Product Description: plasmepsin V
SignalP Peptide: N/A
# Transmembrane Domains: 2
EC Numbers: 3.4.23.- (Aspartic endopeptidases.)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005783 | endoplasmic reticulum |
| Component | GO:0016021 | integral component of membrane |
| Component | GO:0016020 | membrane |
| Component | GO:0097038 | perinuclear endoplasmic reticulum |
| Function | GO:0004190 | aspartic-type endopeptidase activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0006508 | proteolysis |
| Process | GO:0009410 | response to xenobiotic stimulus |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | not expressed | N/A | N/A |
| Ring | expressed | 0.13 | 0.93 |
| Trophozoite | expressed | 0.22 | 0.85 |
| Schizont | expressed | 0.16 | 0.89 |
| Gametocyte | not expressed | 0.18 | 0.89 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1323500
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.136 | MFS: -2.863 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1338700)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I6Z5
"Best" AlphaFill ligand hit: CPS (chaps, Local RMSD=0.08) with 7VE0 (Global RMSD=6.94)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.23.- | Ex: renin | I2YYKCNSDSIAANBSDANEDTAPI-3DMSOPCMBTLCK... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q8I6Z5 | Plasmepsin V | HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL3344151CHEMBL3344152CHEMBL3344153CHEMBL3344154... | |
| A0A0H4FQ60 | Plasmepsin V | OrthoMCL BLAST | CHEMBL3344272 |
Protein Length: 590 | Molecular Weight (kDa): 68.48
UniProt ID(s): Q17SA7, Q17SA8, Q17SA9, Q8I6Z5
PDB ID(s): None
Isoelectric Point: 7.58
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001461 | Aspartic peptidase A1 family |
| InterPro | IPR001969 | Aspartic peptidase, active site |
| InterPro | IPR021109 | Aspartic peptidase domain superfamily |
| InterPro | IPR032861 | Xylanase inhibitor, N-terminal |
| InterPro | IPR033121 | Peptidase family A1 domain |
| InterPro | IPR033866 | Plasmepsin 5 |
| PFam | PF00026 | Peptidase family A1 domain |
| PFam | PF14543 | Xylanase inhibitor, N-terminal |
| Superfamily | SSF50630 | Aspartic peptidase domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 42 | 14 | 27 |
| disruptive | 14 | 63 | 28 | 70 |
| missense | 12 | 52 | 24 | 49 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 13 | 64 | 20 | 34 |
| disruptive | 27 | 124 | 56 | 126 |
| missense | 20 | 86 | 37 | 79 |
PlasmoDB Total SNPs: 262
Non-coding: 186 | Synonymous: 42 | Nonsynonymous: 34 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 15899698 | P. falciparum pro-histoaspartic protease (proHAP) protein peptides bindspecifically to erythrocytes and inhibit the invasion process in vitro. | Valbuena J, Vera R, ..., Patarroyo ME | 10.1515/BC.2005.043 |
| 16024107 | Characterization of plasmepsin V, a membrane-bound aspartic protease homolog inthe endoplasmic reticulum of Plasmodium falciparum. | Klemba M, Goldberg DE | https://pubmed.ncbi.nlm.nih.gov/16024107/ |
| 23387285 | Role of plasmepsin V in export of diverse protein families from the Plasmodiumfalciparum exportome. | Boddey JA, Carvalho TG, ..., Cowman AF | 10.1111/tra.12053 |
| 24983235 | Inhibition of Plasmepsin V activity demonstrates its essential role in proteinexport, PfEMP1 display, and survival of malaria parasites. | Sleebs BE, Lopaticki S, ..., Boddey JA | 10.1371/journal.pbio.1001897 |
| 25849462 | Experimental determination of the membrane topology of the Plasmodium proteasePlasmepsin V. | Tarr SJ, Osborne AR | 10.1371/journal.pone.0121786 |
| 26146842 | Flap flexibility amongst plasmepsins I, II, III, IV, and V: Sequence, structural,and molecular dynamics analyses. | McGillewie L, Soliman ME | 10.1002/prot.24855 |
| 26214367 | Structural basis for plasmepsin V inhibition that blocks export of malariaproteins to human erythrocytes. | Hodder AN, Sleebs BE, ..., Cowman AF | 10.1038/nsmb.3061 |
| 27531685 | Understanding the structural basis of substrate recognition by Plasmodiumfalciparum plasmepsin V to aid in the design of potent inhibitors. | Bedi RK, Patel C, ..., Bhaumik P | 10.1038/srep31420 |
| 30127496 | Plasmepsin V cleaves malaria effector proteins in a distinct endoplasmicreticulum translocation interactome for export to the erythrocyte. | Marapana DS, Dagley LF, ..., Cowman AF | 10.1038/s41564-018-0219-2 |
| 30320974 | Targeting the Plasmodium falciparum plasmepsin V by ligand-based virtualscreening. | Meissner KA, Kronenberger T, ..., Wrenger C | 10.1111/cbdd.13416 |
| 31108131 | Yield improvement and enzymatic dissection of Plasmodium falciparum plasmepsin V. | Loymunkong C, Sittikul P, ..., Boonyalai N | 10.1016/j.molbiopara.2019.111188 |
| 31851913 | Inhibition of Plasmepsin V Activity Blocks Plasmodium falciparumGametocytogenesis and Transmission to Mosquitoes. | Jennison C, Lucantoni L, ..., Boddey JA | 10.1016/j.celrep.2019.11.073 |
| 38334391 | PEXEL is a proteolytic maturation site for both exported and non-exported Plasmodium proteins | Fierro MA, Muheljic A, ..., Beck JR | 10.1128/msphere.00393-23 |