Genome location: Pf3D7_12_v3:1,251,464..1,253,144(-)
Genome classification: Core
Product Description: ATP-dependent protease subunit ClpQ
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 3.4.25.2 (HslU--HslV peptidase);3.5.1.98 (Histone deacetylase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005739 | mitochondrion |
| Function | GO:0004176 | ATP-dependent peptidase activity |
| Function | GO:0003729 | mRNA binding |
| Function | GO:0008233 | peptidase activity |
| Function | GO:0005515 | protein binding |
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 | possibly expressed | 0.01 | 0.99 |
| Trophozoite | expressed | 0.07 | 0.95 |
| Schizont | expressed | 0.03 | 0.98 |
| Gametocyte | expressed | 0.04 | 0.98 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1230400
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: 0.431 | MFS: -2.873 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I5B6
"Best" AlphaFill ligand hit: FEB (n~2~-[(3r)-3-hydroxydodecanoyl]-l-asparaginyl-n~1~-[(1s)-1-(hydroxymethyl)-3-methylbutyl]-l-glutamamide, Local RMSD=0.06) with 3D29 (Global RMSD=4.22)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.25.2 | HslU-HslV peptidase | ATPADPNEMNLVSlactacystindithiothreitol3,4-dichloroisocoumarinacety-Leu-Leu-norleucinaldiisopropyl fluorophosphateN-acetyl-Leu-Leu-norleucinalphenylmethylsulfonyl fluoridebenzyloxycarbonyl-Leu-Leu-norvalinal... |
| 3.5.1.98 | histone deacetylase | EDTAPAOASAHAFOXPFK228MCP30shRNAsiRNAMS-275LAQ824MC1575MC1568... |
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 | 2 | 10 | 9 | 11 |
| disruptive | 0 | 3 | 0 | 9 |
| missense | 0 | 3 | 0 | 9 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 21 | 6 | 12 |
| disruptive | 0 | 13 | 6 | 30 |
| missense | 0 | 8 | 6 | 27 |
PlasmoDB Total SNPs: 97
Non-coding: 90 | Synonymous: 7 | Nonsynonymous: 0 | Stop Codon: 0
Protein Length: 207 | Molecular Weight (kDa): 22.871
UniProt ID(s): Q8I5B6
PDB ID(s): None
Isoelectric Point: 8.15
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001353 | Proteasome, subunit alpha/beta |
| InterPro | IPR022281 | ATP-dependent protease, HslV subunit |
| InterPro | IPR029055 | Nucleophile aminohydrolases, N-terminal |
| PFam | PF00227 | Proteasome, subunit alpha/beta |
| Superfamily | SSF56235 | Nucleophile aminohydrolases, N-terminal |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 17270290 | Characterization and localization of Plasmodium falciparum homolog of prokaryoticClpQ/HslV protease. | Ramasamy G, Gupta D, Mohmmed A, Chauhan VS | 10.1016/j.molbiopara.2007.01.002 |
| 20561525 | Mitochondrial localization of the threonine peptidase PfHslV, a ClpQ ortholog inPlasmodium falciparum. | Tschan S, Kreidenweiss A, ..., Mordmuller B | 10.1016/j.ijpara.2010.05.006 |
| 22113196 | Disruption of a mitochondrial protease machinery in Plasmodium falciparum is anintrinsic signal for parasite cell death. | Rathore S, Jain S, ..., Mohmmed A | 10.1038/cddis.2011.118 |
| 27381095 | The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum. | Bunnik EM, Batugedara G, ..., Le Roch KG | 10.1186/s13059-016-1014-0 |
| 34494883 | A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology. | van Esveld SL, Meerstein-Kessel L, ..., Huynen MA | 10.1128/mSphere.00614-21 |
| 27864322 | Escherichia coli Proteome Microarrays Identified the Substrates of ClpYQProtease | Tsai CH, Ho YH, ..., Chen CS | 10.1074/mcp.M116.065482 |
| 29629859 | The ClpY-ClpQ protease regulates multicellular development in Bacillus subtilis | Yu Y, Yan F, ..., Guo JH | 10.1099/mic.0.000658 |
| 30009761 | The proteasome as a target to combat malaria: hits and misses | Krishnan KM, Williamson KC | 10.1016/j.trsl.2018.04.007 |
| 23521916 | The prokaryotic ClpQ protease plays a key role in growth and development of mitochondria in Plasmodium falciparum | Jain S, Rathore S, ..., Mohmmed A | 10.1111/cmi.12142 |
| 24533266 | The proteasome of malaria parasites: A multi-stage drug target forchemotherapeutic intervention? | Aminake MN, Arndt HD, Pradel G | 10.1016/j.ijpddr.2011.12.001 |
| 34655017 | Protein degradation control and regulation of bacterial survival and pathogenicity: the role of protein degradation systems in bacteria | Dong S, Chen H, Zhou Q, Liao N | 10.1007/s11033-021-06744-9 |
| 21266546 | Unfolding and translocation pathway of substrate protein controlled by structurein repetitive allosteric cycles of the ClpY ATPase | Kravats A, Jayasinghe M, Stan G | 10.1073/pnas.1014278108 |
| 21803990 | Stepwise activity of ClpY (HslU) mutants in the processive degradation ofEscherichia coli ClpYQ (HslUV) protease substrates | Hsieh FC, Chen CT, ..., Wu WF | 10.1128/JB.05128-11 |