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Protein

Aldehyde oxidase 1

Gene

AOX1

Organism
Cavia porcellus (Guinea pig)
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.2 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] clusterBy similarityNote: Binds 2 [2Fe-2S] clusters per subunit.By similarity
  • FADBy similarityNote: Binds 1 FAD per subunit.By similarity
  • 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.1 Publication

Kineticsi

  1. KM=0.41 mM for 6-deoxypenciclovir (at 37 degrees Celsius and pH 7)1 Publication
  2. KM=0.17 mM for famciclovir (at 37 degrees Celsius and pH 7)1 Publication
  1. Vmax=209 nmol/min/mg enzyme with 6-deoxypenciclovir as substrate1 Publication
  2. Vmax=439 nmol/min/mg enzyme with famciclovir as substrate1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi43 – 431Iron-sulfur 1 (2Fe-2S)By similarity
Metal bindingi48 – 481Iron-sulfur 1 (2Fe-2S)By similarity
Metal bindingi51 – 511Iron-sulfur 1 (2Fe-2S)By similarity
Metal bindingi73 – 731Iron-sulfur 1 (2Fe-2S)By similarity
Binding sitei112 – 1121MolybdopterinBy similarity
Metal bindingi113 – 1131Iron-sulfur 2 (2Fe-2S)By similarity
Metal bindingi116 – 1161Iron-sulfur 2 (2Fe-2S)By similarity
Metal bindingi148 – 1481Iron-sulfur 2 (2Fe-2S)By similarity
Metal bindingi150 – 1501Iron-sulfur 2 (2Fe-2S)By similarity
Binding sitei352 – 3521FADBy similarity
Binding sitei356 – 3561FADBy similarity
Binding sitei365 – 3651FADBy similarity
Binding sitei409 – 4091FAD; via amide nitrogenBy similarity
Binding sitei800 – 8001Molybdopterin; via amide nitrogenBy similarity
Binding sitei1041 – 10411Molybdopterin; via amide nitrogenBy similarity
Binding sitei1197 – 11971MolybdopterinBy similarity
Active sitei1264 – 12641Proton acceptor; for azaheterocycle hydroxylase activityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi262 – 2698FADBy similarity

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

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

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
OrganismiCavia porcellus (Guinea pig)
Taxonomic identifieri10141 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaHystricognathiCaviidaeCavia
Proteomesi
  • UP000005447 Componenti: Unassembled WGS sequence

Subcellular locationi

  • Cytoplasm 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13321332Aldehyde oxidase 1PRO_0000425242Add
BLAST

Expressioni

Tissue specificityi

Expressed in liver.1 Publication

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10141.ENSCPOP00000021102.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 91882Fe-2S ferredoxin-typePROSITE-ProRule annotationAdd
BLAST
Domaini234 – 419186FAD-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.
COG4631. LUCA.
OrthoDBiEOG7QRQSZ.

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.

