Detailed view for Tb927.1.2110

Basic information

TDR Targets ID: 15502
Trypanosoma brucei, Calpain-like protein 1.2

Source Database / ID:  TriTrypDB  GeneDB

pI: 4.9208 | Length (AA): 682 | MW (Da): 75538 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 0

Pfam domains

PF00648   Calpain family cysteine protease
PF09149   Domain of unknown function (DUF1935)

Gene Ontology

Mouse over links to read term descriptions.
GO:0008150   biological_process  
GO:0005575   cellular_component  
GO:0003674   molecular_function  
GO:0005622   intracellular  
GO:0004198   calcium-dependent cysteine-type endopeptidase activity  
GO:0006508   proteolysis  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models:

There are 6 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
25 143 2fe0 (A) 8 129 45.00 0 1 0.750987 -0.81
30 138 1r75 (A) 14 130 32.00 0 0.8 0.615324 -0.96
147 659 1kfx (L) 7 532 20.00 0 1 0.781599 0.98
172 492 1ziv (A) 36 334 31.00 0 1 0.695175 0.47
202 455 2nqa (A) 73 304 33.00 0 0.98 0.481934 0.8
6 114 5gmy (A) 67 190 32.00 0.76 0.06 0.91074 2.31

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 60-80% percentile Procyclic. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% 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_146880)

Species Accession Gene Product
Leishmania braziliensis LbrM.20.5400   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
Leishmania donovani LdBPK_201230.1   cysteine peptidase, Clan CA, family C2, putative
Leishmania infantum LinJ.20.1230   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
Leishmania major LmjF.20.1190   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
Leishmania mexicana LmxM.20.1190   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
Trypanosoma brucei gambiense Tbg972.1.1240   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
Trypanosoma brucei Tb927.1.2110 this record   Calpain-like protein 1.2
Trypanosoma cruzi TcCLB.508999.200   cysteine peptidase, Clan CA, family C2, putative
Trypanosoma cruzi TcCLB.506563.210   cysteine peptidase, Clan CA, family C2, putative

Essentiality

Tb927.1.2110 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.1.2110 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.1.2110 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.1.2110 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.1.2110 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
cell morphogenesis (GO:0000902) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
regulation of cell motility (GO:0051270) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
cell cycle (GO:0007049) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
mitochondrion organization and biogenesis (GO:0007005) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
regulation of cell motility (GO:0051270) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
endocytosis (GO:0006897) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
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 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 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 log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or 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

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Leishmania major calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Leishmania major small myristoylated protein-3, putative 115 aa 40.9% 110 aa Compounds References
Leishmania major calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative 414 aa 30.4% 418 aa Compounds References
Leishmania major hypothetical protein, conserved,calpain-like cysteine peptidase, Clan CA, family C2 146 aa 39.1% 128 aa Compounds References
Leishmania major small myristoylated protein-1 131 aa 43.5% 124 aa Compounds References

Obtained from network model

Ranking Plot


Putative Drugs List


Compound Raw Global Species
0.0609 0.7008 0.7593
0.0753 0.7578 0.7577
0.0634 0.4523 0.717
0.0632 0.7561 0.7561

Assayability

Assay information

  • Assay for Cathepsin B (3.4.22.1 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

Reagent availability

No reagent availability information for this target.

Bibliographic References

21 literature references were collected for this gene.

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User comments

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Gene identifier Tb927.1.2110 (Trypanosoma brucei), Calpain-like protein 1.2
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