O35078 · OXDA_RAT
- ProteinD-amino-acid oxidase
- GeneDao
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids346 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the oxidative deamination of D-amino acids with broad substrate specificity (PubMed:21700703, PubMed:21981077).
Required to catabolize D-amino acids synthesized endogenously, of gastrointestinal bacterial origin or obtained from the diet, and to use these as nutrients (By similarity).
Regulates the level of D-amino acid neurotransmitters in the brain, such as D-serine, a co-agonist of N-methyl D-aspartate (NMDA) receptors, and may modulate synaptic transmission (PubMed:23631755).
Catalyzes the first step of the racemization of D-DOPA to L-DOPA, for possible use in an alternative dopamine biosynthesis pathway (By similarity).
Also catalyzes the first step of the chiral inversion of N(gamma)-nitro-D-arginine methyl ester (D-NNA) to its L-enantiomer L-NNA that acts as a nitric oxide synthase inhibitor (By similarity).
The hydrogen peroxide produced in the reaction provides protection against microbial infection; it contributes to the oxidative killing activity of phagocytic leukocytes and protects against bacterial colonization of the small intestine (By similarity).
Enzyme secreted into the lumen of the intestine may not be catalytically active and could instead be proteolytically cleaved into peptides with antimicrobial activity (By similarity).
The hydrogen peroxide produced in the reaction may also play a role in promoting cellular senescence in response to DNA damage (By similarity).
Could act as a detoxifying agent which removes D-amino acids accumulated during aging (PubMed:7903300).
Required to catabolize D-amino acids synthesized endogenously, of gastrointestinal bacterial origin or obtained from the diet, and to use these as nutrients (By similarity).
Regulates the level of D-amino acid neurotransmitters in the brain, such as D-serine, a co-agonist of N-methyl D-aspartate (NMDA) receptors, and may modulate synaptic transmission (PubMed:23631755).
Catalyzes the first step of the racemization of D-DOPA to L-DOPA, for possible use in an alternative dopamine biosynthesis pathway (By similarity).
Also catalyzes the first step of the chiral inversion of N(gamma)-nitro-D-arginine methyl ester (D-NNA) to its L-enantiomer L-NNA that acts as a nitric oxide synthase inhibitor (By similarity).
The hydrogen peroxide produced in the reaction provides protection against microbial infection; it contributes to the oxidative killing activity of phagocytic leukocytes and protects against bacterial colonization of the small intestine (By similarity).
Enzyme secreted into the lumen of the intestine may not be catalytically active and could instead be proteolytically cleaved into peptides with antimicrobial activity (By similarity).
The hydrogen peroxide produced in the reaction may also play a role in promoting cellular senescence in response to DNA damage (By similarity).
Could act as a detoxifying agent which removes D-amino acids accumulated during aging (PubMed:7903300).
Catalytic activity
- a D-alpha-amino acid + H2O + O2 = a 2-oxocarboxylate + H2O2 + NH4+
- D-alanine + H2O + O2 = H2O2 + NH4+ + pyruvateThis reaction proceeds in the forward direction.
- D-cysteine + H2O + O2 = 2-oxo-3-sulfanylpropanoate + H2O2 + NH4+This reaction proceeds in the forward direction.
- D-dopa + H2O + O2 = 3-(3,4-dihydroxyphenyl)pyruvate + H2O2 + NH4+This reaction proceeds in the forward direction.
- D-leucine + H2O + O2 = 4-methyl-2-oxopentanoate + H2O2 + NH4+This reaction proceeds in the forward direction.
- D-methionine + H2O + O2 = 4-methylsulfanyl-2-oxobutanoate + H2O2 + NH4+This reaction proceeds in the forward direction.
- D-phenylalanine + H2O + O2 = 3-phenylpyruvate + H2O2 + NH4+This reaction proceeds in the forward direction.
- D-proline + O2 = 1-pyrroline-2-carboxylate + H2O2This reaction proceeds in the forward direction.
- D-serine + H2O + O2 = 3-hydroxypyruvate + H2O2 + NH4+This reaction proceeds in the forward direction.
- D-tryptophan + H2O + O2 = H2O2 + indole-3-pyruvate + NH4+This reaction proceeds in the forward direction.
- D-valine + H2O + O2 = 3-methyl-2-oxobutanoate + H2O2 + NH4+This reaction proceeds in the forward direction.
Cofactor
Activity regulation
Inhibited by benzoate, anthranilate and luvadaxistat (PubMed:21981077, PubMed:37289348).
Inhibited by 3-hydroxyquinolin-2(1h)-one, 4-hydroxy-6-[2-(7-hydroxy-2-oxo-4-phenyl-2h-chromen-6- Yl)ethyl]pyridazin-3(2h)-one and 3-(7-hydroxy-2-oxo-4-phenyl-2h-chromen-6-Yl)propanoic acid (PubMed:19438227, PubMed:25001371).
Inhibited by 3-hydroxyquinolin-2(1h)-one, 4-hydroxy-6-[2-(7-hydroxy-2-oxo-4-phenyl-2h-chromen-6- Yl)ethyl]pyridazin-3(2h)-one and 3-(7-hydroxy-2-oxo-4-phenyl-2h-chromen-6-Yl)propanoic acid (PubMed:19438227, PubMed:25001371).
