About Gene List

PF3D7_1009000 (DPH5)

Genome location: Pf3D7_10_v3:370,903..372,283(+)

Genome classification: Core

Function and Localization

Product Description: diphthine methyl ester synthase, putative

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.1.1.314 (Diphthine methyl ester synthase)

Curated GO (PlasmoDB):

Type GO Term Name
Function GO:0004164 diphthine synthase activity
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 possibly expressed N/A N/A
Ring expressed 0.32 0.84
Trophozoite expressed 0.25 0.84
Schizont expressed 0.04 0.98
Gametocyte expressed 0.11 0.94

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1009000

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: 0.907 | MFS: -2.095 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IJV5

"Best" AlphaFill ligand hit: SAH (s-adenosyl-l-homocysteine, Local RMSD=0.60) with 2DV4 (Global RMSD=2.19)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.1.1.314 diphthine methyl ester synthase No BRENDA inhibitors

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_101531

Most Similar Human Ortholog: Q9H2P9

TM-align score: 0.96 | RMSD: 1.41

Seq Identity: 0.46 | Length: 272 / 274

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000117543 diphthamide biosynthesis 5

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 4 12 12 23
disruptive 2 19 15 38
missense 2 19 15 37

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 4 30 17 28
disruptive 5 63 36 79
missense 5 52 35 58

PlasmoDB Total SNPs: 110

Non-coding: 87 | Synonymous: 9 | Nonsynonymous: 12 | Stop Codon: 2

Protein Information

Protein Length: 274 | Molecular Weight (kDa): 31.735

UniProt ID(s): Q8IJV5

PDB ID(s): None

Isoelectric Point: 6.04

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000878 Tetrapyrrole methylase
InterPro IPR004551 Diphthine synthase
InterPro IPR035996 Tetrapyrrole methylase superfamily
PFam PF00590 Tetrapyrrole methylase
Superfamily SSF53790 Tetrapyrrole methylase superfamily

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
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
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