Detailed view for Tbg972.9.2700

Basic information

TDR Targets ID: 542851
Trypanosoma brucei gambiense, cAMP-specific phosphodiesterase, putative
Source Database / ID: 

pI: 5.8774 | Length (AA): 930 | MW (Da): 103650 | Paralog Number: 1

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

Druggability Group : DG

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

PF00233   3'5'-cyclic nucleotide phosphodiesterase
PF01590   GAF domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0004114   3',5'-cyclic-nucleotide phosphodiesterase activity  
GO:0008081   phosphoric diester hydrolase activity  
GO:0005515   protein binding  
GO:0007165   signal transduction  

Metabolic Pathways

Purine metabolism (KEGG)
Morphine addiction (KEGG)

Structural information

Modbase 3D models:

There are 2 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
215 916 3ibj (B) 224 900 24.00 0 1 0.903339 0.5
586 918 4i15 (A) 586 918 99.99 0 1 1.65436 -2.05

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

No expression data available for this gene

Orthologs

Ortholog group members (OG5_127318)

Species Accession Gene Product
Candida albicans CaO19.10489   similar to S. cerevisiae PDE2 (YOR360C) cAMP phosphodiesterase
Candida albicans CaO19.2972   similar to S. cerevisiae PDE2 (YOR360C) cAMP phosphodiesterase
Dictyostelium discoideum DDB_G0268634   cGMP-specific phosphodiesterase
Drosophila melanogaster Dmel_CG34341   Phosphodiesterase 11
Drosophila melanogaster Dmel_CG8279   Phosphodiesterase 6
Echinococcus granulosus EgrG_000678400   dual 3'5' cyclic AMP and GMP phosphodiesterase
Echinococcus multilocularis EmuJ_000678400   dual 3',5' cyclic AMP and GMP phosphodiesterase
Homo sapiens ENSG00000128655   phosphodiesterase 11A
Homo sapiens ENSG00000138735   phosphodiesterase 5A, cGMP-specific
Leishmania braziliensis LbrM.15.1250   cAMP specific phosphodiesterase, putative
Leishmania braziliensis LbrM.15.1480   cAMP specific phosphodiesterase, putative
Leishmania donovani LdBPK_151540.1   cAMP specific phosphodiesterase, putative
Leishmania infantum LinJ.15.1540   cAMP specific phosphodiesterase, putative
Leishmania infantum LinJ.15.1550   cAMP specific phosphodiesterase, putative
Leishmania mexicana LmxM.15.1480   cAMP specific phosphodiesterase, putative
Leishmania mexicana LmxM.15.1481   cAMP specific phosphodiesterase, putative
Mus musculus ENSMUSG00000053965   phosphodiesterase 5A, cGMP-specific
Mus musculus 241489   phosphodiesterase 11A
Saccharomyces cerevisiae YOR360C   3',5'-cyclic-nucleotide phosphodiesterase PDE2
Schistosoma japonicum Sjp_0021620   Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11, putative
Schistosoma japonicum Sjp_0215050   expressed protein
Schistosoma japonicum Sjp_0021610   Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11, putative
Schistosoma japonicum Sjp_0134390   Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11, putative
Schistosoma mansoni Smp_179590   camp/cgmp cyclic nucleotide phosphodiesterase
Schmidtea mediterranea mk4.006743.01  
Schmidtea mediterranea mk4.006234.04  
Schmidtea mediterranea mk4.012753.02  
Schmidtea mediterranea mk4.006743.02  
Schmidtea mediterranea mk4.023897.00  
Schmidtea mediterranea mk4.010357.01  
Schmidtea mediterranea mk4.006234.06   Putative camp/cgmp cyclic nucleotide phosphodiesterase
Schmidtea mediterranea mk4.008467.01  
Trypanosoma brucei gambiense Tbg972.9.2710   cAMP-specific phosphodiesterase, putative
Trypanosoma brucei gambiense Tbg972.9.2700   cAMP-specific phosphodiesterase, putative
Trypanosoma brucei Tb927.9.5100   cAMP-specific phosphodiesterase
Trypanosoma brucei Tb927.9.5040   cAMP-specific phosphodiesterase
Trypanosoma congolense TcIL3000_9_1670   cAMP-specific phosphodiesterase, putative
Trypanosoma congolense TcIL3000_0_03910   cAMP-specific phosphodiesterase
Trypanosoma cruzi TcCLB.509943.20   cAMP specific phosphodiesterase, putative
Trypanosoma cruzi TcCLB.508277.110   cAMP specific phosphodiesterase, putative
Trypanosoma cruzi TcCLB.508277.100   cAMP specific phosphodiesterase, putative
Trypanosoma cruzi TcCLB.509943.11   cAMP specific phosphodiesterase, putative
Toxoplasma gondii TGME49_200295   hypothetical protein
Trichomonas vaginalis TVAG_043880   calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_333170   cone cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_416790   rod cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_230840   conserved hypothetical protein
Trichomonas vaginalis TVAG_446730   cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_371830   cAMP and cAMP-inhibited cGMP 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_495630   conserved hypothetical protein
Trichomonas vaginalis TVAG_265300   cAMP/cGMP cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_138390   cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_437180   cAMP-specific phosphodiesterase, putative
Trichomonas vaginalis TVAG_335090   cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_172570   calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_136710   cAMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_059390   high-affinity cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_260330   cAMP-specific phosphodiesterase, putative
Trichomonas vaginalis TVAG_261720   cGMP-inhibited 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_119150   high-affinity cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_055620   rod cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_499580   cAMP-specific phosphodiesterase, putative
Trichomonas vaginalis TVAG_405840   calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_083500   cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_426800   calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_046890   rod cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_407110   cGMP-dependent 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_186700   cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_346760   high-affinity cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_438020   conserved hypothetical protein
Trichomonas vaginalis TVAG_134900   cAMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_271730   cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_195020   cone cGMP-specific 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_027930   conserved hypothetical protein
Trichomonas vaginalis TVAG_163530   calcium/calmodulin-dependent 3,5-cyclic nucleotide phosphodiesterase, putative
Trichomonas vaginalis TVAG_225750   cGMP-dependent 3,5-cyclic phosphodiesterase, putative
Trichomonas vaginalis TVAG_052120   high-affinity cGMP-specific 3,5-cyclic phosphodiesterase, putative

