Detailed view for LmjF.36.2390

Basic information

TDR Targets ID: 23976
Leishmania major, sterol 24-c-methyltransferase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.4934 | Length (AA): 353 | MW (Da): 39981 | Paralog Number: 1

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

PF08241   Methyltransferase domain
PF08498   Sterol methyltransferase C-terminal

Gene Ontology

Mouse over links to read term descriptions.
GO:0008168   methyltransferase activity  
GO:0008152   metabolic process  
GO:0006694   steroid biosynthetic 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
7 274 1qzz (A) 90 353 17.00 0 0.99 0.84 -0.02
44 322 1tpy (A) 3 284 14.00 0 1 1 -0.85
50 324 1kpg (A) 9 286 17.00 0 1 1.01 -0.8
6 268 3k6r (A) 15 264 15.00 0 1 0.757742 0.61
27 257 2igt (A) 54 294 12.00 0 0.4 0.617091 0.81
44 321 1tpy (A) 3 283 15.00 0 1 0.990335 -0.52
50 324 1kpg (A) 9 286 16.00 0 1 0.994837 -0.65
53 308 2fk8 (A) 21 282 16.00 0 1 0.941012 -0.55
68 161 3gdh (A) 648 748 32.00 0.23 0.42 0.367189 0.45

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
Lower 20-40% percentile amastigotes. Fernandes MC
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile 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_129172)

Species Accession Gene Product
Arabidopsis thaliana AT1G76090   24-methylenesterol C-methyltransferase 3
Arabidopsis thaliana AT1G20330   24-methylenesterol C-methyltransferase 2
Arabidopsis thaliana AT5G13710   cycloartenol-c-24-methyltransferase
Brugia malayi Bm1_45250   S-adenosyl-methionine cycloartenol-C24-methyltransferase
Candida albicans CaO19.9199   SAM:delta 24-methyltransferase involved in ergosterol biosynthesis
Candida albicans CaO19.1631   SAM:delta 24-methyltransferase involved in ergosterol biosynthesis
Caenorhabditis elegans CELE_H14E04.1   Protein H14E04.1
Dictyostelium discoideum DDB_G0288907   hypothetical protein
Leishmania braziliensis LbrM.35.2600   sterol 24-c-methyltransferase, putative
Leishmania donovani LdBPK_362510.1   sterol 24-c-methyltransferase, putative
Leishmania infantum LinJ.36.2520   sterol 24-c-methyltransferase, putative
Leishmania infantum LinJ.36.2510   sterol 24-c-methyltransferase, putative
Leishmania major LmjF.36.2380   sterol 24-c-methyltransferase, putative
Leishmania major LmjF.36.2390   sterol 24-c-methyltransferase, putative
Leishmania mexicana LmxM.36.2390   sterol 24-c-methyltransferase, putative
Leishmania mexicana LmxM.36.2380   sterol 24-c-methyltransferase, putative
Loa Loa (eye worm) LOAG_00971   hypothetical protein
Oryza sativa 9269350   Os03g0807600
Oryza sativa 4331540   Os03g0136200
Oryza sativa 4342690   Os07g0206700
Saccharomyces cerevisiae YML008C   sterol 24-C-methyltransferase
Trypanosoma brucei gambiense Tbg972.10.8450   sterol 24-c-methyltransferase, putative
Trypanosoma brucei Tb927.10.6910   Sterol methyltransferase, putative
Trypanosoma brucei Tb11.v5.0496   sterol 24-c-methyltransferase, putative
Trypanosoma brucei Tb927.10.6950   sterol 24-c-methyltransferase, putative
Trypanosoma cruzi TcCLB.505683.10   sterol 24-c-methyltransferase, putative
Trypanosoma cruzi TcCLB.504191.10   sterol 24-c-methyltransferase, putative
Trypanosoma cruzi TcCLB.510185.10   sterol 24-c-methyltransferase, putative

