Detailed view for PF3D7_0826100

Basic information

TDR Targets ID: 712
Plasmodium falciparum, E3 ubiquitin-protein ligase, putative
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 4.9324 | Length (AA): 8591 | MW (Da): 1005144 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 2

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

PF00632   HECT-domain (ubiquitin-transferase)
PF14377   Domain of unknown function (DUF4414)

Gene Ontology

Mouse over links to read term descriptions.
GO:0005622   intracellular  
GO:0016881   acid-amino acid ligase activity  
GO:0005089   Rho guanyl-nucleotide exchange factor activity  
GO:0004842   ubiquitin-protein ligase activity  
GO:0003824   catalytic activity  
GO:0035023   regulation of Rho protein signal transduction  
GO:0006511   ubiquitin-dependent protein catabolic process  
GO:0006464   protein modification process  

Metabolic Pathways

Ubiquitin mediated proteolysis (KEGG)

Structural information

Modbase 3D models:

There are 23 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
8214 8583 1zvd (A) 374 741 40.00 0 1 0.66 -1.49
1404 2193 3s5k (A) 130 961 22.00 0.36 0.99 0.0501567 1.51
2125 2404 4wat (A) 147 488 26.00 0.15 0.92 0.172792 0.12
3046 3334 3uau (A) 22 315 23.00 0.078 0.91 0.19484 0.6
4677 4794 4l3r (A) 42 159 10.00 0 0.02 0.0560353 -1.49
5091 5299 1yo8 (A) 729 958 30.00 0.00059 0.05 -0.198472 2.38
5543 6015 3sze (A) 248 775 24.00 0.019 0.95 0.106258 1.04
6623 6730 3ult (A) 6 113 31.00 0.0021 0.27 0.445771 -1.56
7405 7904 4cmq (A) 424 1044 22.00 0.68 0.81 0.0214004 1.48
8196 8583 3olm (A) 416 802 37.00 0 1 0.350464 -0.68
8210 8583 3h1d (A) 3992 4366 52.00 0 1 0.741734 -1.08
8211 8583 1zvd (A) 371 741 39.00 0 1 0.405718 -0.92
2120 2399 4wat (A) 147 488 27.00 0.075 0.83 0.183438 0.03
3039 3327 3uau (A) 22 315 23.00 0.078 0.91 0.195487 0.6
4653 4771 4l3r (A) 49 162 11.00 0 0.01 0.00877108 -1.36
5297 6287 4hat (C) 15 1048 8.00 0 0.08 -0.0285854 -0.09
5527 6001 3sze (A) 248 775 24.00 0.0038 0.88 0.100168 1.04
5736 6965 1epw (A) 3 1215 16.00 0 0.76 -0.143727 1.05
6434 6949 4n5a (A) 18 544 9.00 0 0.02 -0.0849531 -0.19
6613 6711 3ult (A) 6 113 35.00 0.005 0.07 0.39634 -1.27
8184 8571 3olm (A) 416 802 37.00 0 1 0.351127 -0.68
8198 8571 3h1d (A) 3992 4366 52.00 0 1 0.742395 -1.08
8199 8571 1zvd (A) 371 741 39.00 0 1 0.406378 -0.92

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 early trophozoite, Sporozoite. PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, sporozoite, early ring, early schizont, late ring, late trophozoite, Oocyst, Ring, Female Gametocyte, Male Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, gametocyte, merozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs. Otto TD
Show/Hide expression data references
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.

Orthologs

Ortholog group members (OG5_127551)

