Detailed view for Tb927.10.4040

Basic information

TDR Targets ID: 19836
Trypanosoma brucei, 3-keto-dihydrosphingosine reductase
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.9837 | Length (AA): 348 | MW (Da): 38046 | Paralog Number: 0

Signal peptide: Y | GPI Anchor: | Predicted trans-membrane segments: 1

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

PF00106   short chain dehydrogenase

Gene Ontology

Mouse over links to read term descriptions.
GO:0016491   oxidoreductase activity  
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  

Metabolic Pathways

Sphingolipid metabolism (KEGG)
Global map (KEGG)

Structural information

Modbase 3D models:

There are 5 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
31 269 2jah (A) 5 231 34.00 0 1 1.09568 -0.64
36 180 1wma (A) 7 140 41.00 0.00000000036 1 0.818767 -0.14
36 72 2yut (A) 3 36 29.00 0 0.34 0.236622 0.62
37 338 3ko8 (A) 4 296 24.00 0.6 1 0.831716 0.71
37 110 1ek6 (A) 6 81 35.00 0.051 0.95 0.675744 -0.8

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_128149)

Species Accession Gene Product
Arabidopsis thaliana AT5G19200   3-ketodihydrosphinganine reductase-like protein
Arabidopsis thaliana AT3G06060   3-ketodihydrosphinganine reductase-like protein
Brugia malayi Bm1_37690   oxidoreductase, short chain dehydrogenase/reductase family protein
Brugia malayi Bm1_37695   hypothetical protein
Candida albicans CaO19.6131   3-ketosphinganine reductase
Candida albicans CaO19.13550   3-ketosphinganine reductase
Caenorhabditis elegans CELE_Y37E11AM.3   Protein Y37E11AM.3
Dictyostelium discoideum DDB_G0272883   3-dehydrosphinganine reductase
Dictyostelium discoideum DDB_G0274015   3-dehydrosphinganine reductase
Drosophila melanogaster Dmel_CG10425   CG10425 gene product from transcript CG10425-RA
Echinococcus granulosus EgrG_000109500   3 ketodihydrosphingosine reductase
Entamoeba histolytica EHI_200770   3-ketodihydrosphingosine reductase protein, putative
Echinococcus multilocularis EmuJ_000109500   3 ketodihydrosphingosine reductase
Homo sapiens ENSG00000119537   3-ketodihydrosphingosine reductase
Leishmania braziliensis LbrM.34.0370   short chain dehydrogenase, putative
Leishmania donovani LdBPK_350330.1   short chain dehydrogenase, putative
Leishmania infantum LinJ.35.0330   short chain dehydrogenase, putative
Leishmania major LmjF.35.0330   3-keto-dihydrosphingosine reductase
Leishmania mexicana LmxM.34.0330   short chain dehydrogenase, putative
Loa Loa (eye worm) LOAG_06611   hypothetical protein
Loa Loa (eye worm) LOAG_06610   hypothetical protein
Mus musculus ENSMUSG00000009905   3-ketodihydrosphingosine reductase
Neospora caninum NCLIV_019810   3-ketodihydrosphingosine reductase TSC10 (EC 1.1.1.102), related
Oryza sativa 4330439   Os02g0701900
Plasmodium berghei PBANKA_1007100   conserved Plasmodium protein, unknown function
Plasmodium falciparum PF3D7_0409500   conserved Plasmodium protein, unknown function
Plasmodium knowlesi PKNH_0307600   NAD(P)-binding protein/reductase, putative
Plasmodium vivax PVX_000770   hypothetical protein, conserved
Plasmodium yoelii PY04092   hypothetical protein
Saccharomyces cerevisiae YBR265W   3-dehydrosphinganine reductase
Schistosoma japonicum Sjp_0074380   ko:K04708 3-dehydrosphinganine reductase [EC1.1.1.102], putative
Schistosoma mansoni Smp_141720   3-keto-dihydrosphingosine reductase
Schmidtea mediterranea mk4.000801.06   3-keto-dihydrosphingosine reductase
Schmidtea mediterranea mk4.005011.00   3-keto-dihydrosphingosine reductase
Trypanosoma brucei gambiense Tbg972.10.5030   short-chain dehydrogenase, putative
Trypanosoma brucei Tb927.10.4040   3-keto-dihydrosphingosine reductase
Trypanosoma congolense TcIL3000_10_3370   short-chain dehydrogenase, putative
Trypanosoma cruzi TcCLB.506959.64   3-keto-dihydrosphingosine reductase
Trypanosoma cruzi TcCLB.510997.10   3-keto-dihydrosphingosine reductase
Trichomonas vaginalis TVAG_468060   short-chain dehydrogenase, putative

