P49366 · DHYS_HUMAN
- ProteinDeoxyhypusine synthase
- GeneDHPS
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids369 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a critical lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue (PubMed:30661771).
This is the first step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF-5A factor and is essential for its function
This is the first step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF-5A factor and is essential for its function
Catalytic activity
- [eIF5A protein]-L-lysine + spermidine = [eIF5A protein]-deoxyhypusine + propane-1,3-diamine
Cofactor
Pathway
Protein modification; eIF5A hypusination.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 105-109 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: SNLIS | ||||||
Binding site | 131-133 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: TAG | ||||||
Binding site | 136-137 | spermidine (UniProtKB | ChEBI) | ||||
Sequence: EE | ||||||
Binding site | 137 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 238 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 243 | spermidine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 283 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 288 | spermidine (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 308-309 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: TA | ||||||
Binding site | 314-316 | spermidine (UniProtKB | ChEBI) | ||||
Sequence: GSD | ||||||
Binding site | 323-329 | spermidine (UniProtKB | ChEBI) | ||||
Sequence: EAVSWGK | ||||||
Active site | 329 | Nucleophile | ||||
Sequence: K | ||||||
Binding site | 342-343 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: DA |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Molecular Function | deoxyhypusine synthase activity | |
Molecular Function | identical protein binding | |
Biological Process | glucose homeostasis | |
Biological Process | peptidyl-lysine modification to peptidyl-hypusine | |
Biological Process | positive regulation of cell population proliferation | |
Biological Process | positive regulation of T cell proliferation | |
Biological Process | spermidine catabolic process | |
Biological Process | spermidine metabolic process | |
Biological Process | translation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDeoxyhypusine synthase
- EC number
- Short namesDHS
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP49366
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Involvement in disease
Neurodevelopmental disorder with seizures and speech and walking impairment (NEDSSWI)
- Note
- DescriptionAn autosomal recessive disorder characterized by global developmental delay with intellectual disability and poor speech acquisition, and walking difficulties due to hypotonia, hypertonia, spasticity, or poor coordination. Additional features include seizures, mild dysmorphic features, and variable short stature.
- See alsoMIM:618480
Natural variants in NEDSSWI
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_082649 | 173 | N>S | in NEDSSWI; decreased deoxyhypusine synthase activity; dbSNP:rs758100382 | |
VAR_082650 | 305-306 | missing | in NEDSSWI; loss of deoxyhypusine synthase activity |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 106 | Strongly reduced NAD and spermidine binding. Reduced activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 109 | Strongly reduced spermidine binding. Reduced activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 137 | Strongly reduced NAD binding. Strongly reduced formation of covalent intermediate. | ||||
Sequence: E → A | ||||||
Natural variant | VAR_082649 | 173 | in NEDSSWI; decreased deoxyhypusine synthase activity; dbSNP:rs758100382 | |||
Sequence: N → S | ||||||
Natural variant | VAR_043005 | 174 | in dbSNP:rs10425108 | |||
Sequence: E → D | ||||||
Mutagenesis | 238 | Strongly reduced NAD binding. Strongly reduced formation of covalent intermediate. | ||||
Sequence: D → A | ||||||
Mutagenesis | 243 | Reduces spermidine binding by 98%. Strongly reduced formation of covalent intermediate. | ||||
Sequence: D → A | ||||||
Mutagenesis | 287 | Reduces covalent intermediate formation and deoxyhypusine synthesis by 99.5%. Retains low spermidine cleavage activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 288 | Reduces spermidine binding by 98%. Strongly reduced NAD binding. Strongly reduced formation of covalent intermediate. | ||||
Sequence: H → A | ||||||
Mutagenesis | 305 | Strongly reduced NAD binding. No effect on enzyme activity. | ||||
Sequence: Y → A | ||||||
Natural variant | VAR_082650 | 305-306 | in NEDSSWI; loss of deoxyhypusine synthase activity | |||
Sequence: Missing | ||||||
Mutagenesis | 313 | Strongly reduced NAD binding. | ||||
Sequence: D → A | ||||||
Mutagenesis | 316 | Reduces spermidine binding by 98%. Loss of covalent intermediate formation and deoxyhypusine synthesis. | ||||
Sequence: D → A | ||||||
Mutagenesis | 317 | Strongly reduced NAD binding. No effect on enzyme activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 323 | Reduces spermidine binding by 98%. Strongly reduced formation of covalent intermediate. | ||||
Sequence: E → A | ||||||
Mutagenesis | 327 | Reduces spermidine binding by 98%. Loss of covalent intermediate formation and deoxyhypusine synthesis. | ||||
Sequence: W → A | ||||||
Mutagenesis | 329 | Loss of covalent intermediate formation and deoxyhypusine synthesis. | ||||
Sequence: K → A or R | ||||||
Mutagenesis | 342 | Strongly reduced NAD binding. Strongly reduced activity. | ||||
Sequence: D → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 475 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000134469 | 1-369 | UniProt | Deoxyhypusine synthase | |||
Sequence: MEGSLEREAPAGALAAVLKHSSTLPPESTQVRGYDFNRGVNYRALLEAFGTTGFQATNFGRAVQQVNAMIEKKLEPLSQDEDQHADLTQSRRPLTSCTIFLGYTSNLISSGIRETIRYLVQHNMVDVLVTTAGGVEEDLIKCLAPTYLGEFSLRGKELRENGINRIGNLLVPNENYCKFEDWLMPILDQMVMEQNTEGVKWTPSKMIARLGKEINNPESVYYWAQKNHIPVFSPALTDGSLGDMIFFHSYKNPGLVLDIVEDLRLINTQAIFAKCTGMIILGGGVVKHHIANANLMRNGADYAVYINTAQEFDGSDSGARPDEAVSWGKIRVDAQPVKVYADASLVFPLLVAETFAQKMDAFMHEKNED | |||||||
Modified residue (large scale data) | 4 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 78 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 78 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homotetramer formed by a dimer of dimers.