Species Accession Gene Product
Arabidopsis thaliana AT1G70320   ubiquitin-protein ligase 2
Arabidopsis thaliana AT1G55860   ubiquitin-protein ligase 1
Babesia bovis BBOV_IV005150   HECT-domain (ubiquitin-transferase) containing protein
Brugia malayi Bm1_31595   Start codon is not identified
Brugia malayi Bm1_31585   WWE domain containing protein
Candida albicans CaO19.911   similar to N terminus of S. cerevisiae TOM1 (YDR457W) ubiquitin-protein ligase
Candida albicans CaO19.912   insertion/frameshifted from N terminal sequence upstream
Candida albicans CaO19.8530   insertion/frameshifted from N terminal sequence upstream
Candida albicans CaO19.8529   similar to N terminus of S. cerevisiae TOM1 (YDR457W) ubiquitin-protein ligase
Candida albicans CaO19.5776   similar to C terminus of S. cerevisiae TOM1 (YDR457W) ubiquitin-protein ligase
Candida albicans CaO19.13198   similar to C terminus of S. cerevisiae TOM1 (YDR457W) ubiquitin-protein ligase
Caenorhabditis elegans CELE_Y67D8C.5   Protein EEL-1
Cryptosporidium hominis Chro.30149   ubiquitin-protein ligase 1
Cryptosporidium hominis Chro.30151   hypothetical protein
Cryptosporidium parvum cgd3_1180   hypothetical protein
Dictyostelium discoideum DDB_G0285063   hypothetical protein
Drosophila melanogaster Dmel_CG8184   CG8184 gene product from transcript CG8184-RD
Echinococcus granulosus EgrG_000717600   E3 ubiquitin protein ligase HUWE1
Entamoeba histolytica EHI_104570   ubiquitin ligase, putative
Echinococcus multilocularis EmuJ_000717600   E3 ubiquitin protein ligase HUWE1
Homo sapiens ENSG00000086758   HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase
Leishmania braziliensis LbrM.07.0290   ubiquitin-protein ligase-like, putative
Leishmania donovani LdBPK_070440.1   ubiquitin-protein ligase-like, putative
Leishmania infantum LinJ.07.0440   ubiquitin-protein ligase-like, putative
Leishmania major LmjF.07.0280   ubiquitin-protein ligase-like, putative
Leishmania mexicana LmxM.07.0280   ubiquitin-protein ligase-like, putative
Loa Loa (eye worm) LOAG_06151   WWE domain-containing protein
Loa Loa (eye worm) LOAG_10582   hypothetical protein
Mus musculus ENSMUSG00000025261   HECT, UBA and WWE domain containing 1
Neospora caninum NCLIV_002120   hypothetical protein
Oryza sativa 4346521   Os09g0252700
Oryza sativa 4352108   Os12g0428600
Oryza sativa 4346522   Os09g0252800
Plasmodium berghei PBANKA_0704500   E3 ubiquitin-protein ligase, putative
Plasmodium falciparum PF3D7_0826100   E3 ubiquitin-protein ligase, putative
Plasmodium knowlesi PKNH_1320300   E3 ubiquitin-protein ligase, putative
Plasmodium vivax PVX_089055   E3 ubiquitin-protein ligase, putative
Plasmodium yoelii PY00959   hypothetical protein
Plasmodium yoelii PY07433   hypothetical protein
Plasmodium yoelii PY01030   HECT-domain, putative
Saccharomyces cerevisiae YDR457W   E3 ubiquitin-protein ligase TOM1
Schistosoma japonicum Sjp_0045180   ko:K10592 E3 ubiquitin-protein ligase HUWE1, putative
Schistosoma japonicum Sjp_0045150   ko:K10592 E3 ubiquitin-protein ligase HUWE1, putative
Schistosoma mansoni Smp_167680.2   hypothetical protein
Schistosoma mansoni Smp_167680.1   hypothetical protein
Schistosoma mansoni Smp_167690   ubiquitin-protein ligase
Schmidtea mediterranea mk4.005247.01   Ubiquitin-protein ligase,putative
Schmidtea mediterranea mk4.005247.00  
Trypanosoma brucei gambiense Tbg972.8.1210   ubiquitin-protein ligase, putative
Trypanosoma brucei Tb927.8.1590   ubiquitin-protein ligase, putative
Trypanosoma congolense TcIL3000_8_1450   ubiquitin-protein ligase, putative
Trypanosoma cruzi TcCLB.508971.50   ubiquitin-protein ligase-like, putative
Toxoplasma gondii TGME49_295710   HECT-domain (ubiquitin-transferase) domain-containing protein
Theileria parva TP01_0228   hypothetical protein
Theileria parva TP01_0229   ubiquitin-protein ligase, putative
Trichomonas vaginalis TVAG_393150   ubiquitin protein ligase, putative

Essentiality

PF3D7_0826100 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.1590 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.8.1590 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.8.1590 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.1590 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_Y67D8C.5 Caenorhabditis elegans embryonic lethal wormbase
CELE_Y67D8C.5 Caenorhabditis elegans larval lethal wormbase
PBANKA_0704500 Plasmodium berghei Essential plasmo
TGME49_295710 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

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

Druggability index (range: 0 to 1): 0.5

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 PF3D7_0826100 (Plasmodium falciparum), E3 ubiquitin-protein ligase, putative
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