Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Aldehyde oxidase 1

Gene

Aox1

Organism
Rattus norvegicus (Rat)
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 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.5 Publications

Catalytic activityi

An aldehyde + H2O + O2 = a carboxylate + H2O2.1 Publication
Retinal + O2 + H2O = retinoate + H2O2.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • [2Fe-2S] cluster1 PublicationNote: Binds 2 [2Fe-2S] clusters per subunit.1 Publication
  • FAD1 PublicationNote: Binds 1 FAD per subunit.1 Publication
  • Mo-molybdopterinBy similarityNote: Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.By similarity

Enzyme regulationi

Inhibited by menadione and isovanillin. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor. Inhibited by the flavonoids quercetin, myricetin and genistein. Nitric oxide generation is inhibited by raloxifene and competitively inhibited by an increase in oxygen levels.3 Publications

Kineticsi

  1. KM=0.37 mM for 6-deoxypenciclovir (at 37 degrees Celsius and pH 7)2 Publications
  2. KM=0.08 mM for famciclovir (at 37 degrees Celsius and pH 7)2 Publications
  3. KM=3.0 mM for nitrite2 Publications
  4. KM=24 µM for NADH2 Publications
  5. KM=9.6 µM for 4-(dimethylamino)cinnamaldehyde2 Publications
  1. Vmax=26 nmol/min/mg enzyme with 6-deoxypenciclovir as substrate2 Publications
  2. Vmax=41 nmol/min/mg enzyme with famciclovir as substrate2 Publications
  3. Vmax=0.85 µmol/sec/mg enzyme for nitrite reduction with NADH as electron donor2 Publications
  4. Vmax=1.35 µmol/sec/mg enzyme for nitrite reduction with 4-(dimethylamino)cinnamaldehyde as electron donor2 Publications

pH dependencei

Optimum pH is 6.0 for nitrite oxide generation. Activity decreases below pH 5.0 and above pH 8.0 (PubMed:19801639).1 Publication

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 sitei353FADBy similarity1
Binding sitei357FADBy similarity1
Binding sitei366FADBy similarity1
Binding sitei410FAD; via amide nitrogenBy similarity1
Binding sitei801Molybdopterin; via amide nitrogenBy similarity1
Binding sitei1042Molybdopterin; via amide nitrogenBy similarity1
Binding sitei1198MolybdopterinBy similarity1
Active sitei1265Proton acceptor; for azaheterocycle hydroxylase activityBy similarity1

Regions

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

GO - Molecular functioni

GO - Biological processi

  • drug metabolic process Source: RGD
  • xanthine catabolic process Source: GO_Central
  • xenobiotic metabolic process Source: RGD
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. 5301.
SABIO-RKQ9Z0U5.

Names & Taxonomyi

Protein namesi
Recommended name:
Aldehyde oxidase 1 (EC:1.2.3.11 Publication)
Alternative name(s):
Azaheterocycle hydroxylase 1 (EC:1.17.3.-)
Gene namesi
Name:Aox1
Synonyms:Ao
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620528. Aox1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1641355.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001661081 – 1333Aldehyde oxidase 1Add BLAST1333

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1063PhosphoserineBy similarity1

Post-translational modificationi

The N-terminus is blocked.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Z0U5.
PRIDEiQ9Z0U5.

PTM databases

iPTMnetiQ9Z0U5.
PhosphoSitePlusiQ9Z0U5.

Expressioni

Tissue specificityi

Expression in liver (at protein level). Also detected in heart, lung, spleen and kidney.2 Publications

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000059651.

Chemistry databases

BindingDBiQ9Z0U5.

Structurei

3D structure databases

ProteinModelPortaliQ9Z0U5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

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.
InParanoidiQ9Z0U5.
KOiK00157.
PhylomeDBiQ9Z0U5.

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.

