AOXA_BOVIN
ID AOXA_BOVIN Reviewed; 1339 AA.
AC P48034; Q3MHE7;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Aldehyde oxidase 1 {ECO:0000250|UniProtKB:Q06278};
DE EC=1.2.3.1 {ECO:0000250|UniProtKB:O54754};
DE AltName: Full=Azaheterocycle hydroxylase 1;
DE EC=1.17.3.-;
GN Name=AOX1 {ECO:0000250|UniProtKB:Q06278}; Synonyms=AO;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 43-48; 187-218 AND 538-573,
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, HOMODIMER, AND BLOCKAGE
RP OF N-TERMINUS.
RC TISSUE=Liver;
RX PubMed=8537361; DOI=10.1074/jbc.270.52.31037;
RA Calzi M.L., Raviolo C., Ghibaudi E., de Gioia L., Salmona M., Cazzaniga G.,
RA Kurosaki M., Terao M., Garattini E.;
RT "Purification, cDNA cloning, and tissue distribution of bovine liver
RT aldehyde oxidase.";
RL J. Biol. Chem. 270:31037-31045(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP IDENTIFICATION OF PARALOGS.
RX PubMed=23263164; DOI=10.1007/s00018-012-1229-5;
RA Kurosaki M., Bolis M., Fratelli M., Barzago M.M., Pattini L., Perretta G.,
RA Terao M., Garattini E.;
RT "Structure and evolution of vertebrate aldehyde oxidases: from gene
RT duplication to gene suppression.";
RL Cell. Mol. Life Sci. 70:1807-1830(2013).
CC -!- FUNCTION: Oxidase with broad substrate specificity, oxidizing aromatic
CC azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium
CC and phthalazine, as well as aldehydes, such as benzaldehyde, retinal,
CC pyridoxal, and vanillin. Plays a key role in the metabolism of
CC xenobiotics and drugs containing aromatic azaheterocyclic substituents.
CC Is probably involved in the regulation of reactive oxygen species
CC homeostasis. May be a prominent source of superoxide generation via the
CC one-electron reduction of molecular oxygen. May also catalyze nitric
CC oxide (NO) production via the reduction of nitrite to NO with NADH or
CC aldehyde as electron donor. May play a role in adipogenesis.
CC {ECO:0000269|PubMed:8537361}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aldehyde + H2O + O2 = a carboxylate + H(+) + H2O2;
CC Xref=Rhea:RHEA:16829, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:17478,
CC ChEBI:CHEBI:29067; EC=1.2.3.1;
CC Evidence={ECO:0000250|UniProtKB:O54754};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O2 + retinal = H(+) + H2O2 + retinoate;
CC Xref=Rhea:RHEA:56736, ChEBI:CHEBI:15035, ChEBI:CHEBI:15036,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240; Evidence={ECO:0000250|UniProtKB:O54754};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:O54754};
CC Note=Binds 2 [2Fe-2S] clusters per subunit.
CC {ECO:0000250|UniProtKB:O54754};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:O54754};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:O54754};
CC -!- COFACTOR:
CC Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302;
CC Evidence={ECO:0000250|UniProtKB:O54754};
CC Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC {ECO:0000250|UniProtKB:O54754};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q06278}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8537361}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in liver, lung and spleen.
CC Also expressed in kindey, eye, testis, duodenum, esophagus and thymus
CC (at protein level). {ECO:0000269|PubMed:8537361}.
CC -!- PTM: The N-terminus is blocked.
CC -!- MISCELLANEOUS: AOX genes evolved from a xanthine oxidoreductase
CC ancestral precursor via a series of gene duplication and
CC suppression/deletion events. Different animal species contain a
CC different complement of AOX genes encoding an equivalent number of AOX
CC isoenzymes. In mammals, the two extremes are represented by certain
CC rodents such as mice and rats, which are endowed with 4 AOX genes, and
CC by humans, whose genome is characterized by a single active gene
CC (PubMed:23263164). {ECO:0000305|PubMed:23263164}.
CC -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; X87251; CAA60701.1; -; mRNA.
DR EMBL; BC105265; AAI05266.1; -; mRNA.
DR PIR; S46980; S46980.
DR RefSeq; NP_788841.1; NM_176668.3.
DR AlphaFoldDB; P48034; -.
DR SMR; P48034; -.
DR STRING; 9913.ENSBTAP00000012827; -.
DR PaxDb; P48034; -.
DR PeptideAtlas; P48034; -.
DR PRIDE; P48034; -.
DR GeneID; 338074; -.
DR KEGG; bta:338074; -.
DR CTD; 316; -.
DR eggNOG; KOG0430; Eukaryota.
DR InParanoid; P48034; -.
DR OrthoDB; 48717at2759; -.
DR BRENDA; 1.2.3.1; 908.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0004031; F:aldehyde oxidase activity; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0043546; F:molybdopterin cofactor binding; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR002888; 2Fe-2S-bd.
DR InterPro; IPR036884; 2Fe-2S-bd_dom_sf.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type.
DR InterPro; IPR006058; 2Fe2S_fd_BS.
DR InterPro; IPR000674; Ald_Oxase/Xan_DH_a/b.
DR InterPro; IPR036856; Ald_Oxase/Xan_DH_a/b_sf.
DR InterPro; IPR016208; Ald_Oxase/xanthine_DH.
DR InterPro; IPR014313; Aldehyde_oxidase.
DR InterPro; IPR008274; AldOxase/xan_DH_Mopterin-bd.
DR InterPro; IPR037165; AldOxase/xan_DH_Mopterin-bd_sf.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR InterPro; IPR005107; CO_DH_flav_C.
DR InterPro; IPR036683; CO_DH_flav_C_dom_sf.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR002346; Mopterin_DH_FAD-bd.
