Q06278 · AOXA_HUMAN
- ProteinAldehyde oxidase
- GeneAOX1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1338 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium and phthalazine, 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. May also 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.
Miscellaneous
AOX 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).
Catalytic activity
- an aldehyde + H2O + O2 = a carboxylate + H+ + H2O2
- H2O + O2 + retinal = H+ + H2O2 + retinoate
Cofactor
Protein has several cofactor binding sites:
Note: Binds 2 [2Fe-2S] clusters per subunit.
Note: Binds 1 FAD per subunit.
Note: Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
Activity regulation
Is very potently inhibited by raloxifene (PubMed:26842593).
Also inhibited by estradiol, ethinyl estradiol, hydralazine, menadione, isovanillin and thioridazine. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor (PubMed:22031625, PubMed:22522748, PubMed:22996261, PubMed:26322824, PubMed:9224775).
Also inhibited by estradiol, ethinyl estradiol, hydralazine, menadione, isovanillin and thioridazine. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor (PubMed:22031625, PubMed:22522748, PubMed:22996261, PubMed:26322824, PubMed:9224775).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
4.6 μM | benzaldehyde | in the presence of 2,6-dichlorophenol indophenol as electron acceptor | ||||
45.18 μM | benzaldehyde | in the presence of ferricyanide as electron acceptor | ||||
1.3 μM | phthalazine | 7.5 | 25 | |||
8.96 μM | phthalazine | in the presence of 2,6-dichlorophenol indophenol as electron acceptor | ||||
125.7 μM | phthalazine | in the presence of ferricyanide as electron acceptor | ||||
0.78 μM | phenanthridine | in the pres 2,6-dichlorophenol indophenol as electron acceptor | ||||
25.5 μM | phenanthridine | in the presence of ferricyanide as electron acceptor | ||||
26.53 μM | phenanthridine | in the presence of molecular oxygen as electron acceptor | ||||
3.9 μM | phenanthridine | 7.5 | 25 | |||
5.2 μM | chloroquinazolinone | 7.5 | 25 | |||
0.42 mM | 6-deoxypenciclovir | 7 | 37 | |||
0.15 mM | famciclovir | 7 | 37 | |||
6.3 μM | N-[(2-dimethylamino)ethyl]acridine-4-carboxamide | 7.4 | 37 |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
16 nmol/min/mg | with 6-deoxypenciclovir as substrate | ||||
61 nmol/min/mg | with famciclovir as substrate | ||||
2.3 nmol/min/mg | with N-[(2-dimethylamino)ethyl]acridine-4-carboxamide as substrate |
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.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 44 | [2Fe-2S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 49 | [2Fe-2S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 52 | [2Fe-2S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 74 | [2Fe-2S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 113 | Mo-molybdopterin (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 114 | [2Fe-2S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 117 | [2Fe-2S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 149 | [2Fe-2S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 151 | [2Fe-2S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 151 | Mo-molybdopterin (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 264-271 | FAD (UniProtKB | ChEBI) | ||||
Sequence: VIMGNTSV | ||||||
Binding site | 345 | FAD (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 354 | FAD (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 358 | FAD (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 367 | FAD (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 411 | FAD (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 806-807 | Mo-molybdopterin (UniProtKB | ChEBI) | ||||
Sequence: AF | ||||||
Binding site | 1047 | Mo-molybdopterin (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 1088-1091 | Mo-molybdopterin (UniProtKB | ChEBI) | ||||
Sequence: GSVV | ||||||
