Genome location: Pf3D7_14_v3:1,557,114..1,561,108(-)
Genome classification: Core
Product Description: cleavage and polyadenylation specificity factor subunit 3, putative
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: None
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005847 | mRNA cleavage and polyadenylation specificity factor complex |
| Component | GO:0005634 | nucleus |
| Function | GO:0008409 | 5'-3' exonuclease activity |
| Function | GO:0003723 | RNA binding |
| Function | GO:0004521 | endoribonuclease activity |
| Process | GO:0006398 | mRNA 3'-end processing by stem-loop binding and cleavage |
| Process | GO:0006379 | mRNA cleavage |
| Process | GO:0006378 | mRNA polyadenylation |
| 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 | 0.37 | 0.82 |
| Trophozoite | expressed | 0.38 | 0.77 |
| Schizont | not expressed | 0.08 | 0.95 |
| Gametocyte | not expressed | 0.35 | 0.80 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1438500
Resistome Missense Mutations: G289C, Y408N, S444C
Resistome Compounds with Missense Mutations: AN13762, AN13956
Resistome # Samples with Disruptive Mutations: 4 (4 missense, 4 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.121 | MFS: -3.09 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1302400)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IL83
"Best" AlphaFill ligand hit: U5P (uridine-5'-monophosphate, Local RMSD=0.18) with 3IEL (Global RMSD=2.13)
No associated EC numbersNo evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_101260
Most Similar Human Ortholog: C9JZH6
TM-align score: 0.96 | RMSD: 1.12
Seq Identity: 0.50 | Length: 136 / 876
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000119203 | cleavage and polyadenylation specific factor 3 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 40 | 22 | 70 |
| disruptive | 14 | 70 | 55 | 121 |
| missense | 13 | 68 | 54 | 106 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 11 | 87 | 50 | 64 |
| disruptive | 19 | 166 | 84 | 208 |
| missense | 17 | 149 | 73 | 158 |
PlasmoDB Total SNPs: 115
Non-coding: 60 | Synonymous: 34 | Nonsynonymous: 19 | Stop Codon: 2
Protein Length: 876 | Molecular Weight (kDa): 101.185
UniProt ID(s): Q8IL83
PDB ID(s): None
Isoelectric Point: 5.15
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001279 | Metallo-beta-lactamase |
| InterPro | IPR011108 | Zn-dependent metallo-hydrolase, RNA specificity domain |
| InterPro | IPR021718 | Pre-mRNA 3'-end-processing endonuclease polyadenylation factor C-term |
| InterPro | IPR022712 | Beta-Casp domain |
| InterPro | IPR036866 | Ribonuclease Z/Hydroxyacylglutathione hydrolase-like |
| PFam | PF07521 | Zn-dependent metallo-hydrolase, RNA specificity domain |
| PFam | PF10996 | Beta-Casp domain |
| PFam | PF11718 | Pre-mRNA 3'-end-processing endonuclease polyadenylation factor C-term |
| PFam | PF16661 | Metallo-beta-lactamase |
| Superfamily | SSF56281 | Ribonuclease Z/Hydroxyacylglutathione hydrolase-like |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 23181666 | Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. | Oehring SC, Woodcroft BJ, ..., Voss TS | 10.1186/gb-2012-13-11-r108 |
| 28148555 | Targeting Toxoplasma gondii CPSF3 as a new approach to control toxoplasmosis. | Palencia A, Bougdour A, ..., Hakimi MA | 10.15252/emmm.201607370 |
| 28262680 | A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage andpolyadenylation specificity factor homologue. | Sonoiki E, Ng CL, ..., Rosenthal PJ | 10.1038/ncomms14574 |
| 36288402 | Sequences and proteins that influence mRNA processing in Trypanosoma brucei:Evolutionary conservation of SR-domain and PTB protein functions | Waithaka A, Maiakovska O, ..., Clayton C | 10.1371/journal.pntd.0010876 |
| 37967558 | Anticancer benzoxaboroles block pre-mRNA processing by directly inhibiting CPSF3 | Tao Y, Budhipramono A, ..., Nijhawan D | 10.1016/j.chembiol.2023.10.019 |
| 37772733 | Molecular targets for Chagas disease: validation, challenges and lead compounds for widely exploited targets | Laureano de Souza M, Lapierre TJWJD, ..., Ferreira RS | 10.1080/14728222.2023.2264512 |
| 36304107 | Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborolemodes of action in the African Trypanosome | Sharma A, Cipriano M, ..., Mensa-Wilmot K | 10.1016/j.isci.2022.105302 |
| 35378143 | CRISPR/Cas9-based precision tagging of essential genes in bloodstream formAfrican trypanosomes | Kovarova J, Novotna M, ..., Horn D | 10.1016/j.molbiopara.2022.111476 |
| 34752454 | Transcriptional differentiation of Trypanosoma brucei during in vitro acquisitionof resistance to acoziborole | Steketee PC, Giordani F, ..., Barrett MP | 10.1371/journal.pntd.0009939 |
| 37992178 | Therapeutic targeting of CPSF3-dependent transcriptional termination in ovarian cancer | Shen P, Ye K, ..., Zhuang G | 10.1126/sciadv.adj0123 |
| 37627085 | CPSF3 Promotes Pre-mRNA Splicing and Prevents CircRNA Cyclization in Hepatocellular Carcinoma | Huang Y, Ji H, ..., Zhu Q | 10.3390/cancers15164057 |