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O54754 (AOXA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aldehyde oxidase 1

EC=1.2.3.1
Alternative name(s):
Azaheterocycle hydroxylase 1
EC=1.17.3.-
Retinal oxidase
Gene names
Name:Aox1
Synonyms:Ao, Ro
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1333 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Oxidase 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 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. Ref.2 Ref.5 Ref.6 Ref.8

Catalytic activity

An aldehyde + H2O + O2 = a carboxylate + H2O2. Ref.2 Ref.6

Retinal + O2 + H2O = retinoate + H2O2. Ref.2 Ref.6

Cofactor

Binds 2 2Fe-2S clusters per subunit (Ref.6).

Binds 1 FAD per subunit (Ref.6).

Binds 1 molybdenum-molybdopterin (Mo-MPT) cofactor per subunit (Ref.6).

Subunit structure

Homodimer.

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

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. Ref.1 Ref.4 Ref.7 Ref.8

Developmental stage

Expressed in adult liver but not in neonatal or embryonic liver. Not detected in preadipocytes but strongly induced in mature adipocytes. Ref.3 Ref.5

Induction

Repressed by pioglitazone, fenofibrate and PPARA agonists. Induced by testosterone. Ref.1 Ref.5

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 (Ref.7).

Sequence similarities

Belongs to the xanthine dehydrogenase family.

Contains 1 2Fe-2S ferredoxin-type domain.

Contains 1 FAD-binding PCMH-type domain.

Biophysicochemical properties

Kinetic parameters:

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) (Ref.6). In Ref.6, 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.

KM=3.8 µM for retinal (at 37 degrees Celsius and pH 7.8) (Ref.2) Ref.2 Ref.6

KM=97.7 µM for benzaldehyde (at 30 degrees Celsius and pH 7.5) (Ref.6)

KM=11.4 µM for phthalazine (at 30 degrees Celsius and pH 7.5) (Ref.6)

KM=55.8 µM for retinal (at 30 degrees Celsius and pH 7.5) (Ref.6)

KM=17.5 mM for acetaldehyde (at 30 degrees Celsius and pH 7.5) (Ref.6)

Vmax=807 nmol/min/mg enzyme with retinal as substrate (at 37 degrees Celsius and pH 7.8) (Ref.2)

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13331333Aldehyde oxidase 1
PRO_0000166106

Regions

Domain4 – 91882Fe-2S ferredoxin-type
Domain235 – 420186FAD-binding PCMH-type
Nucleotide binding263 – 2708FAD By similarity

Sites

Active site12651Proton acceptor; for azaheterocycle hydroxylase activity Probable
Metal binding431Iron-sulfur 1 (2Fe-2S) By similarity
Metal binding481Iron-sulfur 1 (2Fe-2S) By similarity
Metal binding511Iron-sulfur 1 (2Fe-2S) By similarity
Metal binding731Iron-sulfur 1 (2Fe-2S) By similarity
Metal binding1131Iron-sulfur 2 (2Fe-2S) By similarity
Metal binding1161Iron-sulfur 2 (2Fe-2S) By similarity
Metal binding1481Iron-sulfur 2 (2Fe-2S) By similarity
Metal binding1501Iron-sulfur 2 (2Fe-2S) By similarity
Binding site1121Molybdopterin By similarity
Binding site3531FAD By similarity
Binding site3571FAD By similarity
Binding site3661FAD By similarity
Binding site4101FAD; via amide nitrogen By similarity
Binding site8011Molybdopterin; via amide nitrogen By similarity
Binding site10421Molybdopterin; via amide nitrogen By similarity
Binding site11981Molybdopterin By similarity

Natural variations

Natural variant1091H → Q in strain: 129/Sv.
Natural variant1681A → G in strain: C57BL/6 X CBA and 129/Sv.
Natural variant4491R → T in strain: C57BL/6 X CBA.
Natural variant4921R → A in strain: C57BL/6 X CBA, requires 2 nucleotide substitutions.
Natural variant686 – 6872KQ → NE in strain: 129/Sv.
Natural variant8571E → D in strain: 129/Sv.
Natural variant9831E → D in strain: C57BL/6 X CBA.
Natural variant11691N → D in strain: C57BL/6 X CBA and 129/Sv.
Natural variant13291C → W in strain: C57BL/6 X CBA and 129/Sv.