Binding site | 1203 | Mo-molybdopterin (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 1268 | Mo-molybdopterin (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Active site | 1270 | Proton acceptor; for azaheterocycle hydroxylase activity | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Molecular Function | 2 iron, 2 sulfur cluster binding | |
Molecular Function | aldehyde oxidase activity | |
Molecular Function | FAD binding | |
Molecular Function | flavin adenine dinucleotide binding | |
Molecular Function | identical protein binding | |
Molecular Function | iron ion binding | |
Molecular Function | molybdopterin cofactor binding | |
Molecular Function | NAD binding | |
Molecular Function | protein homodimerization activity | |
Biological Process | lipid metabolic process | |
Biological Process | xenobiotic metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAldehyde oxidase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ06278
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 44 | Disrupts protein stability. | ||||
Sequence: C → W | ||||||
Natural variant | VAR_061136 | 314 | in dbSNP:rs58185012 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_047517 | 802 | decreases homodimerization but nearly no effect on kinetic parameters; dbSNP:rs41309768 | |||
Sequence: R → C | ||||||
Natural variant | VAR_070256 | 921 | increases homodimerization; abolishes enzymatic activity on phenanthridine; decreases turnover number with benzaldehyde, phtalazine and chloroquinazolinone as substrate, while nearly no effect on the KM; dbSNP:rs56199635 | |||
Sequence: R → H | ||||||
Natural variant | VAR_070257 | 1135 | increases homodimerization and turnover number with phenanthridine as substrate; nearly no effect on kinetic parameters with benzaldehyde, phtalazine and chloroquinazolinone as substrate; dbSNP:rs55754655 | |||
Sequence: N → S | ||||||
Mutagenesis | 1269 | No effect on dimerization. Loss of oxidase activity. | ||||
Sequence: G → R | ||||||
Natural variant | VAR_070258 | 1271 | no effect on dimerization; no effect on oxidase activity; dbSNP:rs141786030 | |||
Sequence: S → L | ||||||
Natural variant | VAR_047518 | 1297 | increases homodimerization and turnover number with phenanthridine as substrate; nearly no effect on kinetic parameters with benzaldehyde, phtalazine and chloroquinazolinone as substrate; dbSNP:rs3731722 | |||
Sequence: H → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,642 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 chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000166104 | 1-1338 | Aldehyde oxidase | |||
Sequence: MDRASELLFYVNGRKVIEKNVDPETMLLPYLRKKLRLTGTKYGCGGGGCGACTVMISRYNPITKRIRHHPANACLIPICSLYGAAVTTVEGIGSTHTRIHPVQERIAKCHGTQCGFCTPGMVMSIYTLLRNHPEPTLDQLTDALGGNLCRCTGYRPIIDACKTFCKTSGCCQSKENGVCCLDQGINGLPEFEEGSKTSPKLFAEEEFLPLDPTQELIFPPELMIMAEKQSQRTRVFGSERMMWFSPVTLKELLEFKFKYPQAPVIMGNTSVGPEVKFKGVFHPVIISPDRIEELSVVNHAYNGLTLGAGLSLAQVKDILADVVQKLPEEKTQMYHALLKHLGTLAGSQIRNMASLGGHIISRHPDSDLNPILAVGNCTLNLLSKEGKRQIPLNEQFLSKCPNADLKPQEILVSVNIPYSRKWEFVSAFRQAQRQENALAIVNSGMRVFFGEGDGIIRELCISYGGVGPATICAKNSCQKLIGRHWNEQMLDIACRLILNEVSLLGSAPGGKVEFKRTLIISFLFKFYLEVSQILKKMDPVHYPSLADKYESALEDLHSKHHCSTLKYQNIGPKQHPEDPIGHPIMHLSGVKHATGEAIYCDDMPLVDQELFLTFVTSSRAHAKIVSIDLSEALSMPGVVDIMTAEHLSDVNSFCFFTEAEKFLATDKVFCVGQLVCAVLADSEVQAKRAAKRVKIVYQDLEPLILTIEESIQHNSSFKPERKLEYGNVDEAFKVVDQILEGEIHMGGQEHFYMETQSMLVVPKGEDQEMDVYVSTQFPKYIQDIVASTLKLPANKVMCHVRRVGGAFGGKVLKTGIIAAVTAFAANKHGRAVRCVLERGEDMLITGGRHPYLGKYKAGFMNDGRILALDMEHYSNAGASLDESLFVIEMGLLKMDNAYKFPNLRCRGWACRTNLPSNTAFRGFGFPQAALITESCITEVAAKCGLSPEKVRIINMYKEIDQTPYKQEINAKNLIQCWRECMAMSSYSLRKVAVEKFNAENYWKKKGLAMVPLKFPVGLGSRAAGQAAALVHIYLDGSVLVTHGGIEMGQGVHTKMIQVVSRELRMPMSNVHLRGTSTETVPNANISGGSVVADLNGLAVKDACQTLLKRLEPIISKNPKGTWKDWAQTAFDESINLSAVGYFRGYESDMNWEKGEGQPFEYFVYGAACSEVEIDCLTGDHKNIRTDIVMDVGCSINPAIDIGQIEGAFIQGMGLYTIEELNYSPQGILHTRGPDQYKIPAICDMPTELHIALLPPSQNSNTLYSSKGLGESGVFLGCSVFFAIHDAVSAARQERGLHGPLTLNSPLTPEKIRMACEDKFTKMIPRDEPGSYVPWNVPI | ||||||
Modified residue | 1068 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Abundant 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).
