Genome location: Pf3D7_14_v3:1,498,758..1,499,902(-)
Genome classification: Core
Product Description: ATP-dependent Clp protease proteolytic subunit
SignalP Peptide: MQGLLLFMLICINFCKC
# Transmembrane Domains: 0
EC Numbers: 3.4.21.92 (Endopeptidase Clp)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0009368 | endopeptidase Clp complex |
| Function | GO:0004176 | ATP-dependent peptidase activity |
| Function | GO:0051117 | ATPase binding |
| Function | GO:0004252 | serine-type endopeptidase activity |
| Process | GO:0006515 | protein quality control for misfolded or incompletely synthesized proteins |
| 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 | not expressed | N/A | N/A |
| Ring | not expressed | 0.05 | 0.97 |
| Trophozoite | expressed | 0.41 | 0.74 |
| Schizont | possibly expressed | 0.08 | 0.94 |
| Gametocyte | expressed | 0.29 | 0.83 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1436800
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: 0.173 | MFS: -2.556 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IL98
"Best" AlphaFill ligand hit: 5C2 (1-(propan-2-yl)-n-{[2-(thiophen-2-yl)-1,3-oxazol-4-yl]methyl}-1h-pyrazolo[3,4-b]pyridine-5-carboxamide, Local RMSD=0.07) with 5DL1 (Global RMSD=1.79)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.21.92 | Endopeptidase Clp | NEMNeohydrincyclomarinrufomycin ICAANDENYALAAkappa-caseinphosphoarginineCAANDENYALAA-NH2Xaa-Tyr-Leu-Tyr-TrpHigh salt concentrationsdiisopropylfluorophosphatediisopropyl fluorophosphate... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q16740 | ATP-dependent Clp protease proteolytic subunit, mitochondrial | OrthoDB | CHEMBL4472444CHEMBL4466041CHEMBL4459457CHEMBL4472444... |
Protein Length: 244 | Molecular Weight (kDa): 28.325
UniProt ID(s): Q8IL98
Isoelectric Point: 9.38
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001907 | ATP-dependent Clp protease proteolytic subunit |
| InterPro | IPR023562 | Clp protease proteolytic subunit /Translocation-enhancing protein TepA |
| InterPro | IPR029045 | ClpP/crotonase-like domain superfamily |
| PFam | PF00574 | Clp protease proteolytic subunit /Translocation-enhancing protein TepA |
| Superfamily | SSF52096 | ClpP/crotonase-like domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 1 | 11 | 5 | 22 |
| disruptive | 2 | 7 | 6 | 30 |
| missense | 2 | 6 | 4 | 25 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 23 | 10 | 16 |
| disruptive | 8 | 24 | 17 | 54 |
| missense | 3 | 19 | 13 | 40 |
PlasmoDB Total SNPs: 44
Non-coding: 37 | Synonymous: 6 | Nonsynonymous: 1 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 19789896 | Atypical caseinolytic protease homolog from Plasmodium falciparum possessesunusual substrate preference and a functional nuclear localization signal. | Lin W, Chan M, Sim TS | 10.1007/s00436-009-1612-9 |
| 20545854 | A cyanobacterial serine protease of Plasmodium falciparum is targeted to theapicoplast and plays an important role in its growth and development. | Rathore S, Sinha D, ..., Mohmmed A | 10.1111/j.1365-2958.2010.07251.x |
| 23192353 | Structural insights into the inactive subunit of the apicoplast-localizedcaseinolytic protease complex of Plasmodium falciparum. | El Bakkouri M, Rathore S, ..., Houry WA | 10.1074/jbc.M112.416560 |
| 23521916 | The prokaryotic ClpQ protease plays a key role in growth and development ofmitochondria in Plasmodium falciparum. | Jain S, Rathore S, ..., Mohmmed A | 10.1111/cmi.12142 |
| 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 |
| 32482878 | Plastid biogenesis in malaria parasites requires the interactions and catalyticactivity of the Clp proteolytic system. | Florentin A, Stephens DR, ..., Muralidharan V | https://pubmed.ncbi.nlm.nih.gov/32482878/ |