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Protein

Aldehyde oxidase 1

Gene

Aox1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Also plays a role in the reductive metabolism of the xenobiotic imidacloprid (IMI) via its nitroreduction to nitrosoguanidine (IMI-NNO) and aminoguanidine (IMI-NNH2). 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. Cannot use xanthine and hypoxanthine as substrate.4 Publications

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:23263164).1 Publication

Catalytic activityi

An aldehyde + H2O + O2 = a carboxylate + H2O2.2 Publications
Retinal + O2 + H2O = retinoate + H2O2.2 Publications

Cofactori

Protein has several cofactor binding sites:

Kineticsi

kcat is 317.6 min(-1) for benzaldehyde oxidation, 128.1 min(-1) for phthalazine oxidation, 49.5 min(-1) for retinal oxidation, and 519.9 min(-1) for acetaldehyde oxidation (at 30 degrees Celsius and pH 7.5) (PubMed:19401776). In PubMed:19401776, the measures are done with the recombinant protein, which is only 20% active, due to an incomplete saturation of the molybdenum cofactor with the sulfido ligand.1 Publication
  1. KM=3.8 µM for retinal (at 37 degrees Celsius and pH 7.8)2 Publications
  2. KM=97.7 µM for benzaldehyde (at 30 degrees Celsius and pH 7.5)2 Publications
  3. KM=11.4 µM for phthalazine (at 30 degrees Celsius and pH 7.5)2 Publications
  4. KM=55.8 µM for retinal (at 30 degrees Celsius and pH 7.5)2 Publications
  5. KM=17.5 mM for acetaldehyde (at 30 degrees Celsius and pH 7.5)2 Publications
  1. Vmax=807 nmol/min/mg enzyme with retinal as substrate (at 37 degrees Celsius and pH 7.8)2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi43Iron-sulfur 1 (2Fe-2S)By similarity1
Metal bindingi48Iron-sulfur 1 (2Fe-2S)By similarity1
Metal bindingi51Iron-sulfur 1 (2Fe-2S)By similarity1
Metal bindingi73Iron-sulfur 1 (2Fe-2S)By similarity1
Binding sitei112MolybdopterinBy similarity1
Metal bindingi113Iron-sulfur 2 (2Fe-2S)By similarity1
Metal bindingi116Iron-sulfur 2 (2Fe-2S)By similarity1
Metal bindingi148Iron-sulfur 2 (2Fe-2S)By similarity1
Metal bindingi150Iron-sulfur 2 (2Fe-2S)By similarity1
Binding sitei150MolybdopterinBy similarity1
Binding sitei344FAD; via amide nitrogenBy similarity1
Binding sitei353FADBy similarity1
Binding sitei357FADBy similarity1
Binding sitei366FADBy similarity1
Binding sitei410FAD; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei1042Molybdopterin; via carbonyl oxygenBy similarity1
Binding sitei1198MolybdopterinBy similarity1
Binding sitei1263Molybdopterin; via carbonyl oxygenBy similarity1
Active sitei1265Proton acceptor; for azaheterocycle hydroxylase activity1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi263 – 270FADBy similarity8

GO - Molecular functioni

GO - Biological processi

  • drug metabolic process Source: UniProtKB
  • oxidation-reduction process Source: MGI
  • xanthine catabolic process Source: GO_Central

Keywordsi

Molecular functionOxidoreductase
Ligand2Fe-2S, FAD, Flavoprotein, Iron, Iron-sulfur, Metal-binding, Molybdenum

Enzyme and pathway databases

BRENDAi1.2.3.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Aldehyde oxidase 1Imported (EC:1.2.3.12 Publications)
Alternative name(s):
Azaheterocycle hydroxylase 1 (EC:1.17.3.-)
Retinal oxidase
Gene namesi
Name:Aox1Imported
Synonyms:Ao, Ro
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:88035. Aox1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi806V → E: Decreases substrate affinity and activity on benzaldehyde, phthalazine and acetaldehyde, while increases affinity for more hydrophobic aldehydes like retinal. Abolishes catalytic activity; when associated with R-884. 1 Publication1
Mutagenesisi884M → R: Abolishes catalytic activity on phthalazine and acetaldehyde. Decreases catalytic efficiency on benzaldehyde and retinal. Abolishes catalytic activity; when associated with E-806. 1 Publication1
Mutagenesisi1265E → Q: Abolishes catalytic activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1641354.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001661061 – 1333Aldehyde oxidase 1Add BLAST1333

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1063PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO54754.
PaxDbiO54754.
PRIDEiO54754.

PTM databases

iPTMnetiO54754.
PhosphoSitePlusiO54754.