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
P49366-1
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.
- NameLong
- Length369
- Mass (Da)40,971
- Last updated1996-02-01 v1
- Checksum5314FED620AC9EE7
P49366-2
- NameShort
- NoteInactive.
- Differences from canonical
- 262-308: Missing
P49366-3
- Name3
- Differences from canonical
- 1-68: MEGSLEREAPAGALAAVLKHSSTLPPESTQVRGYDFNRGVNYRALLEAFGTTGFQATNFGRAVQQVNA → MPIIPAFWEAEAGGSREEEFETSLAN
Computationally mapped potential isoform sequences
There are 12 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B4E3M2 | B4E3M2_HUMAN | DHPS | 139 | ||
M0R0V2 | M0R0V2_HUMAN | DHPS | 159 | ||
M0R0J4 | M0R0J4_HUMAN | DHPS | 68 | ||
M0R1T2 | M0R1T2_HUMAN | DHPS | 138 | ||
M0R1T4 | M0R1T4_HUMAN | DHPS | 115 | ||
M0R253 | M0R253_HUMAN | DHPS | 132 | ||
M0R264 | M0R264_HUMAN | DHPS | 182 | ||
M0QXT2 | M0QXT2_HUMAN | DHPS | 27 | ||
M0QX43 | M0QX43_HUMAN | DHPS | 132 | ||
M0QZT3 | M0QZT3_HUMAN | DHPS | 56 | ||
M0QYZ7 | M0QYZ7_HUMAN | DHPS | 90 | ||
Q5J8M5 | Q5J8M5_HUMAN | DHPS | 277 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_047564 | 1-68 | in isoform 3 | |||
Sequence: MEGSLEREAPAGALAAVLKHSSTLPPESTQVRGYDFNRGVNYRALLEAFGTTGFQATNFGRAVQQVNA → MPIIPAFWEAEAGGSREEEFETSLAN | ||||||
Sequence conflict | 11 | in Ref. 3; AAB02175/AAB02179 | ||||
Sequence: A → R | ||||||
Sequence conflict | 13-14 | in Ref. 3; AAB02175/AAB02179 | ||||
Sequence: AL → R | ||||||
Sequence conflict | 85 | in Ref. 3; AAB02175/AAB02179 | ||||
Sequence: A → G | ||||||
Sequence conflict | 196 | in Ref. 3; AAB02175/AAB02179 | ||||
Sequence: T → I | ||||||
Sequence conflict | 199 | in Ref. 3; AAB02175/AAB02179 | ||||
Sequence: V → A | ||||||
Sequence conflict | 220 | in Ref. 3; AAB02175/AAB02179 | ||||
Sequence: V → A | ||||||
Sequence conflict | 228 | in Ref. 11; AA sequence | ||||
Sequence: H → K | ||||||
Alternative sequence | VSP_001351 | 262-308 | in isoform Short | |||
Sequence: Missing | ||||||
Sequence conflict | 296-297 | in Ref. 3; AAB02179 | ||||
Sequence: MR → SG | ||||||
Sequence conflict | 311 | in Ref. 3; AAB02179 | ||||
Sequence: E → EE |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L39068 EMBL· GenBank· DDBJ | AAA86282.1 EMBL· GenBank· DDBJ | mRNA | ||
U40579 EMBL· GenBank· DDBJ | AAA96151.1 EMBL· GenBank· DDBJ | mRNA | ||
U32178 EMBL· GenBank· DDBJ | AAB02179.1 EMBL· GenBank· DDBJ | mRNA | ||
U26266 EMBL· GenBank· DDBJ | AAB02175.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ001701 EMBL· GenBank· DDBJ | CAA04940.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ001702 EMBL· GenBank· DDBJ | CAA04940.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ001703 EMBL· GenBank· DDBJ | CAA04940.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ001704 EMBL· GenBank· DDBJ | CAA04940.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U79262 EMBL· GenBank· DDBJ | AAB50208.1 EMBL· GenBank· DDBJ | mRNA | ||
AL520040 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AK291553 EMBL· GenBank· DDBJ | BAF84242.1 EMBL· GenBank· DDBJ | mRNA | ||
AC010422 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471106 EMBL· GenBank· DDBJ | EAW84288.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC000333 EMBL· GenBank· DDBJ | AAH00333.1 EMBL· GenBank· DDBJ | mRNA | ||
BC014016 EMBL· GenBank· DDBJ | AAH14016.1 EMBL· GenBank· DDBJ | mRNA |