Essentiality

Tbg972.9.2700 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb09.160.3590 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb09.160.3590 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb09.160.3590 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb09.160.3590 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
Tb09.160.3630 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb09.160.3630 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb09.160.3630 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb09.160.3630 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
TGME49_200295 Toxoplasma gondii Probably non-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
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • 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.

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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

68 chemical compounds are associated with this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Canis lupus famiaris Phosphodiesterase 5A Compounds References
Leishmania major Class I phosphodiesterase PDEB1 Compounds References
Rattus norvegicus Phosphodiesterase 5A Compounds References
Homo sapiens phosphodiesterase 5A, cGMP-specific Compounds References
Bos taurus Phosphodiesterase 5A Compounds References
Homo sapiens phosphodiesterase 11A Compounds References
Trypanosoma brucei cAMP-specific phosphodiesterase Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Bos taurus Phosphodiesterase 6A 859 aa 25.4% 788 aa Compounds References
Bos taurus Phosphodiesterase 721 aa 30.7% 664 aa Compounds References
Canis lupus familiaris Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha 861 aa 26.1% 712 aa Compounds References
Bos taurus Phosphodiesterase 6 853 aa 25.5% 793 aa Compounds References
Rattus norvegicus cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A 794 aa 30.3% 661 aa Compounds References
Bos taurus Phosphodiesterase 6C 855 aa 26.1% 788 aa Compounds References
Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

  • ChEMBL
  • Inhibition of Trypanosoma brucei PDEB1 at 100 uM
  • ChEMBL
  • Inhibition of Trypanosoma brucei PDEB1 using cAMP as substrate at 10 uM preincubated for 10 mins prior substrate addition by spectrophotometry
  • ChEMBL
  • Inhibition of Trypanosoma brucei PDEB1 using cAMP as substrate at 100 uM preincubated for 10 mins prior substrate addition by spectrophotometry
  • ChEMBL
  • Inhibition of Trypanosoma brucei TbrPDEB1
  • ChEMBL
  • Inhibition of Trypanosoma brucei His-tagged catalytic domains of TbrPDEB1 expressed in Escherichia coli BL21 assessed as conversion of cAMP to AMP after 20 mins by PDELight assay
  • ChEMBL
  • Inhibition of Trypanosoma brucei recombinant TbrPDEB1 expressed in Sf21 insect cells assessed as reduction of [3H]-cAMP hydrolysis by scintillation proximity assay
  • ChEMBL
  • Inhibition of Trypanosoma brucei full length PDEB1 expressed in insect SF21 cells using cAMP as substrate by scintillation proximity assay
  • ChEMBL
  • Inhibition of Trypanosoma brucei PDEB1
  • ChEMBL
  • Inhibition of Trypanosoma brucei recombinant PDEB1 at 10 uM pre-incubated for 5 mins prior to substrate addition
  • ChEMBL
  • Inhibition of Trypanosoma brucei recombinant PDEB1 pre-incubated for 5 mins prior to substrate addition
  • ChEMBL
  • Inhibition of recombinant Trypanosoma brucei PDEB1 using [3H]-cAMP as substrate after 15 mins by scintillation proximity assay

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier Tbg972.9.2700 (Trypanosoma brucei gambiense), cAMP-specific phosphodiesterase, putative
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