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Protein

Aldehyde oxidase 1

Gene

AOX1

Organism
Oryctolagus cuniculus (Rabbit)
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 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. Cannot use hypoxanthine and all-trans-retinol as substrate.4 Publications

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:

Enzyme regulationi

Inhibited by hydralazine and menadione. Not inhibited by BOF-4272 or allopurinol, xanthine dehydrogenase potent inhibitors. In contrast to guinea pig, human and rat, isovanillin is not an inhibitor but a substrate for AOX1 in rabbit.2 Publications

Kineticsi

  1. KM=8 µM for all-trans-retinal2 Publications
  2. KM=13 µM for 9-cis-retinal2 Publications
  3. KM=0.9 mM for 13-cis-retinal2 Publications
  4. KM=0.11 mM for N-methylnicotinamide2 Publications
  5. KM=94.7 µM for O22 Publications
  6. KM=0.44 mM for 6-deoxypenciclovir (at 37 degrees Celsius and pH 7)2 Publications
  7. KM=45 µM for isovanillin (at 37 degrees Celsius and pH 7)2 Publications
  1. Vmax=192 nmol/min/mg enzyme with all-trans-retinal as substrate2 Publications
  2. Vmax=57 nmol/min/mg enzyme with 9-cis-retinal as substrate2 Publications
  3. Vmax=105 nmol/min/mg enzyme with 13-cis-retinal as substrate2 Publications
  4. Vmax=267 nmol/min/mg enzyme with N-methylnicotinamide as substrate2 Publications
  5. Vmax=114 nmol/min/mg enzyme with 6-deoxypenciclovir as substrate2 Publications
  6. Vmax=211 nmol/min/mg enzyme with isovanillin as substrate2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi44 – 441Iron-sulfur 1 (2Fe-2S)By similarity
Metal bindingi49 – 491Iron-sulfur 1 (2Fe-2S)By similarity
Metal bindingi52 – 521Iron-sulfur 1 (2Fe-2S)By similarity
Metal bindingi74 – 741Iron-sulfur 1 (2Fe-2S)By similarity
Binding sitei113 – 1131MolybdopterinBy similarity
Metal bindingi114 – 1141Iron-sulfur 2 (2Fe-2S)By similarity
Metal bindingi117 – 1171Iron-sulfur 2 (2Fe-2S)By similarity
Metal bindingi149 – 1491Iron-sulfur 2 (2Fe-2S)By similarity
Metal bindingi151 – 1511Iron-sulfur 2 (2Fe-2S)By similarity
Binding sitei354 – 3541FADBy similarity
Binding sitei358 – 3581FADBy similarity
Binding sitei367 – 3671FADBy similarity
Binding sitei411 – 4111FAD; via amide nitrogenBy similarity
Binding sitei802 – 8021Molybdopterin; via amide nitrogenBy similarity
Binding sitei1043 – 10431Molybdopterin; via amide nitrogenBy similarity
Binding sitei1199 – 11991MolybdopterinBy similarity
Active sitei1266 – 12661Proton acceptor; for azaheterocycle hydroxylase activityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi264 – 2718FADBy similarity

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

2Fe-2S, FAD, Flavoprotein, Iron, Iron-sulfur, Metal-binding, Molybdenum

Enzyme and pathway databases

BRENDAi1.2.3.1. 1749.

Names & Taxonomyi

Protein namesi
Recommended name:
Aldehyde oxidase 1 (EC:1.2.3.1)
Alternative name(s):
Azaheterocycle hydroxylase 1 (EC:1.17.3.-)
Retinal oxidase
Retinoic acid synthase
Gene namesi
Name:AOX1
Synonyms:AO
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL1641356.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13341334Aldehyde oxidase 1PRO_0000166107Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1064 – 10641PhosphoserineBy similarity

Post-translational modificationi

The N-terminus is blocked.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiP80456.

Expressioni

Tissue specificityi

Very high expression in liver and lung. High expression in kidney, pancreas, brain stem and spinal cord. Moderate expression in heart, testis, eye, cerebral cortex and cerebellum. Low expression in stomach and muscle.2 Publications

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000012025.

Chemistry

BindingDBiP80456.

