DPH2: Dipthamide Biosynthesis 2
A key enzyme in diphthamide modification of eukaryotic elongation factor 2 (eEF2)
Gene Information Card
| Symbol | DPH2 |
|---|---|
| Full Name | DPH2 homolog, diphthamide biosynthesis 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.1 |
| NCBI Gene ID | 1802 ncbi.nlm.nih.gov/gene/1802 |
| Ensembl ID | ENSG00000117519 |
| UniProt ID | Q9BQC3 |
| OMIM ID | 603456 |
| HGNC ID | 3003 |
| Aliases | DPH2L1, DPH2L, DPH2 homolog |
Description
DPH2 encodes a component of the diphthamide biosynthesis pathway, which modifies histidine 715 of eukaryotic elongation factor 2 (eEF2). This modification is essential for proper protein synthesis and is targeted by diphtheria toxin. DPH2 functions as a methyltransferase in the first step of diphthamide synthesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Diphthamide deficiency syndrome | Loss-of-function mutations in DPH2 impair diphthamide modification of eEF2, leading to developmental delay, neurological abnormalities, and increased sensitivity to diphtheria toxin. | ClinVar, OMIM |
| Cancer (various) | Somatic mutations in DPH2 may alter protein synthesis fidelity and contribute to tumorigenesis, though specific mechanisms remain under investigation. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.2 | Low |
| Liver | 6.1 | Low |
| Heart | 5.4 | Low |
| Kidney | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.3 | Moderate expression |
| HeLa | 7.6 | Low expression |
| K562 | 6.9 | Low expression |
| A549 | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.556C>T (p.Arg186Trp) | Missense | Rare | Impaired diphthamide synthesis |
| c.832G>A (p.Gly278Arg) | Missense | Rare | Reduced enzyme activity |
Mutation functional classification
Loss of Function (LOF)
Most reported DPH2 mutations are loss-of-function, leading to diphthamide deficiency and cellular sensitivity to diphtheria toxin.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DPH2.
Dominant Negative (DN)
No dominant-negative mutations have been described for DPH2.
View complete mutation data：
Gene Ontology (GO)
| • transferase activity (GO:0016740) | • diphthamide biosynthetic process (GO:0017172) |
| • cytosol (GO:0005829) | • cytoplasm (GO:0005737) |
| • methyltransferase activity (GO:0008168) |
Pathways
• Diphthamide biosynthesis (Reactome: R-HSA-5358491)
• Eukaryotic translation elongation (Reactome: R-HSA-156842)
Protein Summary
DPH2 is a 42 kDa protein that localizes to the cytosol and functions as a methyltransferase in the first step of diphthamide biosynthesis. It catalyzes the transfer of a methyl group from S-adenosylmethionine to the imidazole ring of histidine 715 on eEF2. This modification is critical for maintaining translational fidelity and is the target of diphtheria toxin ADP-ribosylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DPH2 Knockout HEK293 Cell Line | EDJ-KQ2883 | Human | 1802 | Details Get a Quote |
| DPH2 Knockout A-549 Cell Line | EDJ-KQ23941 | Human | 1802 | Details Get a Quote |
| DPH2 Knockout HCT 116 Cell Line | EDJ-KQ23942 | Human | 1802 | Details Get a Quote |
| DPH2 Knockout HeLa Cell Line | EDJ-KQ22571 | Human | 1802 | Details Get a Quote |
