About Gene List

PF3D7_1413800 (DPH1)

Genome location: Pf3D7_14_v3:546,796..549,599(+)

Genome classification: Core

Function and Localization

Product Description: diphthamide biosynthesis protein 1, putative

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.5.1.108 (2-(3-amino-3-carboxypropyl)histidine synthase);6.3.2.22 (Transferred entry: 6.3.1.14)

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 possibly expressed 0.54 0.73
Trophozoite possibly expressed 0.23 0.87
Schizont possibly expressed 0.11 0.93
Gametocyte not expressed 0.18 0.89

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1413800

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: Non - Mutable in CDS

MIS: 0.739 | MFS: -2.403 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8ILV7

"Best" AlphaFill ligand hit: SAH (s-adenosyl-l-homocysteine, Local RMSD=0.07) with 6BXO (Global RMSD=2.19)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.5.1.108 2-(3-amino-3-carboxypropyl)histidine synthase No BRENDA inhibitors
6.3.2.22 diphthine-ammonia ligase No BRENDA inhibitors

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_101267

Most Similar Human Ortholog: K7EQQ6

TM-align score: 0.91 | RMSD: 0.96

Seq Identity: 0.51 | Length: 49 / 487

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000108963 diphthamide biosynthesis 1

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 5 28 14 37
disruptive 2 24 19 50
missense 2 23 18 41

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 7 65 23 41
disruptive 13 105 58 162
missense 7 79 43 111

PlasmoDB Total SNPs: 86

Non-coding: 63 | Synonymous: 20 | Nonsynonymous: 3 | Stop Codon: 0

Protein Information

Protein Length: 487 | Molecular Weight (kDa): 57.437

UniProt ID(s): Q8ILV7

PDB ID(s): None

Isoelectric Point: 8.65

Protein Domain Annotations:

Source Family ID Description
InterPro IPR016435 Diphthamide synthesis DPH1/DPH2
InterPro IPR035435 Diphthamide synthesis DHP1/DPH2, eukaryotes and archaea
PFam PF01866 Diphthamide synthesis DPH1/DPH2
Superfamily N/A N/A

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
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
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
38097404 Diphthamide - a conserved modification of eEF2 with clinical relevance Schaffrath R, Brinkmann U 10.1016/j.molmed.2023.11.008