Detailed view for Tb927.8.2640

Basic information

TDR Targets ID: 16487
Trypanosoma brucei, ubiquitin-activating enzyme E1, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.8968 | Length (AA): 1055 | MW (Da): 116407 | 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

PF00899   ThiF family
PF09358   Ubiquitin fold domain
PF10585   Ubiquitin-activating enzyme active site

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0004839   ubiquitin activating enzyme activity  
GO:0008641   small protein activating enzyme activity  
GO:0005524   ATP binding  
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  
GO:0006464   protein modification process  

Metabolic Pathways

Ubiquitin mediated proteolysis (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
2 1051 4ii2 (A) 14 1011 38.00 0 1 1.33336 0
5 1052 5l6h (A) 13 1024 39.00 0 1 1.38966 -0.15
7 151 1tt5 (A) 9 160 31.00 0.0000000022 1 0.505741 -0.37
609 866 1z7l (A) 629 889 44.00 0 1 0.79085 -0.75

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_127070)

Species Accession Gene Product
Arabidopsis thaliana AT2G30110   ubiquitin-activating enzyme E1 1
Arabidopsis thaliana AT5G06460   ubiquitin-activating enzyme E1 2
Babesia bovis BBOV_II007710   ubiquitin-activating enzyme E1, putative
Brugia malayi Bm1_50525   ube1-prov protein
Candida albicans CaO19.7438   ubiquitin-activating enzyme
Caenorhabditis elegans CELE_C47E12.5   Protein UBA-1, isoform B
Cryptosporidium hominis Chro.40260   ubiquitin-activating enzyme e1
Cryptosporidium parvum cgd4_2300   ubiquitin-activating enzyme E1 (UBA)
Dictyostelium discoideum DDB_G0270272   ubiquitin activating enzyme E1
Dictyostelium discoideum DDB_G0277047   hypothetical protein
Drosophila melanogaster Dmel_CG1782   Ubiquitin activating enzyme 1
Echinococcus granulosus EgrG_000491100   ubiquitin modifier activating enzyme 6
Echinococcus granulosus EgrG_000711500   ubiquitin modifier activating enzyme 1
Entamoeba histolytica EHI_038690   ubiquitin-activating enzyme E1 1, putative
Entamoeba histolytica EHI_020270   ubiquitin-activating enzyme, putative
Echinococcus multilocularis EmuJ_000491100   ubiquitin modifier activating enzyme 6
Echinococcus multilocularis EmuJ_000711500   ubiquitin modifier activating enzyme 1
Giardia lamblia GL50803_10661   Ubiquitin-conjugating enzyme E1
Homo sapiens ENSG00000130985   ubiquitin-like modifier activating enzyme 1
Homo sapiens ENSG00000182179   ubiquitin-like modifier activating enzyme 7
Homo sapiens 55236   ubiquitin-like modifier activating enzyme 6
Leishmania braziliensis LbrM.23.0700   ubiquitin-activating enzyme e1, putative
Leishmania donovani LdBPK_230710.1   ubiquitin-activating enzyme E1, putative
Leishmania infantum LinJ.23.0710   ubiquitin-activating enzyme e1, putative
Leishmania major LmjF.23.0550   ubiquitin-activating enzyme e1, putative
Leishmania mexicana LmxM.23.0550   ubiquitin-activating enzyme e1, putative
Loa Loa (eye worm) LOAG_03774   ube1-prov protein
Mus musculus ENSMUSG00000001924   ubiquitin-like modifier activating enzyme 1
Mus musculus ENSMUSG00000032596   ubiquitin-like modifier activating enzyme 7
Mus musculus ENSMUSG00000035898   ubiquitin-like modifier activating enzyme 6
Mus musculus ENSMUSG00000069053   ubiquitin-activating enzyme, Chr Y
Neospora caninum NCLIV_042500   Ubiquitin-activating enzyme E1, related
Oryza sativa 4344380   Os07g0692900
Oryza sativa 4332529   Os03g0294900
Oryza sativa 9267214   Os03g0613100
Oryza sativa 4349557   Os11g0106400
Oryza sativa 9271171   Os12g0105950
Plasmodium berghei PBANKA_1440700   ubiquitin-activating enzyme E1, putative
Plasmodium falciparum PF3D7_1225800   ubiquitin-activating enzyme E1
Plasmodium knowlesi PKNH_1445200   ubiquitin-activating enzyme E1, putative
Plasmodium yoelii PY01879   Uba1 gene product-related
Saccharomyces cerevisiae YKL210W   E1 ubiquitin-activating protein UBA1
Schistosoma japonicum Sjp_0065510   ko:K03178 ubiquitin-activating enzyme E1, putative
Schistosoma japonicum Sjp_0063670   Ubiquitin-like modifier-activating enzyme 6, putative
Schistosoma mansoni Smp_162630.2   ubiquitin-activating enzyme E1
Schmidtea mediterranea mk4.026123.02  
Schmidtea mediterranea mk4.000467.00   Putative ubiquitin-activating enzyme e1
Schmidtea mediterranea mk4.000925.11   Putative ubiquitin-activating enzyme e1
Schmidtea mediterranea mk4.026123.00   Putative clathrin coat associated protein ap-50
Schmidtea mediterranea mk4.018920.02   Putative clathrin coat associated protein ap-50
Schmidtea mediterranea mk4.000102.06   Ubiquitin-like modifier-activating enzyme 6
Schmidtea mediterranea mk4.018920.01  
Schmidtea mediterranea mk4.018920.00  
Schmidtea mediterranea mk4.004540.00  
Trypanosoma brucei gambiense Tbg972.8.2140   ubiquitin-activating enzyme e1, putative
Trypanosoma brucei Tb927.8.2640   ubiquitin-activating enzyme E1, putative
Trypanosoma congolense TcIL3000_8_2480   ubiquitin-activating enzyme E1, putative
Trypanosoma cruzi TcCLB.508043.30   ubiquitin-activating enzyme E1, putative
Trypanosoma cruzi TcCLB.504427.250   ubiquitin-activating enzyme E1, putative
Theileria parva TP02_0689   ubiquitin-protein ligase, putative
Trichomonas vaginalis TVAG_300590   ubiquitin-activating enzyme E1, putative
Trichomonas vaginalis TVAG_006110   ubiquitin-activating enzyme E1, putative
Trichomonas vaginalis TVAG_090800   ubiquitin-activating enzyme E1c, putative

Essentiality

Tb927.8.2640 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.2640 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.8.2640 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.8.2640 this record Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb927.8.2640 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_C47E12.5 Caenorhabditis elegans adult lethal wormbase
CELE_C47E12.5 Caenorhabditis elegans embryonic lethal wormbase
CELE_C47E12.5 Caenorhabditis elegans slow growth wormbase
CELE_C47E12.5 Caenorhabditis elegans sterile wormbase
YKL210W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1440700 Plasmodium berghei Dispensable plasmo
Show/Hide essentiality data references
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) decreased (PATO:0000468) 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: decreased cell proliferation (significant loss of fitness) in bloodstream forms (stage 6 days). 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 procyclic forms . 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): 0.2

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
Homo sapiens ubiquitin-like modifier activating enzyme 6 Compounds References
Homo sapiens ubiquitin-like modifier activating enzyme 7 Compounds References
Homo sapiens ubiquitin-like modifier activating enzyme 1 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
0.0041 0.3299 0.6519
0.0086 0.4095 1
0.0086 0.4095 1
0.0072 0.2948 1
0.0086 0.4095 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

5 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 Tb927.8.2640 (Trypanosoma brucei), ubiquitin-activating enzyme E1, putative
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