Product Description: plastid replication-repair enzyme
SignalP Peptide: MLLYKFYFLYFLLVHLSLC
# Transmembrane Domains: 0
EC Numbers: 2.7.7.7 (DNA-directed DNA polymerase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Function | GO:0008408 | 3'-5' exonuclease activity |
| Function | GO:0003678 | DNA helicase activity |
| Function | GO:0003896 | DNA primase activity |
| Function | GO:0003887 | DNA-directed DNA polymerase activity |
| Function | GO:0005515 | protein binding |
| Function | GO:0003697 | single-stranded DNA binding |
| Process | GO:0045004 | DNA replication proofreading |
| Process | GO:0034599 | cellular response to oxidative stress |
| Process | GO:0033259 | plastid DNA replication |
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 | 0.11 | 0.95 |
| Trophozoite | expressed | 0.81 | 0.57 |
| Schizont | expressed | 0.14 | 0.92 |
| Gametocyte | not expressed | 0.45 | 0.75 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1411400
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: 0.121 | MFS: -2.938 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1031100)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8ILY1
"Best" AlphaFill ligand hit: POP (pyrophosphate 2-, Local RMSD=0.38) with 4DSK (Global RMSD=4.13)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.7.7.7 | DNA-directed DNA polymerase | KClEDTANH4+dATPNH4ClddTTPMK886UracilalliinsucroseethanolAllicin... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P19821 | DNA polymerase I, thermostable | Thermus aquaticus | OrthoMCL BLAST | CHEMBL274335CHEMBL276202CHEMBL274096CHEMBL350251... |
Ortholog Group (OrthoMCL): OG6_103182
Most Similar Human Ortholog: A0A2R8Y746
TM-align score: 0.87 | RMSD: 1.87
Seq Identity: 0.46 | Length: 125 / 2016
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000107815 | twinkle mtDNA helicase |
Protein Length: 2016 | Molecular Weight (kDa): 235.818
UniProt ID(s): Q8ILY1
PDB ID(s): 5DKT, 5DKU, 7SXL, 7SXQ
Isoelectric Point: 9.28
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001098 | DNA-directed DNA polymerase, family A, palm domain |
| InterPro | IPR002298 | DNA polymerase A |
| InterPro | IPR002562 | 3'-5' exonuclease domain |
| InterPro | IPR012337 | Ribonuclease H-like superfamily |
| InterPro | IPR027417 | P-loop containing nucleoside triphosphate hydrolase |
| InterPro | IPR034154 | Archaeal primase DnaG/twinkle, TOPRIM domain |
| InterPro | IPR043502 | DNA/RNA polymerase superfamily |
| PFam | PF00476 | DNA-directed DNA polymerase, family A, palm domain |
| PFam | PF01612 | 3'-5' exonuclease domain |
| PFam | PF13481 | |
| Superfamily | SSF52540 | P-loop containing nucleoside triphosphate hydrolase |
| Superfamily | SSF53098 | Ribonuclease H-like superfamily |
| Superfamily | SSF56672 | DNA/RNA polymerase superfamily |
| Superfamily | SSF56731 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 25 | 111 | 59 | 147 |
| disruptive | 60 | 211 | 135 | 351 |
| missense | 38 | 179 | 123 | 294 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 46 | 220 | 92 | 152 |
| disruptive | 103 | 525 | 230 | 549 |
| missense | 62 | 417 | 196 | 410 |
PlasmoDB Total SNPs: 195
Non-coding: 20 | Synonymous: 126 | Nonsynonymous: 49 | 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 |
| 15926203 | The plastidic DNA replication enzyme complex of Plasmodium falciparum. | Seow F, Sato S, ..., Barrett MP | 10.1016/j.molbiopara.2005.02.002 |
| 21856338 | The primase domain of PfPrex is a proteolytically matured, essential enzyme ofthe apicoplast. | Lindner SE, Llinas M, Keck JL, Kappe SH | 10.1016/j.molbiopara.2011.08.002 |
| 24267922 | Plasmodium falciparum single-stranded DNA-binding protein (PfSSB) interacts withPfPrex helicase and modulates its activity. | Bhowmick K, Dhar SK | 10.1111/1574-6968.12343 |
| 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 |
| 32636411 | The proofreading activity of Pfprex from Plasmodium falciparum can preventmutagenesis of the apicoplast genome by oxidized nucleotides. | Sharma M, Narayanan N, Nair DT | 10.1038/s41598-020-67853-2 |
| 35220686 | Pfprex from Plasmodium falciparum can bypass oxidative stress-induced DNAlesions. | Sharma M, Nair DT | 10.1111/febs.16414 |