Detailed view for Tb11.v5.0196

Basic information

TDR Targets ID: 11468
Trypanosoma brucei, Proteasome subunit A N-terminal signature/Proteasome subunit, putative

Source Database / ID:  TriTrypDB  GeneDB

pI: 5.1936 | Length (AA): 266 | MW (Da): 29335 | 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

PF00227   Proteasome subunit
PF10584   Proteasome subunit A N-terminal signature

Gene Ontology

Mouse over links to read term descriptions.
GO:0019773   proteasome core complex, alpha-subunit complex  
GO:0005839   proteasome core complex  
GO:0004298   threonine endopeptidase activity  
GO:0004175   endopeptidase activity  
GO:0051603   proteolysis involved in cellular protein catabolic process  
GO:0006511   ubiquitin-dependent protein catabolic process  

Metabolic Pathways

Proteasome (KEGG)

Structural information

Modbase 3D models:

There are 3 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
3 234 1ryp (C) 3 239 32.00 0 1 1.27378 -0.51
4 243 5le5 (B) 3 246 30.00 0 1 1.30286 -0.56
4 238 5le5 (E) 4 237 49.00 0 1 1.55686 -0.94

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:

  • 1FNT:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 1Z7Q:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Procyclic. Siegel TN
Upregulation Percent Ranking Stage Dataset
Lower 20-40% 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_127884)

Species Accession Gene Product
Arabidopsis thaliana AT1G47250   20S proteasome alpha subunit F2
Arabidopsis thaliana AT5G42790   proteasome alpha subunit F1
Babesia bovis BBOV_IV000320   proteasome subunit alpha type 1
Brugia malayi Bm1_26725   Proteasome subunit alpha type 1
Brugia malayi Bm1_17805   proteasome subunit alpha type 1
Candida albicans CaO19_7178   hypothetical protein
Candida albicans CaO19.7178   proteasome alpha-subunit
Caenorhabditis elegans CELE_CD4.6   Protein PAS-6
Cryptosporidium hominis Chro.20222   proteasome A type subunit
Cryptosporidium parvum cgd2_2050   proteasome subunit alpha type 1, NTN hydrolase
Dictyostelium discoideum DDB_G0282363   20S proteasome subunit C2
Drosophila melanogaster Dmel_CG4904   Proteasome alpha6 subunit
Drosophila melanogaster Dmel_CG5648   Proteasome alpha6 subunit, Testis-specific
Echinococcus granulosus EgrG_000750500   20S proteasome subunit alpha 6
Echinococcus granulosus EgrG_000750600   cyclin
Entamoeba histolytica EHI_086080   proteasome subunit alpha type 1, putative
Echinococcus multilocularis EmuJ_000750500   20S proteasome subunit alpha 6
Echinococcus multilocularis EmuJ_000750600   cyclin
Giardia lamblia GL50803_7962   20S proteasome alpha subunit 6
Homo sapiens ENSG00000129084   proteasome (prosome, macropain) subunit, alpha type, 1
Leishmania braziliensis LbrM.35.1750   proteasome alpha 1 subunit, putative
Leishmania donovani LdBPK_361670.1   proteasome subunit alpha type-1, putative
Leishmania infantum LinJ.36.1670   proteasome alpha 1 subunit, putative
Leishmania major LmjF.36.1600   proteasome alpha 1 subunit, putative
Leishmania mexicana LmxM.36.1600   proteasome alpha 1 subunit, putative
Loa Loa (eye worm) LOAG_09359   proteasome subunit alpha type 1
Mus musculus ENSMUSG00000030751   proteasome (prosome, macropain) subunit, alpha type 1
Neospora caninum NCLIV_067980   Proteasome subunit alpha type (EC 3.4.25.1), related
Oryza sativa 4328215   Os02g0133800
Plasmodium berghei PBANKA_1301400   proteasome subunit alpha type-1, putative
Plasmodium falciparum PF3D7_1474800   proteasome subunit alpha type-1, putative
Plasmodium knowlesi PKNH_1245100   proteasome subunit alpha type-1, putative
Plasmodium vivax PVX_118620   proteasome subunit alpha type-1, putative
Plasmodium yoelii PY00267   proteasome subunit alpha type 1
Saccharomyces cerevisiae YMR314W   proteasome core particle subunit alpha 6
Schistosoma japonicum Sjp_0200730   ko:K06634 cyclin H, putative
Schistosoma japonicum Sjp_0200740   ko:K02725 20S proteasome subunit alpha 6, putative
Schistosoma mansoni Smp_170730   proteasome subunit alpha 1 (T01 family)
Schmidtea mediterranea mk4.006997.01   Proteasome subunit alpha type-1
Schmidtea mediterranea mk4.004243.00   CyclinH-like protein
Schmidtea mediterranea mk4.004704.00   Proteasome subunit alpha type-1
Schmidtea mediterranea mk4.006997.00   Proteasome subunit alpha type-1
Trypanosoma brucei gambiense Tbg972.10.7380   proteasome alpha 1 subunit, putative,20S proteasome subunit alpha-6, (putative)
Trypanosoma brucei Tb11.v5.0196   Proteasome subunit A N-terminal signature/Proteasome subunit, putative
Trypanosoma congolense TcIL3000_10_5090   proteasome subunit alpha type-1, putative
Trypanosoma cruzi TcCLB.506167.40   proteasome subunit alpha type-1, putative
Toxoplasma gondii TGME49_278050   proteasome subunit alpha type 1, putative
Theileria parva TP02_0930   proteasome subunit alpha type 1, putative
Theileria parva TP02_0927   proteasome subunit alpha type 1, putative
Trichomonas vaginalis TVAG_206040   Family T1, proteasome alpha subunit, threonine peptidase

Essentiality

Tb11.v5.0196 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.6030 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.6030 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.6030 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.10.6030 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_CD4.6 Caenorhabditis elegans embryonic lethal wormbase
CELE_CD4.6 Caenorhabditis elegans larval arrest wormbase
CELE_CD4.6 Caenorhabditis elegans larval lethal wormbase
CELE_CD4.6 Caenorhabditis elegans slow growth wormbase
CELE_CD4.6 Caenorhabditis elegans sterile wormbase
YMR314W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1301400 Plasmodium berghei Essential plasmo
TGME49_278050 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

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) 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) decreased (PATO:0000468) procyclic (PLO:0034) 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 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 proteasome (prosome, macropain) subunit, alpha type, 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
0.0116 0.2754 0.4871
0.0129 0.3321 0.4871
0.0135 0.331 0.4858
0.0257 0.3456 0.4993
0.014 0.3321 0.4871
0.014 0.3321 0.4871
0.0264 0.3319 0.4887
0.014 0.3335 0.4887
0.0124 0.3526 0.3692
0.014 0.3321 0.4871
0.026 0.3323 0.4887
0.0121 0.3529 0.3671
0.0234 0.3335 0.4887
0.0243 0.3335 0.4887
0.014 0.3321 0.4871
0.0113 0.3321 0.4871
0.014 0.3335 0.4887
0.0252 0.3335 0.4887

Assayability

Assay information

  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Trypanosoma brucei ( 2 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Tb11.v5.0196 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Trypanosoma brucei ( 2 )

Bibliographic References

35 literature references were collected for this gene.

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Gene identifier Tb11.v5.0196 (Trypanosoma brucei), Proteasome subunit A N-terminal signature/Proteasome subunit, putative
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