Protein: Aldehyde oxidase 1 (EC 1.2.3.1) (Azaheterocycle hydroxylase 1) (EC 1.17.3.-) (Q9Z0U5)
Organism: Rattus norvegicus (Rat)
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 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. Is a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also catalyzes nitric oxide (NO) production; under anaerobic conditions, reduces nitrite to NO with NADH or aldehyde as electron donor, but under aerobic conditions, NADH is the preferred substrate. These reactions may be catalyzed by several isozymes. May play a role in adipogenesis.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:17353002}.
Sequence: MDPPQLLFYVNGQKVVENNVDPEMMLLPYLRKNLRLTGTKYGCGGGGCGACTVMISRYNPSTKSIRHHPVNACLTPICSLYGTAVTTVEGIGNTRTRLHPVQERIAKCHSTQCGFCTPGMVMSMYALLRNHPEPSLDQLTDALGGNLCRCTGYRPIIDACKTFCRASGCCESKENGVCCLDQGINGSAEFQEGDETSPELFSEKEFQPLDPTQELIFPPELMRIAEKQPPKTRVFYSNRMTWISPVTLEELVEAKFKYPGAPIVMGYTSVGPEVKFKGVFHPIIISPDRIEELSIINQTGDGLTLGAGLSLDQVKDILTDVVQKLPEETTQTYRALLKHLRTLAGSQIRNMASLGGHIVSRHLDSDLNPLLAVGNCTLNLLSKDGKRQIPLSEQFLRKCPDSDLKPQEVLVSVNIPCSRKWEFVSAFRQAQRQQNALAIVNSGMRVLFREGGGVIKELSILYGGVGPTTIGAKNSCQKLIGRPWNEEMLDTACRLVLDEVTLAGSAPGGKVEFKRTLIISFLFKFYLEVLQGLKREDPGHYPSLTNNYESALEDLHSKHHWRTLTHQNVDSMQLPQDPIGRPIMHLSGIKHATGEAIYCDDMPAVDRELFLTFVTSSRAHAKIVSIDLSEALSLPGVVDIITADHLQDATTFGTETLLATDKVHCVGQLVCAVIADSETRAKQAAKHVKVVYRDLEPLILTIEEAIQHKSFFESERKLECGNVDEAFKIADQILEGEIHIGGQEHFYMETQSMLVVPKGEDGEIDIYVSTQFPKHIQDIVAATLKLSVNKVMCHVRRVGGAFGGKVGKTSIMAAITAFAASKHGRAVRCTLERGEDMLITGGRHPYLGKYKVGFMRDGRIVALDVEHYCNGGSSLDESLWVIEMGLLKMDNAYKFPNLRCRGWACRTNLPSHTALRGFGFPQAGLVTEACVTEVAIRCGLSPEQVRTINMYKQIDNTHYKQEFSAKTLFECWRECMAKCSYSERKTAVGKFNAENSWKKRGMAVIPLKFPVGVGSVAMGQAAALVHIYLDGSALVSHGGIEMGQGVHTKMIQVVSRELKMPMSSVHLRGTSTETVPNTNASGGSVVADLNGLAVKDACQTLLKRLEPIISKNPQGTWKDWAQTAFDQSVSLSAVGYFRGYESNINWEKGEGHPFEYFVYGAACSEVEIDCLTGDHKNIRTDIVMDVGHSINPALDIGQVEGAFIQGMGLYTIEELSYSPQGILYSRGPNQYKIPAICDIPTEMHISFLPPSEHSNTLYSSKGLGESGVFLGCSVFFAIHDAVRAARQERGISGPWKLTSPLTPEKIRMACEDKFTKMIPRDEPGSYVPWNIPV
InterPro domains: - IPR001041: 2Fe-2S ferredoxin-type iron-sulfur binding domain (domain) [4-91]
- IPR016166: FAD-binding domain, PCMH-type (domain) [235-420]
- IPR006058: 2Fe-2S ferredoxin, iron-sulphur binding site (binding_site) [43-51]
- IPR036884: [2Fe-2S]-binding domain superfamily (homologous_superfamily) [99-219]
- IPR016208: Aldehyde oxidase/xanthine dehydrogenase-like (family) [2-1332]
- IPR022407: Oxidoreductase, molybdopterin binding site (binding_site) [801-836]
- IPR036010: 2Fe-2S ferredoxin-like superfamily (homologous_superfamily) [5-91]
- IPR016167: FAD-binding, type PCMH, subdomain 1 (homologous_superfamily) [227-290]
- IPR002346: Molybdopterin dehydrogenase, FAD-binding (domain) [239-416]
- IPR036856: Aldehyde oxidase/xanthine dehydrogenase, a/b hammerhead superfamily (homologous_superfamily) [548-697]
- IPR037165: Aldehyde oxidase/xanthine dehydrogenase, molybdopterin binding domain superfamily (homologous_superfamily) [697-1316]
- IPR000674: Aldehyde oxidase/xanthine dehydrogenase, a/b hammerhead (domain) [593-696]
- IPR016169: FAD-binding, type PCMH, subdomain 2 (homologous_superfamily) [291-418]
- IPR002888: [2Fe-2S]-binding (domain) [87-161]
- IPR005107: CO dehydrogenase flavoprotein, C-terminal (domain) [425-529]
- IPR036318: FAD-binding, type PCMH-like superfamily (homologous_superfamily) [199-418]
- IPR036683: CO dehydrogenase flavoprotein, C-terminal domain superfamily (homologous_superfamily) [421-535]
- IPR014313: Aldehyde oxidase (family) [4-1333]
- IPR008274: Aldehyde oxidase/xanthine dehydrogenase, first molybdopterin binding domain (domain) [717-950]
- IPR012675: Beta-grasp domain superfamily (homologous_superfamily) [3-92]
Interaction partners: - Nicotinamide N-methyltransferase
- Aldehyde dehydrogenase 1A1
- Cytochrome P450 3A1
- Cytochrome P450 1A2
- Amine oxidase [flavin-containing] A
- Amine oxidase [flavin-containing] B
- Retinaldehyde dehydrogenase 3
- Cytochrome P450 1A1
- Alpha-aminoadipic semialdehyde dehydrogenase
- Aldehyde dehydrogenase, mitochondrial
