Detailed view for Tb927.10.1510

Basic information

TDR Targets ID: 16196
Trypanosoma brucei, CCR4-NOT transcription complex subunit 1
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.8825 | Length (AA): 2326 | MW (Da): 259128 | Paralog Number: 0

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

Druggability Group : DG1

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

PF04054   CCR4-Not complex component, Not1
PF12842   Domain of unknown function (DUF3819)
PF16415   CCR4-NOT transcription complex subunit 1 CAF1-binding domain
PF16417   CCR4-NOT transcription complex subunit 1 TTP binding domain

Gene Ontology

Mouse over links to read term descriptions.
No GO information for this protein.

Metabolic Pathways

RNA degradation (KEGG)

Structural information

Modbase 3D models:

There are 7 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
423 803 4b8b (A) 354 745 17.00 0 1 0.332212 0.33
643 810 4j8s (A) 822 992 23.00 0 1 0.52552 -1.42
865 1088 5anr (A) 1065 1294 38.00 0 1 0.697627 -1.5
1698 2299 4cqo (A) 1846 2361 32.00 0 1 0.460348 -0.5
1721 1764 4dt5 (A) 19 62 30.00 0 0.14 0.333641 -0.31
1775 2297 4cqo (A) 1878 2359 33.00 0 1 0.50784 -0.73
1924 2297 4c0e (A) 1806 2191 29.00 0 1 0.529599 -1.11

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
Upper 60-80% 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_128127)

Species Accession Gene Product
Arabidopsis thaliana AT1G02080   CCR4-NOT transcription complex subunit 1 domain protein
Babesia bovis BBOV_IV003100   transcriptional regulatory protein, putative
Brugia malayi Bm1_41195   CCR4-Not complex component, Not1 family protein
Candida albicans CaO19.1084   similar to S. cerevisiae CDC39 (YCR093W) component of the cytoplasmic mRNA deadenylase and CCR4-NOT transcription factor complex
Candida albicans CaO19.8685   similar to S. cerevisiae CDC39 (YCR093W) component of the cytoplasmic mRNA deadenylase and CCR4-NOT transcription factor complex
Caenorhabditis elegans CELE_F57B9.2   Protein LET-711
Cryptosporidium hominis Chro.60241   transcription regulatory protein
Cryptosporidium parvum cgd6_2060   cdc39p protein-like; C-terminal Not1, CCR4-Not complex component; Not1
Dictyostelium discoideum DDB_G0276029   hypothetical protein
Drosophila melanogaster Dmel_CG34407   CG34407 gene product from transcript CG34407-RG
Echinococcus granulosus EgrG_001152600   CCR4 Not complex component Not1
Echinococcus multilocularis EmuJ_001152600   CCR4 Not complex component, Not1
Homo sapiens ENSG00000125107   CCR4-NOT transcription complex, subunit 1
Leishmania braziliensis LbrM.21.0890   hypothetical protein, conserved
Leishmania donovani LdBPK_210880.1   CCR4-NOT transcription complex subunit 1
Leishmania infantum LinJ.21.0880   hypothetical protein, conserved
Leishmania major LmjF.21.0800   hypothetical protein, conserved
Leishmania mexicana LmxM.21.0800   hypothetical protein, conserved
Loa Loa (eye worm) LOAG_04910   hypothetical protein
Loa Loa (eye worm) LOAG_06063   CCR4-NOT transcription complex component
Mus musculus 620499   predicted gene 6158
Mus musculus ENSMUSG00000036550   CCR4-NOT transcription complex, subunit 1
Neospora caninum NCLIV_042980   hypothetical protein
Oryza sativa 9272729   Os10g0556801
Oryza sativa 4331296   Os03g0102300
Plasmodium berghei PBANKA_0943100   CCR4-NOT transcription complex subunit 1, putative
Plasmodium falciparum PF3D7_1103800   CCR4-NOT transcription complex subunit 1, putative
Plasmodium knowlesi PKNH_0901400   CCR4-NOT transcription complex subunit 1, putative
Plasmodium vivax PVX_090878   hypothetical protein, conserved
Plasmodium vivax PVX_090876   CCR4-NOT transcription complex subunit 1, putative
Plasmodium yoelii PY01940   similar to KIAA1007 protein-related
Plasmodium yoelii PY01432   hypothetical protein
Saccharomyces cerevisiae YCR093W   CCR4-NOT core subunit CDC39
Schistosoma japonicum Sjp_0004950   CCR4-NOT transcription complex subunit 1, putative
Schistosoma japonicum Sjp_0127850   expressed protein
Schistosoma japonicum Sjp_0047400   IPR000571,Zinc finger, CCCH-type;IPR007198,Ssl1-like;IPR000194,ATPase, F1/V1/A1 complex, alpha/beta subunit, nucleotide-binding,
Schistosoma mansoni Smp_133320   ccr4-not transcription complex
Schmidtea mediterranea mk4.015281.00  
Schmidtea mediterranea mk4.001778.09   Not1
Schmidtea mediterranea mk4.001778.08   CCR4-NOT transcription complex subunit 1
Trypanosoma brucei gambiense Tbg972.10.1760   hypothetical protein, conserved,regulator of transcription factor TFIID, putative
Trypanosoma brucei Tb927.10.1510   CCR4-NOT transcription complex subunit 1
Trypanosoma congolense TcIL3000_10_1310   CCR4-NOT transcription complex subunit 1
Trypanosoma cruzi TcCLB.509247.30   General negative regulator of transcription subunit 1
Toxoplasma gondii TGME49_291140   CCR4-Not complex component, Not1 protein
Theileria parva TP01_1063   hypothetical protein, conserved

Essentiality

Tb927.10.1510 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.1510 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.10.1510 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.1510 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.10.1510 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F57B9.2 Caenorhabditis elegans adult lethal wormbase
CELE_F57B9.2 Caenorhabditis elegans embryonic lethal wormbase
CELE_F57B9.2 Caenorhabditis elegans larval arrest wormbase
YCR093W Saccharomyces cerevisiae inviable yeastgenome
TGME49_291140 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) decreased (PATO:0000468) 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: decreased cell proliferation (significant loss of fitness) in bloodstream forms (stage 6 days). 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

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

1 literature reference was collected for this gene.

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Gene identifier Tb927.10.1510 (Trypanosoma brucei), CCR4-NOT transcription complex subunit 1
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