Detailed view for PF3D7_0922200

Basic information

TDR Targets ID: 4897
Plasmodium falciparum, S-adenosylmethionine synthetase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 6.7133 | Length (AA): 402 | MW (Da): 44844 | 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

PF00438   S-adenosylmethionine synthetase, N-terminal domain
PF02772   S-adenosylmethionine synthetase, central domain
PF02773   S-adenosylmethionine synthetase, C-terminal domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0006556   S-adenosylmethionine biosynthetic process  
GO:0004478   methionine adenosyltransferase activity  
GO:0005524   ATP binding  
GO:0006730   one-carbon compound metabolic process  

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
9 393 1qm4 (A) 17 394 58.00 0 1 1.68 -1.04
9 399 1rg9 (A) 1 379 49.00 0 1 1.6 -0.74
7 394 2obv (A) 0 394 57.00 0 1 1.66217 -1.06
8 401 3iml (A) 2 387 50.00 0 1 1.4841 -0.44
8 395 4ndn (A) 15 395 59.00 0 1 1.66077 -0.86
9 401 1p7l (A) 1 381 48.00 0 1 1.52561 -0.6

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 - 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, gametocyte, merozoite, sporozoite, early ring, early schizont, early trophozoite, late ring, late schizont, late trophozoite, Oocyst, Ring, Sporozoite, Female Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile Male Gametocyte. Lasonder E
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.
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • 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_126734)

Species Accession Gene Product
Arabidopsis thaliana AT3G17390   S-adenosylmethionine synthase 4
Arabidopsis thaliana AT1G02500   S-adenosylmethionine synthetase 1
Arabidopsis thaliana AT4G01850   S-adenosylmethionine synthase 2
Arabidopsis thaliana AT2G36880   S-adenosylmethionine synthase 3
Babesia bovis BBOV_III009750   s-adenosylmethionine synthetase, putative
Brugia malayi Bm1_09230   S-adenosylmethionine synthetase
Candida albicans CaO19.8272   likely S-adenosylmethionine synthetase similar to S. cerevisiae SAM2 (YDR502C)
Candida albicans CaO19.657   likely S-adenosylmethionine synthetase similar to S. cerevisiae SAM2 (YDR502C)
Caenorhabditis elegans CELE_C06E7.3   Protein SAMS-4, isoform B
Caenorhabditis elegans CELE_C06E7.1   Protein SAMS-3, isoform C
Caenorhabditis elegans CELE_T13A10.11   Protein SAMS-5, isoform B
Caenorhabditis elegans CELE_C49F5.1   Protein SAMS-1
Cryptosporidium hominis Chro.70301   methionine adenosyltransferase
Cryptosporidium parvum cgd7_2650   s-adenosylmethionine synthetase (SAM)
Dictyostelium discoideum DDB_G0291179   S-adenosylmethionine synthetase
Drosophila melanogaster Dmel_CG2674   S-adenosylmethionine Synthetase
Escherichia coli b2942   S-adenosylmethionine synthetase
Echinococcus granulosus EgrG_000177400   S adenosylmethionine synthase type 1
Entamoeba histolytica EHI_004920   S-adenosylmethionine synthetase, putative
Entamoeba histolytica EHI_195110   S-adenosylmethionine synthetase, putative
Entamoeba histolytica EHI_174250   S-adenosylmethionine synthetase, putative
Echinococcus multilocularis EmuJ_000177400   S adenosylmethionine synthase type 1
Giardia lamblia GL50803_5659   S-adenosylmethionine synthetase
Homo sapiens ENSG00000151224   methionine adenosyltransferase I, alpha
Homo sapiens ENSG00000168906   methionine adenosyltransferase II, alpha
Leishmania braziliensis LbrM.30.3550   S-adenosylmethionine synthetase
Leishmania donovani LdBPK_303560.1   S-adenosylmethionine synthetase
Leishmania infantum LinJ.30.3580   S-adenosylmethionine synthetase
Leishmania infantum LinJ.30.3560   S-adenosylmethionine synthetase
Leishmania major LmjF.30.3500   S-adenosylmethionine synthetase
Leishmania major LmjF.30.3520   S-adenosylmethionine synthetase
Leishmania mexicana LmxM.29.3500   S-adenosylmethionine synthetase
Loa Loa (eye worm) LOAG_06217   methionine adenosyltransferase
Mycobacterium leprae ML0544   Probable S-adenosylmethionine synthase MetK (MAT) (AdoMet synthetase) (Methionine adenosyltransferase)
Mus musculus ENSMUSG00000053907   methionine adenosyltransferase II, alpha
Mus musculus ENSMUSG00000037798   methionine adenosyltransferase I, alpha
Mycobacterium tuberculosis Rv1392   Probable S-adenosylmethionine synthetase MetK (mat) (AdoMet synthetase) (methionine adenosyltransferase)
Mycobacterium ulcerans MUL_1791   S-adenosylmethionine synthetase
Neospora caninum NCLIV_016880   S-adenosylmethionine synthetase (EC 2.5.1.6), related
Oryza sativa 4337733   Os05g0135700
Oryza sativa 4325163   Os01g0293000
Plasmodium berghei PBANKA_0823100   S-adenosylmethionine synthetase, putative
Plasmodium falciparum PF3D7_0922200   S-adenosylmethionine synthetase
Plasmodium knowlesi PKNH_0720200   S-adenosylmethionine synthetase, putative
Plasmodium vivax PVX_099525   S-adenosylmethionine synthetase, putative
Plasmodium yoelii PY06246   S-adenosylmethionine synthetase
Saccharomyces cerevisiae YLR180W   methionine adenosyltransferase SAM1
Saccharomyces cerevisiae YDR502C   methionine adenosyltransferase SAM2
Schistosoma japonicum Sjp_0215070   ko:K00789 S-adenosylmethionine synthetase [EC2.5.1.6], putative
Schistosoma japonicum Sjp_0317260   S-adenosylmethionine synthetase isoform type-1, putative
Schistosoma mansoni Smp_002080   S-adenosylmethionine synthetase
Schmidtea mediterranea mk4.002822.01   S-adenosylmethionine synthase
Schmidtea mediterranea mk4.028997.00  
Schmidtea mediterranea mk4.003057.01   S-adenosylmethionine synthase
Schmidtea mediterranea mk4.021769.00   S-adenosylmethionine synthase
Schmidtea mediterranea mk4.002441.01  
Schmidtea mediterranea mk4.016392.02  
Trypanosoma brucei gambiense Tbg972.6.4700   S-adenosylmethionine synthetase, putative
Trypanosoma brucei gambiense Tbg972.6.4670   S-adenosylmethionine synthetase, putative
Trypanosoma brucei gambiense Tbg972.6.4690   S-adenosylmethionine synthetase, putative
Trypanosoma brucei gambiense Tbg972.6.4720   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4910   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4890   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4860   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4840   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4880   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4920   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4850   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4900   S-adenosylmethionine synthetase, putative
Trypanosoma brucei Tb927.6.4870   S-adenosylmethionine synthetase, putative
Trypanosoma congolense TcIL3000_6_4330   S-adenosylmethionine synthetase, putative
Trypanosoma congolense TcIL3000_0_37490   S-adenosylmethionine synthetase, putative
Trypanosoma cruzi TcCLB.510445.50   S-adenosylmethionine synthetase, putative
Trypanosoma cruzi TcCLB.506945.160   S-adenosylmethionine synthetase, putative
Toxoplasma gondii TGME49_240690   S-adenosyl methionine synthetase
Treponema pallidum TP0794   S-adenosylmethionine synthetase
Theileria parva TP04_0893   S-adenosylmethionine synthetase, putative
Trichomonas vaginalis TVAG_145700   S-adenosylmethionine synthetase, putative
Trichomonas vaginalis TVAG_317070   S-adenosylmethionine synthetase, putative
Trichomonas vaginalis TVAG_403830   S-adenosylmethionine synthetase, putative
Trichomonas vaginalis TVAG_252200   S-adenosylmethionine synthetase, putative
Trichomonas vaginalis TVAG_453040   S-adenosylmethionine synthetase, putative
Trichomonas vaginalis TVAG_243700   S-adenosylmethionine synthetase, putative
Trichomonas vaginalis TVAG_484900   S-adenosylmethionine synthetase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0699   S-adenosylmethionine synthetase