H9TB17-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPSTLYFYV NGRRVTEKNV DPETMLLPYL GRNLRLTGTK YGCGGGGCGA
60 70 80 90 100
CTVMVSRYDR GTGQIRHYPA CACLTPLCSL HGAAVTTVEG VGSTRTRLHP
110 120 130 140 150
VQERIAKSHG TQCGFCTPGM VMSLYALLRS HPQPSEEQLL EALAGNLCRC
160 170 180 190 200
TGYRPILDAG KTFCKTSGCC QSKENGVCCL DQGVNGVQEA EGEQTSQELC
210 220 230 240 250
SEEEFVPLDP TQELIFPPEL MILAQKQPQK SRVFTGDRVT WISPVTLKDL
260 270 280 290 300
LEAKAKNPRA PVVMGNTSVG PEMKFKGVFH PVIISPDGIE ELSVIKQGNE
310 320 330 340 350
GLTLGAGLSL AQVQDVLADV VQQLPEEKTQ TLCALLKQLR TLAGSQIRNM
360 370 380 390 400
ASLGGHIMSR HLDSDLNPVL AAASCTLHVP SQEGDRQIPL DEHFLSRSPS
410 420 430 440 450
ADLRPQEVLL SVTIPYSRKW EFVSAFRQAQ RKRSARAIVN VGMRVFFGAG
460 470 480 490 500
DGVISELCIL YGGVGPAIVC ATDACRKLVG RHWTEEMLDE ACRLVLGEVA
510 520 530 540 550
IPGAAPGGRV EFRRTLLVSF LFRFYLQVSQ SLSRMDPGRY PSLVGKYESA
560 570 580 590 600
LEDLCLGHHQ RTFELQSADA KQLPQDPIGR PIMHLSGIKH TTGEAIYCDD
610 620 630 640 650
MPLVDRELSL AFVTSSRAHA AILSMDLSEA LSLPGVVDIV TAEHLGDANS
660 670 680 690 700
FAKETLLATD KVLCVGHLVC AVIADSEVQA KRAAEKVKIV YQDLEPLILT
710 720 730 740 750
IEEAIQHDSF FETERKLESG DVAEAFRTAE QVLEGSIHMG GQEHFYMETQ
760 770 780 790 800
SMLAVPKGED QEIDLYVSTQ FPTYIQEIVA STLKLPVNKV MCHVRRVGGA
810 820 830 840 850
FGGKVGKTAI LAAITAFAAL KHCRAVRCIL ERGEDMLITG GRHPYLGKYK
860 870 880 890 900
VGFRNNGQVV ALDMEHYSNA GSTLDESLMV VEMGLLKMEN AYKFPNLRCR
910 920 930 940 950
GHACKTNLPS NTALRGFGFP QSGLITEACI VEVAARCGLS PEEVREVNMY
960 970 980 990 1000
RGTEQTHYGQ EIHTQRLAQC WSECKAKATF SLRRAAVDRF NAGSPWKKRG
1010 1020 1030 1040 1050
LAMVPLKFPV GLGSVAMGQA AALVHVYLDG SVLLTHGGIE MGQGVHTKMI
1060 1070 1080 1090 1100
QVVSRELKMP MANVHLRGTS TETVPNANVS GGSVVADLNG LAVKDACQTL
1110 1120 1130 1140 1150
LKRLEPIISK NPKGTWKEWA QAAFDQSISL SAIGYFRGYD ADMDWEKGKG
1160 1170 1180 1190 1200
HPFEYFVYGA ACSEVEIDCL TGNHKNIRTD IVMDVGRSIN PALDLGQVEG
1210 1220 1230 1240 1250
AFIQGMGLYT SEELKYGPQG ALYTRGPDQY KIPAVCDVPA ELHVFFLPPS
1260 1270 1280 1290 1300
KNSNTLYSSK GLGESGVFLG CSVLFAIWDA VSAARRERGL PGTLALSCPL
1310 1320 1330
TPEKIRMACE DRFTKMIPRD TPGSYVPWDV VV
Length:1,332
Mass (Da):145,275
Last modified:February 19, 2014 - v2
Checksum:i348556EBE581FE04
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti519 – 5191S → N in AFG18181 (PubMed:23263164).Curated
Sequence conflicti677 – 6771E → G in AFG18181 (PubMed:23263164).Curated
Sequence conflicti695 – 6951E → G in AFG18181 (PubMed:23263164).Curated
Sequence conflicti1137 – 11371R → T in AFG18181 (PubMed:23263164).Curated
Sequence conflicti1201 – 12011A → P in AFG18181 (PubMed:23263164).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JQ280309 mRNA. Translation: AFG18181.1.
AAKN02051283 Genomic DNA. No translation available.
RefSeqiNP_001295371.1. NM_001308442.1.

Genome annotation databases

GeneIDi100720210.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JQ280309 mRNA. Translation: AFG18181.1.
AAKN02051283 Genomic DNA. No translation available.
RefSeqiNP_001295371.1. NM_001308442.1.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10141.ENSCPOP00000021102.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100720210.

Organism-specific databases

CTDi316.

Phylogenomic databases

eggNOGiKOG0430. Eukaryota.
COG4631. LUCA.
OrthoDBiEOG7QRQSZ.

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

« Hide 'large scale' publications
  1. "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: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION OF PARALOGS.
  2. "A high-resolution map of human evolutionary constraint using 29 mammals."
    Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S., Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B., Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.
    , Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M., Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M., Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D., Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J., Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S., Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A., Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R., Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R., Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C., Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E., Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N., Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.
    Nature 478:476-482(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: 2N.
  3. "Substrate specificity of human liver aldehyde oxidase toward substituted quinazolines and phthalazines: a comparison with hepatic enzyme from guinea pig, rabbit, and baboon."
    Beedham C., Critchley D.J., Rance D.J.
    Arch. Biochem. Biophys. 319:481-490(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AZAHETEROCYCLE OXIDASE, SUBSTRATE SPECIFICITY.
  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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiAOXA_CAVPO
AccessioniPrimary (citable) accession number: H9TB17
Secondary accession number(s): H0WDM9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 19, 2014
Last sequence update: February 19, 2014
Last modified: April 13, 2016
This is version 22 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

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.