Detailed view for LmjF.07.0090

Basic information

TDR Targets ID: 23888
Leishmania major, methionine synthase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.3581 | Length (AA): 1252 | MW (Da): 138590 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 0

Druggability Group : DG3

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

PF00809   Pterin binding enzyme
PF02310   B12 binding domain
PF02574   Homocysteine S-methyltransferase
PF02607   B12 binding domain
PF02965   Vitamin B12 dependent methionine synthase, activation domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0042558   pteridine and derivative metabolic process  
GO:0005622   intracellular  
GO:0031419   cobalamin binding  
GO:0008898   homocysteine S-methyltransferase activity  
GO:0008705   methionine synthase activity  
GO:0008270   zinc ion binding  
GO:0004156   dihydropteroate synthase activity  
GO:0050897   cobalt ion binding  
GO:0046872   metal ion binding  
GO:0009396   folic acid and derivative biosynthetic process  
GO:0009086   methionine biosynthetic process  
GO:0044237   cellular metabolic process  

Structural information

Modbase 3D models:

There are 9 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
12 632 1q7z (A) 4 559 27.00 0 1 0.65 -0.71
363 644 1f6y (A) 1 262 23.00 0 1 0.44 -0.96
665 1252 1k7y (A) 653 1225 50.00 0 1 1.02 -1.18
770 893 1y80 (A) 89 209 29.00 0 1 0.6 -1.66
11 643 4ccz (A) 18 651 59.00 0 1 1.16169 -0.75
247 605 3mcm (B) 5 420 15.00 0 1 0.248941 0.88
361 646 3k13 (A) 351 636 63.00 0 1 1.09443 -1.55
663 1252 3bul (A) 651 1225 50.00 0 1 1.03835 -0.76
921 1252 2o2k (A) 926 1263 50.00 0 1 0.932176 -1.06

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
Mid 40-60% percentile amastigotes, metacyclic. Fernandes MC
Show/Hide expression data references
  • Fernandes MC Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

Orthologs

Ortholog group members (OG5_129374)

Species Accession Gene Product
Caenorhabditis elegans CELE_R03D7.1   Protein METR-1
Dictyostelium discoideum DDB_G0284699   5-methyltetrahydrofolate:L-homocysteine S-methyltransferase
Escherichia coli b4019   homocysteine-N5-methyltetrahydrofolate transmethylase, B12-dependent
Homo sapiens ENSG00000116984   5-methyltetrahydrofolate-homocysteine methyltransferase
Leishmania braziliensis LbrM.07.0090   cobalamin-dependent methionine synthase, putative
Leishmania donovani LdBPK_070240.1   cobalamin-dependent methionine synthase, putative
Leishmania infantum LinJ.07.0240   cobalamin-dependent methionine synthase, putative
Leishmania major LmjF.07.0090   methionine synthase, putative
Leishmania mexicana LmxM.07.0090   cobalamin-dependent methionine synthase, putative
Mycobacterium leprae ML1307   Probable 5-methyltetrahydrofolate--homocystein methyltransferase MetH (Methionine synthase, vitamin-B12 dependent isozyme) (MS)
Mus musculus ENSMUSG00000021311   5-methyltetrahydrofolate-homocysteine methyltransferase
Mycobacterium tuberculosis Rv2124c   5-methyltetrahydrofolate--homocystein methyltransferase MetH (methionine synthase, vitamin-B12 dependent isozyme) (ms)
Mycobacterium ulcerans MUL_0395   B12-dependent methionine synthase
Schmidtea mediterranea mk4.036688.01  
Schmidtea mediterranea mk4.009744.00  
Schmidtea mediterranea mk4.036688.02   Probable methionine synthase
Schmidtea mediterranea mk4.009659.03  

Essentiality

LmjF.07.0090 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b4019 Escherichia coli non-essential goodall
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
  • 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
  • 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

Druggability index (range: 0 to 1): 0.2

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 5-methyltetrahydrofolate-homocysteine 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
0.0128 0.3279 1
0.0115 0.3336 1
0.1864 0.3815 1
0.0119 0.3356 1
0.0112 0.3311 0.7263
0.1429 0.3893 1
0.177 0.4032 0.4184
0.0351 0.3376 1
0.0072 0.2575 0.3535
0.0195 0.2968 0.8374
0.0112 0.3157 1
0.0566 0.4313 1
0.0169 0.2921 0
0.0139 0.3617 1
0.0352 0.3404 1
0.0769 0.4821 1
0.0112 0.3311 0.7263
0.0126 0.2579 1
0.0682 0.3504 0.9439
0.0568 0.324 0
0.0278 0.321 1
0.0769 0.4821 1
0.057 0.4617 1
0.0246 0.3384 0.5
0.2111 0.3829 1
0.0361 0.3559 1
0.0342 0.3917 1
0.0731 0.6115 1
0.0123 0.2983 1
0.0231 0.3221 1
0.0246 0.3059 0.5
0.177 0.4032 0.4184
0.2111 0.3829 1
0.18 0.3989 1
0.0112 0.3556 1
0.0112 0.3506 1
0.0123 0.3223 1
0.0053 1 1
0.0114 0.303 1
0.177 0.4032 0.4184
0.0352 0.3404 1
0.1429 0.3893 1
0.177 0.4032 0.4184
0.177 0.4032 0.4184
0.1429 0.3893 1
0.0529 0.5293 1
0.0246 0.3059 0.5
0.177 0.4032 0.4184
0.0123 0.3279 1
0.0378 0.2802 0
0.177 0.4032 0.4184
0.024 0.3601 1
0.0509 0.3634 1
0.0773 0.5815 1
0.0367 0.3367 0.5
0.0139 0.3617 1
0.0139 0.3506 0.5
0.0113 0.2888 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 LmjF.07.0090 (Leishmania major), methionine synthase, putative
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