Detailed view for PF3D7_1457500

Basic information

TDR Targets ID: 2878
Plasmodium falciparum, vacuolar protein sorting-associated protein 4
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 8.2776 | Length (AA): 419 | MW (Da): 48259 | Paralog Number: 0

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

Druggability Group : DG3

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

PF00004   ATPase family associated with various cellular activities (AAA)
PF04212   MIT (microtubule interacting and transport) domain
PF09336   Vps4 C terminal oligomerisation domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0017111   nucleoside-triphosphatase activity  
GO:0016887   ATPase activity  
GO:0005524   ATP binding  
GO:0000166   nucleotide binding  
GO:0006886   intracellular protein transport  

Metabolic Pathways

Endocytosis (KEGG)

Structural information

Modbase 3D models:

There are 8 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
2 394 1e32 (A) 107 458 28.00 0 1 1.07 0.2
3 77 1yxr (A) 2 77 37.00 0.00000019 1 0.87 -2.42
104 418 1xwi (A) 124 444 48.00 0 1 1.31 -0.75
1 79 2v6x (A) 1 79 32.00 0.000068 1 0.802944 -2.01
6 77 1yxr (A) 5 77 40.00 0.000011 1 0.827238 -1.72
54 412 3cf3 (A) 417 760 25.00 0.000000057 1 1.0227 0.57
104 418 3eih (A) 123 436 49.00 0 1 1.39419 -0.79
104 418 1xwi (A) 124 444 50.00 0 1 1.37719 -0.62

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

Orthologs

Ortholog group members (OG5_127508)

Species Accession Gene Product
Arabidopsis thaliana AT2G27600   suppressor of K+ transport growth defect 1 protein
Babesia bovis BBOV_II000190   ATPase, AAA family
Brugia malayi Bm1_48695   vps4b-prov protein
Candida albicans CaO19.11814   likely AAA ATPase similar to S. cerevisiae VPS4 (YPR173C) AAA ATPase involved in vacuolar sorting
Candida albicans CaO19.4339   likely AAA ATPase similar to S. cerevisiae VPS4 (YPR173C) AAA ATPase involved in vacuolar sorting
Caenorhabditis elegans CELE_Y34D9A.10   Protein VPS-4
Cryptosporidium hominis Chro.10381   AAA-family ATPase
Cryptosporidium parvum cgd1_3390   katanin p60/fidgetin family AAA ATpase
Dictyostelium discoideum DDB_G0284347   AAA ATPase domain-containing protein
Drosophila melanogaster Dmel_CG6842   Vacuolar protein sorting 4
Echinococcus granulosus EgrG_000486200   vacuolar protein sorting associated protein 4A
Entamoeba histolytica EHI_118900   vacuolar sorting protein-associating protein 4A (VPS4), putative
Echinococcus multilocularis EmuJ_000486200   vacuolar protein sorting associated protein 4A
Giardia lamblia GL50803_101906   SKD1 protein
Giardia lamblia GL50803_16795   Topoisomerase II
Homo sapiens 27183   vacuolar protein sorting 4 homolog A (S. cerevisiae)
Homo sapiens ENSG00000119541   vacuolar protein sorting 4 homolog B (S. cerevisiae)
Leishmania braziliensis LbrM.29.2470   vacuolar protein sorting-associated protein 4
Leishmania donovani LdBPK_292610.1   vacuolar protein sorting-associated protein 4
Leishmania infantum LinJ.29.2610   vacuolar protein sorting-associated protein 4
Leishmania major LmjF.29.2500   vacuolar protein sorting-associated protein 4
Leishmania mexicana LmxM.08_29.2500   vacuolar protein sorting-associated protein 4
Loa Loa (eye worm) LOAG_10512   hypothetical protein
Loa Loa (eye worm) LOAG_15599   vps4b-prov protein
Loa Loa (eye worm) LOAG_13423   vps4b-prov protein
Mus musculus 20479   vacuolar protein sorting 4b (yeast)
Mus musculus ENSMUSG00000031913   vacuolar protein sorting 4a (yeast)
Neospora caninum NCLIV_058350   vacuolar sorting ATPase Vps4, putative
Oryza sativa 4328374   Os02g0159900
Oryza sativa 4325480   Os01g0141100
Plasmodium berghei PBANKA_1321200   vacuolar protein sorting-associated protein 4, putative
Plasmodium falciparum PF3D7_1457500   vacuolar protein sorting-associated protein 4
Plasmodium knowlesi PKNH_1224300   vacuolar protein sorting-associated protein 4, putative
Plasmodium yoelii PY00672   suppressor protein of bem1/bed5 double mutants
Saccharomyces cerevisiae YPR173C   AAA family ATPase VPS4
Schistosoma japonicum Sjp_0218650   Vacuolar protein sorting-associating protein 4A, putative
Schistosoma mansoni Smp_025510   skd/vacuolar sorting
Schmidtea mediterranea mk4.000019.07  
Schmidtea mediterranea mk4.000449.12   Putative skd/vacuolar sorting
Schmidtea mediterranea mk4.000159.10  
Trypanosoma brucei gambiense Tbg972.3.3440   katanin, putative,serine peptidase, Clan SJ, family S16, putative
Trypanosoma brucei Tb927.3.3280   vacuolar protein sorting-associated protein 4, putative
Trypanosoma congolense TcIL3000_0_42410   vacuolar protein sorting-associated protein 4, putative
Trypanosoma cruzi TcCLB.506699.40   katanin-like protein, putative
Trypanosoma cruzi TcCLB.508153.330   vacuolar protein sorting-associated protein 4, putative
Trypanosoma cruzi TcCLB.510323.4   katanin, putative
Theileria parva TP03_0351   vacuolar sorting protein 4, putative
Trichomonas vaginalis TVAG_021390   AAA ATPase, putative
Trichomonas vaginalis TVAG_185830   skd/vacuolar sorting, putative
Trichomonas vaginalis TVAG_443370   skd/vacuolar sorting, putative

Essentiality

PF3D7_1457500 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.3.3280 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.3.3280 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.3.3280 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.3.3280 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_Y34D9A.10 Caenorhabditis elegans embryonic lethal wormbase
CELE_Y34D9A.10 Caenorhabditis elegans larval arrest wormbase
CELE_Y34D9A.10 Caenorhabditis elegans larval lethal wormbase
CELE_Y34D9A.10 Caenorhabditis elegans slow growth wormbase
CELE_Y34D9A.10 Caenorhabditis elegans sterile wormbase
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • 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
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930

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): 0.2

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

No literature references available for this target.

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Gene identifier PF3D7_1457500 (Plasmodium falciparum), vacuolar protein sorting-associated protein 4
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