Detailed view for Tb927.3.780

Basic information

TDR Targets ID: 14761
Trypanosoma brucei, proteasome alpha 7 subunit
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.5631 | Length (AA): 237 | MW (Da): 25463 | 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:0019538   protein metabolic 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
2 237 5le5 (U) 5 243 28.00 0 1 1.35528 -0.15
3 237 5dsv (C) 4 239 44.00 0 1 1.55506 -0.79
3 237 1ryp (G) 4 242 39.00 0 1 1.54806 -0.82

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

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_127755)

Species Accession Gene Product
Arabidopsis thaliana AT2G27020   20S proteasome alpha subunit G1
Babesia bovis BBOV_IV007800   proteasome subunit alpha, putative
Brugia malayi Bm1_16260   proteasome subunit alpha type 3
Candida albicans CaO19.6582   yeast proteasome subunit YC1
Candida albicans CaO19_6582   hypothetical protein
Candida albicans CaO19.13935   yeast proteasome subunit YC1
Caenorhabditis elegans CELE_ZK945.2   Protein PAS-7
Cryptosporidium hominis Chro.30260   proteasome subunit alpha type 3
Cryptosporidium parvum cgd3_2200   proteasome subunit alpha type 3, NTN hydrolase fold
Dictyostelium discoideum DDB_G0267408   20S proteasome subunit C8
Drosophila melanogaster Dmel_CG1519   Proteasome alpha7 subunit
Echinococcus granulosus EgrG_000196100   Proteasome subunit alpha beta
Entamoeba histolytica EHI_029210   proteasome subunit alpha type 3, putative
Entamoeba histolytica EHI_098060   proteasome subunit alpha type 3, putative
Echinococcus multilocularis EmuJ_000196100   Proteasome, subunit alpha beta
Giardia lamblia GL50803_11486   20S proteasome alpha subunit 7
Homo sapiens ENSG00000100567   proteasome (prosome, macropain) subunit, alpha type, 3
Leishmania braziliensis LbrM.27.0200   proteasome alpha 7 subunit, putative
Leishmania donovani LdBPK_270190.1   proteasome alpha 7 subunit, putative
Leishmania infantum LinJ.27.0190   proteasome alpha 7 subunit, putative
Leishmania major LmjF.27.0190   proteasome alpha 7 subunit, putative
Leishmania mexicana LmxM.27.0190   proteasome alpha 7 subunit, putative
Loa Loa (eye worm) LOAG_06229   proteasome subunit alpha type 3
Mus musculus 19167   proteasome (prosome, macropain) subunit, alpha type 3
Neospora caninum NCLIV_059790   proteasome subunit alpha type 3, putative
Oryza sativa 4339169   Os05g0490800
Oryza sativa 4327357   Os01g0811100
Onchocerca volvulus OVOC11117   Notchless protein homolog
Plasmodium berghei PBANKA_0808200   proteasome subunit alpha type-3, putative
Plasmodium falciparum PF3D7_0317000   proteasome subunit alpha type-3, putative
Plasmodium knowlesi PKNH_0824800   proteasome subunit alpha type-3, putative
Plasmodium vivax PVX_095380   proteasome subunit alpha type-3, putative
Plasmodium yoelii PY00152   Proteasome A-type and B-type, putative
Saccharomyces cerevisiae YOR362C   proteasome core particle subunit alpha 7
Schistosoma japonicum Sjp_0217470   ko:K02727 20S proteasome subunit alpha 7, putative
Schistosoma mansoni Smp_092280   proteasome subunit alpha 3 (T01 family)
Schmidtea mediterranea mk4.000339.06   Proteasome subunit alpha type-3
Trypanosoma brucei gambiense Tbg972.3.400   proteasome alpha 7 subunit
Trypanosoma brucei Tb927.3.780   proteasome alpha 7 subunit
Trypanosoma congolense TcIL3000_3_150   proteasome alpha 7 subunit, putative
Trypanosoma congolense TcIL3000_0_36040   proteasome alpha 7 subunit
Trypanosoma cruzi TcCLB.507775.50   proteasome alpha 7 subunit, putative
Trypanosoma cruzi TcCLB.511867.50   proteasome alpha 7 subunit, putative
Toxoplasma gondii TGME49_216450   peptidase, T1 family protein
Theileria parva TP03_0293   proteasome subunit alpha type 3, putative
Trichomonas vaginalis TVAG_185200   Family T1, proteasome alpha subunit, threonine peptidase

Essentiality

Tb927.3.780 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.3.780 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.3.780 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.3.780 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.3.780 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_ZK945.2 Caenorhabditis elegans embryonic lethal wormbase
CELE_ZK945.2 Caenorhabditis elegans larval lethal wormbase
CELE_ZK945.2 Caenorhabditis elegans slow growth wormbase
YOR362C Saccharomyces cerevisiae inviable yeastgenome
PBANKA_0808200 Plasmodium berghei Essential plasmo
TGME49_216450 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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

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) 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) 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

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, 3 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
0.0138 0.3373 0.4951
0.0123 0.359 0.3736
0.0115 0.3384 0.4963
0.0247 0.3398 0.4979
0.0262 0.3518 0.5084
0.0269 0.3381 0.4979
0.0142 0.3384 0.4963
0.0142 0.3384 0.4963
0.0237 0.3398 0.4979
0.0264 0.3386 0.4979
0.0142 0.3398 0.4979
0.0142 0.3384 0.4963
0.0142 0.3384 0.4963
0.0256 0.3398 0.4979
0.0131 0.3384 0.4963
0.0118 0.2806 0.4963
0.0142 0.3398 0.4979
0.0126 0.3587 0.3758

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
    Tb927.3.780 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 Tb927.3.780 (Trypanosoma brucei), proteasome alpha 7 subunit
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