Detailed view for Tb927.2.3910

Basic information

TDR Targets ID: 55131
Trypanosoma brucei, beta-ketoacyl-ACP synthase

Source Database / ID:  TriTrypDB  GeneDB

pI: 7.2375 | Length (AA): 500 | MW (Da): 52044 | Paralog Number: 0

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

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

PF00109   Beta-ketoacyl synthase, N-terminal domain
PF02801   Beta-ketoacyl synthase, C-terminal domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  
GO:0006633   fatty acid biosynthetic process  

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
8 500 1ox0 (A) 0 408 33.00 0 1 1.1226 0.7
12 497 2ix4 (A) 31 458 46.00 0 1 1.3863 -0.02
12 499 1j3n (A) 2 407 42.00 0 1 1.2736 -0.01
12 500 3kzu (A) 2 418 41.00 0 1 1.3263 -0.16

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 60-80% percentile Procyclic. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile 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_126985)

Species Accession Gene Product
Arabidopsis thaliana AT2G04540   3-oxoacyl-[acyl-carrier-protein] synthase
Arabidopsis thaliana AT1G74960   3-oxoacyl-[acyl-carrier-protein] synthase II
Arabidopsis thaliana AT5G46290   beta-ketoacyl-[acyl carrier protein] synthase I
Brugia malayi Bm1_36100   Beta-ketoacyl synthase, N-terminal domain containing protein
Candida albicans CaO19.13398   potential beta-keto-acyl synthase similar to S. cerevisiae CEM1 (YER061C) mitochondrial enzyme involved in hexadecanal biosynthe
Candida albicans CaO19.5977   potential beta-keto-acyl synthase similar to S. cerevisiae CEM1 (YER061C) mitochondrial enzyme involved in hexadecanal biosynthe
Caenorhabditis elegans CELE_F10G8.9   Protein F10G8.9, isoform A
Cryptosporidium hominis Chro.40326   hypothetical protein
Chlamydia trachomatis CT_770   3-oxoacyl-ACP synthase
Dictyostelium discoideum DDB_G0275269   hypothetical protein
Drosophila melanogaster Dmel_CG12170   CG12170 gene product from transcript CG12170-RA
Escherichia coli b1095   3-oxoacyl-[acyl-carrier-protein] synthase II
Echinococcus granulosus EgrG_000839600   3 oxoacyl acyl carrier protein synthase
Echinococcus multilocularis EmuJ_000839600   3 oxoacyl (acyl carrier protein) synthase
Homo sapiens ENSG00000151093   3-oxoacyl-ACP synthase, mitochondrial
Leishmania braziliensis LbrM.33.3000   beta-ketoacyl synthase family protein, putative,3-oxoacyl-acyl carrier protein synthase ii, putative
Leishmania donovani LdBPK_332860.1   beta-ketoacyl synthase family protein, putative
Leishmania infantum LinJ.33.2860   beta-ketoacyl synthase family protein, putative,3-oxoacyl-acyl carrier protein synthase ii, putative
Leishmania major LmjF.33.2720   beta-ketoacyl synthase family protein, putative,3-oxoacyl-acyl carrier protein synthase ii, putative
Leishmania mexicana LmxM.32.2720   beta-ketoacyl synthase family protein, putative,3-oxoacyl-acyl carrier protein synthase ii, putative
Loa Loa (eye worm) LOAG_05714   beta-ketoacyl synthase domain-containing protein
Mycobacterium leprae ML1655   3-oxoacyl-[acyl-carrier-protein] synthase 1 KasA (BETA-KETOACYL-ACP SYNTHASE) (KAS I)
Mycobacterium leprae ML1656   3-oxoacyl-[acyl-carrier-protein] synthase 2 KasB (BETA-KETOACYL-ACP SYNTHASE) (KAS I)
Mus musculus ENSMUSG00000021786   3-oxoacyl-ACP synthase, mitochondrial
Mycobacterium tuberculosis Rv2245   3-oxoacyl-[acyl-carrier protein] synthase 1 KasA (beta-ketoacyl-ACP synthase) (KAS I)
Mycobacterium tuberculosis Rv2246   3-oxoacyl-[acyl-carrier protein] synthase 2 KasB (beta-ketoacyl-ACP synthase) (KAS I)
Mycobacterium ulcerans MUL_1304   3-oxoacyl-(acyl carrier protein) synthase II
Mycobacterium ulcerans MUL_1303   3-oxoacyl-(acyl carrier protein) synthase II
Neospora caninum NCLIV_000530   3-oxoacyl-(Acyl-carrier-protein) synthase II, related
Oryza sativa 4335962   Os04g0445700
Oryza sativa 4343906   Os07g0616200
Oryza sativa 4328619   Os02g0196900
Oryza sativa 4340392   Os06g0196600
Plasmodium berghei PBANKA_1125100   3-oxoacyl-acyl-carrier protein synthase, putative
Plasmodium falciparum PF3D7_0626300   3-oxoacyl-acyl-carrier protein synthase I/II
Plasmodium knowlesi PKNH_1123500   3-oxoacyl-(acyl-carrier-protein) synthase, putative
Plasmodium vivax PVX_114420   3-oxoacyl-[acyl-carrier-protein] synthase i/ii, putative
Plasmodium yoelii PY04452   3-oxoacyl-acyl-carrier protein synthase I/II
Saccharomyces cerevisiae YER061C   fatty acid synthase CEM1
Schistosoma japonicum Sjp_0091870   ko:K09458 3-oxoacyl-[acyl-carrier-protein] synthase II [EC2.3.1.179], putative
Schistosoma mansoni Smp_009150.2   3-oxoacyl-[ACP] synthase
Schmidtea mediterranea mk4.052381.01   3-oxoacylAWw-acyl-carrier-protein+AF0- synthase, mitochondrial
Schmidtea mediterranea mk4.002539.02   3-oxoacylAWw-acyl-carrier-protein+AF0- synthase, mitochondrial
Trypanosoma brucei gambiense Tbg.972.2.2150   beta-ketoacyl synthase family protein, putative
Trypanosoma brucei Tb927.2.3910   beta-ketoacyl-ACP synthase
Trypanosoma congolense TcIL3000_2_510   beta-ketoacyl synthase family protein, putative
Trypanosoma congolense TcIL3000_0_40860   beta-ketoacyl synthase family protein, putative
Trypanosoma cruzi TcCLB.504157.20   beta-ketoacyl synthase family protein, putative
Trypanosoma cruzi TcCLB.511109.120   beta-ketoacyl synthase family protein, putative
Toxoplasma gondii TGME49_293590   3-oxoacyl-acyl-carrier protein synthase I/II, putative
Wolbachia endosymbiont of Brugia malayi Wbm0739   3-oxoacyl-ACP synthase

