Product Description: subtilisin-like protease 1
SignalP Peptide: MMLNKKVVALCTLTLHLFCIFLCLGKEVRS
# Transmembrane Domains: 0
EC Numbers: 3.4.21.62 (Subtilisin)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0044311 | exoneme |
| Component | GO:0016020 | membrane |
| Component | GO:0020026 | merozoite dense granule |
| Component | GO:0020004 | symbiont-containing vacuolar space |
| Component | GO:0020003 | symbiont-containing vacuole |
| Function | GO:0004252 | serine-type endopeptidase activity |
| Function | GO:0008236 | serine-type peptidase activity |
| Process | GO:0035891 | exit from host cell |
| Process | GO:0006509 | membrane protein ectodomain proteolysis |
| Process | GO:0016485 | protein processing |
| 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 | expressed | N/A | N/A |
| Ring | possibly expressed | 0.14 | 0.93 |
| Trophozoite | possibly expressed | 0.05 | 0.97 |
| Schizont | expressed | 0.56 | 0.81 |
| Gametocyte | possibly expressed | 0.06 | 0.97 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0507500
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: 0.42 | MFS: -2.54 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1107100)
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_1107100)
Modification: Mutated | RMgm-4602
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I0V0
"Best" AlphaFill ligand hit: DFP (diisopropyl phosphonate, Local RMSD=0.13) with 1SUE (Global RMSD=7.44)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.21.62 | Subtilisin | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q7KAN4 | Subtilisin-like protease 1 | Plasmodium falciparum | OrthoMCL BLAST | CHEMBL3310712CHEMBL3310822CHEMBL3310709CHEMBL3326345... |
Protein Length: 688 | Molecular Weight (kDa): 77.647
PDB ID(s): None
Isoelectric Point: 5.92
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000209 | Peptidase S8/S53 domain |
| InterPro | IPR015500 | Peptidase S8, subtilisin-related |
| InterPro | IPR017314 | Peptidase S8A, subtilisin-like peptidase 1, plasmodium |
| InterPro | IPR022398 | Peptidase S8, subtilisin, His-active site |
| InterPro | IPR023827 | Peptidase S8, subtilisin, Asp-active site |
| InterPro | IPR023828 | Peptidase S8, subtilisin, Ser-active site |
| InterPro | IPR034204 | Subtilisin SUB1-like catalytic domain |
| InterPro | IPR036852 | Peptidase S8/S53 domain superfamily |
| InterPro | IPR041089 | SUB1 protease prodomain ProdP9 |
| PFam | PF00082 | Peptidase S8/S53 domain |
| PFam | PF18213 | SUB1 protease prodomain ProdP9 |
| Superfamily | SSF52743 | Peptidase S8/S53 domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 30 | 19 | 38 |
| disruptive | 26 | 58 | 28 | 78 |
| missense | 14 | 41 | 21 | 65 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 10 | 54 | 29 | 33 |
| disruptive | 45 | 110 | 42 | 117 |
| missense | 21 | 80 | 39 | 73 |
PlasmoDB Total SNPs: 125
Non-coding: 71 | Synonymous: 36 | Nonsynonymous: 18 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 9722575 | A subtilisin-like protein in secretory organelles of Plasmodium falciparummerozoites. | Blackman MJ, Fujioka H, ..., Hackett F | 10.1074/jbc.273.36.23398 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 12764150 | Functional characterization of the propeptide of Plasmodium falciparumsubtilisin-like protease-1. | Jean L, Hackett F, Martin SR, Blackman MJ | 10.1074/jbc.M303827200 |
| 18083098 | Subcellular discharge of a serine protease mediates release of invasive malariaparasites from host erythrocytes. | Yeoh S, O'Donnell RA, ..., Blackman MJ | 10.1016/j.cell.2007.10.049 |
| 19214190 | A multifunctional serine protease primes the malaria parasite for red blood cellinvasion. | Koussis K, Withers-Martinez C, ..., Blackman MJ | 10.1038/emboj.2009.22 |
| 21220481 | Global identification of multiple substrates for Plasmodium falciparum SUB1, anessential malarial processing protease. | Silmon de Monerri NC, Flynn HR, ..., Blackman MJ | 10.1128/IAI.00902-10 |
| 22984267 | Proteolytic activation of the essential parasitophorous vacuole cysteine proteaseSERA6 accompanies malaria parasite egress from its host erythrocyte. | Ruecker A, Shea M, ..., Blackman MJ | 10.1074/jbc.M112.400820 |
| 23414065 | Molecular determinants of binding to the Plasmodium subtilisin-like protease 1. | Fulle S, Withers-Martinez C, ..., Finn PW | 10.1021/ci300581z |
| 29459732 | A protease cascade regulates release of the human malaria parasite Plasmodiumfalciparum from host red blood cells. | Thomas JA, Tan MSY, ..., Blackman MJ | 10.1038/s41564-018-0111-0 |
| 33975947 | Peptidic boronic acids are potent cell-permeable inhibitors of the malariaparasite egress serine protease S UB1 | Lidumniece E, Withers-Martinez C, ..., Jirgensons A | 10.1073/pnas.2022696118 |
| 38386597 | Prodomain-driven enzyme dimerization: a pH-dependent autoinhibition mechanismthat controls Plasmodium Sub1 activity before merozoite egress | Martinez M, Bouillon A, ..., Barale J-C | 10.1128/mbio.00198-24 |