Detailed view for Tb927.11.5970

Basic information

TDR Targets ID: 18098
Trypanosoma brucei, phosphoinositide-specific phospholipase C

Source Database / ID:  TriTrypDB  GeneDB

pI: 7.4881 | Length (AA): 714 | MW (Da): 80449 | 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

PF00168   C2 domain
PF00387   Phosphatidylinositol-specific phospholipase C, Y domain
PF00388   Phosphatidylinositol-specific phospholipase C, X domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0035556   GO:intracellular signal transduction  

GO:0016020   membrane  
GO:0008081   phosphoric diester hydrolase activity  
GO:0005509   calcium ion binding  
GO:0004629   phospholipase C activity  
GO:0004435   phosphoinositide phospholipase C activity  
GO:0007242   intracellular signaling cascade  
GO:0007165   signal transduction  
GO:0006629   lipid metabolic process  

Structural information

Modbase 3D models:

There are 5 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
60 712 3qr1 (A) 118 768 28.00 0 1 1.14157 0.11
104 166 2kff (A) 56 115 13.00 0 0.3 0.305235 -1.54
107 147 1oqp (A) 110 148 41.00 0.077 0.97 0.568923 -0.61
115 714 1djx (B) 160 755 37.00 0 1 1.16034 0.08
590 697 3fdw (A) 376 483 16.00 0.092 0.02 0.141661 0.91

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. 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_127346)

Species Accession Gene Product
Arabidopsis thaliana AT5G58670   phosphoinositide phospholipase C 1
Arabidopsis thaliana AT5G58700   phosphoinositide phospholipase C 4
Arabidopsis thaliana AT2G40116   phosphoinositide phospholipase C 6
Arabidopsis thaliana AT3G55940   phosphoinositide phospholipase C 7
Arabidopsis thaliana AT3G08510   phosphoinositide phospholipase C 2
Arabidopsis thaliana AT5G58690   phosphoinositide phospholipase C 5
Arabidopsis thaliana AT4G38530   putative phosphoinositide phospholipase C 3
Babesia bovis BBOV_IV011070   phospholipase C gamma 1, putative
Brugia malayi Bm1_31705   Phosphatidylinositol-specific phospholipase C, X domain containing protein
Candida albicans CaO19_5506   hypothetical protein
Candida albicans CaO19.5506   phospholipase C
Caenorhabditis elegans CELE_R05G6.8   Protein PLC-4
Cryptosporidium hominis Chro.40288   phospholipase C, delta
Cryptosporidium parvum cgd4_2560   phospholipase C, delta 1 ortholog with 2 EF hands plus phospholipase C domain plus C2 domain
Dictyostelium discoideum DDB_G0292736   phosphoinositide-specific phospholipase C
Homo sapiens 113026   phospholipase C, delta 3
Homo sapiens ENSG00000115556   phospholipase C, delta 4
Homo sapiens ENSG00000187091   phospholipase C, delta 1
Leishmania braziliensis LbrM.22.1590   phosphoinositide-specific phospholipase C, putative
Leishmania donovani LdBPK_302970.1   phospholipase c-like protein
Leishmania donovani LdBPK_221530.1   phosphoinositide-specific phospholipase C, putative
Leishmania infantum LinJ.22.1530   phosphoinositide-specific phospholipase C, putative
Leishmania infantum LinJ.30.2970   phospholipase c-like protein
Leishmania major LmjF.30.2950   phospholipase c-like protein
Leishmania major LmjF.22.1680   phosphoinositide-specific phospholipase C, putative
Leishmania mexicana LmxM.29.2950   phospholipase c-like protein
Loa Loa (eye worm) LOAG_02789   phosphatidylinositol-specific phospholipase C
Mus musculus ENSMUSG00000026173   phospholipase C, delta 4
Mus musculus ENSMUSG00000010660   phospholipase C, delta 1
Mus musculus ENSMUSG00000020937   phospholipase C, delta 3
Neospora caninum NCLIV_064970   Phospholipid phospholipase C beta isoform, related
Oryza sativa 4344391   Os07g0694000
Oryza sativa 4332497   Os03g0289300
Oryza sativa 4337686   Os05g0127200
Onchocerca volvulus OVOC9265  
Onchocerca volvulus OVOC4175  
Saccharomyces cerevisiae YPL268W   phosphatidylinositol phospholipase C
Trypanosoma brucei gambiense Tbg972.11.6720   phosphoinositide-specific phospholipase C, putative
Trypanosoma brucei Tb927.11.5970   phosphoinositide-specific phospholipase C
Trypanosoma congolense TcIL3000.11.6490   phosphoinositide-specific phospholipase C, putative
Trypanosoma cruzi TcCLB.504149.160   phosphoinositide-specific phospholipase C, putative
Theileria parva TP01_0775   phospholipase C, putative

Essentiality

Tb927.11.5970 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.3780 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.3780 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb11.02.3780 this record Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb11.02.3780 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
YPL268W Saccharomyces cerevisiae inviable yeastgenome
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • 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
  • 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.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) increased (PATO:0000470) 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: increased cell proliferation (significant gain of fitness) in bloodstream forms (stage 3 days). References: 21363968
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 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
Species Known druggable target Linked compounds Reference
Homo sapiens phospholipase C, delta 1 Compounds References
Rattus norvegicus 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-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
0.0121 1 1
0.0072 0.2639 1
0.0057 0.3491 0.5
0.005 0.2612 0.5
0.0058 0.5 0.5
0.0109 0.4866 0.5
0.0125 0.3893 0.3893
0.0107 0.5 0.5
0.0018 0.5 0.5
0.0071 0.2549 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

1 literature reference was 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 Tb927.11.5970 (Trypanosoma brucei), phosphoinositide-specific phospholipase C
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