Detailed view for Tb927.11.2470

Basic information

TDR Targets ID: 17649
Trypanosoma brucei, metallo-peptidase, Clan MF, Family M17
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.3766 | Length (AA): 565 | MW (Da): 60586 | Paralog Number: 2

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

PF00883   Cytosol aminopeptidase family, catalytic domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005737   cytoplasm  
GO:0005622   intracellular  
GO:0030145   manganese ion binding  
GO:0008235   metalloexopeptidase activity  
GO:0004177   aminopeptidase activity  
GO:0019538   protein metabolic process  
GO:0006508   proteolysis  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in 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
3 559 5nth (A) 3 538 43.00 0 1 1.49364 -0.67
14 557 5ntd (A) 7 518 46.00 0 1 1.49483 -0.6
15 559 5nsk (A) 9 520 48.00 0 1 1.4934 -0.58
17 559 5ntf (A) 10 519 48.00 0 1 1.51786 -0.66

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
  • 4EFD:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5NSK:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5NSM:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5NSQ:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 5NTD:
  • 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_129785)

Species Accession Gene Product
Brugia malayi Bm1_00830   Aminopeptidase ZK353.6 in chromosome III
Caenorhabditis elegans CELE_ZK353.6   Protein LAP-1
Drosophila melanogaster Dmel_CG7340   granny smith
Escherichia coli b2523   aminopeptidase B
Homo sapiens ENSG00000215440   aminopeptidase-like 1
Leishmania braziliensis LbrM.33.2840   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Leishmania braziliensis LbrM.11.0410   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Leishmania donovani LdBPK_332700.1   metallo-peptidase, Clan MF, Family M17
Leishmania infantum LinJ.33.2700   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Leishmania infantum LinJ.11.0640   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Leishmania major LmjF.11.0630   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Leishmania major LmjF.33.2570   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Leishmania mexicana LmxM.32.2570   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Leishmania mexicana LmxM.11.0630   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Loa Loa (eye worm) LOAG_09171   aminopeptidase in chromosome III
Mus musculus ENSMUSG00000039263   aminopeptidase-like 1
Trypanosoma brucei gambiense Tbg972.11.2720   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Trypanosoma brucei gambiense Tbg972.11.7420   aminopeptidase, putative,metallo-peptidase, Clan MF, Family M17
Trypanosoma brucei Tb11.v5.0360   aminopeptidase, putative
Trypanosoma brucei Tb927.11.6590   metallo-peptidase, Clan MF, Family M17
Trypanosoma brucei Tb927.11.2470   metallo-peptidase, Clan MF, Family M17
Trypanosoma congolense TcIL3000_0_35010   metallo-peptidase, Clan MF, Family M17
Trypanosoma cruzi TcCLB.504153.140   metallo-peptidase, Clan MF, Family M17
Trypanosoma cruzi TcCLB.508799.240   metallo-peptidase, Clan MF, Family M17

Essentiality

Tb927.11.2470 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.0070 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.0070 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb11.02.0070 this record Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb11.02.0070 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
Tb11.02.4440 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.4440 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb11.02.4440 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.4440 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b2523 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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.
  • 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
  • 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

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 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) 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): 0.3

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Non orthologous druggable targets
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

13 literature references were collected for this gene.

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Gene identifier Tb927.11.2470 (Trypanosoma brucei), metallo-peptidase, Clan MF, Family M17
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