Detailed view for PF3D7_0817000

Basic information

TDR Targets ID: 774
Plasmodium falciparum, NEDD8-activating enzyme E1 catalytic subunit, putative
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.51 | Length (AA): 389 | MW (Da): 45703 | Paralog Number: 0

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

Druggability Group : DG2

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

PF00899   ThiF family

Gene Ontology

Mouse over links to read term descriptions.
GO:0019781   NEDD8 activating enzyme activity  
GO:0016881   acid-amino acid ligase activity  
GO:0008641   small protein activating enzyme activity  
GO:0005524   ATP binding  
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  
GO:0006464   protein modification process  
GO:0045116   protein neddylation  

Metabolic Pathways

Ubiquitin mediated proteolysis (KEGG)

Structural information

Modbase 3D models:

There are 9 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
6 283 1y8q (A) 30 337 15.00 0 1 0.35 -1.47
6 401 1y8q (B) 11 548 23.00 0 1 0.19 -0.82
657 1218 1xzp (A) 34 450 30.00 0 1 0.43 0.67
657 716 1xzp (B) 34 92 37.00 0.000013 0.89 0.56 -0.73
1 389 1y8q (B) 7 533 23.00 0 1 0.933 0
2 388 3dbh (B) 40 438 26.00 0 1 1.10586 0.22
6 217 1jw9 (B) 25 242 19.00 0.00000000043 1 0.871087 -0.61
8 135 4p22 (A) 68 190 22.00 0.0021 1 0.648249 -0.52
15 121 1jwa (B) 34 139 31.00 0.0000021 0.97 0.656264 -0.07

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

Orthologs

Ortholog group members (OG5_128095)

Species Accession Gene Product
Arabidopsis thaliana AT5G19180   NEDD8-activating enzyme E1 catalytic subunit
Babesia bovis BBOV_I001030   ThiF family domain containing protein
Brugia malayi Bm1_35445   Ectopic membrane ruffles in embryo protein 1
Candida albicans CaO19.11685   Ubiquitin activating enzyme
Candida albicans CaO19.4209   Ubiquitin activating enzyme
Caenorhabditis elegans CELE_F11H8.1   Protein RFL-1
Cryptosporidium hominis Chro.80201   ubiquitin-activating enzyme
Cryptosporidium parvum cgd8_1730   Uba3p like ubiquitin activating enzyme E1
Dictyostelium discoideum DDB_G0283891   NEDD8-activating enzyme E1 catalytic subunit
Drosophila melanogaster Dmel_CG13343   Ubiquitin activating enzyme 3
Echinococcus granulosus EgrG_000970100   NEDD8 activating enzyme E1 catalytic subunit
Entamoeba histolytica EHI_098550   ubiquitin-activating enzyme, putative
Echinococcus multilocularis EmuJ_000970100   NEDD8 activating enzyme E1 catalytic subunit
Homo sapiens ENSG00000144744   ubiquitin-like modifier activating enzyme 3
Leishmania braziliensis LbrM.01.0690   ubiquitin activating enzyme, putative
Leishmania donovani LdBPK_010730.1   ubiquitin activating enzyme, putative
Leishmania infantum LinJ.01.0730   ubiquitin activating enzyme, putative
Leishmania major LmjF.01.0710   ubiquitin activating enzyme, putative
Leishmania mexicana LmxM.01.0710   ubiquitin activating enzyme, putative
Loa Loa (eye worm) LOAG_01766   ectopic membrane ruffles in embryo protein 1
Mus musculus ENSMUSG00000030061   ubiquitin-like modifier activating enzyme 3
Neospora caninum NCLIV_040320   ubiquitin-activating enzyme, putative
Oryza sativa 4325169   Os01g0271500
Plasmodium berghei PBANKA_0713800   NEDD8-activating enzyme E1 catalytic subunit, putative
Plasmodium falciparum PF3D7_0817000   NEDD8-activating enzyme E1 catalytic subunit, putative
Plasmodium knowlesi PKNH_0503400   NEDD8-activating enzyme E1 catalytic subunit, putative
Plasmodium vivax PVX_089560   ubiquitin-activating enzyme E1C, putative
Saccharomyces cerevisiae YPR066W   NEDD8-activating protein UBA3
Schistosoma japonicum Sjp_0033200   ko:K10686 ubiquitin-activating enzyme E1 C, putative
Schistosoma japonicum Sjp_0090040   NEDD8-activating enzyme E1 catalytic subunit, putative
Schistosoma japonicum Sjp_0124080   ko:K06917 tRNA 2-selenouridine synthase, putative
Schistosoma japonicum Sjp_0131750   NEDD8-activating enzyme E1 catalytic subunit, putative
Schistosoma mansoni Smp_151760   ubiquitin-activating enzyme E1C
Schmidtea mediterranea mk4.001703.08   NEDD8-activating enzyme E1 catalytic subunit
Trypanosoma brucei gambiense Tbg972.9.2440   ubiquitin-activating enzyme e1, putative
Trypanosoma brucei Tb927.9.4620   NEDD8 activating enzyme subunit, putative
Trypanosoma congolense TcIL3000_9_1520   ubiquitin-activating enzyme E1, putative
Trypanosoma cruzi TcCLB.510155.120   ubiquitin activating enzyme, putative
Trypanosoma cruzi TcCLB.511585.130   ubiquitin activating enzyme, putative
Toxoplasma gondii TGME49_264880   NEDD8-activating enzyme E1 catalytic subunit
Theileria parva TP01_0601   hypothetical protein, conserved
Trichomonas vaginalis TVAG_161040   molybdopterin biosynthesis moeb protein, putative

Essentiality

PF3D7_0817000 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb09.160.3210 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb09.160.3210 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb09.160.3210 Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb09.160.3210 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F11H8.1 Caenorhabditis elegans embryonic lethal wormbase
TGME49_264880 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • 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
  • 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
  • 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
  • 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.

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): 0.1

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 ubiquitin-like modifier activating enzyme 3 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
0.0625 0.2979 1
0.0434 0.2876 1
0.0576 0.2831 1
0.0253 0.3022 0.6242
0.0373 0.3034 0.7229
0.0089 0.2921 1
0.0393 0.2696 1
0.0373 0.3034 0.7229
0.018 0.2909 1
0.018 0.2909 1
0.046 0.2921 1
0.0484 0.302 1
0.0245 0.2504 0.5
0.0283 0.2774 1
0.0165 0.2876 1
0.0432 0.2622 1
0.0414 0.2967 1
0.0576 0.2831 1
0.0546 0.3094 1
0.0121 0.2891 1
0.0582 0.3094 1
0.0471 0.306 1
0.0414 0.2967 1
0.0619 0.2941 1
0.0613 0.2543 1
0.0502 0.2876 1
0.0635 0.2962 1
0.0635 0.2962 1
0.0528 0.3068 1
0.0233 0.2768 1
0.0576 0.2831 1
0.0471 0.306 1
0.0488 0.3084 1
0.0193 0.2876 1
0.0397 0.2671 1
0.0686 0.3086 1
0.0638 0.2833 1
0.0246 0.2564 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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

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Gene identifier PF3D7_0817000 (Plasmodium falciparum), NEDD8-activating enzyme E1 catalytic subunit, putative
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