Essentiality

PF3D7_0922200 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.6.4840 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.6.4840 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.6.4840 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.6.4840 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b2942 Escherichia coli essential goodall
CELE_T13A10.11 Caenorhabditis elegans embryonic lethal wormbase
CELE_T13A10.11 Caenorhabditis elegans larval arrest wormbase
CELE_T13A10.11 Caenorhabditis elegans larval lethal wormbase
CELE_T13A10.11 Caenorhabditis elegans slow growth wormbase
CELE_T13A10.11 Caenorhabditis elegans sterile wormbase
CELE_C49F5.1 Caenorhabditis elegans slow growth wormbase
CELE_C49F5.1 Caenorhabditis elegans sterile wormbase
CELE_C06E7.1 Caenorhabditis elegans larval arrest wormbase
CELE_C06E7.1 Caenorhabditis elegans larval lethal wormbase
CELE_C06E7.1 Caenorhabditis elegans slow growth wormbase
CELE_C06E7.1 Caenorhabditis elegans sterile wormbase
CELE_C06E7.3 Caenorhabditis elegans larval lethal wormbase
CELE_C06E7.3 Caenorhabditis elegans slow growth wormbase
TGME49_240690 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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

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
Rattus norvegicus S-adenosylmethionine synthetase alpha and beta forms Compounds References
Rattus norvegicus S-adenosylmethionine synthetase gamma form Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Rattus norvegicus S-adenosylmethionine synthetase (MAT 1 and MAT 2) 395 aa 57.4% 390 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0035 0.3507 0
0.0157 0.3644 0.3644
0.0081 1 0.5
0.0157 0.3644 0.3644
0.0104 0.5 0.5
0.0081 1 0.5
0.0149 0.3035 1
0.0075 0.5 0.5
0.0089 0.5 0.5
0.0233 0.5 0.5
0.008 0.5 0.5
0.0161 1 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

  • Pfal008828AAA;
  • Type Source Notes
    soluble recombinant protein Structural Genomics for Pathogenic Protozoa (SGPP) Pfal008828; Recombinant protein: full-length; Source: P falciparum; Methionine adenosyltransferase ;

Bibliographic References

1 literature reference was collected for this gene.

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Gene identifier PF3D7_0922200 (Plasmodium falciparum), S-adenosylmethionine synthetase
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