O94760 · DDAH1_HUMAN
- ProteinN(G),N(G)-dimethylarginine dimethylaminohydrolase 1
- GeneDDAH1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids285 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
Catalytic activity
- H2O + N(omega),N(omega)-dimethyl-L-arginine = dimethylamine + L-citrullineThis reaction proceeds in the forward direction.
Activity regulation
Inhibited by zinc ions (By similarity).
Enzyme purified in the absence of 1,10-phenanthroline contains on average 0.4 zinc atoms per subunit. Inhibited by 4-hydroxy-nonenal through the formation of a covalent adduct with His-173. Competitively inhibited by N5-iminopropyl-ornithine.
Enzyme purified in the absence of 1,10-phenanthroline contains on average 0.4 zinc atoms per subunit. Inhibited by 4-hydroxy-nonenal through the formation of a covalent adduct with His-173. Competitively inhibited by N5-iminopropyl-ornithine.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
69 μM | asymmetric dimethylarginine (ADMA) | |||||
54 μM | monomethyl-L-arginine (MMA) | |||||
3.1 μM | S-methyl-L-thiocitrulline |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
356 nmol/min/mg | with ADMA | ||||
154 nmol/min/mg | with NMA |
pH Dependence
Optimum pH is 8.5.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 30 | substrate | ||||
Sequence: L | ||||||
Binding site | 73 | substrate | ||||
Sequence: D | ||||||
Binding site | 78-79 | substrate | ||||
Sequence: ED | ||||||
Binding site | 98 | substrate | ||||
Sequence: R | ||||||
Binding site | 145 | substrate | ||||
Sequence: R | ||||||
Active site | 173 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 268 | substrate | ||||
Sequence: V | ||||||
Active site | 274 | Nucleophile | ||||
Sequence: C | ||||||
Binding site | 274 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Molecular Function | amino acid binding | |
Molecular Function | catalytic activity | |
Molecular Function | dimethylargininase activity | |
Molecular Function | metal ion binding | |
Biological Process | arginine catabolic process | |
Biological Process | arginine metabolic process | |
Biological Process | citrulline metabolic process | |
Biological Process | negative regulation of cell population proliferation | |
Biological Process | negative regulation of cellular response to hypoxia | |
Biological Process | negative regulation of vascular permeability | |
Biological Process | nitric oxide mediated signal transduction | |
Biological Process | nitric oxide metabolic process | |
Biological Process | positive regulation of angiogenesis | |
Biological Process | positive regulation of nitric oxide biosynthetic process | |
Biological Process | regulation of systemic arterial blood pressure |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameN(G),N(G)-dimethylarginine dimethylaminohydrolase 1
- EC number
- Short namesDDAH-1; Dimethylarginine dimethylaminohydrolase 1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO94760
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 30 | Reduces enzyme activity and affinity for asymmetric dimethylarginine about 12-fold. | ||||
Sequence: L → A | ||||||
Mutagenesis | 78 | Reduces enzyme activity about 1000-fold, and affinity for asymmetric dimethylarginine about 100-fold. | ||||
Sequence: E → A | ||||||
Mutagenesis | 271 | Reduces enzyme activity about 10-fold, and affinity for asymmetric dimethylarginine about 7-fold. | ||||
Sequence: L → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 309 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000171118 | 2-285 | N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 | |||
Sequence: AGLGHPAAFGRATHAVVRALPESLGQHALRSAKGEEVDVARAERQHQLYVGVLGSKLGLQVVELPADESLPDCVFVEDVAVVCEETALITRPGAPSRRKEVDMMKEALEKLQLNIVEMKDENATLDGGDVLFTGREFFVGLSKRTNQRGAEILADTFKDYAVSTVPVADGLHLKSFCSMAGPNLIAIGSSESAQKALKIMQQMSDHRYDKLTVPDDIAANCIYLNIPNKGHVLLHRTPEEYPESAKVYEKLKDHMLIPVSMSELEKVDGLLTCCSVLINKKVDS | ||||||
Modified residue | 222 | S-nitrosocysteine | ||||
Sequence: C | ||||||
Modified residue | 274 | S-nitrosocysteine | ||||
Sequence: C |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Detected in brain, liver, kidney and pancreas, and at low levels in skeletal muscle.
Gene expression databases
Organism-specific databases
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O94760-1
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
- Length285
- Mass (Da)31,122
- Last updated2007-01-23 v3
- ChecksumCD8875DF267EF39B
O94760-2
- Name2
- Differences from canonical
- 1-103: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B4DYP1 | B4DYP1_HUMAN | DDAH1 | 185 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_043813 | 1-103 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB001915 EMBL· GenBank· DDBJ | BAA37117.1 EMBL· GenBank· DDBJ | mRNA | ||
BX648145 EMBL· GenBank· DDBJ | CAI45988.1 EMBL· GenBank· DDBJ | mRNA | ||
AC092807 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL078459 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL360219 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471097 EMBL· GenBank· DDBJ | EAW73199.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC033680 EMBL· GenBank· DDBJ | AAH33680.1 EMBL· GenBank· DDBJ | mRNA | ||
BC043235 EMBL· GenBank· DDBJ | AAH43235.2 EMBL· GenBank· DDBJ | mRNA |