Structurei

3D structure databases

ProteinModelPortaliP80456.
SMRiP80456. Positions 4-166.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 92882Fe-2S ferredoxin-typePROSITE-ProRule annotationAdd
BLAST
Domaini236 – 421186FAD-binding PCMH-typePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the xanthine dehydrogenase family.Curated
Contains 1 2Fe-2S ferredoxin-type domain.PROSITE-ProRule annotation
Contains 1 FAD-binding PCMH-type domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0430. Eukaryota.
COG4630. LUCA.
COG4631. LUCA.
HOGENOMiHOG000191197.
HOVERGENiHBG004182.
InParanoidiP80456.
KOiK00157.

Family and domain databases

Gene3Di1.10.150.120. 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.
InterProiIPR002888. 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]
PfamiPF01315. 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]
PIRSFiPIRSF000127. Xanthine_DH. 1 hit.
SMARTiSM01008. Ald_Xan_dh_C. 1 hit.
SM01092. CO_deh_flav_C. 1 hit.
[Graphical view]
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.
PROSITEiPS00197. 2FE2S_FER_1. 1 hit.
PS51085. 2FE2S_FER_2. 1 hit.
PS51387. FAD_PCMH. 1 hit.
PS00559. MOLYBDOPTERIN_EUK. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P80456-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPAPELLFY VNGRKVVEKQ VDPETMLLPY LRKKLRLTGT KYGCGGGGCG
60 70 80 90 100
ACTVMISRYN RVTKKIRHYP VNACLTPICS LYGAAVTTVE GIGSTTTRLH
110 120 130 140 150
PVQERIAKFH GTQCGFCTPG MVMSMYALLR NHPEPTLDQL ADALGGNLCR
160 170 180 190 200
CTGYRPIIEA YKTFCKTSDC CQNKENGFCC LDQGINGLPE VEEENQTRPN
210 220 230 240 250
LFSEEEYLPL DPTQELIFPP ELMTMAEKQP QRTRVFSGER MMWISPVTLK
260 270 280 290 300
ALLEAKSTYP QAPVVMGNTS VGPGVKFKGI FHPVIISPDS IEELNVVSHT
310 320 330 340 350
HSGLTLGAGL SLAQVKDILA DVVQKVPEEN AQTYRALLKH LGTLAGSQIR
360 370 380 390 400
NMASLGGHII SRHLDSDLNP LLAVGNCTLN VLSKEGERQI PLDEQFLSRC
410 420 430 440 450
PEADLKPQEI LASVHIPYSR KWEFVLAFRQ AQRKQNALAI VNSGMRVFFG
460 470 480 490 500
EGDGIIRELA ISYGGVGPTI ICAKNSCQKL IGRSWNEEML DTACRLILDE
510 520 530 540 550
VSLPGSAPGG KVEFKRTLII SFLFKFYLEV SQILKRMAPG LSPHLADKYE
560 570 580 590 600
SALQDLHARY SWSTLKDQDV DARQLSQDPI GHPVMHLSGV KHATGEAIYL
610 620 630 640 650
DDMPAVDQEL FMAFVTSPRA HAKIVSTDLL EALSLPGVVD IVTAEHLQDG
660 670 680 690 700
NTFYTEKLLA ADEVLCVGQL VCAVIAESEV QAKQAAKQVK IVYEDLEPVI
710 720 730 740 750
LSIEEAIEQK SFFEPERKLE YGNVDEAFKV VDQILEGEIH MGGQEHFYME
760 770 780 790 800
TQSVLVVPKG EDQEMDVYAS TQFPKYIQDM VAAVLKLPVN KVMCHVKRVG
810 820 830 840 850
GAFGGKVFKA SIMAAIAAFA ANKHGRAVRC ILERGEDMLI TGGRHPYLGK
860 870 880 890 900
YKAGFMNDGR IVALDVEHYS NGGCSLDESL LVIEMGLLKM ENAYKFPNLR
910 920 930 940 950
CRGWACRTNL PSNTAFRGFG FPQAGLITEC CITEVAAKCG LSPEKVRAIN
960 970 980 990 1000
FYKEIDQTPY KQEINAKNLT QCWNECLAKS SYFQRKVAVE KFNAENYWKQ
1010 1020 1030 1040 1050
RGLAIIPFKY PRGLGSVAYG QAAALVHVYL DGSVLVTHGG IEMGQGVHTK
1060 1070 1080 1090 1100
MIQVVSRELK MPMSNVHLRG TSTETVPNTN ASGGSVVADL NGLAVKDACQ
1110 1120 1130 1140 1150
TLLKRLEPII NKNPQGTWKE WAQAAFDKSI SLSATGYFRG YDSNIDWDKG
1160 1170 1180 1190 1200
EGHPFEYFVY GAACSEVEID CLTGDHKTIR TDIVMDVGYS INPALDIGQV
1210 1220 1230 1240 1250
EGAFIQGMGL YTIEELHYSP QGILYSRGPN QYKIPAICDI PAELNVTFLP
1260 1270 1280 1290 1300
PSEKSNTLYS SKGLGESGVF MGCSVFFAIR EAVCAARQAR GLSAPWKLSS
1310 1320 1330
PLTPEKIRMA CEDKFTKMIP RDKPGSYVPW NVPV
Length:1,334
Mass (Da):147,138
Last modified:May 15, 2002 - v2
Checksum:i0747A0569C2C062A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009345 mRNA. Translation: BAA81726.1.
RefSeqiNP_001075459.1. NM_001081990.1.
UniGeneiOcu.2359.