Essentiality

Tb927.10.4040 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.4040 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.4040 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.4040 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.4040 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
YBR265W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1007100 Plasmodium berghei Dispensable plasmo
Show/Hide essentiality data references
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • 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
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84

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 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

Druggability index (range: 0 to 1): 0.4

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
Species Target Length Identity Alignment span Linked Drugs Reference
Cochliobolus lunatus 17-beta-hydroxysteroid-dehydrogenase 270 aa 24.9% 217 aa Compounds References
Macaca mulatta Hydroxysteroid 11-beta dehydrogenase 1 140 aa 32.7% 150 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0005 0.5 0.5
0.0009 0.5 0.5
0.0408 0.5144 1
0.0046 0.3082 0
0.0009 0.5 0.5
0.0068 1 1
0.0035 1 1
0.0009 0.5 0.5
0.0013 0.5 0.5
0.016 0.577 1
0.0076 1 1
0.0009 0.5 0.5
0.0171 0.4063 0.5
0.0073 0.3811 1
0.0402 1 1
0.007 1 1
0.011 0.3568 1
0.007 0.2916 1
0.0012 0.5 0.5
0.0009 0.5 0.5
0.0057 0.284 0.6352
0.0118 1 1
0.007 1 1
0.0073 0.2873 1
0.0004 0.5 0.5
0.0073 0.3811 1
0.007 0.2916 1
0.0171 0.4063 0.5
0.007 1 1
0.0009 0.5 0.5
0.0021 0.3321 0.5
0.0162 1 1
0.0053 1 1
0.0106 0.5 0.5
0.0004 0.5 0.5
0.0088 1 1
0.0114 1 0.5
0.0222 0.5 0.5
0.0097 0.4304 1
0.0004 0.5 0.5
0.0073 0.3141 1
0.0056 0.875 1
0.0013 1 0.5
0.0067 0.3468 1
0.0056 1 1
0.0084 0.4283 0.4283
0.0085 1 1
0.0218 0.5 0.5
0.0408 0.5144 1
0.0064 0.3508 0.5
0.0026 0.5 0.5
0.0123 0.5 0.5
0.0004 0.5 0.5
0.0113 1 1
0.0021 0.5 0.5
0.008 0.5 0.5
0.0009 0.5 0.5
0.0058 0.3931 1
0.0068 1 1
0.0196 0.8679 1
0.0039 1 1
0.0097 1 1
0.0021 0.3321 0.5
0.0408 0.5144 1
0.0071 0.3141 0.5
0.0082 1 0.5
0.0073 0.4546 1
0.0068 0.2585 0.5
0.0004 0.5 0.5
0.0009 0.5 0.5
0.0005 0.5 0.5
0.0106 1 0.5
0.0093 0.5 0.5
0.0009 0.7374 0.5
0.0106 0.2872 1
0.0131 0.5 0.5
0.0132 0.3658 1
0.0102 0.7451 0.5
0.0196 0.8679 1
0.016 0.577 1
0.0066 0.3586 0.5
0.0016 0.5 0.5
0.0114 1 0.5
0.004 0.5 0.5
0.0089 0.5 0.5
0.0027 0.5 0.5
0.0009 1 0.5
0.0045 1 1
0.0157 0.5 0.5
0.0004 0.5 0.5
0.0165 1 1
0.007 0.2916 1
0.0119 0.2746 1
0.0027 0.5 0.5
0.0089 0.5 0.5
0.0058 1 1
0.0004 0.5 0.5
0.0108 0.5 0.5
0.0019 0.4322 1
0.0012 0.5 0.5
0.0196 0.8679 1
0.0053 1 1
0.0106 1 1
0.0087 0.5 0.5
0.0032 1 1
0.0088 0.6544 1

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.

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

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Gene identifier Tb927.10.4040 (Trypanosoma brucei), 3-keto-dihydrosphingosine reductase
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