Product Description: plasmepsin III
SignalP Peptide: N/A
# Transmembrane Domains: 1
EC Numbers: 3.4.23.- (Aspartic endopeptidases.)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020020 | food vacuole |
| Function | GO:0004190 | aspartic-type endopeptidase activity |
| 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 | expressed | N/A | N/A |
| Ring | expressed | 0.60 | 0.72 |
| Trophozoite | expressed | 0.95 | 0.50 |
| Schizont | expressed | 0.13 | 0.92 |
| Gametocyte | expressed | 0.46 | 0.74 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1408100
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 1 | MFS: -0.66 | #Insertions: 4
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1034400)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q9Y006
"Best" AlphaFill ligand hit: CPS (chaps, Local RMSD=0.15) with 7VE0 (Global RMSD=5.38)
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 |
|---|---|---|---|---|
| Q8IM16 | Plasmepsin IV [1-448] | HOGENOM, OrthoDB, OrthoMCL, OrthoMCL BLAST | phenyl-substituted sulfonamides, 6dphenyl-substituted sulfonamides, 6eCHEMBL588662US9353089, 117... | |
| O60989 | Plasmepsin IV, putative | Plasmodium vivax | HOGENOM, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL575115CHEMBL584189CHEMBL575150CHEMBL584190... |
| P14091 | Cathepsin E | OrthoDB | US9242943, 36CHEMBL588662US9353089, 117US9353089, 176... | |
| P00797 | Renin | Homo sapiens | OrthoDB | 2-aminoquinazoline, 3aCGP 38560Renin nonpeptide inhibitor, 2Renin nonpeptide inhibitor, 3... |
| P06281 | Renin-1 | Mus musculus | OrthoDB | CHEMBL318242CHEMBL321937CHEMBL97865CHEMBL98582... |
| Q6DLW5 | Renin | Macaca mulatta | OrthoDB | CHEMBL1276271Aliskiren HemifumarateIMARIKIREN |
| P07339 | Cathepsin D | Homo sapiens | OrthoDB | Statine-like inhibitor AStatine-like inhibitor 14Statine-like inhibitor 15Statine-like inhibitor 16... |
| P08424 | Renin | Rattus norvegicus | OrthoDB | CHEMBL357253CHEMBL414795CHEMBL265833CHEMBL412950... |
| P0DJD9 | Pepsin A-5 | Homo sapiens | OrthoDB | CHEMBL326831CHEMBL432424Boc-Phe-His-Leu-CF3-Ile-AmpBoc-Phe-His-Leu-CF3-Ile-Amp... |
| P20142 | Gastricsin | Homo sapiens | OrthoDB | CHEMBL313773CHEMBL418948CHEMBL287423CHEMBL62380... |
| P04073 | Gastricsin | Rattus norvegicus | OrthoDB | CHEMBL28888CHEMBL424222CHEMBL28738 |
| P07267 | Saccharopepsin | Saccharomyces cerevisiae | OrthoMCL | CHEMBL311322CHEMBL83697 |
| P46925 | Plasmepsin II | Plasmodium falciparum | OrthoMCL, OrthoMCL BLAST | Statine-like inhibitor AStatine-like inhibitor 14Statine-like inhibitor 15Statine-like inhibitor 16... |
| P39898 | Plasmepsin I | Plasmodium falciparum | OrthoMCL, OrthoMCL BLAST | Statine-like inhibitor AStatine-like inhibitor 14Statine-like inhibitor 15Statine-like inhibitor 16... |
| Q9Y006 | Plasmepsin III | Plasmodium falciparum | OrthoMCL, OrthoMCL BLAST | KNI-10006 |
Ortholog Group (OrthoMCL): OG6_100536
Most Similar Human Ortholog: P14091
TM-align score: 0.78 | RMSD: 3.14
Seq Identity: 0.24 | Length: 351 / 451
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000117984 | cathepsin D |
| ENSG00000131400 | napsin A aspartic peptidase |
| ENSG00000196188 | cathepsin E |
| ENSG00000250644 | novel protein |
Protein Length: 451 | Molecular Weight (kDa): 51.693
Isoelectric Point: 8.08
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001461 | Aspartic peptidase A1 family |
| InterPro | IPR021109 | Aspartic peptidase domain superfamily |
| InterPro | IPR033121 | Peptidase family A1 domain |
| InterPro | IPR034164 | Pepsin-like domain |
| PFam | PF00026 | Peptidase family A1 domain |
| Superfamily | SSF50630 | Aspartic peptidase domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 2 | 26 | 23 | 41 |
| disruptive | 3 | 35 | 20 | 77 |
| missense | 3 | 35 | 18 | 66 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 11 | 62 | 24 | 29 |
| disruptive | 6 | 89 | 58 | 137 |
| missense | 5 | 81 | 49 | 86 |
PlasmoDB Total SNPs: 105
Non-coding: 84 | Synonymous: 14 | Nonsynonymous: 7 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 11782538 | Four plasmepsins are active in the Plasmodium falciparum food vacuole, includinga protease with an active-site histidine. | Banerjee R, Liu J, ..., Goldberg DE | 10.1073/pnas.022630099 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 16624575 | Recombinant expression and partial characterization of an active solublehisto-aspartic protease from Plasmodium falciparum. | Xiao H, Sinkovits AF, ..., Yada RY | 10.1016/j.pep.2006.02.022 |
| 20435072 | Characterization of the monomer-dimer equilibrium of recombinant histo-asparticprotease from Plasmodium falciparum. | Xiao H, Briere LA, Dunn SD, Yada RY | 10.1016/j.molbiopara.2010.04.008 |
| 21136929 | Food vacuole proteome of the malarial parasite Plasmodium falciparum. | Lamarque M, Tastet C, ..., Dubremetz JF | 10.1002/prca.200700112 |
| 21928835 | Structural insights into the activation and inhibition of histo-aspartic proteasefrom Plasmodium falciparum. | Bhaumik P, Xiao H, ..., Wlodawer A | 10.1021/bi201118z |
| 27818095 | Genetic markers associated with dihydroartemisinin-piperaquine failure inPlasmodium falciparum malaria in Cambodia: a genotype-phenotype associationstudy. | Amato R, Lim P, ..., Fairhurst RM | 10.1016/S1473-3099(16)30409-1 |
| 29720620 | Plasmepsin II-III copy number accounts for bimodal piperaquine resistance amongCambodian Plasmodium falciparum. | Bopp S, Magistrado P, ..., Volkman SK | 10.1038/s41467-018-04104-z |
| 16242183 | Structural and active site analysis of plasmepsins of Plasmodium falciparum:potential anti-malarial targets | Bhargavi R, Sastry GM, Murty US, Sastry GN | 10.1016/j.ijbiomac.2005.08.006 |