Essentiality

Tb927.2.3910 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.2.3910 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.2.3910 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.2.3910 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.2.3910 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b1095 Escherichia coli non-essential goodall
PBANKA_1125100 Plasmodium berghei Dispensable plasmo
TGME49_293590 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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
  • 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.
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
cell proliferation (GO:0008283) normal (PATO:0000461) 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: normal cell proliferation (no significant loss or gain of fitness) in bloodstream forms (stage 3 days). References: 21363968
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 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

Druggability index (range: 0 to 1): 0.7


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
Mycobacterium tuberculosis 3-oxoacyl-[acyl-carrier protein] synthase 2 KasB (beta-ketoacyl-ACP synthase) (KAS I) Compounds References
Plasmodium falciparum 3-oxoacyl-acyl-carrier protein synthase I/II Compounds References
Staphylococcus aureus 3-oxoacyl-[acyl-carrier-protein] synthase 2 Compounds References
Mycobacterium tuberculosis 3-oxoacyl-[acyl-carrier protein] synthase 1 KasA (beta-ketoacyl-ACP synthase) (KAS I) 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 0.5 0.5
0.0146 1 1
0.0128 0.5 0.5
0.0157 0.3163 1
0.0329 1 0.5
0.013 1 0.5
0.013 0.3439 0.5
0.0079 0.2615 1
0.0148 0.3483 1
0.0067 1 1
0.0132 0.5 0.5
0.0166 0.3163 1
0.0166 0.303 0.7705
0.0329 1 0.5
0.021 0.4188 1
0.0132 0.5 0.5
0.0148 0.6291 0.5
0.0279 1 0.5
0.0067 1 1
0.0064 1 0.5
0.0205 1 0.5
0.0133 0.3868 1
0.0166 0.303 0.7705
0.0166 0.303 0.7705
0.0274 0.9502 0.5
0.0064 1 0.5
0.0288 1 1
0.0156 0.3163 1
0.0066 0.3212 1
0.0128 0.3443 0.5
0.0143 0.3725 0.5
0.0135 1 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

4 literature references were collected for this gene.

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Gene identifier Tb927.2.3910 (Trypanosoma brucei), beta-ketoacyl-ACP synthase
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