Experimental info

Mutagenesis8061V → 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. Ref.6
Mutagenesis8841M → R: Abolishes catalytic activity on phthalazine and acetaldehyde. Decreases catalytic efficiency on benzaldehyde and retinal. Abolishes catalytic activity; when associated with E-806. Ref.6
Mutagenesis12651E → Q: Abolishes catalytic activity. Ref.6

Sequences

Sequence LengthMass (Da)Tools
O54754 [UniParc].

Last modified May 1, 1999. Version 2.
Checksum: 320CF0A3742F6AC5

FASTA1,333146,678
        10         20         30         40         50         60 
MDPIQLLFYV NGQKVVEKNV DPEMMLLPYL RKNLRLTGTK YGCGGGGCGA CTVMISRYNP 

        70         80         90        100        110        120 
STKAIRHHPV NACLTPICSL HGTAVTTVEG LGNTRTRLHP IQERIAKCHG TQCGFCTPGM 

       130        140        150        160        170        180 
VMSMYALLRN HPEPTLDQLT DALGGNLCRC TGYRPIIDAC KTFCKASACC QSKENGVCCL 

       190        200        210        220        230        240 
DQEINGLAES QEEDKTSPEL FSEEEFLPLD PTQELIFPPE LMRIAEKQPP KTRVFYGERV 

       250        260        270        280        290        300 
TWISPVTLKE LVEAKFKYPQ APIVMGYTSV GPEVKFKGVF HPIIISPDRI EELGVISQAR 

       310        320        330        340        350        360 
DGLTLGAGLS LDQVKDILAD IVQKLPEEKT QTYRALLKHL RTLAGSQIRN MASLGGHIVS 

       370        380        390        400        410        420 
RHLDSDLNPL LAVGNCTLNL LSKDGERRIP LSEEFLRKCP EADLKPQEVL VSVNIPWSRK 

       430        440        450        460        470        480 
WEFVSAFRQA QRQQNALAIV NSGMRVLFRE GGGVIEELSI LYGGVGSTII SAKNSCQRLI 

       490        500        510        520        530        540 
GRPWNEGMLD TRCRLVLDEV TLAASAPGGK VEFKRTLIIS FLFKFYLEVS QGLKREDPGH 

       550        560        570        580        590        600 
SPSLAGNHES ALDDLHSKHP WRTLTHQNVD PAQLPQDPIG RPIMHLSGIK HATGEAIYCD 

       610        620        630        640        650        660 
DMPAVDRELF LTFVTSSRAH AKIVSIDLSE ALSLPGVVDI ITADHLQEAN TFGTETFLAT 

       670        680        690        700        710        720 
DEVHCVGHLV CAVIADSETR AKQAAKQVKV VYQDLAPLIL TIEEAIQHKS FFKSERKLEC 

       730        740        750        760        770        780 
GNVDEAFKIV DQILEGEIHI GGQEHFYMET QSMLVVPKGE DGEIDIYVST QFPKYIQDIV 

       790        800        810        820        830        840 
AATLKLSANK VMCHVRRVGG AFGGKVGKTS ILAAITAFAA SKHGRAVRCI LERGEDMLIT 

       850        860        870        880        890        900 
GGRHPYLGKY KAGFMNEGRI LALDVEHYCN GGCSLDESLW VIEMGLLKLD NAYKFPNLRC 

       910        920        930        940        950        960 
RGWACRTNLP SNTALRGFGF PQAGLVTEAC ITEVAIKCGL SPEQVRTINM YKHVDTTHYK 

