Detailed view for Tb927.11.12250

Basic information

TDR Targets ID: 13206
Trypanosoma brucei, DNA replication licensing factor MCM4
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.577 | Length (AA): 836 | MW (Da): 92821 | 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

PF00493   MCM2/3/5 family
PF14551   MCM N-terminal domain
PF17207   MCM OB domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0042555   MCM complex  
GO:0005575   cellular_component  
GO:0005634   nucleus  
GO:0003678   DNA helicase activity  
GO:0003677   DNA binding  
GO:0005524   ATP binding  
GO:0006270   DNA replication initiation  
GO:0006260   DNA replication  

Metabolic Pathways

DNA replication (KEGG)

Structural information

Modbase 3D models:

There are 3 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
54 738 4r7y (A) 9 1965 37.00 0 1 1.03308 0.68
352 737 4r7z (A) 263 964 40.00 0 1 0.640723 0.61
377 781 3nbx (X) 14 337 17.00 0 0.86 0.29745 1.03

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 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_127631)

Species Accession Gene Product
Arabidopsis thaliana AT2G16440   minichromosome maintenance protein 4
Babesia bovis BBOV_II005160   DNA replication licensing factor MCM4
Brugia malayi Bm1_48490   Yeast mcm
Candida albicans CaO19.3761   DNA synthesis initiation
Candida albicans CaO19.11245   DNA synthesis initiation
Caenorhabditis elegans CELE_Y39G10AR.14   Protein MCM-4
Cryptosporidium hominis Chro.20137   DNA replication licensing factor
Cryptosporidium parvum cgd2_1250   DNA replication licensing factor MCM4 like AAA+ ATpase
Dictyostelium discoideum DDB_G0275623   MCM family protein
Drosophila melanogaster Dmel_CG1616   disc proliferation abnormal
Echinococcus granulosus EgrG_000171000   DNA replication licensing factor MCM4
Entamoeba histolytica EHI_187720   DNA replication licensing factor, putative
Echinococcus multilocularis EmuJ_000171000   DNA replication licensing factor MCM4
Giardia lamblia GL50803_9194   MCM4
Homo sapiens ENSG00000104738   minichromosome maintenance complex component 4
Leishmania braziliensis LbrM.09.0250   minchromosome maintenance (MCM) complex subunit, putative
Leishmania donovani LdBPK_090400.1   DNA replication licensing factor MCM4
Leishmania infantum LinJ.09.0400   minchromosome maintenance (MCM) complex subunit, putative
Leishmania major LmjF.09.0250   minchromosome maintenance (MCM) complex subunit, putative
Leishmania mexicana LmxM.09.0250   minchromosome maintenance (MCM) complex subunit, putative
Loa Loa (eye worm) LOAG_10273   DNA replication licensing factor mcm4-B
Mus musculus ENSMUSG00000022673   minichromosome maintenance deficient 4 homolog (S. cerevisiae)
Neospora caninum NCLIV_060910   DNA replication licensing factor, putative
Plasmodium berghei PBANKA_1415600   DNA replication licensing factor MCM4, putative
Plasmodium falciparum PF3D7_1317100   DNA replication licensing factor MCM4
Plasmodium knowlesi PKNH_1417800   DNA replication licensing factor MCM4, putative
Plasmodium vivax PVX_122675   DNA replication licensing factor MCM4, putative
Plasmodium yoelii PY03411   DNA replication licensing factor MCM4-related
Saccharomyces cerevisiae YPR019W   MCM DNA helicase complex subunit MCM4
Schistosoma japonicum Sjp_0106670   DNA replication licensing factor mcm4-B, putative
Schistosoma japonicum Sjp_0109260   DNA replication licensing factor mcm4-A, putative
Schistosoma japonicum Sjp_0035150   ko:K02212 minichromosome maintenance protein 4 (cell division control protein, putative
Schistosoma mansoni Smp_172530   DNA replication licensing factor MCM4
Schmidtea mediterranea mk4.011053.00   DNA replication licensing factor MCM4
Schmidtea mediterranea mk4.003562.01   DNA replication licensing factor MCM4
Trypanosoma brucei gambiense Tbg972.11.13690   minichromosome maintenance (MCM) complex subunit, putative
Trypanosoma brucei Tb927.11.12250   DNA replication licensing factor MCM4
Trypanosoma congolense TcIL3000.11.12880   DNA replication licensing factor MCM4, putative
Trypanosoma cruzi TcCLB.509023.130   DNA replication licensing factor MCM4, putative
Trypanosoma cruzi TcCLB.511127.140   DNA replication licensing factor MCM4, putative
Toxoplasma gondii TGME49_219700   DNA replication licensing factor MCM4, putative
Theileria parva TP04_0057   DNA replication licensing factor MCM4, putative
Trichomonas vaginalis TVAG_250220   DNA replication licensing factor MCM4, putative

Essentiality

Tb927.11.12250 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.01.4070 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.01.4070 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.01.4070 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb11.01.4070 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_Y39G10AR.14 Caenorhabditis elegans embryonic lethal wormbase
CELE_Y39G10AR.14 Caenorhabditis elegans larval arrest wormbase
CELE_Y39G10AR.14 Caenorhabditis elegans sterile wormbase
YPR019W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1415600 Plasmodium berghei Essential plasmo
TGME49_219700 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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)

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 3 days). References: 21363968
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 procyclic forms . References: 21363968
cell proliferation (GO:0008283) normal (PATO:0000461) procyclic (PLO:0034) 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 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.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

User comments

No user comments are available for this gene. Log in to add comments, or register.

Enter your comment

User ()
Gene identifier Tb927.11.12250 (Trypanosoma brucei), DNA replication licensing factor MCM4
Title for this comment
Comment