Genome location: Pf3D7_13_v3:2,434,692..2,439,303(+)
Genome classification: Core
Product Description: falcilysin
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 3.4.24.- (Metalloendopeptidases.);3.4.24.55 (Pitrilysin)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0020020 | food vacuole |
| Function | GO:0004222 | metalloendopeptidase activity |
| Process | GO:0042540 | hemoglobin catabolic process |
| Process | GO:0016485 | protein processing |
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 | 1.00 | 0.55 |
| Trophozoite | expressed | 1.76 | 0.24 |
| Schizont | expressed | 0.87 | 0.56 |
| Gametocyte | expressed | 0.89 | 0.55 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1360800
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: 0.177 | MFS: -3.277 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1137000)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q76NL8
"Best" AlphaFill ligand hit: CLQ (n4-(7-chloro-quinolin-4-yl)-n1,n1-diethyl-pentane-1,4-diamine, Local RMSD=0.92) with 7DI7 (Global RMSD=1.39)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q76NL8 | Falcilysin | HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL4225532CHEMBL4227329CHEMBL4226440CHEMBL4227286... | |
| Q5JRX3 | Presequence protease, mitochondrial | Homo sapiens | OMA, OrthoDB | Ketopyrrolidine derivativeCHEMBL3233842US11504364, Compound 2CHEMBL3233842... |
| Q8K411 | Presequence protease, mitochondrial | OMA, OrthoDB | Ketopyrrolidine derivativeCHEMBL3233842 |
Ortholog Group (OrthoMCL): OG6_101809
Most Similar Human Ortholog: A0A7I2V3X0
TM-align score: 0.91 | RMSD: 2.64
Seq Identity: 0.23 | Length: 752 / 1193
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000107959 | pitrilysin metallopeptidase 1 |
Protein Length: 1193 | Molecular Weight (kDa): 138.863
PDB ID(s): 3S5H, 3S5I, 3S5K, 3S5M, 8HO4, 8HO5
Isoelectric Point: 6.98
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR007863 | Peptidase M16, C-terminal |
| InterPro | IPR011249 | Metalloenzyme, LuxS/M16 peptidase-like |
| InterPro | IPR011765 | Peptidase M16, N-terminal |
| InterPro | IPR013578 | Peptidase M16C associated |
| PFam | PF00675 | Peptidase M16, N-terminal |
| PFam | PF05193 | Peptidase M16, C-terminal |
| PFam | PF08367 | Peptidase M16C associated |
| Superfamily | SSF63411 | Metalloenzyme, LuxS/M16 peptidase-like |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 71 | 46 | 91 |
| disruptive | 16 | 85 | 46 | 181 |
| missense | 12 | 79 | 46 | 174 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 17 | 141 | 62 | 88 |
| disruptive | 26 | 182 | 93 | 255 |
| missense | 20 | 161 | 87 | 215 |
PlasmoDB Total SNPs: 162
Non-coding: 85 | Synonymous: 47 | Nonsynonymous: 30 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 10542284 | Identification and characterization of falcilysin, a metallopeptidase involved inhemoglobin catabolism within the malaria parasite Plasmodium falciparum. | Eggleson KK, Duffin KL, Goldberg DE | 10.1074/jbc.274.45.32411 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 17074076 | A role for falcilysin in transit peptide degradation in the Plasmodium falciparumapicoplast. | Ponpuak M, Klemba M, ..., Goldberg DE | 10.1111/j.1365-2958.2006.05443.x |
| 28351685 | Transcript and protein expression analysis of proteases in the blood stages ofPlasmodium falciparum. | Weissbach T, Golzmann A, ..., Julius Ngwa C | 10.1016/j.exppara.2017.03.006 |
| 30212465 | Integrative proteomics and bioinformatic prediction enable a high-confidenceapicoplast proteome in malaria parasites. | Boucher MJ, Ghosh S, ..., Yeh E | 10.1371/journal.pbio.2005895 |