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UniProtKB - H9TB17 (AOXA_CAVPO)

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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

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 + H2O2.1 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)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 sitei352FADBy similarity1
Binding sitei356FADBy similarity1
Binding sitei365FADBy similarity1
Binding sitei409FAD; via amide nitrogenBy similarity1
Binding sitei800Molybdopterin; via amide nitrogenBy similarity1
Binding sitei1041Molybdopterin; via amide nitrogenBy similarity1
Binding sitei1197MolybdopterinBy similarity1
Active sitei1264Proton acceptor; for azaheterocycle hydroxylase activityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi262 – 269FADBy similarity8

GO - Molecular functioni

Complete GO annotation...

Keywordsi

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

Enzyme and pathway databases

SABIO-RKiH9TB17.

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Hystricomorpha › Caviidae › Cavia
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)DescriptionActionsGraphical viewLength
ChainiPRO_00004252421 – 1332Aldehyde oxidase 1Add BLAST1332

Expressioni

Tissue specificityi

Expressed in liver.1 Publication

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10141.ENSCPOP00000021102.

Structurei

3D structure databases

SMRiH9TB17.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 912Fe-2S ferredoxin-typePROSITE-ProRule annotationAdd BLAST88
Domaini234 – 419FAD-binding PCMH-typePROSITE-ProRule annotationAdd BLAST186

Sequence similaritiesi

Belongs to the xanthine dehydrogenase family.Curated

Phylogenomic databases

eggNOGiKOG0430. Eukaryota.
COG4631. LUCA.

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.
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.
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.

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)DescriptionActionsGraphical viewLength
Sequence conflicti519S → N in AFG18181 (PubMed:23263164).Curated1
Sequence conflicti677E → G in AFG18181 (PubMed:23263164).Curated1
Sequence conflicti695E → G in AFG18181 (PubMed:23263164).Curated1
Sequence conflicti1137R → T in AFG18181 (PubMed:23263164).Curated1
Sequence conflicti1201A → P in AFG18181 (PubMed:23263164).Curated1

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.

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.

Entry informationi

Entry nameiAOXA_CAVPO
AccessioniPrimary (citable) accession number: H9TB17
Secondary accession number(s): H0WDM9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 19, 2014
Last sequence update: February 19, 2014
Last modified: May 10, 2017
This is version 27 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. SIMILARITY comments
    Index of protein domains and families