MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP000157

UniProt Annotations

Entry Information
Gene Namealdehyde oxidase 1
Protein EntryAOXA_HUMAN
UniProt IDQ06278
SpeciesHuman
Comments
Comment typeDescription
Biophysicochemical PropertiesKinetic parameters: KM=7.1 uM for benzaldehyde (at 25 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; KM=1.3 uM for phthalazine (at 25 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; KM=3.9 uM for phenanthridine (at 25 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; KM=5.2 uM for chloroquinazolinone (at 25 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; KM=0.42 mM for 6-deoxypenciclovir (at 37 degrees Celsius and pH 7) {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; KM=0.15 mM for famciclovir (at 37 degrees Celsius and pH 7) {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; KM=6.3 uM for N-[(2-dimethylamino)ethyl]acridine-4-carboxamide (at 37 degrees Celsius and pH 7.4) {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; Vmax=16 nmol/min/mg enzyme with 6-deoxypenciclovir as substrate {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; Vmax=61 nmol/min/mg enzyme with famciclovir as substrate {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; Vmax=2.3 nmol/min/mg enzyme with N-[(2- dimethylamino)ethyl]acridine-4-carboxamide as substrate {ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}; Note=kcat is 6.4 min(-1) for benzaldehyde oxidation, 5.6 min(-1) for phthalazine oxidation, 12.2 min(-1) for phenanthridine oxidation and 5.6 min(-1) for chloroquinazolinone oxidation.;
Catalytic ActivityAn aldehyde + H(2)O + O(2) = a carboxylate + H(2)O(2).
Catalytic ActivityRetinal + O(2) + H(2)O = retinoate + H(2)O(2).
CautionWas originally thought to be a xanthine dehydrogenase. {ECO:0000305|PubMed:8248161}.
CofactorName=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:49601; Evidence={ECO:0000269|PubMed:22279051}; Note=Binds 2 [2Fe-2S] clusters per subunit. {ECO:0000269|PubMed:22279051};
CofactorName=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:22279051}; Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:22279051};
CofactorName=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302; Evidence={ECO:0000269|PubMed:22279051}; Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit. {ECO:0000269|PubMed:22279051};
Developmental StageNot detected in preadipocytes but strongly induced in mature adipocytes. {ECO:0000269|PubMed:18671973}.
Enzyme RegulationIs very potently inhibited by raloxifene. Also inhibited by estradiol, ethinyl estradiol, hydralazine, menadione, and isovanillin. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor. {ECO:0000269|PubMed:22031625, ECO:0000269|PubMed:22522748, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:9224775}.
FunctionOxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N- methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis. {ECO:0000269|PubMed:20444863, ECO:0000269|PubMed:22031625, ECO:0000269|PubMed:22279051, ECO:0000269|PubMed:22522748, ECO:0000269|PubMed:22996261, ECO:0000269|PubMed:23857892, ECO:0000269|PubMed:7786031, ECO:0000269|PubMed:9224775}.
InductionIn liver, is down-regulated by adiponectin and by the PPARA agonist, fenofibric acid. {ECO:0000269|PubMed:17022944}.
MiscellaneousAOX genes evolved from a xanthine oxidoreductase ancestral precursor via a series of gene duplication and suppression/deletion events. Different animal species contain a different complement of AOX genes encoding an equivalent number of AOX isoenzymes. In mammals, the two extremes are represented by certain rodents such as mice and rats, which are endowed with 4 AOX genes, and by humans, whose genome is characterized by a single active gene (PubMed:22335465). {ECO:0000305|PubMed:22335465}.
Sequence CautionSequence=AAA96650.1; Type=Frameshift; Positions=284, 286, 294, 302; Evidence={ECO:0000305}; Sequence=AAB83966.1; Type=Frameshift; Positions=284, 286, 294, 302; Evidence={ECO:0000305};
SimilarityBelongs to the xanthine dehydrogenase family. {ECO:0000305}.
SimilarityContains 1 2Fe-2S ferredoxin-type domain. {ECO:0000255|PROSITE-ProRule:PRU00465}.
SimilarityContains 1 FAD-binding PCMH-type domain. {ECO:0000255|PROSITE-ProRule:PRU00718}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:18671973, ECO:0000269|PubMed:20444863, ECO:0000269|PubMed:23857892}.
SubunitHomodimer.
Tissue SpecificityAbundant in liver, expressed in adipose tissue and at lower levels in lung, skeletal muscle, pancreas. In contrast to mice, no significant gender difference in AOX1 expression level (at protein level). {ECO:0000269|PubMed:18066686, ECO:0000269|PubMed:18671973, ECO:0000269|PubMed:20444863, ECO:0000269|PubMed:22031625, ECO:0000269|PubMed:22522748, ECO:0000269|PubMed:23857892, ECO:0000269|PubMed:8248161}.
  logo