Q96FX2 · DPH3_HUMAN
- ProteinDiphthamide biosynthesis protein 3
- GeneDPH3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase. Acts as an electron donor to reduce the Fe-S cluster in DPH1-DPH2 keeping the [4Fe-4S] clusters in the active and reduced state. Restores iron to DPH1-DPH2 iron-sulfur clusters which have degraded from [4Fe-4S] to [3Fe-4S] by donating an iron atom to reform [4Fe-4S] clusters, in a manner dependent on the presence of elongation factor 2 and SAM. Associates with the elongator complex and is required for tRNA Wobble base modifications mediated by the elongator complex. The elongator complex is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s 2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).
Catalytic activity
- [3Fe-4S]1+-[protein] + Fe2+-[Dph3] = [3Fe-4S]0-[protein] + Fe3+-[Dph3]
- 2 [3Fe-4S]0-[protein] + 2 Fe2+-[Dph3] + NADH = 2 [4Fe-4S]1+-[protein] + 2 [Dph3] + H+ + NAD+
Cofactor
Pathway
Protein modification; peptidyl-diphthamide biosynthesis.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | ferrous iron binding | |
Molecular Function | iron chaperone activity | |
Biological Process | negative regulation of protein secretion | |
Biological Process | positive regulation of binding | |
Biological Process | protein histidyl modification to diphthamide | |
Biological Process | tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation |
Keywords
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDiphthamide biosynthesis protein 3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96FX2
Proteomes
Organism-specific databases
Disease & Variants
Variants
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The viewer provides 85 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000082620 | 1-82 | Diphthamide biosynthesis protein 3 | |||
Sequence: MAVFHDEVEIEDFQYDEDSETYFYPCPCGDNFSITKEDLENGEDVATCPSCSLIIKVIYDKDQFVCGETVPAPSANKELVKC |
Proteomic databases
PTM databases
Interaction
Subunit
Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, DPH3 and a NADH-dependent reductase (By similarity).
Interacts with SERGEF (PubMed:14980502).
Interacts with SERGEF (PubMed:14980502).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96FX2 | MEOX2 Q6FHY5 | 3 | EBI-465363, EBI-16439278 | |
BINARY | Q96FX2 | PIH1D2 Q8WWB5 | 6 | EBI-465363, EBI-10232538 | |
BINARY | Q96FX2 | SERGEF Q9UGK8 | 8 | EBI-465363, EBI-465368 | |
BINARY | Q96FX2 | ZNF438 Q7Z4V0 | 3 | EBI-465363, EBI-11962468 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 4-60 | DPH-type MB | ||||
Sequence: FHDEVEIEDFQYDEDSETYFYPCPCGDNFSITKEDLENGEDVATCPSCSLIIKVIYD |
Domain
The DPH-type metal-binding (MB) domain can also bind zinc. However, iron is the physiological binding partner as zinc binding impairs the protein electron donor function.
Sequence similarities
Belongs to the DPH3 family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q96FX2-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length82
- Mass (Da)9,240
- Last updated2001-12-01 v1
- Checksum7AC8F3FFF8CE766C
Q96FX2-2
- Name2
- Differences from canonical
- 36-60: Missing
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_012411 | 36-60 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK022970 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
BC010181 EMBL· GenBank· DDBJ | AAH10181.1 EMBL· GenBank· DDBJ | mRNA |