Detailed view for TcCLB.447255.20

Basic information

TDR Targets ID: 37003
Trypanosoma cruzi, Silent information regulator 2 related protein 3

Source Database / ID:  TriTrypDB  GeneDB

pI: 6.4904 | Length (AA): 241 | MW (Da): 26867 | Paralog Number: 1

Signal peptide: N | GPI Anchor: N | 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

PF02146   Sir2 family

Gene Ontology

Mouse over links to read term descriptions.
GO:0036055   GO:protein-succinyllysine desuccinylase activity  

GO:0036054   GO:protein-malonyllysine demalonylase activity  

GO:0008270   zinc ion binding  
GO:0070403   NAD binding  

GO:0006476   protein amino acid deacetylation  
GO:0006342   chromatin silencing  
GO:0045449   regulation of transcription  

Metabolic Pathways

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
1 241 1m2k (A) 8 248 38.00 0 1 1.42 -0.66
5 239 1s5p (A) 40 272 60.00 0 1 1.67 -1.22
2 238 1s5p (A) 40 271 63.00 0 1 1.7318 -0.85
8 209 4utv (A) 49 273 46.00 0 1 1.21257 0.19

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 epimastigote. Smircich P
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile metacyclic. Smircich P
Show/Hide expression data references
  • Smircich P Ribosome profiling reveals translation control as a key mechanism generating differential gene expression in Trypanosoma cruzi.

Orthologs

Ortholog group members (OG5_127825)

Species Accession Gene Product
Candida albicans CaO19.10480   similar to archaebacterial Sir2 family protein
Candida albicans CaO19.2963   similar to archaebacterial Sir2 family protein
Dictyostelium discoideum DDB_G0286671   NAD(+)-dependent deacetylase, silent information regulator protein family protein
Dictyostelium discoideum DDB_G0270928   NAD(+)-dependent deacetylase, silent information regulator protein family protein
Escherichia coli b1120   deacetylase of acs and cheY, chemotaxis regulator
Entamoeba histolytica EHI_007500   Sir2 family transcriptional regulator, putative
Giardia lamblia GL50803_16569   Transcriptional regulator, Sir2 family
Homo sapiens ENSG00000124523   sirtuin 5
Leishmania braziliensis LbrM.20.1640   NAD dependent deacetylase, putative,transcriptional regulator, Sir2 family protein, nicotinic acid mononucleotide 5,6-dimethylbe
Leishmania donovani LdBPK_341900.1   Silent information regulator 2 related protein 3
Leishmania infantum LinJ.34.1900   NAD dependent deacetylase, putative,transcriptional regulator, Sir2 family protein, nicotinic acid mononucleotide 5,6-dimethylbe
Leishmania major LmjF.34.2140   NAD dependent deacetylase, putative,transcriptional regulator, Sir2 family protein, nicotinic acid mononucleotide 5,6-dimethylbe
Leishmania mexicana LmxM.33.2140   NAD dependent deacetylase, putative,transcriptional regulator, Sir2 family protein, nicotinic acid mononucleotide 5,6-dimethylbe
Mycobacterium leprae ML1511   Probable NAD-dependent deacetylase NpdA (Regulatory protein SIR2 homolog)
Mus musculus ENSMUSG00000054021   sirtuin 5
Mycobacterium tuberculosis Rv1151c   Transcriptional regulatory protein
Mycobacterium ulcerans MUL_0992   NAD-dependent deacetylase
Neospora caninum NCLIV_045990   NAD-dependent deacetylase, putative
Plasmodium berghei PBANKA_1343800   transcriptional regulatory protein sir2a
Plasmodium falciparum PF3D7_1328800   transcriptional regulatory protein sir2a
Plasmodium knowlesi PKNH_1271600   transcriptional regulatory protein sir2 homologue, putative
Plasmodium vivax PVX_082385   NAD-dependent deacetylase, putative
Plasmodium yoelii PY01554   transcriptional regulatory protein, Sir2 family
Schistosoma japonicum Sjp_0075430   ko:K01463 sirtuin 5 (silent mating type information regulation 2 homolog) 5 [EC:3.5.1.-], putative
Schistosoma mansoni Smp_055090   chromatin regulatory protein sir2
Schmidtea mediterranea mk4.005077.00   NAD-dependent protein deacylase sirtuin-5, mitochondrial
Trypanosoma brucei gambiense Tbg972.4.2480   NAD dependent deacetylase, putative,transcriptional regulator, Sir2 family protein, nicotinic acid mononucleotide 5,6-dimethylbe
Trypanosoma brucei Tb927.4.2520   Silent information regulator 2 related protein 3
Trypanosoma congolense TcIL3000_0_08380   Silent information regulator 2 related protein 3
Trypanosoma cruzi TcCLB.506559.80   Silent information regulator 2 related protein 3
Trypanosoma cruzi TcCLB.447255.20   Silent information regulator 2 related protein 3
Toxoplasma gondii TGME49_227020   histone deacetylase SIR2
Trichomonas vaginalis TVAG_016210   chromatin regulatory protein sir2, putative
Trichomonas vaginalis TVAG_480900   chromatin regulatory protein sir2, putative
Trichomonas vaginalis TVAG_256040   chromatin regulatory protein sir2, putative

Essentiality

TcCLB.447255.20 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu1171 Mycobacterium tuberculosis non-essential nmpdr
Tb927.4.2520 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.4.2520 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.4.2520 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.4.2520 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b1120 Escherichia coli non-essential goodall
PBANKA_1343800 Plasmodium berghei Dispensable plasmo
TGME49_227020 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • 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.
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

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

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Homo sapiens sirtuin 5 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
0.0103 0.2745 0
0.0463 0.2618 0.4165
0.0346 0.3191 0.3057
0.0463 0.2618 0.4165
0.0303 0.3615 0.343
0.0374 0.3237 0.4009
0.0188 0.3514 0
0.0082 0.3545 0
0.0384 0.3918 0.3918
0.005 0.2654 0.4577
0.0071 0.3553 0.6759
0.0062 1 0.5
0.0355 0.317 0
0.0355 0.4302 0.4302
0.0102 0.2775 0.2243
0.0344 0.4151 0.4151
0.0463 0.2618 0.4165
0.0102 1 1
0.005 0.5 0.5
0.0052 0.2786 0.5253
0.0062 0.5817 0.5
0.0051 0.289 0.289
0.0102 0.3233 0
0.0484 0.3926 0.3917
0.0062 0.378 0.3965
0.0443 0.3868 0.3887
0.0355 0.4302 0.4302
0.0381 0.3261 0.4009
0.0243 0.2966 0.2846
0.0374 0.3089 0.4008
0.0054 0.4224 0.4202
0.0062 1 0.5
0.0082 0.3233 0
0.0218 0.2843 0.3328
0.0062 0.5817 0.5
0.0094 0.4488 0.4206
0.0183 0.2627 0.2597
0.0506 0.434 0.434
0.005 0.3409 1
0.0052 0.2786 0.5253
0.0268 0.2644 0.4053
0.0055 1 1
0.0385 0.3952 0.38
0.0313 0.3727 0.3716
0.0242 0.2974 0.2852
0.0051 0.4224 0.4202
0.0082 0.3545 0
0.0389 0.3921 0.3837
0.0324 0.3422 0.3492
0.0319 0.341 0.3401
0.0467 0.3768 0.3765
0.0062 0.5817 0.5
0.0062 0.5817 0.5
0.0374 0.3237 0.4009
0.0062 0.5817 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

5 literature references were 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 TcCLB.447255.20 (Trypanosoma cruzi), Silent information regulator 2 related protein 3
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