Genome location: Pf3D7_12_v3:1,654,438..1,658,821(+)
Genome classification: Core
Product Description: ATP-dependent zinc metalloprotease FTSH 1
SignalP Peptide: N/A
# Transmembrane Domains: 1
EC Numbers: 3.4.24.- (Metalloendopeptidases.)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005739 | mitochondrion |
| Function | GO:0005524 | ATP binding |
| Function | GO:0004176 | ATP-dependent peptidase activity |
| Function | GO:0004222 | metalloendopeptidase activity |
| Process | GO:0009657 | plastid organization |
| 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 | possibly expressed | N/A | N/A |
| Ring | not expressed | 0.13 | 0.93 |
| Trophozoite | expressed | 0.98 | 0.50 |
| Schizont | expressed | 0.30 | 0.83 |
| Gametocyte | not expressed | 0.32 | 0.82 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1239700
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: -1.017 | #Insertions: 1
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0928500)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I526
"Best" AlphaFill ligand hit: ADP (adenosine-5'-diphosphate, Local RMSD=0.04) with 4KOD (Global RMSD=4.42)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.24.- | Ex: meprin A | GSHSDSATPADPNEMDTTPTXTNFEDTAEGTAPMSFPCMB... |
No evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_100384
Most Similar Human Ortholog: Q9Y4W6
TM-align score: 0.59 | RMSD: 4.24
Seq Identity: 0.37 | Length: 521 / 880
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000141385 | AFG3 like matrix AAA peptidase subunit 2 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 52 | 34 | 62 |
| disruptive | 17 | 62 | 26 | 96 |
| missense | 13 | 57 | 24 | 83 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 13 | 109 | 34 | 48 |
| disruptive | 31 | 148 | 62 | 182 |
| missense | 26 | 118 | 48 | 118 |
PlasmoDB Total SNPs: 145
Non-coding: 93 | Synonymous: 24 | Nonsynonymous: 25 | Stop Codon: 3
Protein Length: 880 | Molecular Weight (kDa): 100.958
UniProt ID(s): Q8I526
PDB ID(s): None
Isoelectric Point: 9.14
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000642 | Peptidase M41 |
| InterPro | IPR003593 | AAA+ ATPase domain |
| InterPro | IPR003959 | ATPase, AAA-type, core |
| InterPro | IPR003960 | ATPase, AAA-type, conserved site |
| InterPro | IPR005936 | Peptidase, FtsH |
| InterPro | IPR027417 | P-loop containing nucleoside triphosphate hydrolase |
| InterPro | IPR037219 | Peptidase M41-like |
| InterPro | IPR041569 | AAA ATPase, AAA+ lid domain |
| PFam | PF00004 | ATPase, AAA-type, core |
| PFam | PF01434 | Peptidase M41 |
| PFam | PF17862 | AAA ATPase, AAA+ lid domain |
| Superfamily | SSF140990 | Peptidase M41-like |
| Superfamily | SSF52540 | P-loop containing nucleoside triphosphate hydrolase |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 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 |
| 24058559 | An FtsH protease is recruited to the mitochondrion of Plasmodium falciparum. | Tanveer A, Allen SM, ..., Habib S | 10.1371/journal.pone.0074408 |
| 28826494 | Small molecule inhibition of apicomplexan Fts H1 disrupts plastid biogenesis inhuman pathogens | Amberg-Johnson K, Hari SB, ..., Yeh E | 10.7554/eLife.29865 |
| 32678064 | A single point mutation in the Plasmodium falciparum Fts H1 metalloproteaseconfers actinonin resistance | Goodman CD, Uddin T, Spillman NJ, McFadden GI | 10.7554/eLife.58629 |