1
0.0235 0.5294 1
0.0121 0.3959 0.3721
0.0139 0.9545 1
0.4471 1 0.5
0.1047 0.9744 1
0.2647 1 0.5
0.4253 1 0.5
0.2859 0.418 1
0.2795 0.6601 1
0.2189 1 0.5
0.3151 1 1
0.0139 0.5 0.5
0.1913 1 0.5
0.0139 0.2594 1
0.1052 1 0.5
0.1037 0.4208 1
0.3281 1 0.5
0.1025 0.3996 1
0.0574 0.3178 1
0.2795 0.6601 1
0.0133 1 0.5
0.2618 1 0.5
0.7163 1 1
0.0574 0.3178 1
0.0241 0.2784 0.5
0.1805 1 1
0.2063 1 0.5
0.0372 0.5 0.5
0.1699 1 0.5
0.2038 1 0.5
0.0415 0.3515 0.9931
0.0139 0.5 0.5
0.0495 1 1
0.3002 0.4789 0.5
0.2328 1 0.5
0.1674 1 0.5
0.1957 1 1
0.0139 0.5 0.5
0.0139 0.5 0.5
0.2063 1 1
0.2614 0.3844 1
0.0116 0.2757 1
0.4684 1 0.5
0.0245 1 0.5
0.0234 0.5 0.5
0.092 1 1
0.0224 0.7332 1
0.0121 0.3959 0.3721
0.2859 0.418 1
0.0362 0.8097 0.5
0.0121 0.4716 1
0.0338 0.2967 1
0.0139 1 1
0.0119 0.4716 1
0.0415 0.3515 0.9931
0.2601 1 0.5
0.0139 1 0.5
0.220725 0.5 0.5
0.0507 0.7099 1
0.012 0.2751 1
0.2782 1 1
0.0947 1 1
0.2614 0.3844 1
0.0249 0.5219 1
0.4355 0.637 1
0.2063 1 1
0.1463 1 0.5
0.0139 0.4491 1
0.0229 1 0.5
0.0139 1 0.5
0.1295 1 1
0.2608 1 1
0.1908 1 0.5
0.0234 1 0.5
0.0358 1 0.5
0.2426 0.7216 1
0.3281 1 0.5
0.0453 1 0.5
0.0139 0.2755 0
0.1384 1 0.5
0.1035 1 0.5
0.0453 0.889 1
0.071 0.8451 0.5
0.3294 1 1
0.0365 0.6302 0.5
0.0139 0.2906 1
0.0122 0.4655 1
0.0085 1 0.5
0.0139 0.4079 0.5
0.1925 1 0.5
0.0249 1 0.5
0.0963 1 1

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_1236800 (Plasmodium falciparum), protein-S-isoprenylcysteine O-methyltransferase, putative
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