Genome location: Pf3D7_08_v3:1,206,438..1,209,016(-)
Genome classification: Core
Product Description: protein disulfide-isomerase
SignalP Peptide: MNRKYFSSLFLFLISFVFESFVRS
# Transmembrane Domains: 1
EC Numbers: 5.3.4.1 (Protein disulfide-isomerase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0009986 | cell surface |
| Component | GO:0005783 | endoplasmic reticulum |
| Component | GO:0005788 | endoplasmic reticulum lumen |
| Component | GO:0020020 | food vacuole |
| Component | GO:0020009 | microneme |
| Component | GO:0005634 | nucleus |
| Component | GO:0020003 | symbiont-containing vacuole |
| Function | GO:0003723 | RNA binding |
| Function | GO:0005515 | protein binding |
| Function | GO:0003756 | protein disulfide isomerase activity |
| Process | GO:0006457 | protein folding |
| Process | GO:0034976 | response to endoplasmic reticulum stress |
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 | 1.24 | 0.48 |
| Trophozoite | expressed | 2.37 | 0.13 |
| Schizont | expressed | 1.19 | 0.49 |
| Gametocyte | expressed | 1.55 | 0.30 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0827900
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: 0.248 | MFS: -2.66 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0702800)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: C0H4Y6
"Best" AlphaFill ligand hit: 2CV (hega-10, Local RMSD=0.18) with 6H7O (Global RMSD=5.10)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 5.3.4.1 | protein disulfide-isomerase | NEM16F16LOC14AsO43-CCF642MA3 018MA3 019acroleinneomycinpeptidesgenisteinkanamycin... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P30101 | Protein disulfide-isomerase A3 | OMA, OrthoDB | CHEMBL4751979 | |
| P07237 | Protein disulfide-isomerase | Homo sapiens | OrthoDB | Juniferdin derivative, 1Juniferdin derivative, 3Juniferdin derivative, 4Juniferdin derivative, 5... |
| P05307 | Protein disulfide-isomerase | OrthoDB | 16F16A |
Ortholog Group (OrthoMCL): OG6_100478
Most Similar Human Ortholog: H7BZJ3
TM-align score: 0.81 | RMSD: 2.46
Seq Identity: 0.33 | Length: 117 / 483
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000167004 | protein disulfide isomerase family A member 3 |
| ENSG00000185624 | prolyl 4-hydroxylase subunit beta |
Protein Length: 483 | Molecular Weight (kDa): 55.514
PDB ID(s): None
Isoelectric Point: 5.55
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR005788 | Disulphide isomerase |
| InterPro | IPR005792 | Protein disulphide isomerase |
| InterPro | IPR013766 | Thioredoxin domain |
| InterPro | IPR017937 | Thioredoxin, conserved site |
| InterPro | IPR036249 | Thioredoxin-like superfamily |
| PFam | PF00085 | Thioredoxin domain |
| PFam | PF13848 | |
| Superfamily | SSF52833 | Thioredoxin-like superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 37 | 12 | 28 |
| disruptive | 6 | 10 | 9 | 36 |
| missense | 6 | 9 | 8 | 29 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 16 | 56 | 18 | 26 |
| disruptive | 12 | 26 | 23 | 54 |
| missense | 8 | 20 | 22 | 43 |
PlasmoDB Total SNPs: 199
Non-coding: 174 | Synonymous: 18 | Nonsynonymous: 6 | Stop Codon: 1
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 17166645 | Biochemical properties and cellular localization of Plasmodium falciparum proteindisulfide isomerase. | Mouray E, Moutiez M, ..., Grellier P | 10.1016/j.biochi.2006.11.001 |
| 19206106 | Characterisation of Plasmodium invasive organelles; an ookinete micronemeproteome. | Lal K, Prieto JH, ..., Sinden RE | 10.1002/pmic.200800404 |
| 21136929 | Food vacuole proteome of the malarial parasite Plasmodium falciparum. | Lamarque M, Tastet C, ..., Dubremetz JF | 10.1002/prca.200700112 |
| 26988354 | Analysis of the interactome of the Ser/Thr Protein Phosphatase type 1 inPlasmodium falciparum. | Hollin T, De Witte C, ..., Khalife J | 10.1186/s12864-016-2571-z |
| 27128092 | Interrogating the Plasmodium Sporozoite Surface: Identification ofSurface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP byMass Spectrometry-Based Proteomics. | Swearingen KE, Lindner SE, ..., Sinnis P | 10.1371/journal.ppat.1005606 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 33906926 | Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH | Sinha A, Baumgarten S, ..., Scherf A | 10.1128/mBio.00661-21 |
| 32523082 | Plasmodium falciparum immunodominant IgG epitopes in subclinical malaria | Azcarate IG, Marin-Garcia P, ..., Bautista JM | 10.1038/s41598-020-66384-0 |