Product Description: ATP-dependent Clp protease proteolytic subunit
SignalP Peptide: MIYLFLFLFLILLKNKKIQT
# 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:0016787 | hydrolase activity |
| Function | GO:0008233 | peptidase activity |
| Function | GO:0005515 | protein binding |
| Function | GO:0004252 | serine-type endopeptidase activity |
| Process | GO:0009657 | plastid organization |
| Process | GO:0006515 | protein quality control for misfolded or incompletely synthesized proteins |
| 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 | not expressed | N/A | N/A |
| Ring | possibly expressed | 0.08 | 0.96 |
| Trophozoite | expressed | 0.87 | 0.55 |
| Schizont | expressed | 0.59 | 0.67 |
| Gametocyte | expressed | 0.70 | 0.62 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0307400
Resistome Missense Mutations: K17R
Resistome Compounds with Missense Mutations: BCH070
Resistome # Samples with Disruptive Mutations: 1 (1 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.12 | MFS: -3.078 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: O97252
"Best" AlphaFill ligand hit: SHV (heptanoic acid, Local RMSD=0.04) with 6PMD (Global RMSD=0.85)
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... | |
| P0A6G7 | ATP-dependent Clp protease proteolytic subunit | OrthoMCL | CHEMBL4444802CHEMBL4448860CHEMBL4551942CHEMBL4483092... |
Ortholog Group (OrthoMCL): OG6_100939
Most Similar Human Ortholog: M0R208
TM-align score: 0.85 | RMSD: 2.05
Seq Identity: 0.44 | Length: 170 / 370
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000125656 | caseinolytic mitochondrial matrix peptidase proteolytic subunit |
Protein Length: 370 | Molecular Weight (kDa): 43.321
UniProt ID(s): O97252
PDB ID(s): 2F6I
Isoelectric Point: 9.98
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 |
| InterPro | IPR033135 | ClpP, histidine active site |
| 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 | 22 | 16 | 31 |
| disruptive | 3 | 30 | 22 | 52 |
| missense | 2 | 28 | 21 | 45 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 3 | 52 | 23 | 29 |
| disruptive | 15 | 84 | 46 | 68 |
| missense | 8 | 68 | 39 | 52 |
PlasmoDB Total SNPs: 65
Non-coding: 48 | Synonymous: 8 | Nonsynonymous: 9 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 10448855 | The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. | Bowman S, Lawson D, ..., Barrell BG | 10.1038/22964 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 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 |
| 28917450 | A novel class of Plasmodial ClpP protease inhibitors as potential antimalarialagents. | Mundra S, Thakur V, ..., Kotra LP | 10.1016/j.bmc.2017.08.049 |
| 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/ |
| 38393536 | Comparative analysis of genes expression involved in type II toxin-antitoxinsystem in Staphylococcus aureus following persister cell formation | Karimaei S, Aghamir SMK, Pourmand MR | 10.1007/s11033-023-09179-6 |
| 38427982 | Interactome Analysis of ClpX Reveals Its Regulatory Role in Metabolism and Photosynthesis in Cyanobacteria | Liu X, Cai F, ..., Ge F | 10.1021/acs.jproteome.3c00610 |
| 38382970 | [Protein degradation in bacteria: focus on the ClpP protease] | Ishikawa F, Homma M, Tanabe G, Uchihashi T | 10.3412/jsb.79.1 |
| 38357296 | BacPROTACs targeting Clp protease: a promising strategy for anti-mycobacterial drug discovery | Bonjorno AF, Pavan AR, ..., Dos Santos JL | 10.3389/fchem.2024.1358539 |