DR InterPro; IPR022407; OxRdtase_Mopterin_BS.
DR PANTHER; PTHR11908; PTHR11908; 1.
DR Pfam; PF01315; Ald_Xan_dh_C; 1.
DR Pfam; PF02738; Ald_Xan_dh_C2; 1.
DR Pfam; PF03450; CO_deh_flav_C; 1.
DR Pfam; PF00941; FAD_binding_5; 1.
DR Pfam; PF00111; Fer2; 1.
DR Pfam; PF01799; Fer2_2; 1.
DR PIRSF; PIRSF000127; Xanthine_DH; 1.
DR SMART; SM01008; Ald_Xan_dh_C; 1.
DR SMART; SM01092; CO_deh_flav_C; 1.
DR SUPFAM; SSF47741; SSF47741; 1.
DR SUPFAM; SSF54292; SSF54292; 1.
DR SUPFAM; SSF54665; SSF54665; 1.
DR SUPFAM; SSF55447; SSF55447; 1.
DR SUPFAM; SSF56003; SSF56003; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR TIGRFAMs; TIGR02969; mam_aldehyde_ox; 1.
DR PROSITE; PS00197; 2FE2S_FER_1; 1.
DR PROSITE; PS51085; 2FE2S_FER_2; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
DR PROSITE; PS00559; MOLYBDOPTERIN_EUK; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; Cytoplasm; Direct protein sequencing; FAD; Flavoprotein; Iron;
KW Iron-sulfur; Lipid metabolism; Metal-binding; Molybdenum; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..1339
FT /note="Aldehyde oxidase 1"
FT /id="PRO_0000166103"
FT DOMAIN 5..92
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 236..421
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 1271
FT /note="Proton acceptor; for azaheterocycle hydroxylase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:O54754"
FT BINDING 44
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 49
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 52
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 74
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 113
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 114
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 117
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 149
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 151
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 151
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 264..271
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 345
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 354
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 358
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 367
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 411
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 807..808
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1048
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1089..1092
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1204
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1269
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT MOD_RES 1069
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT CONFLICT 5
FT /note="S -> A (in Ref. 2; AAI05266)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="M -> I (in Ref. 2; AAI05266)"
FT /evidence="ECO:0000305"
FT CONFLICT 804
FT /note="V -> I (in Ref. 2; AAI05266)"
FT /evidence="ECO:0000305"
FT CONFLICT 1060
FT /note="V -> A (in Ref. 2; AAI05266)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1339 AA; 147611 MW; 3CA7FF9D2B06F655 CRC64;
MEGGSELLFY VNGRKVTEKN VDPETMLLPY LRKKLRLTGT KYGCGGGGCG ACTVMISRYN
PITKKIRHYP ANACLTPICS LYGAAVTTVE GIGSTKTRIH PVQERIAKCH GTQCGFCTPG
MVMSLYTLLR NHPEPTLTQL NDALGGNLCR CTGYRPIINA CKTFCKTSGC CQSKENGVCC
LDQGMNGLPE FEEGNETSLK LFSEEEFLPL DPTQELIFPP ELMTMAEKKT QKTRIFGSDR
MTWISPVTLK ELLEAKVKYP QAPVVMGNTS VGPDMKFKGI FHPVIISPDR IEELSVVNYT
DNGLTLGAAV SLAEVKDILA NVTRKLPEEK TQMYHALLKH LETLAGPQIR NMASLGGHIV
SRHPDSDLNP LLAVGNCTLN LLSKEGRRQI PLNEQFLRKC PSADLKPEEI LISVNIPYSR
KWEFVSAFRQ AQRQQNALAI VNSGMRVCFG KGDGIIRELS IAYGGVGPTT ILANNSCQKL
IGRPWNEEML DAACRLILDE VSLPGSAPGG RVEFKRTLIV SFLFKFYLEV SQILKGMDLV
HYPSLASKYE SALEDLHSRH YWSTLKYQNA DLKQLSQDPI GHPIMHLSGI KHATGEAIYC
DDMPVVDREL FLTFVTSSRA HAKIVSIDVS AALSLPGVVD ILTGEHLPGI NTTFGFLTDA
DQLLSTDEVS CVGQLVCAVI ADSEVQARRA AQQVKIVYQD LEPVILTIEE AIQNKSFFEP
ERKLEYGNVD EAFKMVDQIL EGEIHMGGQE HFYMETQSML VVPKGEDREI DVYVSAQFPK
YIQDITASVL KVSANKVMCH VKRVGGAFGG KVTKTGVLAA ITAFAANKHG RPVRCILERG
EDILITGGRH PYLGKYKAGF MNDGRILALD MEHYNNAGAF LDESLFVIEM GLLKLENAYK
FPNLRCRGWA CRTNLPSNTA LRGFGFPQAG LITEACITEV AAKCGLPPEK VRMINMYKEI
DQTPYKQEIN TKNLTQCWKE CMATSSYTLR KAAVEKFNSE NYWKKKGLAM VPLKYPIGLG
SVAAGQAAAL VHIYLDGSVL VTHGGIEMGQ GVHTKMIQVV SRELRMPLSS IHLRGTSTET
IPNTNPSGGS VVADLNGLAV KDACQTLLKR LKPIISKNPK GTWKDWAQAA FNESISLSAT
GYFRGYESNI NWETGEGHPF EYFVYGAACS EVEIDCLTGA HKNIRTDIVM DVGYSINPAL
DVGQIEGAFI QGMGLYTIEE LNYSPQGVLY TRGPNQYKIP AICDIPMELH ISFLPPSENS
NTLYSSKGLG ESGIFLGCSV FFAIHDAIRA ARQERGLPGP LRLNSPLTPE KIRMACEDKF
TKMIPRDEPG SYVPWSVPI