Genome annotation databases

GeneIDi100008601.
KEGGiocu:100008601.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009345 mRNA. Translation: BAA81726.1.
RefSeqiNP_001075459.1. NM_001081990.1.
UniGeneiOcu.2359.

3D structure databases

ProteinModelPortaliP80456.
SMRiP80456. Positions 4-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000012025.

Chemistry

BindingDBiP80456.
ChEMBLiCHEMBL1641356.

Proteomic databases

PRIDEiP80456.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100008601.
KEGGiocu:100008601.

Organism-specific databases

CTDi316.

Phylogenomic databases

eggNOGiKOG0430. Eukaryota.
COG4630. LUCA.
COG4631. LUCA.
HOGENOMiHOG000191197.
HOVERGENiHBG004182.
InParanoidiP80456.
KOiK00157.

Enzyme and pathway databases

BRENDAi1.2.3.1. 1749.

Miscellaneous databases

PROiP80456.

Family and domain databases

Gene3Di1.10.150.120. 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.
InterProiIPR002888. 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]
PfamiPF01315. 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]
PIRSFiPIRSF000127. Xanthine_DH. 1 hit.
SMARTiSM01008. Ald_Xan_dh_C. 1 hit.
SM01092. CO_deh_flav_C. 1 hit.
[Graphical view]
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.
PROSITEiPS00197. 2FE2S_FER_1. 1 hit.
PS51085. 2FE2S_FER_2. 1 hit.
PS51387. FAD_PCMH. 1 hit.
PS00559. MOLYBDOPTERIN_EUK. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "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], PROTEIN SEQUENCE OF 857-884; 891-943 AND 1272-1293, FUNCTION, TISSUE SPECIFICITY.
    Strain: Japanese white.
    Tissue: Liver.
  2. "Properties of rabbit liver aldehyde oxidase and the relationship of the enzyme to xanthine oxidase and dehydrogenase."
    Turner N.A., Doyle W.A., Ventom A.M., Bray R.C.
    Eur. J. Biochem. 232:646-657(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 203-231 AND 574-597, FUNCTION AS OXIDASE, COFACTOR.
    Tissue: Liver.
  3. "Characteristic properties of retinal oxidase (retinoic acid synthase) from rabbit hepatocytes."
    Tsujita M., Tomita S., Miura S., Ichikawa Y.
    Biochim. Biophys. Acta 1204:108-116(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS OXIDASE, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, HOMODIMER, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, REACTION MECHANISM, BLOCKAGE OF N-TERMINUS, ENZYME REGULATION.
  4. "In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde oxidase from human, guinea pig, rabbit, and rat liver."
    Rashidi M.R., Smith J.A., Clarke S.E., Beedham C.
    Drug Metab. Dispos. 25:805-813(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AZAHETEROCYCLE OXIDASE, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
  5. "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: IDENTIFICATION OF PARALOGS.

Entry informationi

Entry nameiAOXA_RABIT
AccessioniPrimary (citable) accession number: P80456
Secondary accession number(s): Q9XTA9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 15, 2002
Last modified: June 8, 2016
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The reaction follows an ordered Bi-Bi kinetic mechanism. During retinal oxidation, incorporates the oxygen of water into retinoate, but not that of molecular oxygen (PubMed:8305467).1 Publication
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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.