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0016491 (oxidoreductase activity), GO:0043167 (ion binding), GO:0097159 (organic cyclic compound binding), GO:0051540 (metal cluster binding), GO:0005515 (protein binding), GO:0016725 (oxidoreductase activity, acting on CH or CH2 groups), GO:0043546 (molybdopterin cofactor binding), GO:1901265 (nucleoside phosphate binding), GO:0051536 (iron-sulfur cluster binding), GO:0016661 (oxidoreductase activity, acting on other nitrogenous compounds as donors), GO:0043168 (anion binding), GO:0042802 (identical protein binding), GO:0000166 (nucleotide binding), GO:0050660 (flavin adenine dinucleotide binding), GO:0016662 (oxidoreductase activity, acting on other nitrogenous compounds as donors, cytochrome as acceptor), GO:0051537 (2 iron, 2 sulfur cluster binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0009605 (response to external stimulus), GO:0009628 (response to abiotic stimulus), GO:0042221 (response to chemical), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0009607 (response to biotic stimulus), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0007568 (aging), GO:0051707 (response to other organism), GO:0044238 (primary metabolic process), GO:0009266 (response to temperature stimulus), GO:1901564 (organonitrogen compound metabolic process), GO:0044282 (small molecule catabolic process), GO:0043207 (response to external biotic stimulus), GO:0006979 (response to oxidative stress), GO:0046483 (heterocycle metabolic process), GO:0044248 (cellular catabolic process), GO:1901700 (response to oxygen-containing compound), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0010033 (response to organic substance), GO:1901135 (carbohydrate derivative metabolic process), GO:0009408 (response to heat), GO:0010035 (response to inorganic substance), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:1901698 (response to nitrogen compound), GO:0070887 (cellular response to chemical stimulus), GO:0055086 (nucleobase-containing small molecule metabolic process), GO:1902074 (response to salt), GO:0009617 (response to bacterium), GO:0043603 (amide metabolic process), GO:1901575 (organic substance catabolic process), GO:0034655 (nucleobase-containing compound catabolic process), GO:0010038 (response to metal ion), GO:0034097 (response to cytokine), GO:0044270 (cellular nitrogen compound catabolic process), GO:0032496 (response to lipopolysaccharide), GO:0009112 (nucleobase metabolic process), GO:1901565 (organonitrogen compound catabolic process), GO:0071310 (cellular response to organic substance), GO:0019439 (aromatic compound catabolic process), GO:0009116 (nucleoside metabolic process), GO:0046700 (heterocycle catabolic process), GO:0002237 (response to molecule of bacterial origin), GO:0072521 (purine-containing compound metabolic process), GO:0000255 (allantoin metabolic process), GO:1901136 (carbohydrate derivative catabolic process), GO:0033993 (response to lipid), GO:1901361 (organic cyclic compound catabolic process), GO:1901657 (glycosyl compound metabolic process), GO:0042542 (response to hydrogen peroxide), GO:0034656 (nucleobase-containing small molecule catabolic process), GO:0000302 (response to reactive oxygen species), GO:0006144 (purine nucleobase metabolic process), GO:0072523 (purine-containing compound catabolic process), GO:0046113 (nucleobase catabolic process), GO:0070555 (response to interleukin-1), GO:0071345 (cellular response to cytokine stimulus), GO:0009164 (nucleoside catabolic process), GO:0009119 (ribonucleoside metabolic process), GO:1901658 (glycosyl compound catabolic process), GO:0034612 (response to tumor necrosis factor), GO:0042278 (purine nucleoside metabolic process), GO:0010044 (response to aluminum ion), GO:0042454 (ribonucleoside catabolic process), GO:0046128 (purine ribonucleoside metabolic process), GO:0071347 (cellular response to interleukin-1), GO:0071356 (cellular response to tumor necrosis factor), GO:0006145 (purine nucleobase catabolic process), GO:0006152 (purine nucleoside catabolic process), GO:0046085 (adenosine metabolic process), GO:0046102 (inosine metabolic process), GO:0046130 (purine ribonucleoside catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005615 (extracellular space), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0005576 (extracellular region), GO:0042579 (microbody), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005777 (peroxisome)