Detailed view for Tb927.10.15010

Basic information

TDR Targets ID: 12222
Trypanosoma brucei, lipoic acid synthetase, mitochondrial precursor, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.7773 | Length (AA): 409 | MW (Da): 45476 | Paralog Number: 0

Signal peptide: Y | GPI Anchor: | 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

PF04055   Radical SAM superfamily
PF16881   N-terminal domain of lipoyl synthase of Radical_SAM family

Gene Ontology

Mouse over links to read term descriptions.
GO:0051539   4 iron, 4 sulfur cluster binding  
GO:0051536   iron-sulfur cluster binding  
GO:0016992   lipoate synthase activity  
GO:0003824   catalytic activity  
GO:0009107   lipoate biosynthetic process  
GO:0008152   metabolic process  

Metabolic Pathways

Lipoic acid metabolism (KEGG)
Global map (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
24 103 1kwg (A) 444 528 43.00 0.8 0.67 0.516299 0.32
42 203 3nq8 (A) 48 203 15.00 0 0.85 0.667088 -0.91
72 399 5exk (A) 8 309 41.00 0 1 1.28296 -0.74
89 380 4u0p (B) 5 288 42.00 0 1 1.20094 -0.56

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 Procyclic, Bloodstream Form. Siegel TN
Show/Hide expression data references
  • Siegel TN Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites.

Orthologs

Ortholog group members (OG5_127348)

Species Accession Gene Product
Arabidopsis thaliana AT2G20860   lipoic acid synthase 1
Arabidopsis thaliana AT5G08415   lipoyl synthase
Brugia malayi Bm1_23910   lipoic acid synthetase, mitochondrial precursor, putative
Candida albicans CaO19.10290   similar to S. cerevisiae LIP5, mitochondrial lipoate synthase
Candida albicans CaO19.2774   similar to S. cerevisiae LIP5, mitochondrial lipoate synthase
Caenorhabditis elegans CELE_M01F1.3   Protein M01F1.3
Chlamydia trachomatis CT_558   lipoate synthetase
Drosophila melanogaster Dmel_CG5231   Lipoic acid synthase
Escherichia coli b0628   lipoate synthase
Echinococcus granulosus EgrG_001034820   lipoyl synthase, mitochondrial
Echinococcus multilocularis EmuJ_001034820   lipoyl synthase, mitochondrial
Homo sapiens ENSG00000121897   lipoic acid synthetase
Leishmania braziliensis LbrM.19.0670   lipoic acid synthetase, mitochondrial precursor, putative
Leishmania donovani LdBPK_190350.1   lipoic acid synthetase, mitochondrial precursor, putative
Leishmania infantum LinJ.19.0350   lipoic acid synthetase, mitochondrial precursor, putative
Leishmania major LmjF.19.0350   lipoic acid synthetase, mitochondrial precursor, putative
Leishmania mexicana LmxM.19.0350   lipoic acid synthetase, mitochondrial precursor, putative
Loa Loa (eye worm) LOAG_04019   lipoic acid synthetase
Mycobacterium leprae ML0858c   Probable lipoate biosynthesis protein A LipA
Mus musculus ENSMUSG00000029199   lipoic acid synthetase
Mycobacterium tuberculosis Rv2218   Probable lipoate biosynthesis protein A LipA
Mycobacterium ulcerans MUL_1343   lipoyl synthase
Neospora caninum NCLIV_046560   Lipoic acid synthetase, related
Oryza sativa 4336023   Os04g0455800
Oryza sativa 4339289   Os05g0511500
Oryza sativa 4325595   Os01g0769100
Onchocerca volvulus OVOC7524   Lipoyl synthase, mitochondrial homolog
Plasmodium berghei PBANKA_1357500   lipoyl synthase
Plasmodium falciparum PF3D7_1344600   lipoyl synthase
Plasmodium knowlesi PKNH_1256700   lipoyl synthase, putative
Plasmodium vivax PVX_083125   lipoyl synthase, putative
Plasmodium yoelii PY06208   lipoic acid synthetase, putative
Saccharomyces cerevisiae YOR196C   putative lipoate synthase
Schistosoma japonicum Sjp_0302390   ko:K03644 lipoic acid synthetase, putative
Schistosoma japonicum Sjp_0092580   IPR003698,Lipoate synthase,domain-containing
Schistosoma mansoni Smp_010100   lipoic acid synthetase
Schmidtea mediterranea mk4.002599.02   Lipoyl synthase, mitochondrial
Trypanosoma brucei gambiense Tbg972.10.18270   lipoic acid synthetase, mitochondrial precursor, putative
Trypanosoma brucei Tb927.10.15010   lipoic acid synthetase, mitochondrial precursor, putative
Trypanosoma cruzi TcCLB.511291.30   lipoic acid synthetase, mitochondrial precursor, putative
Trypanosoma cruzi TcCLB.506211.10   lipoic acid synthetase, mitochondrial precursor, putative
Toxoplasma gondii TGME49_226400   lipoic acid synthase LIPA
Wolbachia endosymbiont of Brugia malayi Wbm0303   lipoyl synthase

Essentiality

Tb927.10.15010 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu2252 Mycobacterium tuberculosis essential nmpdr
Tb927.10.15010 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.15010 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.15010 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.15010 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b0628 Escherichia coli essential goodall
CELE_M01F1.3 Caenorhabditis elegans embryonic lethal wormbase
CELE_M01F1.3 Caenorhabditis elegans larval arrest wormbase
CELE_M01F1.3 Caenorhabditis elegans slow growth wormbase
PBANKA_1357500 Plasmodium berghei Dispensable plasmo
TGME49_226400 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • 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.
  • 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
  • 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.
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) increased (PATO:0000470) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: increased cell proliferation (significant gain of fitness) in bloodstream forms (stage 6 days). References: 21363968
cell proliferation (GO:0008283) normal (PATO:0000461) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in procyclic forms . References: 21363968
cell proliferation (GO:0008283) increased (PATO:0000470) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: increased cell proliferation (significant gain of fitness) in differentiation of procyclic to bloodstream forms . References: 21363968

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

1 literature reference was collected for this gene.

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Gene identifier Tb927.10.15010 (Trypanosoma brucei), lipoic acid synthetase, mitochondrial precursor, putative
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