AOXA_MACFA
ID AOXA_MACFA Reviewed; 1338 AA.
AC Q5FB27; D6BND8;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 2.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Aldehyde oxidase 1;
DE EC=1.2.3.1 {ECO:0000250|UniProtKB:O54754};
DE AltName: Full=Azaheterocycle hydroxylase 1;
DE EC=1.17.3.-;
GN Name=AOX1;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Hoshino K.;
RT "Molecular cloning and characterization of monkey aldehyde oxidase.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND IDENTIFICATION OF
RP 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 Participates in the bioactivation of prodrugs such as famciclovir,
CC catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir,
CC which is a potent antiviral agent. Is probably involved in the
CC regulation of reactive oxygen species homeostasis. May be a prominent
CC source of superoxide generation via the one-electron reduction of
CC molecular oxygen. May also catalyze nitric oxide (NO) production via
CC the reduction of nitrite to NO with NADH or aldehyde as electron donor.
CC May play a role in adipogenesis (By similarity).
CC {ECO:0000250|UniProtKB:O54754}.
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; Evidence={ECO:0000250};
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:O54754}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O54754}.
CC -!- TISSUE SPECIFICITY: Detected at high levels in liver, also detected in
CC lung, kidney, lacrimal gland and olfactory mucosa.
CC {ECO:0000269|PubMed:23263164}.
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; AB201545; BAD89382.1; -; mRNA.
DR EMBL; FJ751935; ACQ73553.1; -; mRNA.
DR RefSeq; NP_001271673.1; NM_001284744.1.
DR AlphaFoldDB; Q5FB27; -.
DR SMR; Q5FB27; -.
DR STRING; 9541.XP_005573930.1; -.
DR BindingDB; Q5FB27; -.
DR ChEMBL; CHEMBL1641357; -.
DR GeneID; 102131116; -.
DR CTD; 316; -.
DR eggNOG; KOG0430; Eukaryota.
DR OrthoDB; 48717at2759; -.
DR BRENDA; 1.2.3.1; 1793.
DR SABIO-RK; Q5FB27; -.
DR PRO; PR:Q5FB27; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0004031; F:aldehyde oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0043546; F:molybdopterin cofactor binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW 2Fe-2S; Cytoplasm; FAD; Flavoprotein; Iron; Iron-sulfur; Lipid metabolism;
KW Metal-binding; Molybdenum; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1338
FT /note="Aldehyde oxidase 1"
FT /id="PRO_0000166105"
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 1270
FT /note="Proton acceptor; for azaheterocycle hydroxylase
FT activity"
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 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 806..807
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1047
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1088..1091
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1203
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT BINDING 1268
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT MOD_RES 1068
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06278"
FT CONFLICT 184
FT /note="R -> G (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="M -> V (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 284..286
FT /note="VII -> GYN (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 294..302
FT /note="LSVVNHTHN -> PECCKPYTY (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 328
FT /note="G -> E (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="R -> K (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="R -> H (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 549
FT /note="H -> Y (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 605
FT /note="L -> P (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 1105
FT /note="T -> I (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 1139
FT /note="V -> I (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 1301
FT /note="S -> T (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
FT CONFLICT 1338
FT /note="I -> V (in Ref. 1; BAD89382)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1338 AA; 147691 MW; C82ACFAB5FA7019C CRC64;
MDRASELLFY VNGRKVIEKN VDPETMLLPY LRKKLRLTGT KYGCGGGGCG ACTVMISRYN
PITNRIRHHP ANACLIPICS LYGTAVTTVE GIGSTHTRIH PVQERIAKCH GTQCGFCTPG
MVMSIYTLLR NHPEPTLDQL TDALGGNLCR CTGYRPIIDA CKTFCETSGC CQSKENGVCC
LDQRINGLPE FEEGSKTSPK LFAEEEFLPL DPTQELIFPP ELMIMAEKQP QRTRVFGSER
MMWFSPVTLK ELLEFKFKYP QAPVIMGNTS VGPQMKFKGV FHPVIISPDR IEELSVVNHT
HNGLTLGAGL SLAQVKDILA DVVQKLPGEK TQTYHALLKH LGTLAGSQIR NMASLGGHII
SRHPDSDLNP ILAVGNCTLN LLSKEGKRQI PLNEQFLSKC PNADLKPQEI LVSVNIPYSR
KLEFVSAFRQ AQRQENALAI VNSGMRVFFG EGHGIIRELS ISYGGVGPAT ICAKNSCQKL
IGRHWNEEML DTACRLVLEE VSLSGSAPGG RVEFKRTLII SFLFKFYLEV SQILKKMDPI
RYPSLADKHE SALEDLHSKH HCSTLKYQHM GPKQHPEDPI GHPIMHLSGV KHATGEAIYC
DDMPLVDQEL FLTFVTSSRA HAKIVSIDLS EALSMPGVVD VITAEHLSDV NSFCFFTEAE
EFLATDKVFC VGQLVCAVLA DSEVQAKRAA KQVKIVYQDL EPLILTIKEA IQHNSFFEPE
RKLEYGNVDE AFKVVDQILE GEIHMGGQEH FYMETQSMLV VPKGEDQEMD VYVSTQFPKY
IQDIVASTLK LPANKVMCHV KRVGGAFGGK AFKTGVIAAV TAFAANKHGR AVRCVLERGE
DMLITGGRHP YLGKYKAGFM NDGRILALDM EHYSNAGNSL DESLLVIEMG LLKMDNAYKF
PNLRCRGWAC RTNLPSNTAF RGFGFPQAGL ITESCIMEVA AKCGLSPEKV RMINMYKEID
QTPYKQEINA KNLIQCWREC MAVSSYSLRK AAVEKFNAEN YWKKKGLAMV PLKYPVGLGS
RAAGQAAALV HIYLDGSVLV THGGIEMGQG VHTKMIQVVS RELGMPISNV HLRGTSTETV
PNANVSGGSV VADLNGLAVK DACQTLLKRL EPIISKNPKG TWKDWAQTAF DESISLSAVG
YFRGYESDIN WEKGEGHPFE YFVYGAACSE VEIDCLTGDH KNIRTDIVMD VGCSINPAID
IGQIEGAFIQ GMGLYTIEEL NYSPQGVLHT RGPDQYKIPA ICDTPTEFHI SLLPPSENSN
TLYSSKGLGE SGVFLGCSVF FAIHDAVSAA RRERGLHGPL SLNSPLTPEK IRMACEDKFT
KMIPRDEPGS CVPWNVPI