Expressioni

Tissue specificityi

Highest expression in esophagus. Moderately low expression in lung, liver, heart, Harderian gland, olfactory mucosa, skin and testis. In brain, expression is very high in choroid plexus, high in hind brain and low in hippocampus and cerebellum. In spinal cord expression is strongest in anterior horns. Low expression detected in spleen and eye. AOX1 expression in the livers of mice is approximately seven times greater in males than females.4 Publications

Developmental stagei

Expressed in adult liver but not in neonatal or embryonic liver. Not detected in preadipocytes but strongly induced in mature adipocytes.2 Publications

Inductioni

Repressed by pioglitazone, fenofibrate and PPARA agonists. Induced by testosterone.2 Publications

Gene expression databases

CleanExiMM_AOX1.

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

IntActiO54754. 2 interactors.
MINTiMINT-1869370.
STRINGi10090.ENSMUSP00000001027.

Chemistry databases

BindingDBiO54754.

Structurei

3D structure databases

ProteinModelPortaliO54754.
SMRiO54754.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 912Fe-2S ferredoxin-typeAdd BLAST88
Domaini235 – 420FAD-binding PCMH-typeAdd BLAST186

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni801 – 802Molybdopterin bindingBy similarity2
Regioni1083 – 1086Molybdopterin bindingBy similarity4

Sequence similaritiesi

Belongs to the xanthine dehydrogenase family.Curated

Phylogenomic databases

eggNOGiKOG0430. Eukaryota.
COG4630. LUCA.
COG4631. LUCA.
HOGENOMiHOG000191197.
HOVERGENiHBG004182.
InParanoidiO54754.
KOiK00157.
PhylomeDBiO54754.

Family and domain databases

Gene3Di1.10.150.120. 1 hit.
3.10.20.30. 1 hit.
3.30.365.10. 4 hits.
3.30.43.10. 1 hit.
3.30.465.10. 1 hit.
3.90.1170.50. 1 hit.
InterProiView protein in InterPro
IPR002888. 2Fe-2S-bd.
IPR036884. 2Fe-2S-bd_dom_sf.
IPR036010. 2Fe-2S_ferredoxin-like_sf.
IPR001041. 2Fe-2S_ferredoxin-type.
IPR006058. 2Fe2S_fd_BS.
IPR000674. Ald_Oxase/Xan_DH_a/b.
IPR036856. Ald_Oxase/Xan_DH_a/b_sf.
IPR016208. Ald_Oxase/xanthine_DH.
IPR014313. Aldehyde_oxidase.
IPR008274. AldOxase/xan_DH_Mopterin-bd.
IPR037165. AldOxase/xan_DH_Mopterin-bd_sf.
IPR012675. Beta-grasp_dom_sf.
IPR005107. CO_DH_flav_C.
IPR036683. CO_DH_flav_C_dom_sf.
IPR016169. CO_DH_flavot_FAD-bd_sub2.
IPR016166. FAD-bd_2.
IPR036318. FAD-bd_2-like_sf.
IPR016167. FAD-bd_2_sub1.
IPR002346. Mopterin_DH_FAD-bd.
IPR022407. OxRdtase_Mopterin_BS.
PfamiView protein in Pfam
PF01315. Ald_Xan_dh_C. 1 hit.
PF02738. Ald_Xan_dh_C2. 1 hit.
PF03450. CO_deh_flav_C. 1 hit.
PF00941. FAD_binding_5. 1 hit.
PF00111. Fer2. 1 hit.
PF01799. Fer2_2. 1 hit.
PIRSFiPIRSF000127. Xanthine_DH. 1 hit.
SMARTiView protein in SMART
SM01008. Ald_Xan_dh_C. 1 hit.
SM01092. CO_deh_flav_C. 1 hit.
SUPFAMiSSF47741. SSF47741. 1 hit.
SSF54292. SSF54292. 1 hit.
SSF54665. SSF54665. 1 hit.
SSF55447. SSF55447. 1 hit.
SSF56003. SSF56003. 1 hit.
SSF56176. SSF56176. 1 hit.
TIGRFAMsiTIGR02969. mam_aldehyde_ox. 1 hit.
PROSITEiView protein in PROSITE
PS00197. 2FE2S_FER_1. 1 hit.
PS51085. 2FE2S_FER_2. 1 hit.
PS51387. FAD_PCMH. 1 hit.
PS00559. MOLYBDOPTERIN_EUK. 1 hit.

Sequencei

Sequence statusi: Complete.