Essentiality

LmjF.36.2390 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.6950 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.6950 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.6950 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.6950 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
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
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; Q6RW42_LEIDO; azasterol inhibitors. References: 7755579
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania mexicana No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania mexicana No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
plasma membrane (GO:0005886) disrupted (PATO:0001507) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from visible phenotype (ECO:0000176) Leishmania mexicana No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
plasma membrane (GO:0005886) disrupted (PATO:0001507) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from visible phenotype (ECO:0000176) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
plasma membrane (GO:0005886) disrupted (PATO:0001507) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from visible phenotype (ECO:0000176) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
plasma membrane (GO:0005886) disrupted (PATO:0001507) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from visible phenotype (ECO:0000176) Leishmania mexicana No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
plasma membrane (GO:0005886) disrupted (PATO:0001507) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from visible phenotype (ECO:0000176) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
plasma membrane (GO:0005886) disrupted (PATO:0001507) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from visible phenotype (ECO:0000176) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: (azasterols) 623550-27-6; Drug: 383365-51-3; Drug: 383365-46-6; Drug: 185993-05-9; Drug: 171782-23-3. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); Q6RW42_LEIDO; azasterol inhibitors. References: 11796362
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: azasterols. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); azasterol inhibitors. References: 14561091
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: azasterols. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); azasterol inhibitors. References: 14561091
plasma membrane (GO:0005886) disrupted (PATO:0001507) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from visible phenotype (ECO:0000176) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: azasterols. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); azasterol inhibitors. References: 14561091
plasma membrane (GO:0005886) disrupted (PATO:0001507) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from visible phenotype (ECO:0000176) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: azasterols. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; low dose leads to membrane disruption, but not cell death (high dose leads to cell inviability); azasterol inhibitors. References: 14561091
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania major No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: azasterols. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to reduced enzyme activity in vitro; azasterol inhibitors. References: 14561091 16046134
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: azasterols. chemical inhibition with sterol 24-c-methyltransferase (2.1.1.41) inhibitors leads to slow growth of Leishmania sp. in cell assay; Q6RW42_LEIDO; azasterol inhibitors. References: 16046134

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

  • Validation: inhibited in cell-free system
  • annotated by: aaronjr@u.washington.edu.
  • References: 14561091 16046134

Associated compounds / Druggability

Druggability index (range: 0 to 1): 0.6

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
Trypanosoma cruzi sterol 24-c-methyltransferase, putative Compounds References
Trypanosoma cruzi sterol 24-c-methyltransferase, putative Compounds References
Trypanosoma cruzi sterol 24-c-methyltransferase, putative Compounds References
Arabidopsis thaliana cycloartenol-c-24-methyltransferase Compounds References
Glycine max S-adenosyl-L-methionine:delta24-sterol-C-methyltransferase Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Trypanosoma cruzi sterol 24-c-methyltransferase, putative 161 aa 66.5% 161 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0208 0.4356 1
0.0203 0.6968 1
0.019 0.2679 0.5195
0.0615 0.3438 1
0.0194 0.3529 0.3304
0.0599 0.6503 1
0.0385 0.3017 0.3225
0.0623 0.2985 0.2958
0.0384 0.8815 1
0.00879579 0.706853 1
0.078 0.2713 0.7182
0.0187 0.4967 0.4789
0.0812 0.6132 1
0.0208 0.2926 0.3386
0.0187 0.4624 1
0.0192 0.2623 0.9791
0.0385 0.3017 0.3225
0.0199 0.523 1
0.0615 0.3438 1
0.0812 0.6132 1
0.0818 0.4463 1
0.0599 0.6503 1
0.0745 0.3576 0.7161
0.0415 0.2702 0.2691
0.0398 0.3155 0.3155
0.0212 0.2584 0.2603
0.0186 0.4796 1
0.0192 0.4728 1
0.0377 0.2984 0.2943
0.0599 0.6503 1
0.0186 0.4459 1
0.0387 0.3057 0.3057
0.0398 0.322 0.319
0.0377 0.301 0.301
0.0195 0.2681 1
0.0397 0.4471 1
0.0818 0.4463 1
0.0199 0.523 1
0.0194 0.7681 0.5
0.0599 0.6503 1
0.0203 0.2865 0.4434
0.0599 0.6503 1
0.0615 0.3438 1
0.0188 0.316 0.5
0.0637 0.6757 1
0.0206 0.2923 1
0.0186 0.3142 1
0.0763 0.6137 1
0.0192 0.4731 1
0.0812 0.6132 1
0.0195 0.2681 1
0.0187 0.2924 0.5
0.0203 0.2852 0.6007
0.0208 0.2797 0.4737
0.0372 0.2971 0.2971
0.0599 0.6503 1
0.0196 0.3707 0.3527
0.0374 0.3111 0.3109
0.0599 0.6503 1
0.0197 0.7516 0.718
0.0195 0.331 0.3028
0.00879579 0.706853 1
0.0186 0.4459 1
0.0623 0.2985 0.2958
0.0818 0.4432 1
0.0637 0.6757 1
0.0749 0.5913 1
0.0198 0.738 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

9 literature references were collected for this gene.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

User comments

No user comments are available for this gene. Log in to add comments, or register.

Enter your comment

User ()
Gene identifier LmjF.36.2390 (Leishmania major), sterol 24-c-methyltransferase, putative
Title for this comment
Comment