Induction
In liver, is down-regulated by adiponectin and by the PPARA agonist, fenofibric acid.
Developmental stage
Not detected in preadipocytes but strongly induced in mature adipocytes.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q06278 | AOX1 Q06278 | 2 | EBI-3926368, EBI-3926368 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 5-92 | 2Fe-2S ferredoxin-type | ||||
Sequence: SELLFYVNGRKVIEKNVDPETMLLPYLRKKLRLTGTKYGCGGGGCGACTVMISRYNPITKRIRHHPANACLIPICSLYGAAVTTVEGI | ||||||
Domain | 236-421 | FAD-binding PCMH-type | ||||
Sequence: FGSERMMWFSPVTLKELLEFKFKYPQAPVIMGNTSVGPEVKFKGVFHPVIISPDRIEELSVVNHAYNGLTLGAGLSLAQVKDILADVVQKLPEEKTQMYHALLKHLGTLAGSQIRNMASLGGHIISRHPDSDLNPILAVGNCTLNLLSKEGKRQIPLNEQFLSKCPNADLKPQEILVSVNIPYSRK |
Sequence similarities
Belongs to the xanthine dehydrogenase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,338
- Mass (Da)147,918
- Last updated2008-11-25 v2
- Checksum2AB5E543F18C9261
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 41 | in Ref. 1; AAA96650 and 2; AAB83966 | ||||
Sequence: K → P | ||||||
Sequence conflict | 127 | in Ref. 1; AAA96650 and 2; AAB83966 | ||||
Sequence: T → P | ||||||
Sequence conflict | 152 | in Ref. 1; AAA96650 and 2; AAB83966 | ||||
Sequence: T → H | ||||||
Sequence conflict | 227 | in Ref. 1; AAA96650 and 2; AAB83966 | ||||
Sequence: E → D | ||||||
Sequence conflict | 251 | in Ref. 1; AAA96650 | ||||
Sequence: E → D | ||||||
Sequence conflict | 418 | in Ref. 1; AAA96650 and 2; AAB83966 | ||||
Sequence: Y → I | ||||||
Sequence conflict | 501 | in Ref. 2; AAB83966 | ||||
Sequence: V → L | ||||||
Sequence conflict | 627 | in Ref. 2; AAB83966 | ||||
Sequence: I → N | ||||||
Sequence conflict | 929 | in Ref. 1; AAA96650 and 2; AAB83966 | ||||
Sequence: A → V | ||||||
Sequence conflict | 1019 | in Ref. 1; AAA96650 and 2; AAB83966 | ||||
Sequence: G → A |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L11005 EMBL· GenBank· DDBJ | AAA96650.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AF017060 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009441 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009442 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009443 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009444 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009445 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009446 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009447 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009448 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009449 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009450 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009451 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009452 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009453 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009454 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009455 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009456 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009457 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009458 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009459 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009460 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009461 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009462 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009463 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009464 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009465 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009466 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009467 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009468 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009469 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009470 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009471 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009472 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009473 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF009474 EMBL· GenBank· DDBJ | AAB83966.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AF010260 EMBL· GenBank· DDBJ | AAB83968.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB046692 EMBL· GenBank· DDBJ | BAB40305.1 EMBL· GenBank· DDBJ | mRNA | ||
AC007163 EMBL· GenBank· DDBJ | AAX93285.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC080164 EMBL· GenBank· DDBJ | AAY24265.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471063 EMBL· GenBank· DDBJ | EAW70209.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC117179 EMBL· GenBank· DDBJ | AAI17180.1 EMBL· GenBank· DDBJ | mRNA | ||
BC117181 EMBL· GenBank· DDBJ | AAI17182.1 EMBL· GenBank· DDBJ | mRNA |