DPH5

Protein identityUniProt · HPA

UniProt accession

Q9H2P9

Gene

DPH5

Ensembl

ENSG00000117543

Chromosome

1

Canonical length

285 aa

Protein class

Enzymes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoli,Golgi apparatus

OverviewNCBI Gene

This gene encodes a component of the diphthamide synthesis pathway. Diphthamide is a post-translationally modified histidine residue found only on translation elongation factor 2. It is conserved from archaebacteria to humans, and is targeted by diphtheria toxin and Pseudomonas exotoxin A to halt cellular protein synthesis. The yeast and Chinese hamster homologs of this protein catalyze the trimethylation of the histidine residue on elongation factor 2, resulting in a diphthine moiety that is subsequently amidated to yield diphthamide. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

285 residues, UniProt reviewed canonical sequence.

>Q9H2P9|DPH5
     1  MLYLIGLGLG DAKDITVKGL EVVRRCSRVY LEAYTSVLTV GKEALEEFYG RKLVVADREE
    61  VEQEADNILK DADISDVAFL VVGDPFGATT HSDLVLRATK LGIPYRVIHN ASIMNAVGCC
   121  GLQLYKFGET VSIVFWTDTW RPESFFDKVK KNRQNGMHTL CLLDIKVKEQ SLENLIKGRK
   181  IYEPPRYMSV NQAAQQLLEI VQNQRIRGEE PAVTEETLCV GLARVGADDQ KIAAGTLRQM
   241  CTVDLGEPLH SLIITGGSIH PMEMEMLSLF SIPENSSESQ SINGL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DPH5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

33 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DPH5.

Disease | AllUniProt

Conditions DPH5 is implicated in, by any mechanism.

• Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties (NEDSFF) MIM:620070

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 54 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.27

gnomAD pLI

0

gnomAD missense Z

0.48

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• methylation
• protein histidyl modification to diphthamide

Molecular functions

• diphthine methyl ester synthase activity

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• Tetrapyrrole methylase
• Diphthine synthase
• Tetrapyrrole methylase, subdomain 2
• Tetrapyrrole methylase, subdomain 1
• Tetrapyrrole methylase superfamily
• Tetrapyrrole (Corrin/Porphyrin) Methylases

KeywordsUniProt

• Intellectual disability
• Methyltransferase
• Phosphoprotein
• S-adenosyl-L-methionine
• Transferase