Genome location: Pf3D7_11_v3:1,455,197..1,460,871(+)
Genome classification: Core
Product Description: subtilisin-like protease 2
SignalP Peptide: MLNIIYVVSLILIKFIFY
# Transmembrane Domains: 1
EC Numbers: 3.4.21.62 (Subtilisin)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0016021 | integral component of membrane |
| Component | GO:0016020 | membrane |
| Component | GO:0020026 | merozoite dense granule |
| Component | GO:0020009 | microneme |
| Component | GO:0033163 | microneme membrane |
| Component | GO:0044310 | osmiophilic body |
| Component | GO:0005886 | plasma membrane |
| Function | GO:0004252 | serine-type endopeptidase activity |
| Function | GO:0008236 | serine-type peptidase activity |
| Process | GO:0044409 | entry into host |
| Process | GO:0006509 | membrane protein ectodomain proteolysis |
| Process | GO:0051604 | protein maturation |
| Process | GO:0016485 | protein processing |
| Process | GO:0006508 | proteolysis |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | possibly expressed | N/A | N/A |
| Ring | possibly expressed | 0.38 | 0.84 |
| Trophozoite | not expressed | 0.11 | 0.94 |
| Schizont | expressed | 0.47 | 0.85 |
| Gametocyte | possibly expressed | 0.50 | 0.72 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1136900
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: 0.139 | MFS: -2.957 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0911700)
RMgmDB ABS Phenotype: Not tested (Pb ortholog: PBANKA_0911700)
Modification: Tagged | RMgm-1487
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IHZ5
"Best" AlphaFill ligand hit: NHE (2-[n-cyclohexylamino]ethane sulfonic acid, Local RMSD=0.10) with 6QF1 (Global RMSD=5.39)
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... |
Ortholog Group (OrthoMCL): OG6_100121
Most Similar Human Ortholog: A0A669KBG0
TM-align score: 0.47 | RMSD: 3.87
Seq Identity: 0.20 | Length: 303 / 1341
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000169174 | proprotein convertase subtilisin/kexin type 9 |
Protein Length: 1341 | Molecular Weight (kDa): 154.8
PDB ID(s): None
Isoelectric Point: 8.54
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000209 | Peptidase S8/S53 domain |
| InterPro | IPR015500 | Peptidase S8, subtilisin-related |
| InterPro | IPR022398 | Peptidase S8, subtilisin, His-active site |
| InterPro | IPR023828 | Peptidase S8, subtilisin, Ser-active site |
| InterPro | IPR036852 | Peptidase S8/S53 domain superfamily |
| InterPro | IPR040935 | Prodomain subtilisin 2 |
| PFam | PF00082 | Peptidase S8/S53 domain |
| PFam | PF18513 | Prodomain subtilisin 2 |
| 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 | 11 | 77 | 52 | 115 |
| disruptive | 45 | 165 | 90 | 229 |
| missense | 28 | 131 | 75 | 187 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 21 | 160 | 73 | 119 |
| disruptive | 93 | 344 | 174 | 362 |
| missense | 46 | 285 | 134 | 228 |
PlasmoDB Total SNPs: 214
Non-coding: 86 | Synonymous: 71 | Nonsynonymous: 57 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 10339607 | Plasmodium falciparum subtilisin-like protease 2, a merozoite candidate for themerozoite surface protein 1-42 maturase. | Barale JC, Blisnick T, ..., Langsley G | 10.1073/pnas.96.11.6445 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 16322767 | Molecular identification of a malaria merozoite surface sheddase. | Harris PK, Yeoh S, ..., Blackman MJ | 10.1371/journal.ppat.0010029 |
| 16879884 | Plasmodium thrombospondin related apical merozoite protein (PTRAMP) is shed fromthe surface of merozoites by PfSUB2 upon invasion of erythrocytes. | Green JL, Hinds L, ..., Holder AA | 10.1016/j.molbiopara.2006.06.010 |
| 21234230 | Transcriptional activity of Plasmodium subtilisin-like protease 2 (Pf-Sub2)5'untranslated regions and its interaction with hepatocyte growth factor. | Liao S, Liu Y, ..., Park H | 10.3347/kjp.2010.48.4.291 |
| 23834729 | Molecular determinants for subcellular trafficking of the malarial sheddasePfSUB2. | Child MA, Harris PK, ..., Blackman MJ | 10.1111/tra.12092 |
| 27432909 | Comparative Proteomics and Functional Analysis Reveal a Role of Plasmodiumfalciparum Osmiophilic Bodies in Malaria Parasite Transmission. | Suarez-Cortes P, Sharma V, ..., Alano P | 10.1074/mcp.M116.060681 |
| 33287958 | The malaria parasite sheddase S UB2 governs host red blood cell membrane sealingat invasion | Collins CR, Hackett F, ..., Blackman MJ | 10.7554/eLife.61121 |