Q9Z0U5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPPQLLFYV NGQKVVENNV DPEMMLLPYL RKNLRLTGTK YGCGGGGCGA
60 70 80 90 100
CTVMISRYNP STKSIRHHPV NACLTPICSL YGTAVTTVEG IGNTRTRLHP
110 120 130 140 150
VQERIAKCHS TQCGFCTPGM VMSMYALLRN HPEPSLDQLT DALGGNLCRC
160 170 180 190 200
TGYRPIIDAC KTFCRASGCC ESKENGVCCL DQGINGSAEF QEGDETSPEL
210 220 230 240 250
FSEKEFQPLD PTQELIFPPE LMRIAEKQPP KTRVFYSNRM TWISPVTLEE
260 270 280 290 300
LVEAKFKYPG APIVMGYTSV GPEVKFKGVF HPIIISPDRI EELSIINQTG
310 320 330 340 350
DGLTLGAGLS LDQVKDILTD VVQKLPEETT QTYRALLKHL RTLAGSQIRN
360 370 380 390 400
MASLGGHIVS RHLDSDLNPL LAVGNCTLNL LSKDGKRQIP LSEQFLRKCP
410 420 430 440 450
DSDLKPQEVL VSVNIPCSRK WEFVSAFRQA QRQQNALAIV NSGMRVLFRE
460 470 480 490 500
GGGVIKELSI LYGGVGPTTI GAKNSCQKLI GRPWNEEMLD TACRLVLDEV
510 520 530 540 550
TLAGSAPGGK VEFKRTLIIS FLFKFYLEVL QGLKREDPGH YPSLTNNYES
560 570 580 590 600
ALEDLHSKHH WRTLTHQNVD SMQLPQDPIG RPIMHLSGIK HATGEAIYCD
610 620 630 640 650
DMPAVDRELF LTFVTSSRAH AKIVSIDLSE ALSLPGVVDI ITADHLQDAT
660 670 680 690 700
TFGTETLLAT DKVHCVGQLV CAVIADSETR AKQAAKHVKV VYRDLEPLIL
710 720 730 740 750
TIEEAIQHKS FFESERKLEC GNVDEAFKIA DQILEGEIHI GGQEHFYMET
760 770 780 790 800
QSMLVVPKGE DGEIDIYVST QFPKHIQDIV AATLKLSVNK VMCHVRRVGG
810 820 830 840 850
AFGGKVGKTS IMAAITAFAA SKHGRAVRCT LERGEDMLIT GGRHPYLGKY
860 870 880 890 900
KVGFMRDGRI VALDVEHYCN GGSSLDESLW VIEMGLLKMD NAYKFPNLRC
910 920 930 940 950
RGWACRTNLP SHTALRGFGF PQAGLVTEAC VTEVAIRCGL SPEQVRTINM
960 970 980 990 1000
YKQIDNTHYK QEFSAKTLFE CWRECMAKCS YSERKTAVGK FNAENSWKKR
1010 1020 1030 1040 1050
GMAVIPLKFP VGVGSVAMGQ AAALVHIYLD GSALVSHGGI EMGQGVHTKM
1060 1070 1080 1090 1100
IQVVSRELKM PMSSVHLRGT STETVPNTNA SGGSVVADLN GLAVKDACQT
1110 1120 1130 1140 1150
LLKRLEPIIS KNPQGTWKDW AQTAFDQSVS LSAVGYFRGY ESNINWEKGE
1160 1170 1180 1190 1200
GHPFEYFVYG AACSEVEIDC LTGDHKNIRT DIVMDVGHSI NPALDIGQVE
1210 1220 1230 1240 1250
GAFIQGMGLY TIEELSYSPQ GILYSRGPNQ YKIPAICDIP TEMHISFLPP
1260 1270 1280 1290 1300
SEHSNTLYSS KGLGESGVFL GCSVFFAIHD AVRAARQERG ISGPWKLTSP
1310 1320 1330
LTPEKIRMAC EDKFTKMIPR DEPGSYVPWN IPV
Length:1,333
Mass (Da):146,921
Last modified:May 1, 1999 - v1
Checksum:i516B6CE395EB05C8
GO

Polymorphismi

The sequence variants between males and females could be due to differences between individual animals, reflect gender differences or arise from technical problems (PubMed:9920943). The sequence shown here is that of a Sprague-Dawley female.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti119 – 120GM → AR in Sprague-Dawley males; could be unrelated to gender. 2
Natural varianti649A → T in Sprague-Dawley males; could be unrelated to gender. 1 Publication1
Natural varianti1276F → L in Sprague-Dawley males; could be unrelated to gender. 1 Publication1
Natural varianti1315T → R in Sprague-Dawley males; could be unrelated to gender. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110477 mRNA. Translation: AAD16999.1.
AF110478 mRNA. Translation: AAD17000.1.
RefSeqiNP_062236.2. NM_019363.3.
UniGeneiRn.15681.

Genome annotation databases

GeneIDi54349.
KEGGirno:54349.
UCSCiRGD:620528. rat.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110477 mRNA. Translation: AAD16999.1.
AF110478 mRNA. Translation: AAD17000.1.
RefSeqiNP_062236.2. NM_019363.3.
UniGeneiRn.15681.

3D structure databases

ProteinModelPortaliQ9Z0U5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000059651.

Chemistry databases

BindingDBiQ9Z0U5.
ChEMBLiCHEMBL1641355.

PTM databases

iPTMnetiQ9Z0U5.
PhosphoSitePlusiQ9Z0U5.

Proteomic databases

PaxDbiQ9Z0U5.
PRIDEiQ9Z0U5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi54349.
KEGGirno:54349.
UCSCiRGD:620528. rat.

Organism-specific databases

CTDi316.
RGDi620528. Aox1.

Phylogenomic databases

eggNOGiKOG0430. Eukaryota.
COG4630. LUCA.
COG4631. LUCA.
HOGENOMiHOG000191197.
HOVERGENiHBG004182.
InParanoidiQ9Z0U5.
KOiK00157.
PhylomeDBiQ9Z0U5.

Enzyme and pathway databases

BRENDAi1.2.3.1. 5301.
SABIO-RKQ9Z0U5.

Miscellaneous databases

PROiQ9Z0U5.

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...

Entry informationi

Entry nameiAOXA_RAT
AccessioniPrimary (citable) accession number: Q9Z0U5
Secondary accession number(s): Q9R240
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2002
Last sequence update: May 1, 1999
Last modified: November 2, 2016
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Male and female rats possess kinetically distinct forms which may be due to differences in redox states.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

Caution

The experimental design does not allow to distinguish AOX1 from AOX3 in rat liver as the effector of the superoxide and nitric oxide production (PubMed:17353002 and PubMed:19801639).Curated

Keywords - Technical termi

Complete proteome, 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.