       970        980        990       1000       1010       1020 
QEFSAKALSE CWRECMAKCS YFERKAAIGK FNAENSWKKR GMAVIPLKFP VGIGSVAMGQ 

      1030       1040       1050       1060       1070       1080 
AAALVHIYLD GSALVSHGGI EMGQGVHTKM IQVVSRELRM PMSSVHLRGT STETVPNTNA 

      1090       1100       1110       1120       1130       1140 
SGGSVVADLN GLAVKDACQT LLKRLEPIIS KNPQGTWKDW AQTAFDQSIS LSAVGYFRGY 

      1150       1160       1170       1180       1190       1200 
ESNIDWEKGE GHPFEYFVFG AACSEVEINC LTGDHKNIRT NIVMDVGHSI NPALDIGQVE 

      1210       1220       1230       1240       1250       1260 
GAFIQGMGLY TIEELSYSPQ GTLYSRGPNQ YKIPAICDIP TEMHISFLPP SEHSNTLYSS 

      1270       1280       1290       1300       1310       1320 
KGLGESGVFL GCSVFFAIHD AVKAARQERG ISGPWKLNSP LTPEKIRMAC EDKFTKMIPR 

      1330 
DEPGSYVPCN IPV 

« Hide

References

[1]"Molecular cloning of the cDNA coding for mouse aldehyde oxidase: tissue distribution and regulation in vivo by testosterone."
Kurosaki M., Demontis S., Barzago M.M., Garattini E., Terao M.
Biochem. J. 341:71-80(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
Strain: CD-1.
Tissue: Liver.
[2]"Molecular cloning of retinal oxidase/aldehyde oxidase cDNAs from rabbit and mouse livers and functional expression of recombinant mouse retinal oxidase cDNA in Escherichia coli."
Huang D.-Y., Furukawa A., Ichikawa Y.
Arch. Biochem. Biophys. 364:264-272(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS RETINAL OXIDASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, HOMODIMER.
Strain: C57BL/6 X CBA.
Tissue: Liver.
[3]"The mouse aldehyde oxidase gene: molecular cloning, chromosomal mapping and functional characterization of the 5'-flanking region."
Demontis S., Kurosaki M., Saccone S., Salvatore M., Garattini E., Terao M.
Biochim. Biophys. Acta 1489:207-222(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], DEVELOPMENTAL STAGE.
Strain: 129/Sv.
Tissue: Thymus.
[4]"Selective localization of mouse aldehyde oxidase mRNA in the choroid plexus and motor neurons."
Bendotti C., Prosperini E., Kurosaki M., Garattini E., Terao M.
NeuroReport 8:2343-2349(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 561-746, TISSUE SPECIFICITY.
Strain: C57BL/6J.
Tissue: Liver.
[5]"Small-interference RNA-mediated knock-down of aldehyde oxidase 1 in 3T3-L1 cells impairs adipogenesis and adiponectin release."
Weigert J., Neumeier M., Bauer S., Mages W., Schnitzbauer A.A., Obed A., Groeschl B., Hartmann A., Schaeffler A., Aslanidis C., Schoelmerich J., Buechler C.
FEBS Lett. 582:2965-2972(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ADIPOGENESIS, DEVELOPMENTAL STAGE, INDUCTION.
[6]"Site directed mutagenesis of amino acid residues at the active site of mouse aldehyde oxidase AOX1."
Schumann S., Terao M., Garattini E., Saggu M., Lendzian F., Hildebrandt P., Leimkuhler S.
PLoS ONE 4:E5348-E5348(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS OXIDASE, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, HOMODIMER, KINETIC PARAMETERS, REACTION MECHANISM, ACTIVE SITE, MUTAGENESIS OF VAL-806; MET-884 AND GLU-1265.
[7]"Structure and evolution of vertebrate aldehyde oxidases: from gene duplication to gene suppression."
Kurosaki M., Bolis M., Fratelli M., Barzago M.M., Pattini L., Perretta G., Terao M., Garattini E.
Cell. Mol. Life Sci. 70:1807-1830(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, IDENTIFICATION OF PARALOGS.
[8]"Aldehyde oxidase importance in vivo in xenobiotic metabolism: imidacloprid nitroreduction in mice."
Swenson T.L., Casida J.E.
Toxicol. Sci. 133:22-28(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN XENOBIOTIC METABOLISM, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF076216 mRNA. Translation: AAC99382.1.
AB017482 mRNA. Translation: BAA36834.1.
AF121945 expand/collapse EMBL AC list , 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.
CCDSCCDS35575.1.
RefSeqNP_033806.2. NM_009676.2.
UniGeneMm.26787.

