Product Description: diphthine methyltransferase, putative
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 3.1.1.97 (Methylated diphthine methylhydrolase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005768 | endosome |
| Function | GO:0032451 | demethylase activity |
| Process | GO:0070988 | demethylation |
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 | 0.11 | 0.95 |
| Trophozoite | expressed | 0.42 | 0.75 |
| Schizont | expressed | 0.11 | 0.93 |
| Gametocyte | expressed | 0.35 | 0.79 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0608000
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: 0.429 | MFS: -2.733 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_0106600)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0106600)
Modification: Disrupted | RMgm-1635
More info: PhenoPlasm Link
AlphaFill Uniprot ID: C6KSS8
"Best" AlphaFill ligand hit: SIW (keggin (sta), Local RMSD=0.08) with 6Y7O (Global RMSD=3.41)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.1.1.97 | methylated diphthine methylhydrolase | No BRENDA inhibitors |
No evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_103086
Most Similar Human Ortholog: Q9BTV6
TM-align score: 0.85 | RMSD: 2.43
Seq Identity: 0.25 | Length: 320 / 345
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000148399 | diphthamide biosynthesis 7 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 2 | 23 | 12 | 26 |
| disruptive | 8 | 28 | 19 | 50 |
| missense | 8 | 27 | 18 | 48 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 41 | 19 | 27 |
| disruptive | 15 | 56 | 46 | 75 |
| missense | 11 | 49 | 42 | 57 |
PlasmoDB Total SNPs: 155
Non-coding: 137 | Synonymous: 12 | Nonsynonymous: 6 | Stop Codon: 0
Protein Length: 345 | Molecular Weight (kDa): 40.19
UniProt ID(s): C6KSS8
PDB ID(s): None
Isoelectric Point: 6.25
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001680 | WD40 repeat |
| InterPro | IPR036322 | WD40-repeat-containing domain superfamily |
| PFam | PF00400 | WD40 repeat |
| Superfamily | SSF50978 | WD40-repeat-containing domain superfamily |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 23468660 | The amidation step of diphthamide biosynthesis in yeast requires DPH6, a geneidentified through mining the DPH1-DPH5 interaction network | Uthman S, Bar C, ..., Schaffrath R | 10.1371/journal.pgen.1003334 |
| 25352115 | The diphthamide modification pathway from Saccharomyces cerevisiae--revisited | Schaffrath R, Abdel-Fattah W, Klassen R, Stark MJ | 10.1111/mmi.12845 |
| 30335802 | Importance of diphthamide modified EF2 for translational accuracy and competitivecell growth in yeast | Hawer H, Utkur K, ..., Schaffrath R | 10.1371/journal.pone.0205870 |
| 37675463 | DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiencysyndrome in human cells and yeast models | Utkur K, Mayer K, ..., Brinkmann U | 10.1242/dmm.050207 |
| 37662670 | Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamidesynthesis on elongation factor 2 | Arend M, Utkur K, ..., Schaffrath R | 10.15698/mic2023.09.804 |