DPH1

Protein identityUniProt · HPA

UniProt accession

Q9BZG8

Gene

DPH1

Ensembl

ENSG00000108963

Chromosome

17

Canonical length

438 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cell Junctions

OverviewNCBI Gene

The protein encoded by this gene is an enzyme involved in the biosynthesis of diphthamide, a modified histidine found only in elongation factor-2 (EEF2). Diphthamide residues in EEF2 are targeted for ADP-ribosylation by diphtheria toxin and Pseudomonas exotoxin A. Defects in this gene have been associated with both ovarian cancer and autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies. [provided by RefSeq, Oct 2016]

Canonical amino-acid sequenceUniProt

438 residues, UniProt reviewed canonical sequence.

>Q9BZG8|DPH1
     1  MAALVVSGAA EQGGRDGPGR GRAPRGRVAN QIPPEILKNP QLQAAIRVLP SNYNFEIPKT
    61  IWRIQQAQAK KVALQMPEGL LLFACTIVDI LERFTEAEVM VMGDVTYGAC CVDDFTARAL
   121  GADFLVHYGH SCLIPMDTSA QDFRVLYVFV DIRIDTTHLL DSLRLTFPPA TALALVSTIQ
   181  FVSTLQAAAQ ELKAEYRVSV PQCKPLSPGE ILGCTSPRLS KEVEAVVYLG DGRFHLESVM
   241  IANPNVPAYR YDPYSKVLSR EHYDHQRMQA ARQEAIATAR SAKSWGLILG TLGRQGSPKI
   301  LEHLESRLRA LGLSFVRLLL SEIFPSKLSL LPEVDVWVQV ACPRLSIDWG TAFPKPLLTP
   361  YEAAVALRDI SWQQPYPMDF YAGSSLGPWT VNHGQDRRPH APGRPARGKV QEGSARPPSA
   421  VACEDCSCRD EKVAPLAP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DPH1 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)

0.32

Highest tissue expression

55 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DPH1.

Disease | AllUniProt

Conditions DPH1 is implicated in, by any mechanism.

• Developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (DEDSSH1) MIM:616901

Disease | GeneticClinVar

15 pathogenic / likely-pathogenic of 165 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental delay with short stature, dysmorphic facial features, and sparse hair 1
• Developmental delay with short stature, dysmorphic facial features, and sparse hair
• Dandy-Walker syndrome
• Hydrocephalus
• Cerebellar vermis hypoplasia

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)

1.37

gnomAD pLI

0

gnomAD missense Z

-0.18

DepMap mean gene effect

-0.2

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• fibroblast proliferation
• protein histidyl modification to diphthamide

Molecular functions

• 2-(3-amino-3-carboxypropyl)histidine synthase activity
• 4 iron, 4 sulfur cluster binding
• metal ion binding

Cellular components

• 2-(3-amino-3-carboxypropyl)histidine synthase complex
• cell junction
• cytosol
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Diphthamide synthesis DPH1/DPH2
• Diphthamide synthesis DPH1/DPH2, domain 1
• Diphthamide synthesis DPH1/DPH2, domain 3
• Putative diphthamide synthesis protein
• Diphthamide synthesis DPH1/DPH2, domain 2

KeywordsUniProt

• Alternative initiation
• Cytoplasm
• Dwarfism
• Ectodermal dysplasia
• Hypotrichosis
• Intellectual disability
• Iron
• Iron-sulfur
• Metal-binding
• Nucleus
• S-adenosyl-L-methionine
• Transferase
• Tumor suppressor

InteractionsUniProt · HPA

Protein binding partners of DPH1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DPH2
• RBM8A