3D structure databases

ProteinModelPortalO54754.
SMRO54754. Positions 5-165, 200-533, 577-1315.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO54754. 2 interactions.
MINTMINT-1869370.

Chemistry

BindingDBO54754.
ChEMBLCHEMBL1641354.

PTM databases

PhosphoSiteO54754.

Proteomic databases

MaxQBO54754.
PaxDbO54754.
PRIDEO54754.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID11761.
KEGGmmu:11761.

Organism-specific databases

CTD316.
MGIMGI:88035. Aox1.

Phylogenomic databases

eggNOGCOG4630.
HOGENOMHOG000191197.
HOVERGENHBG004182.
InParanoidO54754.
KOK00157.
PhylomeDBO54754.

Gene expression databases

CleanExMM_AOX1.
GenevestigatorO54754.

Family and domain databases

Gene3D1.10.150.120. 1 hit.
3.10.20.30. 1 hit.
3.30.365.10. 6 hits.
3.30.43.10. 1 hit.
3.30.465.10. 1 hit.
3.90.1170.50. 1 hit.
InterProIPR002888. 2Fe-2S-bd.
IPR001041. 2Fe-2S_ferredoxin-type.
IPR006058. 2Fe2S_fd_BS.
IPR000674. Ald_Oxase/Xan_DH_a/b.
IPR016208. Ald_Oxase/xanthine_DH.
IPR014313. Aldehyde_oxidase.
IPR008274. AldOxase/xan_DH_Mopterin-bd.
IPR012675. Beta-grasp_dom.
IPR005107. CO_DH_flav_C.
IPR016169. CO_DH_flavot_FAD-bd_sub2.
IPR016166. FAD-bd_2.
IPR016167. FAD-bd_2_sub1.
IPR002346. Mopterin_DH_FAD-bd.
IPR022407. OxRdtase_Mopterin_BS.
[Graphical view]
PfamPF01315. 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.
[Graphical view]
PIRSFPIRSF000127. Xanthine_DH. 1 hit.
SMARTSM01008. Ald_Xan_dh_C. 1 hit.
SM01092. CO_deh_flav_C. 1 hit.
[Graphical view]
SUPFAMSSF47741. SSF47741. 1 hit.
SSF54292. SSF54292. 1 hit.
SSF54665. SSF54665. 1 hit.
SSF55447. SSF55447. 1 hit.
SSF56003. SSF56003. 1 hit.
SSF56176. SSF56176. 1 hit.
TIGRFAMsTIGR02969. mam_aldehyde_ox. 1 hit.
PROSITEPS00197. 2FE2S_FER_1. 1 hit.
PS51085. 2FE2S_FER_2. 1 hit.
PS51387. FAD_PCMH. 1 hit.
PS00559. MOLYBDOPTERIN_EUK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio279515.
PROO54754.
SOURCESearch...

Entry information

Entry nameAOXA_MOUSE
AccessionPrimary (citable) accession number: O54754
Secondary accession number(s): Q9WU85, Q9Z2Z5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 15, 2002
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot