Detailed view for Tb927.11.2730

Basic information

TDR Targets ID: 10162
Trypanosoma brucei, UDP-galactose 4-epimerase
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.0163 | Length (AA): 395 | MW (Da): 43517 | 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

PF01370   NAD dependent epimerase/dehydratase family

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0005488   binding  
GO:0003978   UDP-glucose 4-epimerase activity  
GO:0003824   catalytic activity  
GO:0050662   coenzyme binding  
GO:0008152   metabolic process  
GO:0006012   galactose metabolic process  
GO:0044237   cellular metabolic process  

Structural information

Modbase 3D models:

There are 2 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
1 381 1gy8 (A) 1 381 99.99 0 1 2.16256 -1.43
2 32 5f5n (A) 7 36 37.00 0 0.8 0.450281 0.2

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:

PDB tag
  • 1GY8:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2CNB:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile Bloodstream Form. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Procyclic. 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_126853)

Species Accession Gene Product
Arabidopsis thaliana AT4G20460   putative UDP-arabinose 4-epimerase 3
Arabidopsis thaliana AT1G63180   UDP-glucose 4-epimerase
Arabidopsis thaliana AT5G44480   putative UDP-arabinose 4-epimerase 4
Arabidopsis thaliana AT4G10960   UDP-glucose 4-epimerase 5
Arabidopsis thaliana AT1G64440   UDP-glucose 4-epimerase
Arabidopsis thaliana AT1G30620   UDP-arabinose 4-epimerase 1
Arabidopsis thaliana AT1G12780   bifunctional UDP-glucose 4-epimerase and UDP-xylose 4-epimerase 1
Arabidopsis thaliana AT3G28530   UDP-glucose 4-epimerase
Arabidopsis thaliana AT4G23920   UDP-glucose 4-epimerase 2
Brugia malayi Bm1_55785   UDP galactose 4'-epimerase
Candida albicans CaO19.11156   likely UDP glucose-4-epimerase similar to S. pombe SPBPB2B2.12c and to S. cerevisiae GAL10 (YBR019C) involved in galactose metab
Candida albicans CaO19.3672   likely UDP glucose-4-epimerase similar to S. pombe SPBPB2B2.12c and to S. cerevisiae GAL10 (YBR019C) involved in galactose metab
Caenorhabditis elegans CELE_C47B2.6   Protein GALE-1, isoform B
Cryptosporidium hominis Chro.40292   UDP-glucose 4-epimerase
Cryptosporidium parvum cgd4_2600   UDP-glucose 4-epimerase
Dictyostelium discoideum DDB_G0275295   UDP-glucose 4-epimerase
Drosophila melanogaster Dmel_CG12030   UDP-galactose 4'-epimerase
Escherichia coli b0759   UDP-galactose-4-epimerase
Echinococcus granulosus EgrG_000984800   UDP glucose 4 epimerase
Entamoeba histolytica EHI_192050   UDP-glucose 4-epimerase, putative
Echinococcus multilocularis EmuJ_000984800   UDP glucose 4 epimerase
Giardia lamblia GL50803_7982   UDP-glucose 4-epimerase
Homo sapiens ENSG00000117308   UDP-galactose-4-epimerase
Leishmania braziliensis LbrM.33.2590   udp-glc 4-epimerase, putative
Leishmania donovani LdBPK_332430.1   udp-glc 4'-epimerase, putative
Leishmania infantum LinJ.33.2430   udp-glc 4-epimerase, putative
Leishmania major LmjF.33.2300   udp-glc 4-epimerase, putative
Leishmania mexicana LmxM.32.2300   udp-glc 4-epimerase, putative
Loa Loa (eye worm) LOAG_00131   UDP galactose 4'-epimerase
Mus musculus ENSMUSG00000028671   galactose-4-epimerase, UDP
Neospora caninum NCLIV_046950   UDP-glucose 4-epimerase (EC 5.1.3.2), related
Oryza sativa 4345415   Os08g0374800
Oryza sativa 4337011   Os04g0618200
Oryza sativa 4339812   Os05g0595100
Oryza sativa 4347638   Os09g0526700
Oryza sativa 4346723   Os09g0323000
Oryza sativa 4344584   Os08g0129700
Oryza sativa 4342364   Os07g0139400
Saccharomyces cerevisiae YBR019C   bifunctional UDP-glucose 4-epimerase/aldose 1-epimerase
Schistosoma japonicum Sjp_0303190   ko:K01784 UDP-glucose 4-epimerase [EC5.1.3.2], putative
Schistosoma mansoni Smp_070780   UDP-glucose 4-epimerase
Schmidtea mediterranea mk4.011065.00   UDP-glucose 4-epimerase
Schmidtea mediterranea mk4.008355.00  
Trypanosoma brucei gambiense Tbg972.11.3030   UDP-galactose 4-epimerase, putative
Trypanosoma brucei Tb927.11.2730   UDP-galactose 4-epimerase
Trypanosoma congolense TcIL3000_0_38310   UDP-galactose 4-epimerase
Trypanosoma cruzi TcCLB.506303.50   UDP-galactose 4-epimerase, putative
Trypanosoma cruzi TcCLB.506811.190   UDP-galactose 4-epimerase
Toxoplasma gondii TGME49_225880   UDP-glucose 4-epimerase
Trichomonas vaginalis TVAG_058150   NAD dependent epimerase/dehydratase, putative
Trichomonas vaginalis TVAG_101620   NAD dependent epimerase/dehydratase, putative
Trichomonas vaginalis TVAG_186740   UDP-glucose 4-epimerase, putative

Essentiality

Tb927.11.2730 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.0330 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.0330 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb11.02.0330 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.0330 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b0759 Escherichia coli non-essential goodall
TGME49_225880 Toxoplasma gondii Probably non-essential 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
  • 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.
  • 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.
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) single cell organism (CARO:0000064) bloodstream stage (PLO:0040) inferred from loss-of-function mutant phenotype (ECO:0000016) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 11983889
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) single cell organism (CARO:0000064) bloodstream stage (PLO:0040) inferred from bioassay (ECO:0000094) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: Drug: compounds 1-7. . References: 16962325
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): 0.3

Known modulators for this target

Compound Source Reference
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Trypanosoma brucei gambiense UDP-galactose 4-epimerase, putative Compounds References
Homo sapiens UDP-galactose-4-epimerase 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
0.0104 0.3328 1
0.0125 0.4664 1
0.0302 1 1
0.0539 0.9741 1
0.0305 0.9022 0.9022
0.0541 1 1
0.0318 1 1
0.011 0.2925 1
0.011 0.2996 1
0.0302 1 1
0.0423 1 1
0.0544 1 0.5
0.0114 0.2984 1
0.0099 1 0.5
0.011 0.3192 1
0.0114 0.2984 1
0.0474 0.2797 1
0.0103 0.3326 1
0.068 0.3377 1
0.0412 1 1
0.0138202 0.333714 1
0.0073 0.4186 0
0.0105 0.2953 0.5
0.0878 0.3315 1
0.0102 0.3323 1

Assayability

Assay information

  • Assay for Uridine 5'-Diphosphogalactose 4-Epimerase (5.1.3.2 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • ChEMBL
  • Inhibition of hexahistidine-tagged Trypanosoma brucei UDP-galactose-4'epimerase expressed in Escherichia coli

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.

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Gene identifier Tb927.11.2730 (Trypanosoma brucei), UDP-galactose 4-epimerase
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