O35078 · OXDA_RAT

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).

Catalytic activity

  • a D-alpha-amino acid + H2O + O2 = a 2-oxocarboxylate + H2O2 + NH4+
    EC:1.4.3.3 (UniProtKB | ENZYME | Rhea)
  • D-alanine + H2O + O2 = H2O2 + NH4+ + pyruvate
    This 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-lysine + H2O + O2 = 6-amino-2-oxohexanoate + H2O2 + NH4+
    This reaction proceeds in the forward direction.
    EC:1.4.3.3 (UniProtKB | ENZYME | Rhea)
  • 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 + H2O2
    This 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

FAD (UniProtKB | Rhea| CHEBI:57692 )

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).

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 mMD-alanine8.325
310 mMD-serine8.325
86 mMD-proline8.325
15 mMD-tryptophan8.325
35 mMD-phenylalanine8.325
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).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site8FAD (UniProtKB | ChEBI)
Binding site9FAD (UniProtKB | ChEBI)
Binding site10FAD (UniProtKB | ChEBI)
Binding site11FAD (UniProtKB | ChEBI)
Binding site36FAD (UniProtKB | ChEBI)
Binding site37FAD (UniProtKB | ChEBI)
Binding site42FAD (UniProtKB | ChEBI)
Binding site43FAD (UniProtKB | ChEBI)
Binding site44FAD (UniProtKB | ChEBI)
Binding site48FAD (UniProtKB | ChEBI)
Binding site49FAD (UniProtKB | ChEBI)
Binding site50FAD (UniProtKB | ChEBI)
Binding site52D-dopa (UniProtKB | ChEBI)
Binding site162FAD (UniProtKB | ChEBI)
Binding site163FAD (UniProtKB | ChEBI)
Binding site181FAD (UniProtKB | ChEBI)
Binding site223D-serine (UniProtKB | ChEBI)
Binding site227D-proline (UniProtKB | ChEBI)
Binding site227D-serine (UniProtKB | ChEBI)
Binding site282D-dopa (UniProtKB | ChEBI)
Binding site282D-proline (UniProtKB | ChEBI)
Binding site282D-serine (UniProtKB | ChEBI)
Binding site282FAD (UniProtKB | ChEBI)
Binding site311FAD (UniProtKB | ChEBI)
Binding site312D-dopa (UniProtKB | ChEBI)
Binding site312D-proline (UniProtKB | ChEBI)
Binding site312D-serine (UniProtKB | ChEBI)
Binding site312FAD (UniProtKB | ChEBI)
Binding site314FAD (UniProtKB | ChEBI)
Binding site315FAD (UniProtKB | ChEBI)
Binding site316FAD (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcell projection
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentextracellular space
Cellular Componentmitochondrial outer membrane
Cellular Componentperoxisomal matrix
Cellular Componentperoxisome
Cellular Componentpresynaptic active zone
Molecular FunctionD-amino-acid dehydrogenase activity
Molecular FunctionD-amino-acid oxidase activity
Molecular FunctionFAD binding
Molecular Functionidentical protein binding
Biological ProcessD-alanine catabolic process
Biological ProcessD-amino acid catabolic process
Biological ProcessD-serine catabolic process
Biological ProcessD-serine metabolic process
Biological Processdigestion
Biological Processdopamine biosynthetic process
Biological Processkilling by host of symbiont cells
Biological ProcessL-leucine metabolic process
Biological Processneutrophil-mediated killing of gram-negative bacterium
Biological Processproline catabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    D-amino-acid oxidase
  • EC number
  • Short names
    DAAO; DAMOX; DAO

Gene names

    • Name
      Dao
    • Synonyms
      Dao1

Organism names

  • Taxonomic identifier
  • Strain
    • Sprague-Dawley
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    O35078

Proteomes

Organism-specific databases

Subcellular Location

Peroxisome matrix
Cytoplasm, cytosol
Secreted
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).

Keywords

Phenotypes & Variants

Variants

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The viewer provides 2 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00001627651-346D-amino-acid oxidase

Post-translational modification

Phosphorylated in the cerebellum; probably not by PRKACA, PRKCA or PRKCE.
May be S-nitrosylated, which partially inactivates the enzyme.

Keywords

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).

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).

Developmental stage

In the liver and kidney, progressively increases during postnatal stages (at protein level).

Interaction

Subunit

Monomer (PubMed:21981077).
Interacts with BSN (via coiled region); the interaction is direct and inhibits DAO enzyme activity (PubMed:21700703).

Protein-protein interaction databases

Chemistry

Structure

Family & Domains

Features

Showing features for region, motif.

TypeIDPosition(s)Description
Region1-16Required for protein stability
Region215-227Active 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
Motif344-346Microbody targeting signal

Sequence similarities

Belongs to the DAMOX/DASOX family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    346
  • Mass (Da)
    38,820
  • Last updated
    1998-01-01 v1
  • Checksum
    2C4697960137A4FE
MRVAVIGAGVIGLSTALCIHERYHPAQPLHMKIYADRFTPFTTSDVAAGLWQPYLSDPSNPQEAEWNQQTFDHLQSCLHSPNAEKMGLALISGYNLFRDEVPDPFWKSTVLGFRKLTPSELDMFPDYSYGWFNTSLLLEGKSYLSWLTERLTERGVKFIHRKVASFEEVVRGGVDVIINCTGVWAGALQADASLQPGRGQIIQVEAPWIKHFILTHDPSLGIYNSPYIIPGSKTVTLGGVFQLGNWSELNSVHDHNTIWKSCCQLEPTLKNARIMGELTGFRPVRPQVRLERERLRFGSSSAEVIHNYGHGGYGLTIHWGCAMEAANLFGKILEEKNLSRMPPSHL

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0G2JUK6A0A0G2JUK6_RATDao250

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AB003400
EMBL· GenBank· DDBJ
BAA22840.1
EMBL· GenBank· DDBJ
mRNA
BC088395
EMBL· GenBank· DDBJ
AAH88395.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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