Product Description: ATP-dependent Clp protease regulatory subunit ClpC
SignalP Peptide: MNVLYIFIAVLILNGILN
# Transmembrane Domains: 1
EC Numbers: 3.4.21.92 (Endopeptidase Clp)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0009368 | endopeptidase Clp complex |
| Function | GO:0005524 | ATP binding |
| Function | GO:0016887 | ATP hydrolysis activity |
| Function | GO:0005515 | protein binding |
| Function | GO:0004252 | serine-type endopeptidase activity |
| Process | GO:0051301 | cell division |
| Process | GO:0034605 | cellular response to heat |
| Process | GO:0009657 | plastid organization |
| Process | GO:0006986 | response to unfolded protein |
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 | 0.13 | 0.94 |
| Trophozoite | expressed | 1.07 | 0.48 |
| Schizont | expressed | 0.75 | 0.63 |
| Gametocyte | expressed | 0.52 | 0.71 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1406600
Resistome Missense Mutations: D1089E
Resistome Compounds with Missense Mutations: MMV665794
Resistome # Samples with Disruptive Mutations: 3 (3 missense, 3 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.155 | MFS: -3.209 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1035600)
RMgmDB ABS Phenotype: Not tested (Pb ortholog: PBANKA_1035600)
Modification: Other | RMgm-436
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IM28
"Best" AlphaFill ligand hit: ANP (phosphoaminophosphonic acid-adenylate ester, Local RMSD=0.32) with 1QVR (Global RMSD=2.48)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.21.92 | Endopeptidase Clp | NEMNeohydrincyclomarinrufomycin ICAANDENYALAAkappa-caseinphosphoarginineCAANDENYALAA-NH2Xaa-Tyr-Leu-Tyr-TrpHigh salt concentrationsdiisopropylfluorophosphatediisopropyl fluorophosphate... |
No evidence of orthology to BindingDB entries
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 70 | 38 | 80 |
| disruptive | 54 | 144 | 92 | 210 |
| missense | 26 | 122 | 81 | 169 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 19 | 155 | 47 | 84 |
| disruptive | 86 | 347 | 159 | 328 |
| missense | 43 | 278 | 128 | 236 |
PlasmoDB Total SNPs: 226
Non-coding: 90 | Synonymous: 73 | Nonsynonymous: 63 | Stop Codon: 0
Protein Length: 1341 | Molecular Weight (kDa): 156.022
UniProt ID(s): Q8IM28
PDB ID(s): None
Isoelectric Point: 7.79
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001270 | ClpA/B family |
| InterPro | IPR003593 | AAA+ ATPase domain |
| InterPro | IPR003959 | ATPase, AAA-type, core |
| InterPro | IPR019489 | Clp ATPase, C-terminal |
| InterPro | IPR027417 | P-loop containing nucleoside triphosphate hydrolase |
| InterPro | IPR036628 | Clp, N-terminal domain superfamily |
| InterPro | IPR041546 | ClpA/ClpB, AAA lid domain |
| PFam | PF00004 | ATPase, AAA-type, core |
| PFam | PF07724 | ATPase, AAA-type, core |
| PFam | PF10431 | Clp ATPase, C-terminal |
| PFam | PF17871 | ClpA/ClpB, AAA lid domain |
| Superfamily | SSF52540 | P-loop containing nucleoside triphosphate hydrolase |
| Superfamily | SSF81923 | Clp, N-terminal domain superfamily |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 20887733 | The Clp chaperones and proteases of the human malaria parasite Plasmodiumfalciparum. | El Bakkouri M, Pow A, ..., Houry WA | 10.1016/j.jmb.2010.09.051 |
| 29141210 | PfClpC Is an Essential Clp Chaperone Required for Plastid Integrity and ClpProtease Stability in Plasmodium falciparum. | Florentin A, Cobb DW, ..., Muralidharan V | 10.1016/j.celrep.2017.10.081 |
| 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/ |
| 36461153 | Pneumococcal proteins ClpC and UvrC as novel host plasminogen binding factors | Hirayama S, Yasui Y, ..., Terao Y | 10.1111/1348-0421.13040 |
| 38357296 | BacPROTACs targeting Clp protease: a promising strategy for anti-mycobacterialdrug discovery | Bonjorno AF, Pavan AR, ..., Dos Santos JL | 10.3389/fchem.2024.1358539 |
| 35819494 | Isolation and molecular characterization of Polychromophilus spp. (Haemosporida:Plasmodiidae) from the Asian long-fingered bat (Miniopterus fuliginosus) andJapanese large-footed bat (Myotis macrodactylus) in Japan | Rosyadi I, Shimoda H, ..., Sato H | 10.1007/s00436-022-07592-7 |