About Gene List

PF3D7_1359300 (DIS3)

Genome location: Pf3D7_13_v3:2,353,589..2,357,798(+)

Genome classification: Core

Function and Localization

Product Description: exosome complex exonuclease RRP44

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 3.1.13.- (Exoribonucleases producing 5'-phosphomonoesters.);3.1.16.1 (Spleen exonuclease)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005737 cytoplasm
Component GO:0000177 cytoplasmic exosome (RNase complex)
Component GO:0005829 cytosol
Component GO:0000178 exosome (RNase complex)
Component GO:0000176 nuclear exosome (RNase complex)
Component GO:0048471 perinuclear region of cytoplasm
Function GO:0000175 3'-5'-exoribonuclease activity
Function GO:0003723 RNA binding
Function GO:0004519 endonuclease activity
Function GO:0005515 protein binding
Function GO:0004540 ribonuclease activity
Process GO:0006401 RNA catabolic process
Process GO:0110064 lncRNA catabolic process
Process GO:0016075 rRNA catabolic process
Process GO:0043488 regulation of mRNA stability

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 expressed 0.40 0.80
Trophozoite expressed 0.71 0.60
Schizont expressed 0.16 0.90
Gametocyte expressed 0.64 0.64

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1359300

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 1 | MFS: -1.136 | #Insertions: 3

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1135600)

  • Relative Growth Rate: 0.18 ± 0.10
  • Confidence: 5.95

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IDB6

"Best" AlphaFill ligand hit: U5P (uridine-5'-monophosphate, Local RMSD=0.42) with 7TUV (Global RMSD=2.58)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
3.1.13.- Ex: poly(A)-specific ribonuclease SDSKClATPADPUDPGTPGDPUTPAMPCMPGMPNEM...
3.1.16.1 spleen exonuclease ATPKClEDTARNAiheparinarseniteATPgammaSUDP-glucosePentamidineacetylationSP-ATPalphaSSP-CTPalphaS...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_101226

Most Similar Human Ortholog: Q9Y2L1

TM-align score: 0.86 | RMSD: 3.67

Seq Identity: 0.30 | Length: 898 / 1073

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000083520 DIS3 homolog, exosome endoribonuclease and 3-5 exoribonuclease

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 16 76 48 72
disruptive 12 153 68 206
missense 9 135 64 187

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 25 158 51 68
disruptive 44 307 136 303
missense 30 268 118 247

PlasmoDB Total SNPs: 177

Non-coding: 94 | Synonymous: 58 | Nonsynonymous: 25 | Stop Codon: 0

Protein Information

Protein Length: 1073 | Molecular Weight (kDa): 126.662

UniProt ID(s): Q8IDB6

PDB ID(s): None

Isoelectric Point: 7.31

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001900 Ribonuclease II/R
InterPro IPR012340 Nucleic acid-binding, OB-fold
InterPro IPR022966 Ribonuclease II/R, conserved site
InterPro IPR041505 Dis3-like cold-shock domain 2
PFam PF00773 Ribonuclease II/R
PFam PF17849 Dis3-like cold-shock domain 2
Superfamily SSF50249 Nucleic acid-binding, OB-fold

Associated Publications

PMID Title Authors DOI/Link
25043062 Exonuclease-mediated degradation of nascent RNA silences genes linked to severemalaria. Zhang Q, Siegel TN, ..., Scherf A 10.1038/nature13468
29664138 Characterization of the Catalytic Subunits of the RNA Exosome-like Complex inPlasmodium falciparum. Jiang N, Yu S, ..., Chen Q 10.1111/jeu.12625
30235972 Disruption of the RNA exosome reveals the hidden face of the malaria parasitetranscriptome. Droll D, Wei G, ..., Zhang Q 10.1080/15476286.2018.1517014
31737630 TRIBE Uncovers the Role of Dis3 in Shaping the Dynamic Transcriptome in MalariaParasites. Liu M, Lu B, ..., Zhang Q 10.3389/fcell.2019.00264
32079470 The cryptic unstable transcripts are associated with developmentally regulatedgene expression in blood-stage Plasmodium falciparum. Yin S, Fan Y, ..., Zhang Q 10.1080/15476286.2020.1732032
36861343 In vivo characterization of the critical interaction between the RNA exosome andthe essential RNA helicase Mtr4 in Saccharomyces cerevisiae Sterrett MC, Farchi D, ..., Corbett AH 10.1093/g3journal/jkad049
38316765 Engineering stringent genetic biocontainment of yeast with a protein stabilityswitch Hoffmann SA, Cai Y 10.1038/s41467-024-44988-8