Biotechnology
In comparison to human DAO, has relatively poor activity on D-serine and other substrates, raising doubts regarding the use of rat as a model system for testing drugs against schizophrenia or amyotrophic lateral sclerosis.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
140 mM | D-alanine | 8.3 | 25 | |||
310 mM | D-serine | 8.3 | 25 | |||
86 mM | D-proline | 8.3 | 25 | |||
15 mM | D-tryptophan | 8.3 | 25 | |||
35 mM | D-phenylalanine | 8.3 | 25 |
kcat is 27 sec-1 with D-alanine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
kcat is 6.4 sec-1 with D-serine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
kcat is 47 sec-1 with D-proline as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
kcat is 3.7 sec-1 with D-tryptophan as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
kcat is 8.5 sec-1 with D-phenylalanine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
kcat is 6.4 sec-1 with D-serine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
kcat is 47 sec-1 with D-proline as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
kcat is 3.7 sec-1 with D-tryptophan as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
kcat is 8.5 sec-1 with D-phenylalanine as substrate (at 25 degrees Celsius and at pH 8.3) (PubMed:21981077).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 8 | FAD (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 9 | FAD (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 10 | FAD (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 11 | FAD (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 36 | FAD (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 37 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 42 | FAD (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 43 | FAD (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 44 | FAD (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 48 | FAD (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 49 | FAD (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 50 | FAD (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 52 | D-dopa (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 162 | FAD (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 163 | FAD (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 181 | FAD (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 223 | D-serine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 227 | D-proline (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 227 | D-serine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 282 | D-dopa (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 282 | D-proline (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 282 | D-serine (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 282 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 311 | FAD (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 312 | D-dopa (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 312 | D-proline (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 312 | D-serine (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 312 | FAD (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 314 | FAD (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 315 | FAD (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 316 | FAD (UniProtKB | ChEBI) | ||||
Sequence: T |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell projection | |
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | extracellular space | |
Cellular Component | mitochondrial outer membrane | |
Cellular Component | peroxisomal matrix | |
Cellular Component | peroxisome | |
Cellular Component | presynaptic active zone | |
Molecular Function | D-amino-acid dehydrogenase activity | |
Molecular Function | D-amino-acid oxidase activity | |
Molecular Function | FAD binding | |
Molecular Function | identical protein binding | |
Biological Process | D-alanine catabolic process | |
Biological Process | D-amino acid catabolic process | |
Biological Process | D-serine catabolic process | |
Biological Process | D-serine metabolic process | |
Biological Process | digestion | |
Biological Process | dopamine biosynthetic process | |
Biological Process | killing by host of symbiont cells | |
Biological Process | L-leucine metabolic process | |
Biological Process | neutrophil-mediated killing of gram-negative bacterium | |
Biological Process | proline catabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameD-amino-acid oxidase
- EC number
- Short namesDAAO; DAMOX; DAO
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionO35078
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Transiently present in the cytosol before being delivered to the peroxisomes (By similarity).
In the cerebellum, a fraction of protein localizes to the presynaptic active zone, where its activity is regulated by protein BSN (PubMed:21700703).
Secreted into the lumen of the small intestine (By similarity).
In the cerebellum, a fraction of protein localizes to the presynaptic active zone, where its activity is regulated by protein BSN (PubMed:21700703).
Secreted into the lumen of the small intestine (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000162765 | 1-346 | D-amino-acid oxidase | |||
Sequence: MRVAVIGAGVIGLSTALCIHERYHPAQPLHMKIYADRFTPFTTSDVAAGLWQPYLSDPSNPQEAEWNQQTFDHLQSCLHSPNAEKMGLALISGYNLFRDEVPDPFWKSTVLGFRKLTPSELDMFPDYSYGWFNTSLLLEGKSYLSWLTERLTERGVKFIHRKVASFEEVVRGGVDVIINCTGVWAGALQADASLQPGRGQIIQVEAPWIKHFILTHDPSLGIYNSPYIIPGSKTVTLGGVFQLGNWSELNSVHDHNTIWKSCCQLEPTLKNARIMGELTGFRPVRPQVRLERERLRFGSSSAEVIHNYGHGGYGLTIHWGCAMEAANLFGKILEEKNLSRMPPSHL |
Post-translational modification
Phosphorylated in the cerebellum; probably not by PRKACA, PRKCA or PRKCE.
May be S-nitrosylated, which partially inactivates the enzyme.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the cerebellum, liver and proximal tubules of the renal cortex (at protein level) (PubMed:17880399, PubMed:20564560, PubMed:21700703, PubMed:26961980, PubMed:2896644).
Absent from spleen (at protein level) (PubMed:21700703).
Absent from spleen (at protein level) (PubMed:21700703).
Induction
Increased in pups born to mothers fed D-alanine during pregnancy and suckling; not induced when mothers fed D-aspartate (PubMed:7903300).
Not induced further in the cerebellum following two weeks of intraperitoneal injections of the antipsychotic haloperidol (PubMed:17880399).
Not induced further in the cerebellum following two weeks of intraperitoneal injections of the antipsychotic haloperidol (PubMed:17880399).
Developmental stage
In the liver and kidney, progressively increases during postnatal stages (at protein level).
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-16 | Required for protein stability | ||||
Sequence: MRVAVIGAGVIGLSTA | ||||||
Region | 215-227 | Active site lid that may open upon substrate/product migration in and out of the active site and close to increase the hydrophobicity of the active site, to make the hydride transfer reaction more efficient | ||||
Sequence: THDPSLGIYNSPY | ||||||
Motif | 344-346 | Microbody targeting signal | ||||
Sequence: SHL |
Sequence similarities
Belongs to the DAMOX/DASOX family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length346
- Mass (Da)38,820
- Last updated1998-01-01 v1
- Checksum2C4697960137A4FE
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JUK6 | A0A0G2JUK6_RAT | Dao | 250 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB003400 EMBL· GenBank· DDBJ | BAA22840.1 EMBL· GenBank· DDBJ | mRNA | ||
BC088395 EMBL· GenBank· DDBJ | AAH88395.1 EMBL· GenBank· DDBJ | mRNA |