O54754-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPIQLLFYV NGQKVVEKNV DPEMMLLPYL RKNLRLTGTK YGCGGGGCGA
60 70 80 90 100
CTVMISRYNP STKAIRHHPV NACLTPICSL HGTAVTTVEG LGNTRTRLHP
110 120 130 140 150
IQERIAKCHG TQCGFCTPGM VMSMYALLRN HPEPTLDQLT DALGGNLCRC
160 170 180 190 200
TGYRPIIDAC KTFCKASACC QSKENGVCCL DQEINGLAES QEEDKTSPEL
210 220 230 240 250
FSEEEFLPLD PTQELIFPPE LMRIAEKQPP KTRVFYGERV TWISPVTLKE
260 270 280 290 300
LVEAKFKYPQ APIVMGYTSV GPEVKFKGVF HPIIISPDRI EELGVISQAR
310 320 330 340 350
DGLTLGAGLS LDQVKDILAD IVQKLPEEKT QTYRALLKHL RTLAGSQIRN
360 370 380 390 400
MASLGGHIVS RHLDSDLNPL LAVGNCTLNL LSKDGERRIP LSEEFLRKCP
410 420 430 440 450
EADLKPQEVL VSVNIPWSRK WEFVSAFRQA QRQQNALAIV NSGMRVLFRE
460 470 480 490 500
GGGVIEELSI LYGGVGSTII SAKNSCQRLI GRPWNEGMLD TRCRLVLDEV
510 520 530 540 550
TLAASAPGGK VEFKRTLIIS FLFKFYLEVS QGLKREDPGH SPSLAGNHES
560 570 580 590 600
ALDDLHSKHP WRTLTHQNVD PAQLPQDPIG RPIMHLSGIK HATGEAIYCD
610 620 630 640 650
DMPAVDRELF LTFVTSSRAH AKIVSIDLSE ALSLPGVVDI ITADHLQEAN
660 670 680 690 700
TFGTETFLAT DEVHCVGHLV CAVIADSETR AKQAAKQVKV VYQDLAPLIL
710 720 730 740 750
TIEEAIQHKS FFKSERKLEC GNVDEAFKIV DQILEGEIHI GGQEHFYMET
760 770 780 790 800
QSMLVVPKGE DGEIDIYVST QFPKYIQDIV AATLKLSANK VMCHVRRVGG
810 820 830 840 850
AFGGKVGKTS ILAAITAFAA SKHGRAVRCI LERGEDMLIT GGRHPYLGKY
860 870 880 890 900
KAGFMNEGRI LALDVEHYCN GGCSLDESLW VIEMGLLKLD NAYKFPNLRC
910 920 930 940 950
RGWACRTNLP SNTALRGFGF PQAGLVTEAC ITEVAIKCGL SPEQVRTINM
960 970 980 990 1000
YKHVDTTHYK QEFSAKALSE CWRECMAKCS YFERKAAIGK FNAENSWKKR
1010 1020 1030 1040 1050
GMAVIPLKFP VGIGSVAMGQ AAALVHIYLD GSALVSHGGI EMGQGVHTKM
1060 1070 1080 1090 1100
IQVVSRELRM PMSSVHLRGT STETVPNTNA SGGSVVADLN GLAVKDACQT
1110 1120 1130 1140 1150
LLKRLEPIIS KNPQGTWKDW AQTAFDQSIS LSAVGYFRGY ESNIDWEKGE
1160 1170 1180 1190 1200
GHPFEYFVFG AACSEVEINC LTGDHKNIRT NIVMDVGHSI NPALDIGQVE
1210 1220 1230 1240 1250
GAFIQGMGLY TIEELSYSPQ GTLYSRGPNQ YKIPAICDIP TEMHISFLPP
1260 1270 1280 1290 1300
SEHSNTLYSS KGLGESGVFL GCSVFFAIHD AVKAARQERG ISGPWKLNSP
1310 1320 1330
LTPEKIRMAC EDKFTKMIPR DEPGSYVPCN IPV
Length:1,333
Mass (Da):146,678
Last modified:May 1, 1999 - v2
Checksum:i320CF0A3742F6AC5
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti109H → Q in strain: 129/Sv. 1
Natural varianti168A → G in strain: C57BL/6 X CBA and 129/Sv. 1
Natural varianti449R → T in strain: C57BL/6 X CBA. 1
Natural varianti492R → A in strain: C57BL/6 X CBA, requires 2 nucleotide substitutions. 1
Natural varianti686 – 687KQ → NE in strain: 129/Sv. 2
Natural varianti857E → D in strain: 129/Sv. 1
Natural varianti983E → D in strain: C57BL/6 X CBA. 1
Natural varianti1169N → D in strain: C57BL/6 X CBA and 129/Sv. 1
Natural varianti1329C → W in strain: C57BL/6 X CBA and 129/Sv. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076216 mRNA. Translation: AAC99382.1.
AB017482 mRNA. Translation: BAA36834.1.
AF121945
, AF121911, AF121912, AF121913, AF121914, AF121915, AF121916, AF121917, AF121918, AF121919, AF121920, AF121921, AF121922, AF121923, AF121924, AF121925, AF121926, AF121927, AF121928, AF121929, AF121930, AF121931, AF121932, AF121933, AF121934, AF121935, AF121936, AF121937, AF121938, AF121939, AF121940, AF121941, AF121942, AF121943, AF121944 Genomic DNA. Translation: AAD31763.1.
CCDSiCCDS35575.1.
RefSeqiNP_033806.2. NM_009676.2.
UniGeneiMm.26787.

Genome annotation databases

GeneIDi11761.
KEGGimmu:11761.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAOXA_MOUSE
AccessioniPrimary (citable) accession number: O54754
Secondary accession number(s): Q9WU85, Q9Z2Z5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 15, 2002
Last sequence update: May 1, 1999
Last modified: November 22, 2017
This is version 156 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families