Genome location: Pf3D7_14_v3:1,164,239..1,166,791(+)
Genome classification: Core
Product Description: diphthamide biosynthesis protein 2, putative
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 6.3.1.14 (Diphthine--ammonia ligase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Process | GO:0017183 | peptidyl-diphthamide biosynthetic process from peptidyl-histidine |
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 | 0.48 | 0.77 |
| Trophozoite | expressed | 0.21 | 0.89 |
| Schizont | possibly expressed | 0.05 | 0.97 |
| Gametocyte | possibly expressed | 0.31 | 0.82 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1429500
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: 0.131 | MFS: -2.934 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1015200)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1015200)
Modification: Disrupted | RMgm-2789
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8ILG9
"Best" AlphaFill ligand hit: SAM (s-adenosylmethionine, Local RMSD=2.68) with 6BXL (Global RMSD=3.20)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 6.3.1.14 | diphthine-ammonia ligase | No BRENDA inhibitors |
No evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_103331
Most Similar Human Ortholog: Q9BQC3
TM-align score: 0.68 | RMSD: 3.12
Seq Identity: 0.19 | Length: 369 / 744
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000132768 | diphthamide biosynthesis 2 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 23 | 21 | 36 |
| disruptive | 53 | 99 | 39 | 131 |
| missense | 19 | 78 | 31 | 110 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 9 | 54 | 30 | 41 |
| disruptive | 81 | 186 | 88 | 182 |
| missense | 35 | 139 | 70 | 125 |
PlasmoDB Total SNPs: 173
Non-coding: 63 | Synonymous: 50 | Nonsynonymous: 60 | Stop Codon: 0
Protein Length: 744 | Molecular Weight (kDa): 88.752
UniProt ID(s): Q8ILG9
PDB ID(s): None
Isoelectric Point: 5.79
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR010014 | Diphthamide synthesis DHP2 |
| InterPro | IPR016435 | Diphthamide synthesis DPH1/DPH2 |
| PFam | PF01866 | Diphthamide synthesis DPH1/DPH2 |
| Superfamily | N/A | N/A |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 31463593 | The asymmetric function of Dph1-Dph2 heterodimer in diphthamide biosynthesis | Dong M, Dando EE, ..., Lin H | 10.1007/s00775-019-01702-0 |
| 34302311 | Spin-Regulated Electron Transfer and Exchange-Enhanced Reactivity in Fe(4) S(4)-Mediated Redox Reaction of the Dph2 Enzyme During the Biosynthesis ofDiphthamide | Feng J, Shaik S, Wang B | 10.1002/anie.202107008 |
| 24422557 | Dph3 is an electron donor for Dph1-Dph2 in the first step of eukaryoticdiphthamide biosynthesis | Dong M, Su X, ..., Lin H | 10.1021/ja4118957 |
| 31566354 | The Crystal Structure of Dph2 in Complex with Elongation Factor 2 Reveals the Structural Basis for the First Step of Diphthamide Biosynthesis | Fenwick MK, Dong M, Lin H, Ealick SE | 10.1021/acs.biochem.9b00718 |
| 31566424 | Forward genetic screen in human podocytes identifies diphthamide biosynthesis genes as regulators of adhesion | Cina DP, Ketela T, ..., Quaggin SE | 10.1152/ajprenal.00195.2019 |
| 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 |
| 38002337 | DPH1 Gene Mutations Identify a Candidate SAM Pocket in Radical Enzyme Dph1*Dph2for Diphthamide Synthesis on EF2 | Utkur K, Schmidt S, ..., Schaffrath R | 10.3390/biom13111655 |
| 34154323 | Dph3 Enables Aerobic Diphthamide Biosynthesis by Donating One Iron Atom toTransform a [3Fe-4S] to a [4Fe-4S] Cluster in Dph1-Dph2 | Zhang Y, Su D, ..., Lin H | 10.1021/jacs.1c03956 |